>> CONTINUING ON WITH PRECEPTATIONS. --PRESENTATIONS AND OUR FIRST SPEAKER IS DR. DAVE I TENSEON WHO IS PROFESSOR OF NEUROLOGICAL SURGERY AT THE CENTER AND DIRECTOR FOR THE CENTER OF SURGICAL QUALITY AND OUTCOMES RESEARCH AT VANDERBILT UNIVERSITY AND HE WILL BE SPEAKING ON FACTORS INFLUENCING PATIENTS ACCEPTANCE OF AND ADHERENCE TO ACTIVE SURVEILLANCE. >> THANK YOU MEMBERS OF THE PANEL, LADIES AND GENTLEMEN, GOOD MORNING. SO I'M GOINGTO SPEAK ON FACTORS INFLUENCING PATIENT'S ACCEPTANCE AND ADHERENCE TO ACTIVE SURVEILLANCE. AND AND TO DO THIS, I THINK IT'S HELPFUL TO HAVE A CONCEPTUAL MODEL TO USE AS A FRAMEWORK FOR DECISION MAKING AND THERE ARE A LOT OF DIFFERENT MODELS OUT THERE BUT I THINK THE ONE THAT FITS US BEST IS ADAPTED FROM THE OTA PENTINE REGIMENY AND THIS IS A A MODEL. WHEN WE THINK ABOUT THIS THROUGHOUT MEDICINE, WE LIKE TO THINK THE PATIENTS ARE SYMPTOMATIC, THEY HAVE A RADICAL AND LOGICAL APPROACH TO DECISION MAKING AND CERTAINLY THAT OCCURS AND YOU CAN SEE THAT HERE IN THE MIDDLE, PATIENTS WHO ARE FACING A DECISION REGUARDING TREATMENT FOR PROSTATE CANCER WILL LOOK AT PREFERENCES SYSTEMATICALLY AND WEIGH THEM ACCORDINGLY. SO THEY'LL THINK OF THINGS LIKE CANCER CONTROL, AVOIDANCE OF SIDE EFFECTS. THINGS LIKE TIME OFF OF WORK AND COSTS AND OTHER FACTORS. BUT I THINK AS A CLINICIAN AND I THINK THE CLINICIANS IN THE ROOM, PROBABLY EVERYONE IN THE ROOM REALIZES THIS, PATIENTS DON'T ACTUALLY ACT COMPLETELY AND LOGICALLY AND RATIONALLY. SO THERE ARE NONSYSTEMATIC OR HERRISTIC FACTORS WHICH AFFECT THESE PREFERENCES AS WELL AND I WOULD SAY YOU CAN DIVIDE THESE INTO MODIFIABLE AND NONMODIFIABLE HERESTICT FACTORS AND WE WILL SPEND TIME TALKING ABOUT THESE BECAUSE I THINK THEY'RE MOST IMPORTANT. YOU THINK ABOUT PRIOR EXPERIENCES ACCIDENT AGE, OTHER ILLNESSES, THESE ARE THINGS THAT DON'T ACTUALLY CHANGE AND THEN HAVE YOU THE MODIFIABLE FACTORS, THINGS LIKE THE DOCTOR RECOMMENDATION, PARTNER AND FAMILY INPUT, PERCEIVED CANCER AGGRESSIVENESS, ET CETERA. THESE FACTORS ARE GOING TO INFLUENCE THE SYSTEMATIC FACTORS AND AFFECT THE VALUES THAT ARE PLACED ON EACH FACTOR. NOW A MAN'S GOING TO PUT THESE ALL TOGETHER AND MAKE HIS DECISION. WHEN HE MAKES HIS DECISION, INITIALLY IF HE CHOOSES INTERVENTION, THAT'S A ONE TIME DECISION, YOU CAN BE THE REVERSE THAT OBVIOUSLY, IF HE CHOOSEs TO GO INTO ACTIVE SURVEILLANCE, THAT'S AN ONGOING DECISION, SO IN OTHER WORDS EVERY TIME HE SEES A DOCTOR, EVERY TIME HE TALKS TO PARTNERS, FAMILY MEMBERS, ME MAY HAVE DOUBTS IN HIS MIND AND THAT GOES ON AND ON AND THOSE FACTORS CONTINUE TO PLAY A ROLE WITH THIS. SO THAT IN MIND AS OUR BACKGROUND, I'M GOING OVER THE GENERAL LITERATURE ON PATIENT FACTORS AND THEN I'LL GO THROUGH EACH OF THESE CATEGORIES INDIVIDUALLY, PARSING THE DIFFERENT FACTORS TO HELP YOU THINK ABOUT IT. SO LET'S START WITH WHY PATIENTS ACCEPT OR REJECT THESE OVER UNIQUE TREATMENTS. THEY LOOKED AT MEN YOU SHOULD UNDER AGE 50 WHO HAD RECENT TREATMENTS AT HOPKINS. THESE ARE MEN WHO ARE ELIGIBLE FOR ACTIVE SURVEILLONSRO ENS. --SURVEILLANCE. THE VAST MAJORITY HAD SURGERY AND 11% HAD RADIATION AND FIVE% CHOSE ACTIVE SURVEILLANCE. WHAT SOURCES THEY USE TO CHOOSE THAT TREATMENT. SO NOW LET'S TAKE A LOOK AT SPECIFICS COMPARISONS, LOOKING AT MEN WHO CHOSE SURGERY OVER ACTIVE SURVEILLANCE AND THOSE OVER SURGERY AND HERE CAN YOU SEE DIFFERENT REASONS IN RED ARE THE MEN WHO HAD SURGERY AND YELLOW THE MEN WHO HAD ACTIVE SURVEILLANCE. SO THE MEN WHO CHOSE THE SURVEILLANCE, WHAT WERE THE MOST COMMON REASONS? THE FIRST MOST IMPORTANT WAS THE BEST CHANCE FOR CARE. SECOND WAS DOCTOR RECOMMENDATION, THIRD WAS TREATMENT SUCCESS RATE, FOURTH WAS TOO YOUNG FOR LESS AGGRESSIVE TREATMENT AND FIFTH WAS THEY WERE ONLY GOING TO BE SATISFIED IF THE PROSTATE WAS REMOVED. A LOT OF THE PATIENTS SAID THIS WAS THE REASON THEY CHOSE THIS. LET'S TURN IT OVER THE OTHER WAY, FOR THE MEN WHO CHOSE ACTIVE SURVEILLANCE, WHO DROVE THEM? YOU HAVE TO READ FROM THE BOTTOM UP. THE CANCER DID NOT REQUIRE A MORE ADDRESSIVE TREATMENT, THE SECOND MOST COMMON WAS THEY WANTED TO AVOID SURGERY SIDE EFFECTS AND THE THIRD IS THEY WANT TO AVOID SURGERY ITSELF. SO WE'RE STARTING TO HEAR THEMES AND AS I GO THROUGH THE OTHER STUDIES, THESE SAME THEMES ARE GOING TO COME UP AGAIN. NOW LET'S LOOK AT RADIATION VERSES ACTIVE SURVEILLANCE DECISION, MOST COMMON REASON WAS TREATMENT SUCCESS RATE, RADIATION IN PURPLE HERE, THE SECOND MOST COMMON REASON WAS THEY KNEW OF OTHER REASONS WHO HAVE BEEN SATISFIED WITH THAT CHOICE. WHY DO MEN CHOOSE ACTIVE SURVEILLANCE OVER RADIATION, THE MOST COMMON REASON, THE ONLY ONE WAS THEY WANTED TO AVOID SIDE EFFECTS. NOW, THIS IS QUANTITATIVE LITERATURE I'VE JUST SHOWN YOU, LET'S TALK ABOUT QUALITATIVE LITERATURE. THIS IS A STUDY FROM CANDAWHO CHOSE ACTIVE SURVEILLANCE AND THEY WERE ASKED SEMISTRUCTURED SURVEILLANCE, AND OUTSIDE ON THEIR DECISION AND THEY USE STANDARD QUALITATIVE METHODS TO IDENTIFY THEMES AND THERE ARE NINE THEME CATEGORYS AND THESE ARE PUT UP IN NO PARTICULAR ORDER. THE FIRST ONE THEY MENTION WAS PATIENTS PERCEPTION OF HIS CANCER SECOND WAS PHYSICIAN RECOMMENDATION, THIRD WAS CONTROL. WHO MAKES THE DECISION, THE PATIENT OR THE DOC? THEN HAVE YOU SEEKING INFORMATION TO MAKE A DECISION ADVICE OF FAMILY AND FRIENDS, PREEXISTING MEDICAL CONDITIONS, AGE AND ABILITY TO COPE ON ACTIVE SURVEILLANCE. NOW TO THE CREDIT OF MY COLLEAGUES IN VANCOUVER, THEY TOOK THIS QUALITATIVE WORK AND THEY SAID, THAT'S INTERESTING WE HAVE THESE, BUT THEY CAN'T ALL BE EQUALLY IMPORTANT, SO LET'S FIGURE OUT WHICH ONES ARE IMPORTANT SO WE CREATE A STANDARDIZED QUESTION AIR AND THEN THEY ASK PARTICIPANTS TO STATE OW IMPORTANT IT WAS FROM A SCALE OF ZERO TO FIVE AND MOST MOST IMPORTANT AND ZERO NOT IMPORTANT AT ALL. THEY SENT THE QUESTIONNAIRE TO 73 MEN ON ACTIVE SURVEILLANCE. THIS TABLE, GIVES YOU THE RANK ORDER, ALL RIGHT, AND HERE YOU HAVE THE MEAN SCORE, ZERO TO FIVE, FIVE BEING THE MOST IMPORTANT, HERE CAN YOU SEE THE MOST IMPORTANT BY FAR WAS THE UROLOGYST OPINION. IT'S ALMOST A FULL POINT HIGHER THAN THE NEXT FACTOR. SO DR. RECOMMENDATION IS VERY IMPORTANT. THEN HAVE YOU CURRENT AGE, THEN HAVE YOU THE SIDE EFFECT QUESTIONS, IMPACT OF TREATMENT ON URINARY AND SEXUAL FUNCTION. THEN YOU HAVE NEED TO HAVE ARE REGULAR BIOPSIES, ACTIVE SURVEILLANCE, ADVICE FROM PARTNER AND SPOUSE INPUT, UROLOGY SPEND MORE TIME WITH ME, TIME FROM TREATMENT AND IT KEEPING GOING DOWN THERE. THE AN IMPORTANT ONE IS ADVICE FROM FRIENDS, FINANCIAL CONCERNS THESE LAST TWO WERE THE LEAST IMPORTANT BUT AT LEAST THEY WEREN'T ZERO OS, BUT THE MORAL OF THE STORY HERE, THE DOCTOR'S OPINION AND THE AGE AND SIDE EFFECT PROFILE ARE HEAVY HITTER WHEN IS IT COMES TO PATIENTS ACTORS HERE'S ANOTHER STUDY, SIMILAR, THIS IS FROM A GROUP IN MIAMI, THEY SEND A SURVEY TO 180 MEN ON A SINGLE PROTOCOL ON A SINGLE CENTER, 57% OF MEN RETURN THE SURVEILL AND AGAIN THE RESPONSE WERE ASKED TO RANK FACTORS TO GO ON ACTIVE, AND TO SAY WHETHER OR NOT IT WAS IMPORTANT TO THEM AT ALL AND WHAT WERE THEIR NUMBER ONE REASONS AND THEY COULD GIVE MORE THAN ONE NUMBER ONE REASON. AND THE PORTION THAT'S RANKED AT ALL, AND THE PORTION WHICH RANKED NUMBER ONE AND YOU COULD RANK MORE THAN ONE THING NUMBER ONE AND THEN AT A CAME UP WITH THIS MEAN RANK WHICH WAS THE COMBINATION OF THE TWO. SO LET'S PAY ATTENTION TO THE MEAN RANK AND WHAT ARE THE IMPORTANT ISSUES ACCORDING TO PATIENT O SINGLE ACTIVE SURVEILLANCE. SO THE PATIENT'S PERCEPTION OF CANCER AGGRESSIVENESS, NOW YOU HAVE DECISION MAKES STYLE, I RESEARCHED THE ALTERNATIVE AND THIS ONE SEEMS BEST FOR THE TYPE OF OF PROSTASTY CANCER I HAVE. NUMBER FOUR WAS MY FAMILY WAS SUPPORTIVE. AN IMPORTANT THEME AGAIN, FAMILY SUPPORT, BUT YOU GET INTO I DEPARTMENT WANT TO HAVE SURGERY SO I WANT TO AVOID,IVE WAS AFRAID OF THE PARTICULAR TREATMENT, THE SIDE EFFECT QUESTIONS, AGAIN, I DIDN'T WANT TO HAVE RADIATION, HERE'S A KEY ONE, I'M NOT ANXIOUS ABOUT LIVING WITH MY PROSTASTY CANCER. PEOPLE TALK ABOUT ANXIOUS ANXIOUS--ANXIETY, WE WILL TALK ABOUT THAT IN THE ADHERENCE PIECE. I HAVE A FRIEND THAT WAS TREATED WAS NOT HAPPY OR TREAT WIDE ACTIVE SURVEILLANCE AND HE WAS HAPPY AND THEN I HAVE OTHER HEALTH ISSUES. SO THAT CO-MORBIDITY PIECE. SO NOW WE'VE BEEN THROUGH THREE OR FOUR VERY GOOD STUDIES WHICH GIVE YOU AN OVERVIEW OF THE FACTORS, I THINK YOU CAN SEE THERE ARE THEMES COMING UP HERE PUT THEM IN THE MODEL BEFORE AND I'D LIKE TO TALK ABOUT FIRST THE SYSTEMATIC FACTORS AND WHAT DO THEY CHOOSE FOR ACTIVE SURVEILLANCE. I WILL HIGHLIGHT THE PIECES OPPOSE TO GO THROUGH ALL OF IT AGAIN. IT'S CLEAR WHEN YOU THINK ABOUT THE DECISION MAKING PROGRESS AND THIS CAN DRIVE THEM TOWARDS OR AWAY FROM ACTIVE SURVEILLANCE, MEN WITH LOWER PROSTASTY CANCER CHOUGH CHOOSE AGGRESSIVE INTERVENTION ARE PRIMARILY MOTIVATE TOTED CONTROL OR CURE THEIR CANCER. THAT'S WHAT COMES UP AGAIN AND AGAIN FROM THAT STUDY FROM HOPKINS THAT SAYS WHY DID YOU CHOOSE SURGERY. I WANTED TOTAL ERADICATION, MEN WITH LOW RISK PROSTATE CANCER WHO EXPECTATIONS LECT ACTIVE SURVEILLANCE, TEND TO PERCEIVE THEIR CANCER AS LESS DANGEROUS AND THEREFORE THEY VALUE THE CANCER CONTROL LESS. NOW HAD THIS IS MY OPINION FROM MY TAKE ON LITERATURE, YOU DON'T HAVE TO TAKE MY WORRIED FOR IT, LET ME SHOW YOU QUALITATIVE STUDIES OF MEN ON ACTIVE SURVEILLANCE, SORT OF BACK UP THIS HYPOTHESIS,--ANOTHER ONE SAID I AM GOING TO WAIT UNTIL I HAVE CANCER BEFORE I CONSIDER TREATMENT. ANOTHER ONE SAID THIS, 50% OF MEN GET PROSTASTY CANCER, SO IT'S NOT THAT BAD, I THINK LARRY SAID HE HAD A PATIENT 60-70% OF MEN GET THIS SO IT'S NOT THAT BIG A DEAL. THEY PERCEIVE THEIR CANCER AS LESS DANGEROUS. SO WITHOUT GOING THROUGH ALL THE PIECES, WHAT ARE THE SYSTEMATIC FACTORS, THE PATIENT OF VALUE AND INFLUENCE OF ACTIVE SURVEILLANCE? THE PERCEPTION TO CANC SER LESS DANGEROUS. IT REDUCES THE DESIRE FOR CANCER CONTROL OR CURE. AND A FEAR OF OTHER TREATMENT AND IT IS CONVENIENCE OF TREATMENT, FOR MANY, ACTIVE SURVEILLANCE IS EASIER AND TAKES TIME FROM THE SHORT ONE THAN THE AGGRESSIVE INTERVENTIONS SO THESE ARE THINGS THAT MEN SYSTEMATICALLY RANK. LIKE I SAID THERE ARE OTHER OUTSIDE INFLUENCES WHICH HAVE A HERESTIC EFFECT, HERESTICT FACTORS. SO LET'S TALK ABOUT THE FIRST NONMODIFIABLE HERESTIC FACTORS. THESE WILL INCREASE UTILIZATION WHICH PORTRAYS MY BIAS ABOUT ACTIVE SURVEILLANCE. BUT LET'S START WITH NONMODIFIABLE FACTORS MPLET IMPORTANT FACTOR IS AGE OF DIAGNOSIS, THIS CLEARLY INFLUENCES ACTSIVE SURVEILLANCE. YOUNGER AGE IS AN IMPORTANT FACTOR IN REJECTING ACTIVE SURVEILLANCE AND THIS IS QUALITATIVE AND QUANTITATIVE STUDIES CONVERSELY OLDER MACHINE, OLDER AGE MAY DRUM MEN FORWARDS ACTIVE SURVEILLANCE IN ONE TODAY, IT WAS THE MOST IMPORTANT FACTOR THAT INFLUENCED THE DECISION TO GO ON ACTIVE SURVEILLANCE. THE OTHER KEY POINT IS THE PRESENCE OF CO-MORBIDITYS WHICH MAY BE ACTIVE SURVEILLANCE. MANY HAVE SHOWN THE DOCUMENT THAT THE PRESENCE OF OTHER MEN DRAW THEM TOWARDS THE ACTIVE SURVEILLANCE. IN ANOTHER 186% NOTE THAD OTHER HEALTH ISSUES AFFECTED THEIR DECISION TO GO ON ACTIVE SURVEILLANCE AND OF COURSE THESE CAN'T BE CHANGED. SO TO DISCUSS THESE NONMODIFIABLE FACTORS AND WE'VE SEEN SOME OF THESE ALREADY, AGE EVER DIAGNOSIS, OTHER COMORBID CONDITIONS AND HERE'S SORT OF A ONE THAT I'M NOT GOING TO SPEND A LOT OF TIME TALKING ABOUT BUT I THINK IS IMPORTANT AND CAN'T BE CHANGED IS A PATIENT'S PRIOR EXPERIENCE WITH CANCER, WHETHER HE HAD IT HIMSELF OR FAMILY MEMBERS OR FRIENDS AND THAT INFLUENCE'S HOW THEY PERCEIVE THEIR CANCER AND HOW THEIR EXPERIENCE IS GOING TO BE AND THEY MAY BE SOMEWHAT MODIFIABLE BUT IN THE END IT'S NOT THAT MODIFIABLE AND I DON'T THINK IT'S A TARGET FOR GOOD INTERVENTION. NOW HAVING SAID THAT, LET'S TALK ABOUT THE HERESTIC FACTORS. THAT COULD BE TARGET FOR INTERVENTIONS TO INCREASE ACTIVE SURVEILLANCE. FIRST AND FOREMOST. DR. RECOMMENDATION, IT IS THE MOST IMPORTANT HERESTIC FACTOR INFLUENCING ACCEPTANCE OF SURVEILLANCE. NEWELLER SOWS TODAYS HAVE DOCUMENT THAD THE DOCTOR, THE UROLOGYST, THEIR RECK LENDATIONS IS THE MOST IMPORTANT FACTOR IN DECISION MAKING. IT WORKS IN TWO WAYS. AS A UROLOGY THE GUY COMES TO ME AND SAYS DOCK WHAT SHOULD I DO. BUT IT'S NOT HOW I ANSWER THAT QUESTION, - ALTHOUGH IT'S IMPORTANT, THERE'S ALSO THE PIECE ABOUT HOW THE DOCTOR COUNCILS THE PATIENT BECAUSE THAT COLORS THE DANGER OF CANCER SO I CAN SAY TO A PATIENT, WELL, YOU CAN DO ACTIVE SURVEILLANCE. SURGERY OR RADIATION BUT I SAY YOU HAVE A BAD CANCER BUT NINE OUT OF 10 GUYS CAN DO THIS MAY COLOR THE PATIENTS AND THERE'S EVIDENCE OUT THERE THAT MEN WHO ELECT TO GO ON ACTIVE SURVEILLANCE MAY BE LESS SUSCEPTIBLE TO THE DR. INFLUENCE AND I WANT TO GO BACK TO THE STUDY FROM HOPKINS AND POINT SOMETHING OUT TO YOU THIS, IS PATIENT REPORTED THE MOST INFLUENTIAL FACTOR IN TREATMENT DECISION MAKING. THIS IS SURGERY THIS, IS RADIATION AND THIS IS ACTIVE SURVEILLANCE. CAN SEE IN THE SURGICAL PATIENTS, THREE OUT OF FOUR SAID THAT DOCTOR'S RECOMMENDATION WAS THE MOST IMPORTANT INFLUENCE AND AS YOU GO FROM ARE SURGERY TO RADIATION TO ACTIVE SURVEILLANCE, CAN YOU SEE THAT IT DROPS OFF, AND THERE'S CLEARICALLY A PATTERN THERE, NOW WHAT REPLACES THIS? OTHER SOURCES. PATIENTS ARE UNCLEAR AND INTERESTINGLY, THE INTERNET. AND THESE GUYS ARE NOT LISTENING TO THE DR. DOCTOR. THAT'S FOR THE FAMILY, THAT'S FAIRLY STANDARD THROUGHOUT. SO THE DOCTOR RECOMMENDATIONS CLEARLY IMPORTANT BUT I MENTION THE FAMILY BUT I SEE THE PIECE AS IMPORTANT, MAYBE NOT AS IMPORTANT AS THE DOCTOR, BUT CLOSE. THIS INFLUENCES PATIENT ACCEPTANCE, THIS HAS BEEN SHOWN IN NUMEROUS STUDIES, AND THEY NOTE THAD THE ADVICE OF PART NETHERLANDS AND OR SPOUSE WAS THE SIX MOST IMPORTANT FACTOR IN PATIENTS SELECTING ACTIVE SURVEILLANCE, WARREN NOTED THAT ACTIVE PATIENTS STATED THAT THEIR FAMILY MEMBERS WERE SUPPORTED AND THAT'S THE KEY POINT. THE FAMILY MEMBER NEEDS TO BE SUPPORTIVE, AS A CLINICIAN AND SOMEONE WHO DOES RESEARCH IN THIS SPACE, I CAN SAY AS A GENERAL RULE PARTNERS AND FAMILY MEMBERS DON'T TEND TO BE SUPPORTIVE OF ACTIVE SURVEILLANCE. PARTNERS AND FAMILY MEMBERS TEND TO WEIGH CANCER CONTROL MUCH MORE HIGHER THAN THE OTHER FACTORS. ALL THEY CARE ABOUT IS GETTING THEIR LOVED ONES FREE OF CANCER AND HAVING THEM LIVE AS LONG AS POSSIBLE. AND THERE'S LITERATURE OUT THERE THAT SAYS THEY ACTUALLY VALUE THE SIDE EFFECTS DIFFERENTLY. SO LET ME GO THROUGH THAT IN GREATER DETAIL. WHAT DO PARTNERS THINK IS IMPORTANT WHEN SELECTING THERAPY. WELL THIS IS A STUDY FROM ENGLAND, IT'S AN OLDER STUDY BUT IT'S VALUABLE. THIS SURVEY, THEY SENT THIS SURVEILL TO 100 PARTNERS OF PATIENTS TO ASK THEM ABOUT DECISION MAKING INFLUENCES, NOW THIS IS WHAT I SINGLE FASCINATING IF YOU LOOK AT THIS, 41% SAID--THE PARTNERS SAID THE SURGERY WAS THE BEST OPTION, 37% SAID THAT RADIATION WAS THE BEST OPTION, 12% PREFER BRACHYTHERAPY AND OTHER HAD NO CLEAR PREFERENCE ON INTERVENTIONS. SO IF YOU'RE A PATIENT, HOW ARE GAG STAND UP TO YOUR PARTNER WHEN THEY SAY, THAT'S A BAD IDEA AND YOU GO HOME TO THAT EVERY DAY, SO THESE MEN HAVE SOME PRESSURES ON THEM. WHEN THE PARTNERS WERE ASKED WHAT WAS MOST IMPORTANT, WHAT WAS NUMBER ONE? TOTAL ERADICATION OF THE CANCER. THAT CAME UP IN 14 PARTNERS WHEN YOU ADD THAT TO SURVIVAL. BEST CHANCE FOR CURE, WHAT THAT SAYS TO ME IS BY FAR AND AWAY, PARTNERS VALUE CANCER CONTROL. IN FACT, TOTAL ERADICATION OF CANCER WAS MORE IMPORTANT THAN THE PATIENT BEING HAPPY WITH HIS DECISION, SO IN THE END, THAT'S WHAT DRIVES THE PARTIENERS, YES THEY CARE ABOUT SIDE EFFECTS, BUT IT'S NOT AS IMPORTANT AS CANCER CONTROL. AND DO PARTNERS VALUE PATIENTS QUALITY OF LIFE LESS THAN THE PATIENT. THIS IS A UTILITY STUDY THAT LOOKS INTO THIS, THEY LOOK AT 168 MEN AND THEIR PARTNER WHO IS DID NOT HAVE CANCER, THEY WERE ELIGIBLE FOR PROSTASTY CANCER SCREENING, THEY ASSESS THE UTILITYS AND THEY COMPARE THE HUSBAND'S UTILITY TO THE WIFE'S UTILITY. NOW LET'S REMEMBER THAT THE A LOWER UTILITY MEANS THEY VALUE IT WORSE. EVERYONE IN THE ROOM WHO ISN'T FAMILIAR WITH THIS, SO NOW LET'S LOOK AT THE TABLE, THESE ARE THE VARIOUS HEALTH STATES THAT CAN OCCUR IN PROSTASTY CANCER, IMPOTENCE, INCONTINENCE AND VARIOUS PROSTASTY CANCER STATES ISSUES THE THIS IS THE COLUMN WHERE THE LIFE'S UTIL PHS WAS LESS THAN THE HOSES SO SHE WAS THORS IT WAS PRETTY WORSE. THIS IS THE COLUMN WHERE IT'S--WHERE THEY WERE ABOUT THE SAME, ABOUT A THIRD OF THE TIME OR LESS, THE HUSBAND, THE WIFE VALUED IT THE SAME. THIS IS THE COLUMN WHERE THE HUSBAND'S UTILITY IS WORSE THAN THE WIVES. SO THE HUSBAND THINKS IT'S WORSE. THE HUSBAND MORE THAN HALF THE TIME FEELS THAT IT'S WORSE THAN THE WIFE. SO THIS TELLS YOU THAT THE HUSBAND THINKS IT'S A SIDE EFFECT ISSUE IS MORE IMPORTANT THAN THE WIFE. AND THAT'S A KEY POINT. SO TO WRAP THIS UP, MODIFIABLE FACTORS WHICH I WOULD ARGUE TARGETED MORE INTERVENTION, THE DOCTOR RECOMMENDATION AND I SAID BEFORE, IT WORKS IN TWO WAYS, PARTNER AND FAMILY MEMBER INFLUENCE AND PATIENT DECISION MAKING STYLE. I'M GOING TO WRAP UP, USE ALL MY TIME AND I WANT TO SAY A FEW WORDADHERENCE. THE SAME PATIENT FACTORS THAT INFLUENCE ACTIVE SURVEILLANCE WILL CHOOSE ACTIVE SURVEILLANCE FOR GOIS THAT HAVE TO CHOOSE IT, THEY REAFFIRM THEIR DECISION ONA DAILY BASIS, SEE A DOCTOR, FRIENDS FAMILY MEMBERS ABOUT PROSTASTY CANCER THEY'RE REAFFIRMING THIS DECISION, NOW SUGGEST THAD MAY CAUSE ANXIOUS BUT IF YOU LOOK AT PERSPECTIVE STUDIES THEY FAILED TO DOCUMENT INCREASED ANXIOUS OR DISSTRESS BUT HERE'S THE KEY POINT IN PATIENTS WHO REMAIN ON ACTIVE SURVEILLANCE. SO IT MAY BE A SELECTION BY US MORE THAN ANYTHING ELSE AND 18th MAY HAVE SOMETHING TO TO DO WITH IT. HOW DO MEN DEAL WITH THIS. AND THIS IS AN INTERVENTION TARGET. PATIENT SUPPORT GROUPS PROBABLY AREN'T HELPFUL AND MAY BE COUNTER PRODUCTIVE, IS AND ONE PATIENT SAID HE HAD TO DEFEND HIMSELF WHEN HE WENT TO THESE GROUPS, YOU HAVE TO CHANGE THE WAY THEY DO BUSINESS. MOST OF THESE MEN DEVELOP SELF-MANAGEMENT STRATEGIES TO DEAL WITH THE ACTIVE SURVEILLANCE. AND THEY PSYCHOLOGICALLY CANCER AS BENIGN, THEY COMMIT TO A NORMAL LIFE AND THEY OFTEN UNDERTAKE CHANGES TO DIET AND EXERCISE TO DEAL WITH ANXIETY AND UNCERTAINTY SO TO WRAP UP THERE ARE NUMEROUS FACTORS THAT ADHERE TO ADACTIVE SURVEILLANCE. THERE ARE HERESTIC FEATURES THAT COULD INCREASE ACTIVE SURVEILLANCE IN APPROPRIATE PATIENTS. THESE COULD TARGET THE DOCTOR RECOMMENDATION AND COUNSELING PIECE ISSUES THE PARTNER FAMILY NUMBER AND SUPPORT AND INPUT, WE COULD TRUE I TO THANK THE PATIENT DECISION MAKING STYLE AND WE CAN DEVELOP INTERVENTIONS TO HELP PATIENTS DEVELOP COPING STRATEGIES WHILE ON ACTIVE SURVEILLANCE. I WANT TO THANK YOU VERY MUCH FOR YOUR ATTENTION. [ APPLAUSE ] >> THANK YOU DR. PENSON. OUR NEXT SPEAKER IS DR. ANN HAMILTON. SHE'S THE PREFESSOR OF CLEANICAL EPIDEMIOLOGY AT THE UNIVERSITY OF SOUTHERN CALIFORNIA AND SHE WILL SPEAK ON REGIONAL, PROVIDER AND ECONOMIC FACTORS ASSOCIATE WIDE THE CHOICE OF ACTIVE SURVEILLANCE IN THE TREATMENT OF MEN WITH LOCALIZED PROSTATE CANCER. >> HI, GOOD MORNING AND THANKS. I REALLY APPRECIATE THE OPPORTUNITY TO TALK TO YOU TODAY. AND I'M GOING TO KIND OF SWITCH GEARS A LITTLE BIT IN TERMS OF THE FOCUS OF MY TALK. I'M GOING TO TALK ABOUT DATA FROM A LARGE CANCER REGISTRY STUDY, LOOKING AT THE PREVALENCE OF ACTIVE SURVEILLANCE IN THE POPULATION. I WOULD WAS--WAS ASKED TO SPEAK ABOUT REGIONAL AND ECONOMIC FACTORS ASSOCIATE WIDE THE CHOICE OF ACTIVE SURVEILLANCE BUT AND I WANT TO LOOK AT THIS BY TAKING INTO ACCOUNT THE FACT OF CLINICAL FACTORS AS WELL. THE DATA SOURCE I'M USING IS THE BREAST AND PROSTATE PATTERNS OF CARE STUDY. IT WAS FUNDED BY THE NATIONAL PROGRAM OF CANCER REGISTRIES AND THAT'S PART OF THE CENTER FOR DISEASE CONTROL AND PREVENTION. AND I JUST WANT THE TO BRIEFLY ACKNOWLEDGE THE CO AUTHORS AS THERE WERE SEVERAL OTHER CANCER REGISTRIES PARTICIPATING. SPECIFICALLY THE CANCER REGISTRIES INCLUDED SEVEN STATES FROM CALIFORNIA WHICH I'M REPRESENTING. GEORGIA, KENTUCKY, LOUISIANA, NORTH CAROLINA, MINNESOTA, WISCONSIN, SO YOU CAN SEE THAT THERE'S A FAIRLY WIDE REPRESENTATION OF DIFFERENT PARTS OF THE COUNTRY INCLUDED IN THIS STUDY. THERE WERE 11,679 CASES OF OF INVASIVE PROSTASTY CANCER INITIALLY SELECTED AND THESE MEN WERE DIAGNOSED IN 2004. THE STUDY PROCEDURES TOOK PLACE DURING 2007 TO 2009. THE MEDICAL STAFF REABSTRACTED CANCER REGISTRY DATA AND OBTAINED ADDITIONAL VARIABLES AS WELL FROM HOSPITAL MEDICAL RECORDS AND FROM OUTPATIENT AND PHYSICIAN RECORDS. WE INCLUDED MANY, MANY, VARIABLES AND GENERALLY YOU COULD CATEGORIZE THEM INTO DEMOGRAPHIC CHARACTERISTICS, CLINICAL AND TUMOR CHARACTERISTICS, WORK UP INFORMATION WHICH WAS USED TO STAGE THE CANCER, DID THEY HAVE A BONE SCAN, PELVIC, CT SCAN, THIS TIME OF THING. AS WELL AS FIRST COURSE OF CANCER DERIVED THERAPY. TREATMENT REGIMEN GIVEN OR PLANNED AT THE TIME OF THE INITIAL CANCER DIAGNOSIS PRIOR TO DISEASE PROGRESSION OR RECURRENCE. IN ADDITION TO THESE RECORDS, THE DATA WE ABSTRACTED FROM THE MEDICAL RECORDS. AND THESE CASES WERE LINKED TO MULTIPLE EXFERNAL DATA SETS. AND THEY INCLUDED CENSUS TRACK VARIABLES BASED ON THE PATIENTS RESIDENTS INCLUDING URBANIZATION,% IN THE WORKING CLASS, POVERTY LEVEL AND EDUCATIONAL ACTINEMENT. THE NUMBER OF UROLOGYSTS PER 100 THIS HAPPENED MEN IN THE COUNTY WHERE THEY LIVED WAS ALSO OBTAINED FROM THE AREA RESOURCE FILE AND WE ALSO LINKED THE DATA TO THE M-PEER FILE, THE DEFINITION IS SHOWN THERE FOR YOU TO OBTAIN THE SPECIALTY AND EUROPE GRADUATION FROM THE MEDICAL SCHOOL FOR THE PHYSICIAN PROVIDING CARE. WHEN THE STUDY WAS COMPLETED ABSTRACTS WERE ABLE TO BE COMPLETED FOR 77% OF THE SELECTED CASES. SOME OF THE RECORDS WERE NO LONGER AVAILABLE AND OTHER REASONS WHY 100% WAS NOT ABLE TO BE OBTAINED. THEN FOR THIS ANALYSIS, I WANTED TO FOCUS ON THE LOCALIZED DISEASE CASES AND SO IN THE END, THERE WERE 8232 INCLUDED IN THE ANALYSIS. 363 WERE ELIMINATED BECAUSE THERE WEREN'T SUFFICIENT DATA FOR CLINICAL RECURRENCE RISK GROUP CLASSIFICATION THEN WE ELEMINATED THE T-THREE, T-FOUR DISEASE CASES. THOSE WITH POSITIVE NOTES OR METASTASIS IF ORDER TO FOCUS ON THE LOCALIZED GROUP AND THEN SINCE WE'RE LOOKING AT PEOPLE WITH NO THERAPY, WE ELIMINATED THOSE WHO HAD NO THERAPY BUT DIED WITHIN SIX MONTHS. JUST BRIEFLY THE DEFINITIONS WE USED, THE CLINICAL RECURRENCE RISK GROUP WAS BASED ON NCCN GUIDELINES AT THE TIME THESE CRASES WERE ABSTRACTED WHICH WAS IN THE VERSION THAT WAS APPLICABLE WASU SO THE LOW RISK GROUP INCLUDED T21, AND TTWOA, AND THE BIOPSY SCORE OF GLEASON SIX AND P10. JUST AS A NOTE, WE HAD 275 OUT OF THE 3242 THIS THIS GROUP--IN THIS GROUP. FOR WHOM WE HAD THE CLINICAL T-STAGE AND THEY EITHER HAD THE LOWER GLEASON OR THE LOWER PSA BUT THE OTHER DAT WAS MISSING--DATA WAS MISSING. SO WE EXCLUDED THEM FROM THE MULTIVARIANT MODEL WHICH IS YOU'LL SEE IN THESE COMES UP. AND THEN THE INTERMEDIATE RISK, TTWO B, T-TWO C, GLEASON SEVEN, APPROXIMATE, SA, OR PSA 10-20 AND THE HIGH RISK GROUP, OF COURSE THERE ARE NO T-THREES IN THIS SAMPLE. THE HIGHER GLEASON SCORES OR HIGHER PSA. WE DID ASSESS CO-MORBIDITY. WE USED SOMETHING CALL THE ACED 27 WHICH IS SOMETIMES CALLED THE PICKA RIEL O INDEX, IT'S SPECIFIC FOR CANCER AND A SIGNIFICANCE DOSE RESPONSE RELATIONSHIP BETWEEN THE SURVEILLAL AS BEEN SHOWN. 23 COMORBID CONDITION WHICH IS ARE ABSTRACTED AND IT INCLUDES SEVERITY SCORE. OVER ALL, AN OVERALL SEVERITY SCORE WAS PRODUCED, NONMILD MODERATE OR SEVERE DETERMINED BY THE HIGHEST RANKING OF A SINGLE CONDITION AND IF THERE WERE TWO CONDITIONS THAT WERE RANKED TWO OR MODERATE, THAT PERSON WAS GIVEN A SEVERE CODE. DENINEED WITHIN THE FIRST SIX MONTHS OF DIAGNOSIS AND THERE WAS MENTION OF A SPECIFIC SURVEILLANCE OR MONITORING PLAN IN THE MEDICAL RECORDS REVIEWED. I'VE ALSO COMPARED THIS GROUP TO THOSE MEN WHO HAD NO THERAPY DURING THIS PERIOD, HOWEVER NO PLAN, NO MONITORING PLAN WAS MENTIONED. AND THE PATIENT LIVED FOR SIX MONTHS. SERBIO ECONOMIC STATUS WAS BASED ON THE LEVELS OF POVERTY AND EDUCATIONAL ATTAINMENT, THOSE PEOPLE IN THE HIGH GROUP H. I.T BOTH THE LOWER PROPORTION BELOW THE FEDERAL POVERTY LEVEL AND THE LOWER PROPORTION OF ADULTS WITHOUT A HIGH SCHOOL EDUCATION. MIDDLE IN.--INCLUDED ONE OF THOSE TWO CRITERIA, AND LOW INCLUDED NEITHER OF THEM. WE WEIGHTED THE DATA ACCORDING TO THE INVERSE OF THE SAMPLING FRACTION SO THAT THE RESULTS WOULD REPRESENT THE POPULATION FROM WHICH THE CASES WERE SELECTED. USE BOTH UNIVARIANT AND MULTIVARIABLE ANALYSIS METHODS AND PROVIDED SEVERAL--SEPARATE MODELS TO PREDICT FACTORS ASSOCIATED WITH BOTH A. S. AND NO THERAPY, NO PLAN AND DID THIS FOR ALL CASES WITH LOCALIZED DISEASE AS WELL AS FOR THOSE IN THE LOW CLINICAL RECURRENCE RISK GROUP. SO OVER ALL WE FOUND JUST SEVEN% OF THE MEN USED A. S. ANOTHER 6.8% HAD NO THERAPY, NO PLAN. AND AS YOU CAN SEE, THE ACTIVE SURVEILLANCE GROUP WAS MUCH HIGHER IN THE--WHOOPS--MUCH MEYER IN THE LOW GROUP--HIGHER IN THE LOW GROUP COMPARED TO THE HIGH CLINICAL RISK GROUP WHERE ONLY TWO OPINIONED SEVEN% USED ACTIVE SURVEILLANCE. WHEREAS NO THERAPY, NO PLAN WAS HIGHEST IN THE LOW GROUP, BUT REALLY KIND OF A SOMEWHAT DROP OFF IN THE INTERMEDIATE AND HYPE AND NOT THE SAME DIRECT RELATIONSHIP THAT YOU SAW WITH ACTIVE SURVEILLANCE. AND HERE I'M PROVIDING A SERIES OF SLIDES THAT SHOW THE PROPORTION RECEIVING A. S. OR NO THERAPY, NO PLAN WITHIN CATEGORIES OF SEVERAL VARIABLES ACTIVE SURVEILLANCE IS ALWAYS SHOWN IN BLUE AND THE NO THERAPY, NO PLAN IN THE MAROON COLOR AND THE P-VALUE INDICATES WHETHER OR NOT THERE WAS A DIFFERENCE BETWEEN ACTIVE SURVEILLANCE AND THE NO THERAPY, NO PLAN GROUP. SO HERE REFLECTING SOME OF THE DATA THAT DR. PENSON JUST INDICATED, THE ACTIVE SURVEILLANCE GROUP, MUCH HIGHER PREVALENCE IN THE OLDEST AGE GROUP WHERE OVER 12% USED ACTIVE SURVEILLANCE. AND IN CONTRAST WITH THE NO THERAPY, NO PLAN, KIND OF A GRADUAL INCREASE WITH AGE, BUT ALSO REACHING THE HIGHEST POINT IN THE OLDEST AGE GROUP. WITH INSURANCE COVERAGE, ACTIVE SURVEILLANCE WAS A MORE COMMONLY OCCURRING IN THOSE RECEIVING MEDICARE ALONE. THE PRIVATE HMO GROUP ALSO INCLUDES THOSE WITH MEDICARE WITH A SUPPLEMENT PRIVATE SUPPLEMENT OR HMO SUPPLEMENT. WHEREAS THE NO THERAPY, NO PLAN GROUP, HAD THE HIGHEST PROPORTION IN THE MEDICAID GROUP. BY RACE ETHNICITY, NOT DIFFERENT FOR ACTIVE SURVEILLANCE, HOWEVER, HAVING NO THERAPY WITH NO PLAN WAS A HIGHER PROPORTION IN THE NONWHITE SUBGROUPS. BY CO-MORBIDITY, ACTIVE SURVEILLANCE AGAIN REFLECTING THE PREVIOUS DATA INCREASED AND WAS HIGHEST AMONG THOSE WITH SEVERE CO-MORBIDITYS. AND THIS IS ALSO THE GROUP WHERE YOU HAD THE HIGHEST PROPORTION WITH NO THERAPY, NO PLAN. AND THEN IF YOU LOOKED AT LCS, NO DIFFERENCE REALLY AMONG THE GROUPS FOR A. S. HOWEVER THE NO THERAPY GROUP WITH NO PLAN WAS HIGHEST IN THE LOW S. E. S. GROUP. THIS SWITCHES GEARS A LITTLE BIT. I'VE LOOKED AT THE OVERALL DISTRIBUTION HERE OF ACCORDING TO UROLOGYST PER HUNDRED THOUSAND MEN WITHIN THE COUNTY WHERE THEY'RE LIVING. SO WHAT YOU CAN SEE HERE IS THAT IF YOU LOOKU OF 9.4 OR MORE UROLOGYSTS PER HUNDRED THOUSAND MEN, ACTUALLY, WE HAD A HIGHER PORTION OF THOSE WITH ACTIVE SURVEILLANCE IN THAT SUBGROUP, AND I'VE ALSO INCLUDED THOSE RECEIVING SURGERY FOR COMPARISON AND AND THE LOWER PROPORTION OF MEN GETTING NO THERAPY IN THOSE AREAS WHERE THERE WERE MORE UROLOGYSTS. AND THEN THIS LOOKS AT THE YEAR OF GRADUATION OF THE UROLOGYST BY THE TYPE OF THERAPY. HERE YOU SEE THAT THERE ARE HIGHER PROPORTIONS OF THE ACTIVE SURVEILLANCE AND NO THERAPY, NO PLAN MEN AMONG UROLOGYST WHO IS GRADUATED A LONGER TIME AGO AND FOR THOSE MEN, FOR THOSE MEN WHO HAD UROLOGYSTS GRADUATE INDEED 1990 OR HIGHER, THERE WAS A HIGHER PROPORTION ACTUALLY OF THOSE RECEIVING SURGERY AND THOSE RECEIVING NO THERAPY, NO PLAN, HOWEVER, IF YOU AT THE STATISTICS OF THIS, THE OVERALL DISTRIBUTION WAS NOT DIFFERENT FOR THOSE WITH ACTIVE SURVEILLANCE VERSES NO THERAPY, NO PLAN, BUT OVERALL THERE WAS A DIFFERENCE WHEN YOU INCLUDED THE SURGICAL MEN. WE LOOKED AT MULTIVARIANT RESULTS INCLUDING ALL THESE VARIABLES IN A MODEL. WE DID NOT FIND THAT THERE IS ANY PREDICTIVE VALUE FOR MARITAL STATUS, INSURANCE COVERAGE, S. E. S. INDEX AND USE OF ACTIVE SURVEILLANCE OR NO THERAPY, NO PLAN. HOWEVER CLINICAL RISK GROUP, AGE OF DIAGNOSIS AND REGISTRY INDEPENDENTLY PREDICTED USE OF BOTH THOSE MANAGEMENT OPTIONS. CO-MORBIDITY PREDICTED USE OF ACTIVE SURVEILLANCE ONLY AND RACE ETHNICITY WAS RELATED TO USE OF NO THERAPY NO PLAN. SPECIFICALLY, TO LOOK AT SOME OF ADJUSTED ODDS RATIOS WE SEE THE REFERENCE GROUP OF 1.0, SHOWN IN THE BLACK BAR. YOU CAN SEE, THE DIFFERENCE HERE WITH CLINICAL RISK GROUP. THOSE IN THE HIGH RISK GROUP WERE ONLY 20% AS LIKELY TO RECEIVE ACTIVE SURVEILLANCE COMPARED TO THOSE IN THE LOW RISK GROUP WHEREAS YOU DID NOT SEE SUCH A RELATIONSHIP AS WE SAW WITH„i THE UNIVARIANT DATA WITH THE NO THERAPY, NO PLAN GROUP. THIS IS BY AGE GROUP AND HERE I'VE SHOWN FOUR SEPARATE MODELS, ALL LOCALIZED AND LOW RISK FOR BOTH ACTIVE SURVEILLANCE AND NO THERAPY NO PLAN. YOU CAN SEE, THE MUCH HIGHER RISK OF RECEIVING ACTIVE SURVEILLANCE IN THE OLDER AGE GROUP WITHIN ACTIVE SURVEILLANCE AND WHILE THERE IS A RELEVANCE OF AGE, FOR NO THERAPY, NO PLAN, IT IS NOT AS DRAMATIC. THIS IS THE ADJUSTED ODDS RATIOS BASED ON CO MORBIDITY AND CEIVERRITY SCORE AND THE MUCH HIGHER LIKELIHOOD OF ACTIVE SURVEILLANCE IN THE SEVERE GROUP. AND NO REAL EFFECT OR NO THERAPY, NO PLAN. AND THIS IS FOR RACE ETHNICITY, THIS IS WHERE YOU SAW HIGHER LIKELIHOOD OF RECEIVING NO THERAPY, NO PLAN FOR THE NONWHITE SUBGROUP AND LEGALLY NO EFFECT FOR ACTIVE SURVEILLANCE. SO IN CONCLUSION, SIMILAR PRIVATE PREVIOUS STUDIES OF WE FOUND A RELATIVELY LO PERCENTAGE OF MEN, RECEIVING ACTIVE SURVEILLANCE IN THE LOW CLINICAL RISK GROUP, THE MAJOR PREDICTORS, AS SHOWN IN OTHER STUDIES, I THINK, OLDER AGE LOW CLINICAL RISK GROUP AND SEVERE CO-MORBIDITYS. SO IT'S--IT SEEMS CLEAR THAT PHYSICIANS OR ACTUALLY MEN ACCEPTING PHYSICIANS ADVICE STILL FEEL MORE COMFORTABLE RECOMMENDING A. S. FOR MEN WITH LOWER LIFE EXPECTANCY AND MORE SEVERE CO-MORBIDITY WHEN IS SURGERY OR OTHER AGGRESSIVE THR ACTIVITIES AND PROJECTSY SYSTEM NOT AN OPTION. IN CONTRAST, MEN RECEIVING NO THERAPY, NO PLAN WERE LIKELY TO BE IN AREAS WITH FEWER NEUROLOGIST WERE LIKELY TO BE NONWHITE AND IN THE UNIVARIANT ANALYSIS, THEY 10ED--TENDED TO BE FROM MORE OTHER S. E. S. AREAS AND THE BOTTOM LINE SEEMS TO BE THAT REGIONAL AND PROVIDER FACTORS SEEM MORE RELATED TO HAVING NO THERAPY AND ACTIVITIES AND PROJECTS WEB CONNECTED NO PLAN THAN TO RECEIVING ACTIVE SURVEILLANCE. AND I DID ADDITIONAL ANALYSIS LOOKING AT SUBSEQUENT THERAPY AFTER SIX MONTHS. IN ACTUALITY, WE HAD ABSTRACTED DATA UP TO A YEAR AND FOUND THAT THE MEN WITH NO THERAPY, NO PLAN AT SIX MONTHS WERE MORE LIKELY TO BE DELAYING CARE, 35% HAD SUBSEQUENT TREATMENT AFTER SIX MONTHS COMPARED TO LESS THAN FIVE% OF THOSE WITHIVE SURVEILLANCE. SOME LIMITATIONS TO NOTE OF COURSE, CANCER REGISTRY DATA ARE HELPFUL IN DETERMINING POPULATION BASED ESTIMATES OF USE OF SPECIFIC THERAPIES BUT ARE LIMITED IN WHAT CAN BE ABSTRACTED FROM MEDICAL RECORDS. WE DON'T ALWAYS HAVE PHYSICIAN AND OUTPATIENT RECORDS AND ALSO WE DON'T HAVE THE COMPLETE DETAILS OF THE SPECIFIC MONITORING PLAN, HOW MANY BIOPSIES, WHAT IS THE COMPLIANCE AND SO ON AND SO FOURTH TO REALLY DEFINE THIS GROUP MORE PRECISELY. HOWEVER, I HAVE SOME RECOMMENDATIONS TO THINK ABOUT I REALLY FEEL THE CANCER REGISTRY RESOURCE IS AN EXCELLENT WAY TO MONITOR THE USE OF ACTIVE SURVEILLANCE AMONG POTENTIALLY ELIGIBLE MEN. HOWEVER, TO BETTER UTILIZE THIS RESOURCE, I FEEL NEW CLINICAL DATA ITEMS NEED TO BE ADDED TO THE VARIABLES BEING ABSTRACTED, SEVERAL VARIABLES HAVE BEEN MENTIONED HERE WITH THE VARIOUS ACTIVE SURVEILLANCE PLANS AMONG DIFFERENT FACILITIES, SUCH AS PSA DENSITY, TUMOR PROPORTION WITHIN BIOPSY CORE, FOR INSTANCE IF THE CRITERIA IS 50% MORE OF A BIOPSY CORE, PERHAPS A YES, NO, VARIABLE COULD BE ADDED. WAS THERE A BIOPSY CORE THAT HAD THAT CHARACTERISTIC. OR THREE OR 94 BIOPSY CORES POSITIVE OR WHATEVER THE SPECIFIC CRITERIA COULD BE DETERMINED. IF DEFINITIVE SELECTION CRITERIA COULD BE DEVELOPED, I THINK CANCER REGISTRIES COULD BE A VALUABLE RESOURCE TO MONITOR THE USE OF ACTIVE SURVEILLANCE AMONG CLINICALLY ELIGIBLE MEN OVER TIME AS WELL AS OBTAINING OUTCOMES AT LEAST SURVIVAL OUTCOMES FOR THESE MEN FOR A POPULATION BASED PERSPECTIVE. THANK YOU. [ APPLAUSE ] >> THANK YOU DR. HAMILTON AND DR. PENSON. COULD YOU JOIN ME ON STAGE? WE ARE OPEN NOW FOR QUESTIONS. THERE ARE QUESTIONS TO THE PANEL. COULD YOU COME TO THE MICROPHONE.„i ED--WANTED TO ASK C PENSON IN PARTICULAR, YOU SEEM TO WORRY THAT PATIENTS WORRY ABOUT SIDE EFFECTS THAN THEIR SPOUSES AND FAMILY SYSTEM THIS GENERALIZABLE TO ALL CANCERS OR SPECIFIC TO PROSTATE THINKING THAT PARTICULARLY THEIR URINARY AND SEXUAL SIDE EFFECTS FOR PROSTASTY THAT WOULDN'T EXIST FOR LUNG OR LIVER OR COLON CANCER? >> I SUSPECT THAT IT IS GENERALIZABLE TO OTHER CANCERS. IF YOU FLIP TODAY THE OTHER WAY AND YOU TALK ABOUT SAY, GYNECOLOGIC CANCERS, I SUSPECT THAT YOU SEE THE EXACT OPPOSITE PATTERN THERE, WHERE THE PATIENT, THE WOMAN MAY BE MORE CONCERNED WITH HER SIDE EFFECT PROFILE WHERE THE HUSBAND OR PARTNER WOULD BE MORE CONCERN BODY SURVEILLAL. IT'S--SURVILE AT. IT'S A UNIQUE ISSUE WITH CANCER WHICH IS HAVE EFFECTS ON THESE CHARGE DOMAINS, SEXUALITY, BODY IMAGE, ET CETERA. >> SO DO WE KNOW ABOUT COLON, LUNG, OTHER CANCERS THAT DON'T HAVE THE POTENTIAL FOR SEXUAL SIDE EFFECTS IS WHAT I,-- >> I DON'T KNOW THE ANSWER TO THAT. >> I THINK THE PATIENT WHO HAS TO LIVE THROUGH WHATEVER IS GOING ON, HAS HAY LOT MORE QUESTIONS. OFTEN THE HUSBAND OR THE SPOUSE WILL SAY, OH, JUST GET IT OVERWITH, WHERE THE PATIENTS RUMINATING ABOUT THE POTENTIAL TOXICITIES OF THE CHEMO THERAPY, THE SURGERY, WHATEVER IT IS. >> OKAY AND THE OTHER QUESTION I HAD, PROSTATE SEEMS TO IN TERMS OF MORBIDITY AND MORTALITY AFFECT BLACKS MORE THAN WHITES. DO YOU HAVE INFORMATION ON HOW BLACKS MIGHT DIFFER IN THEIR VALUES THAN WHITES WOULD? >> SO YES, THIS IS YOUR STUDY, AND ANN YOUR THE LEAD ON THIS STUDY SO YOU SHOULD ANSWER. >> I'M SORRY. SO DR. HAMILTON LEAD A STED LOOKING SPECIFICALLY AT DIFFERENCES BETWEEN BLACKS AND WHITES AND IN THE SEXUAL DOMAINS. >> WELL,„i WE DID FIND THERE WERE DIFFERENCES, HOWEVER, ONCE MANY OTHER VARIABLES WERE CONTROLLED FOR, SUCH AS STAGE EVER DISEASE AND A LOT OF OTHER VARIABLES THAT WE H. I.T AVAILABLE IN THE END, THE DIFFERENCES WENT AWAY. SO THAT IN FACT SO THEY MAY HAVE SPECIFIC DIFFERENCES BUT THEY COULD BE EXPLAINED BY OTHER FACTORS THAN RACE ETHNICITY. >> OKAY, SO I'M JUST TRYING TO GET OUT OF THERE, FOR COUNSELING PEOPLE TO GET THEM TO ACCEPT ACTIVE SURVEILLANCE WOULD WE COUNCIL BLACKS SIMILARLY TO WHITES OR WOULD THERE BE CULTURAL DIFFERENCES. >> I THINK THERE ARE CULTURAL DIFFERENCES. IN THAT STUDY, WE SAW THAT IN GENERAL FIVE YEARS AFRICAN AMERICANS? THE ANALYSIS, TENDED TO HAVE BETTER SEXUAL FUNCTION THAN THE WHITES. I MEAN SEXUAL FUNCTION BOTH ARMS ARE ROTTEN BUT WHEN YOU CAME TO A BOTHER OF HOW MUCH A PROBLEM IT WAS EVEN THOUGH THE AFRICAN AMERICANS HAD MORE FUNCTION, THEY REPORTED MORE BOTHER. SO IF YOU DEVELOP INTERVENTIONS, WHETHER IT'S IN A. S. OR CROSS DECISION MAKING, IT HAS TO BE CULT RULY AND RACIALLY SENSITIVE BECAUSE THE ISSUES THAT AFFECT A AFRICAN AMERICAN MAN, HISPANIC MAN, CAUCASIAN MAN WILL BE DIFFERENT. >> I HAVE A--OH, SURE, DR. PENSON, I'M A PRACTICING UROLOGYST, ONE QUESTION FOR DR. HAMILTON, GOOD STUDY ON THE ACTIVE SURVEILLANCE, THE NO THERAPY, NO PLAN GROUP, DO YOU THINK THAT'S LIKE A UNDER INSURED POORLY INSURED GROUP. SEEMS LIKE IT IS? SO THE COST OF THE TREATMENT IS VERY HIGH, FORTUNATELY AT I SEE THESE STATIONS SO THAT MAY BE A MAJOR DETERRENT TO HAVE IT IF THEY WANT IT AND THEN SECTIONAL SECONDLY, IS, IN THE LOW RISK GROUP, IT WOULD BE NICE TO KNOW HOW MANY OF THOSE PATIENTS ACTUALLY FIT INTO LIKE, THE EPSTEIN CRITERIA, OR WHATEVER CRITERIA, YOU AT ANY POINT USE TO FOLLOW FOR ACTIVE SURVEILLANCE SO THERE MAY BE 8000 PATIENTS IN THAT GROUP, REALLY HOW MANY OF THOSE 8000 PATIENTS WILL FIT THE STRICT CRITERIA THAT WE DEVELOPED, NOT SURE IF YOU HAVE COMEBT O SINGLE THAT OR NOT. >> YOU'RE ASKING ABOUT THEM ASKING OR HAVING THERAPY OR THEY HAVE A REASON? >> IT SOUNDS LIKE THEY DON'T HAVE ACCESS. >> RIGHT, VERY FEW PEOPLE HAD NO INSURANCE WHATSOEVER. AT LEAST THEY HAD PUBLIC INSURANCE OR SOME SORT OF COVERAGE SO IT COULD BE A COMBINATION OF THINGS THAT THEY DIDN'T QUITE KNOW WHAT TO DO OR WHO TO TALK OR OR MAYBE THEY'RE JUST MEN WHO COULDPT MAKE A DECISION QUICKLY BUT I DO THINK THAT THEY'RE--WERE ECONOMIC FACTORS ASSOCIATED WITH RACIAL AND ECONOMIC FACTORS ASSOCIATED THAT DEFINED THAT GROUP, DISTINCT FROM THE ACTIVE SURVEILLANCE GROUP THAT, YOU KNOW INDICATED THERE COULD BE SOME ADDITIONAL PROBLEMS TO FOCUS ON. IN TREATS THAT GROUP. AND I THINK YOUR OTHER QUESTION HAD TO DO WITH WAS THAT AMONG THE LOW RISK GROUP. COULD WE IDENTIFY THOSE PEOPLE MORE SPECIFICALLY ELIGIBLE FOR ACTIVE SURVEILLANCE? >> YEAH, IS THERE A WAY TO IDENTIFY THAT? >> I THINK, BASED ON AVAILABLE CANCER REGISTRY DATA, NO THAT WAS AS GOOD AS I COULD DO. THAT'S I DIDN'T WAS SUGGESTING THAT WE NEEDED MORE VARIABLES. >> I HAVE A QUESTION FOR BOTH PANELISTS ABOUT AGE„i AND HOW IT RELATES TO THEIR ISSUES. IS THERE ANY AGE FOR WHICH THE OLDER CONCEPT OF WATCHFUL WAITING NAMELY NO FOLLOW UP PROTOCOL, NO THERAPY, NO PLAN IS GOING TO BE ACCEPTABLE IN THE CURRENT ERA. YOU KNOW YOU HAVE A GLEASON SIX IN LESS THAN TWO CORES IS THERE ANYONE WHO IS NOT GOING TO MONITOR THEM. >> YOU ALWAYS ASK THE DIFFICULT QUESTIONS. IT'S A GOOD POINT. WE HAVE MANY MEN THAT ARE DIAGNOSED WITH PROSTASTY CANCER WHO HAVE LESS THAN A 10 YEAR LIFE EXPECTANCY AND THAT PATIENT WITH A SMALL FOCUS OF GLEASON SIX DISEASE, IF YOU'RE CONFIDENT THAT'S WHAT IT IS, TELL NOT BE A MAJOR ISSUE. SO YOU COULD MAKE THE ARGUMENT THAT THE OLD WATCHFUL, WAITING PARADIGM FOR THAT PATIENT. THE BIGGER QUESTION IS WILL IT BE ACCEPTABLE TO THE PATIENT. IT GETS INTO THE ISSUE OF ANXIETY AND PROGRESSIVE CANCER ISSUES. IF YOU TELL SOMEONE THEY HAVE CANCER, GLOW GRADE GLEASON SIX CANCER, THEY CAN SAY, LET'S IGF NORIT, DOC AND MY RESPONSE WOULD BE WHY DID YOU LOOK FOR IT IN THE FIRST PLACE IF YOU WEREN'T DOING ANYTHING ABOUT IT. SO FROM THE A SCIENTIFIC STAN POINT, YES, THERE'S A ROLE FOR IT, FROM A PERSPECTIVE, I DON'T KNOW IF IT'S FEASIBLE IN 2000 SOON TO BE 12. >> WE HAVE SOMEONE IN THE AUDIENCE WHO SELF-IDENTIFIED HIMSELF AS GOING THROUGH ACT A. S. AND WOULD THIS BE A GOOD TIME TO TALK ABOUT YOUR DECISION AND THE ROLE YOU MADE--THERE WAS A COMMENT WE SHOULD HAVE HAD A SPEAKER YESTERDAY WHO IS INVOLVED IN ACTIVE SURVEILLANCE AND WE HAVE A VOLUNTEER NOW TODAY. >> GOOD MORNING, MY NAME IS LEWIS SENTOR, AND I'M A 65 YEAR-OLD MARRIED CLINICALLY TRAINED HOSPITAL CHAP LANAND CERTIFIED PASTORAL CANCER WHAT WAS DIAGNOSED WITH ADENO CARCINOMA PROSTATE CANCER ON JULY 18th OF THIS YEAR, FOLLOWING A BLOOD TEST WHICH REVEALED A PSA OF NINE PUBLICITY ONE. IT MADE AN POINTMENT TO SEE A UROLOGYST WHO DID A D. R. E., DIGITAL RECTAL EXAM AND RECOMMENDED EVEN THOUGH HE DIDN'T THINK HE FELT ANYTHING, HE SAID LET'S GO FOR A BIOPSY ANYWAY, I DID GET A BIOPSY, 14 CORES WERE TAKEN AND I WAS GIVEN A GLEASON SCORE OF THREE PLUS THREE-SIX AND HE CALLED ME INTO HIS ROOM AND SAID, WELL THE GOOD NEWS IS YOU'RE IN GREAT SHAPE, YOU LOOK LIKE YOUR A HEALTHY GUY, RUN, DIETS GOOD, THE BAD NEWS IS THAT I DID FIND ADNEUROECTODERMAL CARCINOMA BUT IT'S NOT A BIG THING. IT'S JUST BEGINNING AND I DON'T THINK YOU SHOULD BE WORRIED BECAUSE I WORK WITH A CLINIC IN VIRGINIA, VIENNA, VIRGINIA AND WE DO BRACHYTHERAPY THERE. HERE'S THE WEB SITE, CAN YOU READ ABOUT IT AND ALL WE NEED TO DO IS PUT IN A COUPLE SEEDS AND YOU'LL BE FIND. IT SOUNDED REAL GOOD, EASY, HEARD ABOUT IT WORKING AS PROSTATE CHAP LAN. BUT WHEN I GOT HOME, I DID SOME RESEARCH ON IT, BEING A LITTLE SKEPTICAL SOMETIMES WITH DOCTORS RECOMMENDING ME DOING AND I STARTED LOOKING TO THE WHOLE GOOD OF ACTIVE SURVEILLANCE, REMEMBERING THAT I HAD READ A BOOK 15 YEARS AGO BY DIRK BENEDICT CALLED CONFESSIONS OF A CAMMA CASY COWBOY, WHEN R THEY HAD SEVERE PROSTASTY CANCER AND THROUGH DIET AND CONS ULTATION WITH HIRSCH O KUSHE, A MACROBIOTIC, HE COMPLETELY STARVED THE CANCER OUT OF HIS SYSTEM. I DID GO FOR A SECOND OPINION TO ANOTHER UROLOGYST HERE IN D. C., ANOTHER ONE OF THE TOP TENREC MENDED ON THE INTERNET IS THE BEST UROLOGYST IN D. C. AND HE SAID, WELL I DID HAVE THE BIOPSIES LOOKED AT AGAIN IN THE LAB AT THE HOSPITAL, IT DEFINITELY A--OH IS THERE, YOU HAD HE SAYS YOU DON'T WANT TO DO THAT BRACHYTHERAPY STUFF. HE SAID NOW, I WORK WITH SIBLY HOSPITAL D/j STUFF AND HE SAID, I DON'T THINK IT WILL BE VERY MUCH OF A PROBLEM AT ALL AFTER YOU DO A LITTLE BIT MORE OF THIS SURVEILLANCE THAT YOU'RE DOING FOR YOU TO GO AHEAD AND GET THE THERAPY, RADIATION THERAPY, HE SAID BUT YOU HAVE TO REALLY MAKE SURE BY THE END OF THE YEAR, YOU DON'T WANT TO KEEP GOING WITH THIS LOADED GUN. THE SURVEILLANCE THING WITHOUT DOING SOMETHING, BECAUSE THIS IS A SERIES CANCER. QUESTION: WHAT IS A SERIOUS CANCER? IS ADENO CARCINOMA OR ARE THERE 16 DIFFERENT FLAVORS OF ADENO CARCINOMA. I STILL DON'T KNOW WHAT HE MEANT BY THIS IS AS A SERIOUS CANCER. CANCER IS SERIOUS BUT IT DOESN'T ALWAYS MEAN A DEATH SENTENCE. I'VE BEEN MARRIED TO A DENTAL HIGENERATEDDIST FOR 25 YEARS, WE HAVE BEEN VERY DIET ORIENTED AND WE EXERCISE A LOT AND I HAVE CHOSEN ALONG WITH A LOT OF SUPPORT FROMgA HER, TO CONTINUE NOW FOR IT'S BEEN FOUR AND HALF MONTHS WITH THE ACTIVE SURVEILLANCE WHICH HAS BEEN TALKED ABOUT IN HERE AS A SELF-MANAGEMENT PROGRAM I HAVE BEEN READING VORACIOUSLY ON THE INTERNET, READING EVERY MEDICAL JOURNAL I CAN ABOUT THIS COMING TO CONFERENCES LIKE THIS WHICH I DID FINDOT INTERNET, THANK GOD AND I HAVE COMPLETE CHANGED MY DIET TO EATING ALMOST ALL RAW FLOODS AND DRINKING CAMBUCHA, AND DRINKING CHLORRA FILL, AND I INCREASED MY EXERCISE TO WALKING AND WEIGHTS AND I HAVE A FAMILY HISTORY OF SIS ILLEGALSIAN BLOOD AND NO ONE IN THE FAMILY HAS EVER HAD CANCER OR ANY KIND OF HEART ATTACKS BUT THEY'RE ALL RACKED WITH ARTHRITIS FROM TOO MUCH PASTA. SO THIS IS BASICALLY HAS BEEN MY JOURNEY FOR FOUR MONTHS. MY CURRENT BLOOD TEST IS 6.5. CHOLESTEROL 246, 213 TO 192 AND I CONTINUED TO BRING THAT ALL DOWN. THE PROBLEM I HAD IS I'VE NEVER SEEN A GENERAL PRACTITIONER THAT WANTS TO TAKE ANY TIME ASK DEAL WITH ME IN THIS JOURNEY. I FOUND ONE, HE SAW ME FOR THREE MINUTES, THE EXCUSE ME, CAME BACK 14 MINUTES LATER, I THOUGHT HE HAD LEFT, AND DIDN'T EVEN DRESS AND SAY, I'M SORRY, YOU KNOW IT WAS LONGER THAN I THOUGHT. WHEN I DID CONFRONT HIM AS A CHAPLAIN, I THOUGHT, YOU KNOW I WORKED WITH DOCTORS, HE WAS EXTREMELY ANGRY AT ME FOR EVEN QUESTIONING HIM AND FROM THERE ON, THE WHOLE THING WENT SOUR AND I SAID I'M NOT COMING BACK. SO THE WHOLE QUESTION IS HOW DO YOU FIND SOMEONE? YOU KNOW, I SUPPORTED PEOPLE AS A CHAPLAIN BECAUSE A LOT OF TIMES, THE DOCTOR DIDN'T TAKE ENOUGH TIME TO REALLY TALK TO THEM. YOU KNOW YOUR BP IS 185 FOR 69 AND HE SAID I DON'T KNOW WHAT HE SAID AND I WOULD GO IN THE ROOM TO LISTEN TO THEIR JOURNEY AND NOW I'M IN THE POSITION WHERE I'M TRYING TO FIND THAT. >> THANK YOU SO MUCH FOR SHARING YOUR EXPERIENCE WITH US. >> [ APPLAUSE ] >> I WANT TO THANK YOU FOR SHARING THAT ON BEHALF OF THE PANEL. IT'S INSIGHTFUL. I HAVE A QUESTION FOR DR. PENSON. THE ISSUE OF ANXIETY AND PATIENTS THERE'S BEEN THE IMPLICATION THAT THERE'S BUILDING ANXIETY AND THAT'S WHAT LEADS TO PATIENTS DROPPING OUT AND YOU MENTION THAT PROTECTIVE STUDIES FAILED TO DOCUMENT AND PATIENT WHO IS REMAIN ON IT. NOW, IT LOOKS LIKE ABOUT 50% OF PATIENTS WHO START ON A. S. DROP OUT BY ABOUT FIVE YEARS BUT A QUARTER DROP OUT BY ONE OR TWO YEARS. AND THE STUDY VS NOT BEEN PARTICULARLY RIGOROUS ABOUT TRACKING WHY THEY DROPPED OUT. OTHER THAN MOST OF THAT IS NOT FOR DISEASE PROGRESSION. DO--IS THERE INDICATION SO CLEARLY THE PATIENT WHO IS STAY ON IT, ARE NOT SUFFERING FROM ANXIOUS BUT COULD THAT ATTRITION, THAT ATTRITION HOW MUCH OF THAT IS DUE TO ANXIOUS AND DO WE KNOW THAT. >> THAT'S A GREAT QUESTION AND I THINK THE SHORT ANSWER IS WE DON'T REALLY KNOW. IF YOU LOOK AT THE PERSPECTIVE STUDIES THAT COME FROM THE PRIMATESUS STUDY CHRKS IS A EUROPEAN STUDY, VAN DEMBURG IS THE FIRST AUTHOR AND THEY STATE THERE'S NO INCREASED ANXIOUS BUT THERE'S A PROBLEM WITH SELECTION BIAS BECAUSE THEY TEND TO LOOK AT PATIENT WHO IS STAY ON IT. THERE ARE HITS THAT SOME OF THEM GO OFF BECAUSE THEY HAVE INCREASED ANXIOUS AND UNCERTAINTY AND THERE ARE CERTAINLY STUDIES OUT THERE THAT LOOK AT PERSONALITIES TYPES. THERE'S ONE STUDY I DIDN'T INCLUDE IT BECAUSE IT WAS A LITTLE TOO WOODY ALLEN FOR ME THAT BASICALLY SAID THAT MEN WITH A NEUROTIC PERSONALITY TYPE TRY TO STAY ON ATIVE SURVEILLANCE DO NOT DO WELL WITH IT BUT THE THERE ARE OTHER ISSUES AS WELL THAT DRIVE THESE MEN OFF. THERE'S ANXIOUS, PRESSURE FROM FAMILY MEMBERS, PRESSURES FROM THEIR PHYSICIANS SO I THINK FROM'S AN ISSUE WITH ANXIOUS BUT THERE'S ALSO OTHER FACTORS AS WELL. BEST„i I CAN TELL. >> IF I COULD FOLLOW UP, COULD YOU MENTION AT THE END, SORT OF A PROGRAM OF SUPPORT AND I GUESS THERE'S STATE AND TRADING ANXIOUS AND IS THERE A ROLE FOR SCREENING ANXIOUS, SORT OF A BASELINE, STATE ANXIOUS AND TRADE ANXIOUS ASTERISKS BASELINE AND IS THERE A ROLE FOR DEALING WITH ANXIOUS, SO INSTEAD OF JUST MONITORING MEN WITH NEEDLES AND ULTRA SOUNDS ACTUALLY HAVING COUNSELORS AND TREATING THEM AS WE TREAT OTHER CONDITIONS THAT REQUIRE POSITIVE REQUIRE PSYCHOLOGICAL REPORT. >> A COUPLE SEATS HAVE USED THE S. T. A. I. STUDENT AND IT DOESN'T PREDICT GOING OFF OF ACTIVE SURVEILLANCE, THE PROBLEM IS THAT THE STUDIES ARE SMALL NUMBERS SO DO YOU HAVE THE SAMPLE SIZE TO MAKE THAT CONCLUSION. BUT I THINK THERE IS SOMETHING TO THERE MAY BE SOMETHING TO MONITORING IT. THAT'S OPINION ANY SORT OF TOOL YOU DEVELOP, AND I THINK THERE'S NEED FOR GIVING PATIENTS A TOOL SET, TO STAY ON ANXIOUS, TO STAY ON ACTIVE SURVEILLANCE WILL HAVE TO DO WITH ANXIETY AND UNSUPPORT. THAT'S A CLEAR THEME. >> I'M JUST WONDERING IN LIGHT OF THE STORY OF GROSSLY INADEQUATE COUNSELING WHICH I SUSPECT IS ALL TOO COMMON, IF YOU COULD COMMENT FROM OUR OTHER REALM WHERE WE'RE GOING AND WHERE WE SHOULD BE GOING IN TERMS OF CASE AND ADEQUATE COUNSELING AND BRIEFLY, AND YOU KNOW IN YOUR EXPERIENCE WHERE WE NEED TO BE GOING IN TERMS OF IMPROVING THIS CRITICAL CONVERSATION. >> THANKS MATT. >> COUNCILLING HAS BEEN PROPOSED AS A QUALITY CARE IN PROSTASTY CANCER THE PQRA I QUALITY CARE INDICATOR IN COLLABORATION WITH ASCO AND A NUMBER OF OTHER UP GROUPS AND WHEN THAT INDICATOR WENT TO THE NATIONAL QUALITY FORMEN WAS REJECTED.„i THERE'S DOCUMENTATION THAT THERE KEY BEEN COUNCILLING DOES NOT GET UP TO KIEWNSLING AND THE UROLOGYST COULD SAY, SURGERY OR ACTIVE SURVEILLANCE BUT IF I WAS YOU, ANY SANE PERSON WOULD DO SURGERY SO THAT'S NOT REALLY COUNCILLING IS IT. SO THE QUESTION I WOULD PUT BACK TO YOU AND I DON'T KNOW THE ANSWER IS, IS THERE A NEED FOR SOME SORT OF STANDARDIZED COUNSELING TOOL THAT WAS USED AND THAT WAS BROUGHT UP BY THE NQF PANEL. >> WE'RE GOING TO HAVE TO GO ON THE NEXT SET OF SPEAKERS WILL THERE BE ANOTHER HOUR FOR DISCUSSIONQA+&v AFTER THIS NECKS SESSION, THE NEXT QUESTION WE'RE ADDRESSING IS: WHAT ARE THE PATIENT-EXPERIENCED COMPARATIVE SHORT AND LONG-TERM HEALTH OUTCOMES OF ACTIVE SURVEILLANCE VERSUS IMMEDIATE TREATMENT WITH CURIAATIVE INTENT FOR LOCALIZED PROSTATE CANCER AND OUR FIRST SPEAKER HERE IS DR. MACK ROACH AND HE'S THE PROFESSOR OF THE DEPARTMENTS OF RAD YAGIATION ONCOLOGY AND UROLOGY AND CHAIRMAN OF THE DEPARTMENT WITH THE UCSF, AND HIS PRESENTATION IS OVERVIE OF--OVERVIEW OF RANDOMIZED c#xŤJ=11 LOCALIZED PROSTASTY CANCER. >> YESTERDAY THERE WERE SEVERAL QUESTIONS THAT WERE RAISED REGUARDING THE ROLE OF RANDOMIZED TRIALS AND PROSTASTY CANCER, THAT'S REALLY THE FOCUS OF THIS PRESENTATION, IT'S INTERESTING HOW FEW PEOPLE ARE AWARE OF THE RANDOMIZED TRIALS. THE RELEVANCE OF THIS ISSUE OF TREATMENT IS NOT TO THE ISSUE OF ACTIVE SURVEILLANCE. IT ALSO AFFECTS THE ISSUE OF EARLY DETECTION AND SCREENING. YOU SCREEN PATIENTS. YOU DIAGNOSE THEM AND THEN THEY HAVE TO DECIDE WHETHER THEY WANT TO DO ACTIVE SURVEILLANCE OR TREATMENT. IF ACTIVE SURVEILLANCE IS NOT SAVE, IT PARTLY DEPENDS UPON HOW EFFECTIVE TREATMENT BY BE SO IT'S WHETHER THE DELAY WOULD ADVERSELY IMPACT THE OUTCOME AND THE TREATMENT AND EFFECTIVE AT PROLONGED SURVIVAL. IF TREATMENT IS NOT EFFECTIVE THEN DELAYS MAY BE IRRELEVANT AND IF TREATMENT IS SUCCESSFUL REGUARDLESS OF THE EXTENT OF DISEASE, THEN THE DELAYS IN TREATMENT MAY ALSO BE RELEVANT. THAT IS IF PATIENTS HAVE THE METASTATIC DISEASE AND YOU GIVE THEM A BILL AND CURE THEM, WE WOULDN'T HAVE THESE DISCUSSIONSCREENING AND ACTIVE SURVEILLANCE. AND THE FACT IS THAT ALTHOUGH MODERATELY AFFECTED, THE AVAILABLE TREATMENTS ARE NOT CURED OF PATIENTS WITH ADVANCED DISEASE AND SUCH SO THAT DELAYS MAY HAVE AN ADVERSE EFFECT ON OUTCOME. IN THIS REVIEW, I WILL FOCUS EXCLUSIVELY ON PROSPECTIVE RANDOMIZED TRIALS. NO POPULATION BASED DATA, NO RETROSPECTIVE STUDIES. ONLY RANDOMIZED TRIALS. AND I WILL ARGUE THAT THERE'S A LARGE AND GROWING BODY OF LEVEL ONE EVIDENCE THAT THERE ARE SUBSETS OF MEN WHO CLEARLY BENEFIT FROM ONE TREATMENT TO ANOTHER TREATMENT AND THAT CERTAIN TREATMENTS SHOULD CLEARLY BE AVOIDED. NOW THESE ARE TYPICALLY NOT MEN IN THESE STUDIES WHO ARE CANDIDATES FOR ACTIVE SURVEILLANCE, HOWEVER THERE'S SMALL NUMBERS OF MEN WHO MIGHT BE. THE BULK OF THESIS PATIENTS OTHER THAN NOT THE PATIENTS FOR WHOM ACTIVE SURVEILLANCE WOULD BE AN APPROPRIATE ISSUE. SO THERE ARE AT LEAST AND I CAN'T GUARANTEE THAT I CAPTURED ALL OF THEM 50 ABDOMEN ORDER OF MICRONSIZED--RANDOMIZED TRIALS OF MEN WITH CLINICALLY LOCALIZED PROSTATE CANCER. NOW THERE ARE SOME I EXCLUDED INTENTIONAL INCLUDING SOME FROM THE STUDIES IN WHICH THE STUDIES WERE GROSSLY UNDERPOWERED WHEN LOOKING AT OBSERVATION VERSES TREATMENT. AND SOME IN WHICH THE END POINT OF THE TRIALS WERE NOT SURVIVAL BASE, SMALL STUDIES LOOKING AT PSA CONTROL RACE, BUTTAST LEAST 50 RANDOMIZED TRIAL FOR WHICH THERE WAS SOME SIZE TO JUSTIFY A SURVIVAL CONSIDERATION AT LEAST. AND THIS, IS NOTABLILY IN TACK CONTRAST TO THE REPORT FROM THE U.S. PREVENTATIVE TASK FORCE IN WHICH THEY ONLY CHOOSE TO EVALUATE 22 RANDOMIZED TRIALS TO SPEND TIME AND I WILL TALK ABOUT THAT. I THINK THIS IS A CRITICAL SHORT COMING IN THEIR REPORT AND MY AGESSAL FOR INCLUDING THESE AND SUGGESTING THAT IT'S RELEVANT TO THE U.S. PREVENTATIVE TASK FORCE ISSUE IS THAT THE THIRD QUESTION THAT THEY ATTEMPTED TO ADDRESS WAS WHAT ARE THE BENEFITS OF TREATMENT OF EARLY STAGE OR SCREENING DETECTED PROSTATE CANCER. AND I WOULD ARGUE THAT THEIR QUESTION WAS NOT ADEQUATELY ADDRESSED BY THESE TWO TRIALS BECAUSE THEY IGNORED WHETHER THERE WERE SUBSETS OF THE PATIENTS WHO WERE DIAGNOSED BY CREEPING AND BENEFIT AS OPPOSE TO MAKING A GENERAL STATEMENT ACROSS THE BOARD FOR ALL PATIENTS. THEY DIDN'T SPECIFY HOW MUCH OF IMPROVEMENT AND SURVIVAL MIGHT BE EXPECTED. THEY DIDN'T ADDRESS WHAT TYPES OF TREATMENTS SHOULD BE INCLUDED IN SUCH AN ANALYSIS. THEY DIDN'T SPECIFY WHEN THE BENEFIT MIGHT BE SEEN AND THIS IS REALLY VERY CRITICAL. THIS IS FROM A REVIEW PUBLICKED IN WHICH--PUBLISHED IN WHICH YOU CAN SEE IN THE CIRCLES, THESE ARE THE NUMBER„i NEEDED TO TREAT CALCULATIONS AND THEY VARY BY DURATION OF FOLLOW UP. SO THAT INITIALLY IN A COHORT OF PATIENT FIST YOUR FOLLOW UP IS--PATIENTS IF YOUR FOLLOW UP IS TOO SHORT, THE NUMBERS NEEDED TO TREAT WOULD BE QUITE LARGE WITH LONGER FOLLOW UP AS IT DIVERGE, THE NUMBER NEEDED TO TREAT IS MUCH SMALLER AND THIS IS BASED ON AN ANALYSIS OF PATIENTS THAT ARE EVALUATED AFTER SCREENING AND LOOK AT THE VALUE OF SCREENING. NUMBER NEEDED TO TREAT AND NUMBER NEATED TO SCREEN. DID SO I'M GOING TO BRIEFLY RUN THROUGH THESE SLIDES THAT HAVE IN THEM 50 RANDOMIZED TRIALS. THIS IS THE FIRST TABLE, I DON'T EXPECT YOU TO BE ABLE TO READ IT BUT THE FIRST IS A TRIAL OF RANDOM PROSTATECTOMY VERSES WATCHFUL WAITING. THAT IS THE TABLE CIRCLED WITH THE RED LINES AROUND IT. AND THE BOTTOM IS A RANDOMIZED TRIAL LOOKING AT PATIENT WHO IS ARE FOUND TO HAVE POSITIVE LYMPHNODES AFTER RADICAL PROSTATECTOMY WHO ARE RANDOMIZED BETWEEN IMMEDIATE HORMONE THERAPY OR DELAYED HORMONE THERAPY. THE IS ITEDS--STUDIES LISTED IN BETWEEN THAT ARE STUDIES WHICH WERE GIVEN TO PATIENTS WITH RADICAL PROSTATECTOMY AND WERE NOT ACTIVE. WE KNOW THAT THIS PRIOR TO RADICAL HOSTECTOMY, IN LOCALIZED PROSTATE CANCER SH'S NOT BE DONE. THESE ARE THE SURVIVAL CURVES SHOWING RADICAL VERSES DELAYED TREATMENT. AND THE SURVILAL OF ADJUVANT HORMONAL THERAPY AFTER RADICAL PROSTATECTOMY. THE NEXT TRIALS THAT I'LL SHOW YOU IS A THREE TRIALS THAT LOOKED AT THE ROLE OF RADIATION AFTER SURGE SURGERY, THIS IS RELEVANT BECAUSE IT'S NOT SIMPLY A MATTER OF WHETHER PATIENTS HAVE SURGERY OR NOT TREATMENT IN THE PATIENT WHO IS HAVE SURGERY, THERE'S ADDITIONAL BENEFIT THAT CAN BE RENDERED POTENTIALLY WITH POST OPERATING GLOBALLY RADIATION. THE FIRST TRIAL LISTED IS THE ONE WITH THE LONGEST FOLLOW UP, THE AMERICAN STUDY WHICH SHOWS AN OVERALL SURVIVAL ADVANTAGE WITH THE ADDITION OF RADIATION AFTER SURGERY, THE OTHER TWO STUDIES HAVE RELATIVELY SHORT FOLLOW UP, THEY DO SHOW AN IMPROVEMENT IN FREEDOM FROM PROGRESSION AND THEY HAVE NOT YET SHOWN A SURVIVAL ADVANTAGE BUT I THINK MORE FOLLOW UP IS NEEDED. THIS IS THE SURVIVAL CURVE DIFFERENCE WITH EARLY RADIO THERAPY. THESE ARE STUDIES WHO RANDOMIZE PATIENTS WHO DO RADIATION ORsQU3– RADIATION VERSES CRY SO SURGERY. THEY'RE ALL NEGATIVE STUDIES DEPENDING ON YOUR INTERPRETATION BUT THEY DON'T ANSWER THE QUESTION, THEY'RE UNDERPOWERED STUDIES BY AND LARGE. THESE ARE STUDIES USING RADIATION AND AGAIN YOU CANNOT READ IT,1 IN THE SENSE THAT NONE OF THEM SHOW SURVIVAL. THESE ARE STUDIES LOOKING AT HIGHER DOSE RADIATION, VERSES LOWER DOSE RADIATION TYPICALLY, RADIATION GIVEN IN DIFFERENT WAYS WITH BRACKY THERAPY AND SO FORTH, AND SO THESE ARE NOT A STUDY THAT TRANSFORM THE WAY THAT WE DO TREATMENT EXCEPT TO REDUCE THE RISK OF RESURENS. --RECURRENCE. THESE ARE R. T.O. G. STUDIES WHICH ARE LARGE STUDIES THAT LOOK AT RADIATION ALONE VERSES RADIATION PLUS HORMONAL THERAPY. THESE ARE MEN WITH LOCALLY ADVANCED DISEASE WITH THE ACCEPTION OF THE FIRST STUDY WHICH I OUTLINE IN YELLOW. THIS IS ACTUALLY A POST OPERATING GLOBALLY STUDY WHICH I COULD HAVE INCLUDED IN THE OTHER STUDY BUT THIS IS A STUDY LOOKING AT RADIATION PLUS OR MINUS THE EARLY USE OF AN ANTIANTIGEN WHICH SHOWS IMPROVEMENT IN PROGRESSION PREE SURVIVAL AND THE DELAY IN THE TIME TO METASTATIC DISEASE AND WITH LONGER FOLLOW UP, I EXPECT IT MAY SHOW A SURVIVAL ADVANTAGE BUT IT'S NOT YET SHOWN THAT. THE OTHER STUDY IS A 2000 PATIENT STUDY, PATIENTS WITH RANDOMIZED TO RADIATION ALONE, RADIATION PLUS FOUR MONTHS OF HORMONE THERAPY THIS, SHOWS AN OVERALL SURVIVAL ADVANTAGE WITH A MODEL NUMBER NEEDED TO TREAT. THE LAST TWO STUDIES ARE ALSO STUDIES IN WHICH LONG-TERM HORMONE THERAPY AND VERY HIGH RISK PATIENTS SHOWED AN OVERALL SURVIVAL ADVANTAGE. SO BY AND LARGE, THESE STUDIES ESSENTIALLY, ALL OF THESE WERE POSITIVE, EVEN THE ONE NOT CIRCLED IN RED, AND DELAY AND THE TIME OF METASTATIC AND A 25% REDUCTION IN OVERALL MORTALITY AT 15 YEARS. THESE ARE VERY IMPRESSIVE PHASE THREE TRIALS. THESE ARE SOME OF THE CURVES FROM THE 2000 PATIENTS STUDIES SHOWING OVERALL SURVIVAL ADVANCE WITH THE ISSUE WITH THE USE OF FOUR MONTHS OF HORMONE THERAPY. THESE ARE THE LONG-TERM STUDIES SHOWING IMPROVEMENT AND SURVIVAL WITH LONG-TERM HORMONE THOAR ACTIVITIES AND PROJECTSY--THERAPY. THESE ARE NONR. T.O. G. ABDOMEN ORDER OF MICRONSIZED RILES--RANDOMIZED TRIALS, THESE SHOW THE VUVIVAL OF--SURVIVAL, THEY DON'T SHOW THE RED LINE AROUND. LOOK AT FOUR MONTHS VERSUS EIGHT MONTHS AND SHOWED NO DIFFERENCE. THE BOTTOM STUDY BY CROOKED ALL SHOWED THREE VERSES EIGHT AND SHOWED NO DIFFERENCE AND THE FINAL STUDY WAS THROUGH THREE YEARS VERSUS RADIATION ALONE WHICH SHOWED AN OVERALL SURVIVAL ADVANTAGE. SO THE FIRST STUDY, THE TROG STUDY WAS PATIENTS WITH LOCALIZED DISEASE, SHOWED IMPROVE SIX MONTHS SURVIVAL. THE STUDY ON THE RIGHT SHOWED THAT THREE YEARS WAS BETTER THAN SIX MONTHS AND THESE ARE AGAIN ALL PHASE THREE PERSPECTIVE RANDOMIZED TRIAL SHOWING THE TREATMENT IN RESULTS IN OVERALL SURVIVAL ADVANTAGE. AND FINALLY THIS IS TABLE FIVE FROM A MANUSCRIPT BEING SUBMITTED AND THESE LOOK AT ANTIGEN DEPRIVATION STUDY, VERSUS WATCHFUL WAITING. AND THIS IS ANDROGEN DEPRIVATION STUDY VERSES THERAPY. SO THE EARLY STUDIES SUGGEST THAT ANDROGEN THERAPY ALONE WAS SUPERIOR TO OBSERVATION ALONE. THIS IS AN IMPORTANT STUDY BECAUSE WE THEN WENT ON IN THE LAST THREE--THE LAST TWO STUDIES AND LOOKED AT WELL, IF ANTIGEN DEPRIVATION RAVISION WAS BETTER THAN WATCHFUL WAITING, WHAT ROLL DOES RADIO THERAPY HAVE IN THOSE PATIENTS SO THEY'RE THREE TRIALS AND THE TWO THAT ARE PUBLISHED TO DATE, SHOW THAT ANTIGEN DEPRIVATION THERAPY PLUS RADIATION PROLONGS OVERALL SURVIVAL COMPARED TO ANDROGEN DIPRIVATION THERAPY ALONE. THIS IS VERY IMPORTANT AND AGAIN, THE U.S. PREVENTATIVE TASK FORCE MAY RECOMMENDATIONS REGUARDING THE VALUE OF TREATMENT BASED ON TWO TRIALS AND I HAVE JUST REVIEWED WITH YOU 50 TRIALS. NOW WHAT OF THESE TRIALS, THESE ARE THE CURRENT TWO TRIALS SHOWING THE RADIATION AND DEPRIVATION THERAPIES. SO MY CONCLUSIONS ARE: THE RADICAL PROSTATECTOMY PROLONG SURVIVAL COMPARED TO WATCHFUL WAITING. THE ANDROGEN DEPRIVATION THERAPY APPEARS TO BE MORE EFFECTIVE THAN OBSERVATION. THERE'S NO ROLE FOR ANDROGEN PROSTATECTOMY BUT PATIENTS WITH POSITIVE NODES DO BENEFIT FROM ADJUVANT HORMONAL THERAPY. THERE APPEARS TO BE SURVIVAL ADVANTAGE WITH THE USE OF THERAPY IN THOSE PATIENTS. POST OPERATIVE RADIATION DELAYS THE TIME TO RECURRENCE AND MAY IMPROVE SURVIVAL. THE ADDITION OF ANTIANTIGEN THERAPY IN PATIENTS IN THE POST OPERATIVE SETTING DELAYS THE TIME TO CLINICAL FAIL AND YOU ARE WITH LONGER FOLLOW UP, THIS MAY RESULT IN THE SURVIVAL ADVANTAGE. THE RELATIVE EFFECTIVENESS OF RADICAL PROSTATECTOMY, AND RADIO THERAPY AND CRYOSURGERY COMPARED TO EXTERNAL RADIAL THERAPY REMAINS UNRESOLVED. THESE STUDIES ARE UNDER POWERED. AND THE USE OF HIGH DOSE EXTERNAL BEAM RADIATION IMPROVES PSA CONTROL BUT IS NOT YET IMPROVE OVER ALL SURVIVAL. HYPOFRACTIONATION, THESE ARE SHORTER COURSES OF HIGH DOSES OF RADIATION HAVE RESULTED AND GENERATE CONFLICTING RESULTS AND IS AN AREA FOR 80IVE RESEARCH BUT SO FAR IT'S UNCLEAR WHEN WHETHER THEY IMPROVE OUTCOMES. AND I'LL SKIP THE PARTICLE THERAPY. EXTERNAL BEAM RADIATION THERAPY PLUS ANDROGEN DEPRIVATION THERAPY IS FOR PATIENTS WITH INTERMEDIATE AND HIGH RISK DISEASE OR MANY STUDIES TO SUPPORT THE STATEMENT, HIGH RISK PARTYS BENEFIT FROM LONG-TERM ANDROGEN DEPRIVATION THERAPY AND WHILE THOSE WITH INTERMEDIATE RISK REQUIRE ONLY FOUR TO SIX MONTHS OF ANDROGEN DEPRIVATION THERAPY AND FINALLY, ANDROGEN DEPRIVATION THERAPY IS BETTER THAN ANDROGEN DEPRIVATION THERAPY ALONE IN PATIENTS WITH LOCALLY ADVANCED PROSTATE CANCER AND ADJUVANT ANTIANDROGEN THERAPY MAY BE BENEFICIAL IN POST OPEN MEETING PATIENTS IF YOU TAKE THESE TOGETHER, THE NUMBER NEEDED TO TREAT, WHICH IS A CALCULATION USED TO ASSESS WHETHER A LOT OF PATIENTS NEED TO BE TREATED UNNECESSARILY IS RELATIVELY FAVORABLE, THAT THESE ARE ACTUALLY REASONABLY SMALL NUMBERS NEEDED TO TREAT TO SHOW BENEFIT WHAT THESE TREATMENT APPROACHES. SO THE DATA FOUND IN EACH TRIAL PROVIDE CLEAR EVIDENCE OF PATIENTS BENEFITING FROM CERTAIN TYPES OF TREATMENT. THESE ARE INVERSE LE PROPORTIONAL TO THE RISK GROUPS WHA. I LOAN BY THAT IS THAT LOW RISK PATIENTS REQUIRE VERY LONG FOLLOW UP AND THEREFORE EVALUATING THE MERITS OF SCREENING AND/OR ACTIVE SURVEILLANCE WOULD REQUIRE VERY LONG FOLLOW UP AND LARGE NUMBERS OF PATIENTS. TREATMENT IS EFFECTIVE BUT ACTIVE SURVEILLANCE SEEMS A REASONABLE OPTION FOR SELECTIVE PATIENTS THOSE WHO ARE NOT INCLUDED IN THESE TREATMENT TRIALS. THE LESSONS LEARNED FROM THESE PATIENTS TREATED ON THESE TREATMENT TRIALS SHOULD BE USED TO INFORM TO THE U.S. FREE RADICALS--PREVEBTATIVE TASK FORCE AND THEY IGNORED SOME OF THESE REVIEWS. THE ABSENCE OF PROOF IS NOT PROOF OF ABSENCE. THANK YOU FOR YOUR ATTENTION. [ APPLAUSE ] >> THANK YOU DR. ROACH. OUR NEXT SPEAKER IS LARS HOLMBERG, PROFESSOR OF CANC IRB EPIDEMIOLOGY, DIVISION OF CANCER STUDIES, KINGS COLLEGE LONDON SCHOOL OF MEDICINE, GUY'S HOSPITAL, RESULTS FROM THE SCANDINAVIAN PROSTATE CANCER GROUP FOUR, TRIAL SPC G-FOUR. >> THANK YOU VERY MUCH, THE SPC G-FOUR TRIAL IS TO TRY TO TRIBUTE TO THIS MEETING. WE FEEL VERY HONORED IF YOU CAN CONTRIBUTE WITH ANY SORT OF KNOWLEDGE TO THIS VERY DIFFICULT QUESTION. NOW THIS TRIAL WAS UNDERTAKEN--OH ESORRY. >> SO THIS IS IT STUDY WAS UNDERTAKING IN 1999, AND RANDOMIZED 695 PATIENTS TO WATCHFUL WAITING OR TO RADICAL PROSTATECTOMY. SO I WOULD REMIND YOU THAT THIS IS WATCHFUL WAITING IS NOT THE ACTIVE SURVEILLANCE THAT WE'RE TALKING ABOUT TODAY. SO THIS IS ANOTHER FORM OF SYMPTOM STEERED TREATMENT WHENEVER SYMPTOM OCCURRED IN THOSE PATIENTS UNDEROBSERVATION. NOW, ONLY AT THE LATER PART OF THE 19 NIEPTS IN SWEDEN PSA SCREENING, TOOK ON MORE FREQUENTLY, SO THIS IS ESSENTIALLY A GROUP OF PATIENTS AS YOU CAN SEE BY THE TUMOR STAGE DISTRIBUTION, THAT ARE NOT SCREENED DETECTED CATEGORY OF PATIENTS: THE PATIENTS HAVING A T-1 C TUMOR IN THIS STUDY IS ONLY 12% IN TOTAL. NOW YOU CAN ALSO SEE THAT IN TERMS OF THE GLEASON SCORES THERE ARE FEW PATIENTS WITH THE GLEASON SCORE WITH 67 ABOVE. AND THIS STUDY WAS WAS TARGETED TO PATIENTS WITH A GLEASON SCORE OF SEVEN AND BELOW, BUT THE REEVALUATION OF THE BIOPSY SPECIMENS IT TURNED OUT WE HAD A DRIFT IN GLEASON AS YOU WOULD SUSPECT FROM THE TALKS AS OF YESTERDAY. NOW WE HAVE ANALYZE TED THE DATA IN THIS SLIDE, WITH THE DISCUSSION TO COMPLETE. THERE WERE DRASTIC DIFFERENCES IN THE TWO TREATMENT OPEN MEETINGS. WE SUSPECTED THERE WOULD BE A BIG DRIFT PERHAPS BETWEEN THE STUDY ARMS THAT WOULD HAVE THREATENED THE VALIDITY OF THE STUDY AND THE STUDY RESULTS. BUT TO DATE IN THE LAST FOLLOW UP, THERE WAS ABOUT 50 PATIENTS IN THE WATCHFUL WAITING ARM THAT HAD UNDERGONE BY THE END OF 2009, SOME SORT OF CURIAATIVE INTENDED TREATMENT. AND IN THE RADICAL PROSTATECTOMY ARM THERE WAS STILL 21 PATIENTS THAT WERE WATCHFUL AND WAITING. SO HERE'S THE TREATMENT NOW AT 15 YEARS OF FOLLOW UP. WE HAVE A MEAN FOLLOW UP OF 12.8 YEARS AT THIS PARTICULAR ANALYSIS, BUT AS YOU CAN SEE FROM THE NUMBERS, AT RISK AT THE BOTTOM, WE HAVE STABLE ESTIMATES, ALL UP TO THE 15 YEARS OF FOLLOW UP. THERE'S AN ABSOLUTE RISK REJECTION AROUND 6 PERCENT WITH THE NUMBERS TREATED OF 17. AND I WOULD UNDERLINE JUST THIS AS DR. RODES SAID IN HIS TALK, THE NUMBERS NEEDING TO TREAT IS SOMETHING WHICH IS NOW IN OUR STUDY OBTAINING TO THE 15 YEAR PERSPECTIVE. IN TERMS OF METASTASIS, WE HAVE A LARGER DIFFERENCE. WE HAD SUSPECTED IN THE FIRST COUPLE OF ANALYSIS WE DID IN THE STUDY THAT THIS WOULD CARRY OVER IN THE LAUNCHER, DIFFERENCE IN PROSTASTY CANCER, DEATH, WITH TIME, BUT IT HAS NOT DONE SO AND SO, WE WILL HAVE TO WAIT WITH AN EVEN LONGER FOLLOW UP TO SEE WHAT THIS MEANS IN THE LONG RUN IN TERMS OF PROSTASTY CANCER DEATH. THE OVERALL MORTALITY, VERY SIMILAR TO THE DIFFERENCE IN PROSTATE CANCER DEATH, STAYING STAYING--SAYING THAT THE MAIN DIFFERENCE BETWEEN THE TWO ARMS WILL LOOK AT THE OVERALL SURVIVAL IS DEPENDENT ON THE DIFFERENCE IN PROSTATE CANCER DEATHS. SO HERE WE HAVE THE NUMBERS NEEDED TO TREAT OF AROUND 16. NOW WE HAVE LOOKED REPEATEDLY ACROSS DIFFERENT SUBGROUPS TO SEE IF WE HAVE SOME SORT OF EFFECT MODIFICATION OR CHANGE BY THIS DIFFERENT PATIENT CHARACTERISTICS, IN THE EFFECTS OF SURGERY. NOW IF YOU LOOK ACROSS THESE LINES ALL THE WAY DOWN TO AGE, YOU WILL SEE THAT THERE IS A SIMILAR DIFFERENCE IN RELATIVE TERMS BETWEEN THE TWO STUDY GROUPS, SO IT'S ABOUT A THIRD% REDUCTION IN RELATIVE TERMS OF PROSTASTY CANCER DEATH IN THESE DIFFERENT SUBGROUPS. SO IN THIS THAT SENSE THERE,'S NO EFFECT MODIFICATION OR INTERACTION BY THESE FACTORS AND THE FACT THAT YOU WILL RANDOMIZE THE PROSTATECTOMY. BUT CLEARLY YOU CAN SEE THAT THE ABSOLUTE RISK PROTECTION WILL BE DIFFERENT WHEN YOU HAVE A DIFFERENT BASELINE RISK AS FAR AS WATCHFUL WAITING. SO, BUT YOU CAN ALSO SEE, I WILL REMIND YOU AND COME BACK TO THAT, THAT FOR AGE, IT SEEMS THAT THE BIGGEST EFFECT IS IN THE LOWER AGE GROUP AND A MAN 65 YEARS AND OLDER DOES MAKE A DIFFERENCE IN THIS ANALYSIS. SO WE HAVE HERE, AN ILLUSTRATION OF THE OLD FACT THAT EVEN RELATIVE RISK REDUCTION, SAY THAT THE LIGHT BLUE ARE THOSE WHO ARE AT RISK OF DYING FROM PROSTASTY CANC AND WE'LL REDUCE THAT BY HALF. NOW IF THE BASELINE RISK IS MUCH LOWER, EVEN AT 50% REDUCTION IN THE MORTALITY HERE WILL MEAN THAT THIS ABSOLUTE RERISK REDUCTION IS MAUL IS MAY BE CLINICALLY QUESTIONABLE TO ITS RELEVANCE. HM. M. I'M SORRY, THERE SEEMS TO BE SOME SLIDES MISSING IN MY PRECEPTATION. NOW IT SEEMS LIKE THE MAIN BENEFIT WAS IN THE MEN UNDER 65. NOW WE HAVE CAUTIONED MANY TIMES, AND I WILL CAUTION YOU YOU HERE THAT THIS IS A SUBGROUP ANALYSIS. THE SUPGROUP ANALYSIS IS DIFFICULT TO INTERPRET AND CAN MISLEAD YOU. SO WE HAVE ALWAYS UNDERLINED THAT THIS SUBGROUP ANALYSIS NEEDS TO BE TAKEN AS A HYPOTHESIS GENERATING SUBGROUP ANALYSIS, RATHER THAN SOMETHING WHICH COULD BE TAKEN AS FIRMLY INTO DECISION MAKING. NOW I WILL ILLUSTRATE TO YOU, WHY IT MAY BE SORT OF DAIMPLEGEROUS TO SAY THERE'S NO EFFECT AT ALL OVER THE AGE OF 65. WE HAVE MODELED OUR DATA MORE CAREFULLY IN COLLABORATION WITH ANDREW?1AN– VICTORS MEMORIAL SLOAN-KETTERING AND WHEN YOU TAKE 60 YEARS AS YOUR POINT OF DEPARTURE FOR PATIENTS, THAT'S THE ANCHORING POINT OF THESE ANALYSIS AND YOU LOOK IN DIFFERENT SUBCATEGORIES, THIS IS AN EXAMPLE OF NOW OF TWO DIFFERENT SUBCATEGORIES, YOU SEE THE DIFFERENCE IN BENEFIT BETWEEN THE TWO ARMS WITH MEN WITH GLEASON TUMORS OF T-TWO-EIGHT AND YOU SEE THE BASELINE. YOU SEE THE BENEFIT ALL THREE THESE AGES. NOW WHEN YOU LOOK AT MEN WITH A T-ONE CTWO TUMOR, DPLEEZON SIX PSA 10 AT THE BASELINE, THE BENEFIT SEEMS MUCH LOWER. SO IT SEEMS LIKE THE RESULT WEES SEE FROM THE OVERANALYSIS IS AN AVERAGE BENEFIT IN WHAT FOLLOWS RODICAL PROSTATECTOMY. BECAUSE YOU NEED TO CONSIDER THAT IT IS NOT ONLY AGE BUT ALSO OTHER FACTORS THE TUMOR STAGE, THAT YOU HAVE TO BE--THAT HAS TO BE TAKEN INTO ACCOUNT WHEN YOU LOOK AT BENEFIT. AND THIS IN THIS ANALYSIS TSEEMS LIKE 65 IS MAYBE NOT THE REAL CUTTING POINT.4 Ö BUT THERE'S VERY LITTLE BENEFIT BEYOND 70 YEARS OF AGE AT THE TIME OF RANDOMIZATION. NOW WE ALSO LOOKED AT THE LOW RISK GROUP, NOW MIND YOU THE LOW RISK GROUP IN THIS STUDY DOES NOT CONTAIN A LOT OF PATIENTS THAT HAD SCREENING DETECTED T-ONE, C DISEASE BECAUSE WE DID NOT HAVE MANY OF THOSE IN THE STUDY AS I TOLD YOU. BUT IF WE DEFINE A LOW RISK GROUP AS LESS THAN PSA 10 OR LESS AT THE TIME OF DIAGNOSIS, GLEASON LESS THAN SEVEN, OR FOUR MEN WHO ONLY HAD A NEEDLE BIOPSY SPECIMEN, WHO GRADE ONE. IN THAT PARTICULAR GROUP, THE ABSOLUTE RISK REDUCTION WAS 4.2% AND THEN, THERE'S SUBSTANTIALLY HIGHER NUMBER NEEDED TO TREAT AND THEN ONE AND THE OTHER ANALYSIS. BUT STILL, THERE WAS AT 15 YEARS, 6.8 PERCENT PROBABILITY OF DYING FROM PROSTASTY CANCER IN--PROSTATE CANCER IN THOSE WHO UNDERWENT RADICAL PROST PROST--PROSTATECTOMY. >> NOW IN THE STUDY, IT WILL ALSO SHOW THAT WE LOOKED AT SELF-REPORTED SYMPTOMS DISSTRESS FROM THESE SYMPTOMS AT AN OVERALL RATING OF QUALITY OF LIFE IN THIS STUDY. SO THERE WERE TWO QUESTIONNAIRE STUDIES DONE WITH QUESTIONNAIRES SPECIFICALLY DEVELOPED FOR THIS PATIENT CATEGORY AND FOR THIS STUDY, SO THERE WAS ONE WHICH WAS SENT OUT AT THE MEDIAN OF FOUR YEAR OR FOLLOW UP, AND THERE WAS ONE WHICH WAS NOW, RECENTLY ANALYZED AND PUBLISHED WHICH WAS THEN DONE AT A 12.2 YEAR FOLLOW UP AT THE MEDIAN. THE RESPONSE RATE FOR THIS QUESTION WAS IN BOTH OF THESE ROUNDS OF QUESTIONNAIRES. HEIGHT WAS OVER 85% IN THE STUDY GROUPS. IN THE LAST FOLLOW UP, THERE WERE 76 WHICH ANSWERED THE QUESTIONNAIRE WHICH WAS THE SAME FOR THE STUDY THE CANCER SPECIFIC QUESTIONS WERE NOT THERE FOR THAT'* POPULATION. YOU CAN SEE THAT IT SEEMS LIKE FOR ERECTILE DYSFUNCTION THAT YOU HAVE A MEDIAN--IMMEDIATE APPEARANCE OF THE SYMPTOMS AS YOU WOULD EXPECT IN THE SURGICAL GROUP AND YOU HAVE A DIFFERENCE HERE IN THIS FIRST FOLLOW UP. HOWEVER, WITH TIME YOU HAVE ALSO RAISING ISSUE WITH THIS IN THE WATCHFUL WAITING GROUP, PROBABLY DEPENDENT ON THAT WE HAVE A HIGH PREVALENCE OF ANDROGEN DEPRIVATION TREATMENT IN THAT GROUP IN TIME. THE PREVALENCE OF THE STRESS DOESN'T CHANGE OVERTIME. SO IT DOESN'T SEEM THAT IT DOESN'T SEEM THAT AND PREULENCE OF THE LEAKAGE, THAT'S PATTERN OF THE DIFFERENCE BETWEEN THE GROUPS STAYS ROUGHLY THE SAME OVERTHIS FOLLOW UP. ONCE AGAIN WE SEE THAT THE PREVALENCE OF DISSTRESS IN THE GROUPS DOES NOT GO AWAY WITH ALTERNATIVE FOLLOW UP; WE HAVE SIMILAR PREVALENCE OF HIGH SOCIETY OR SUBJECTIVE QUALITY OF LIFE IN THE TWO GROUPS IN THE TWO FOLLOW UPS. NOW I THINK THAT HAD THIS IS OFTEN CORRUPTED BUT UNDER THAT, IT'S A MUCH MORE COMPLEX PATTERN OF DIFFERENT SYMPTOMS AND DISSTRESSES OCCURRING IN THE DIFFERENT GROUPS WHICH WILL BE VERY IMPORTANT FOR PATIENT INFORMATION AND COUNSELING IN DECISION MAKING. AND YOU COULD SAY, WELL, WHAT ABOUT THIS TIME DIFFERENCE HERE OF COURSE, MEN HAVE GROWN OLDER, ISN'T THIS JUST SCIENCE OF NORMAL AGING? BUT WHEN YOU COMPARE TO THIS POPULATION CONTROL GROUP, IN THIS LATEST QUESTION AIR ROUND, IT IS ACTUALLY SHOW THAT BOTH THE STUDY ARMS IN SPC G-FOUR ON AVERAGE DO WORSE THAN NORMAL OR I SHOULD SAY THE AVERAGE SWEDISH MAN IN THE POPULATION CONTROLS. WE ALSO DID STUDY OF HEALTH ECONOMY AND THAT WAS DONE IN THE SUBSET OF THE STUDY 212 MEN EQUALLY BALANCED BETWEEN THE TWO STUDY GROUPS AND ALL COSTS IN TERMS OF FOLLOWING THE PATIENT MEDICAL RECORDS THROUGH MEDIAN FOLLOW UP WITH OTHERSMY AND DEPENDING ON THE DIFFERENCE GROUPS AND THEY WILL HAVE DIFFERENT OPTIONS IN TERMS OF CANCER MORTALGITY. THERE WAS ALSO A DIFFERENCE, A SPAN IN THE COST DIFFERENCE BETWEEN THE TWO GROUPS HOWEVER, HOWEVER IT WAS MORE EXPENSIVE IN THE RADICAL PROSTATECTOMY GROUP AND THE AVERAGE DIFFERENCE WAS ABOUT 6000 UROS AND THE COST DIFFERENCE WAS NEARLY ENTIRELY DRIVEN BOY THE FIRST HALF TO ONE YEAR AND DEPENDING ON THE INTERVENTION WITH OPERATION. SO IN CONCLUSION, RADICAL PROSTATECTOMY, FOR THE PROSTATE CANCER, I AGREE FULLY WITH THE CONCLUSION BY DR. ROACH. AND THERE'S AN AVERAGE MODEST EFFECT BUT WE MUST ACKNOWLEDGE THAT IT'S AN AVERAGE EFFECT IN LOOKING AT COMPLEX SUBSET OF PATIENTS SUCH AS THIS. AND IT DIFFERS OVER SPECTRUM OF PATIENT CHARACTERISTICS. IT MIGHT BE OVERSIMPLISTIC AS I UNDERLINE TO SAY, THERE'S NO EFFECT OVER THE AGE OF 65. WE CAUTION MANY TIMES THAT YOU CANNOT DRAW THAT CONCLUSION FROM HERE FROM THE STUDY. THE SIDE EFFECTS ARE SUBSTANTIAL AND THEY APPEAR IN A COMPLEX PATTERN OVER A LONG TIME OR EVEN A LONG TIME OF FOLLOW UP SO IF YOU THINK ABOUT COUNSELING IT MAY BE THAT COUNSELING IS NOT ONLY SOMETHING WHICH NEEDS TO BE DONE IN CONJUNCTION WITH THE INITIAL DIAGNOSIS BUT OVER A LONG TIME THIS WILL CONTINUE TO BE IMPORTANT ALSO IN THE FUTURE AROUND 50% OF THE PATIENTS AT THE LAST TIME OF FOLLOW UP NOW WERE ACTUALLY ALIVE AND WE CAN FOLLOW THESE PATIENTS INTO A LONGER PERIOD OF FOLLOW UP OVER WHEN THEY AGE AND COME INTO A VERY HIGH AGE. AND THESE ARE IN A STUDY WHICH WE CAN CONTRAST AGAINST EACH OTHER FINALLY THE SIDE EFFECTS OCCUR WITH MODERN TREATMENTS THERE'S LARGE VOLUME OF CENTERS IN THE TREATMENTS WHERE IT'S DIFFICULT TO HOLD UP THE QUALITY OF SURGERY AND DIMINISHED SIDE EFFECTS AND THE SIDE EFFECTS ACTUALLY SEE THEM IN THE RATEDICAL PROSTATECTOMY ARM, THEY OCCUR, SORTS OF IMMEDIATELY AND IT'S GOING TO AS THEY POINTED OUT YESTERDAY, THERE'S NO LEAD TIME FOR THAT. HOWEVER IF YOU WOULD BLEND INTO STUDIES SUCH AS OURS. WITH THE DISEASE AND LONG LEAD TIMES, THE LEAD TIMES IN TERMS OF SYMPTOMS AND BOTHER WOULD OF COURSE APPLY TO THE MEN UNDER ACTIVE SURVEILLANCE OR UNDER WATCHFUL WAITING. THANK YOU VERY MUCH. [ APPLAUSE ] >> THANK YOU DR. HOLMBERG, OUR NEXT SPEAKER IS DR. TIMOTHY WILT AND HE IS THE COURSE INVESTIGATOR FOR THE MINNEAPOLIS VETERANS AFFAIRS OF CENTER FOR CHRONIC DISEASE OUTCOMES AND RESEARCH FOR THE UNIVERSITY OF MINNESOTA SCHOOL OF OF MEDICINE. RESULTS FROM THE PROSTATE CANCER INTERVENTION VERSUS OBSERVATION TRIAL OR PIVOT TRIAL. AND. >> THANK YOU IT'S GREAT TO BE ABLE TO TALK ABOUT THE PROSTASTY INTERVENTION VERSES OBSERVATION TRIAL. THE RESULTS OF THIS STUDY WILL STRONGLY SUPPORT THE ROLE OF OBSERVATION FOR MEN WITH LOW RISK DISEASE AND THE FEATURE STUDIES IN MEN WITH HIGH RISK PROTOCOL AND I WILL SHOW THE DAT THROUGHOUT THE TALK. IT'S A RANDOMIZED CLINICAL TRIAL FOR PROSTATE CANCER THE OBJECTIVE OF OUR STUDY WAS TO DETERMINE FOR MEN CAN CLINICALLY LOCALIZED PROSTATE CANCER AND TREAT INDEED THE UNITED STATES DOES THE INTEND TO TREAT WITH RADICAL PROSTATECTOMY REDUCE ALL CAUSE AND CANCER MORTALITY AND IMPROVE HEALTH STATUS AND QUALITY OF LIFE COMPARED TO OBSERVATION. WE INCLUDED MEN IF THEY WERE AGE 75 OR LESS HAD CLINICALLY PROSTASTY CANCER OF ALL GRADES GRADES AND PSA OF LESS THAN 50 NANO GRAMS PER MILL LITER AND WERE CONSIDERED A CANDIDATE FOR RADICAL PROSTATECTOMY AS JUDGED BY THE CLINICIAN AND INCLUDED LIFE EXPECTANCY GREATER THAN 10 YEARS. OUR PRIMARY WAS ALL CAUSE MORTALITY. THE SURGERY MEN HELP LIVE LONGER THAN OBSERVATION, OUR SECONDARYEND POINT WAS PROSTASTY CANCER SPECIFIC MORTALITY. IT DOESN'T REDUCE DEATH CONSIDERED DUE TO PROSTATE CANCER. WE ALSO COLLECTED ADDITIONAL END POINTS INCLUDING PERIOPERATIVE HARMS, HEALTH STATUS, WORRY AND BOTHER, AND ERECTILE, URINAR SCHEBOWEL DYSFUNCTION. 5023 MEN WERE CONSIDERED ELIGIBLE 4292 DECLINE THIS RANDOMIZATION AND 731 WERE RANDOMIZED. 364-RADICAL PROSTATECTOMY AND 367 TO OBSERVATION ATTEMPT FORERALICAL PROSTATECTOMY WAS CONSIDERED IN 89% IN WHICH 84% HAD SOME FORM OF DEFINITIVE ERPT VEKS, RADICAL PROSTATECTOMY WAS IN 36 OR 10% OF THOSE IN THE OBSERVATION ARM. THERE ARE NO DIFFERENCES IN BASELINE CHARACTERISTICS BETWEEN THE OBSERVATION AND THE RADICAL PROSTATECTOMY ARM. THE MEAN AGE WAS 67, HALF HALF WERE BLACK, AND MARRIED. THEY WERE FULLY ACTIVE BASED ON ADL ASKS MEN WERE HEALTHY BASED ON THEY HAD NO CO-MORBIDITYS. THE MEAN PSA WAS 10 WITH A MEDE YON OF ABOUT EIGHT APPROXIMATELY 11% HAD PSA VALUES LESS THAN FOUR AND 10% GREATER THAN 20 IN CONTRAST TO THE SCANDINAVIAN TRIAL PRECEPTED ALMOST HALF OF OUR PATIENTS ALMOST HALF HAD T-1 C NONPAP PALPABLE DISEASE. AS JUDGED BY LOCAL HISTOPATHOLOGY. AND ABOUT 18% GLEASON SCORES OF SKETCH SEVEN% GLEASON SCORES OF EIGHT TO 10. USING DNE CODE, RISK CAT CORY SCORES THAT INCLUDE STAGE AND HISTON PATHOLOGY AND PSA, 40% HAVE AND ONE% HAD HIGH RISK TUMORS. AND USING THE PATHOLOGY, YOU SUBMITTED SPECIMENS ABOUT 2/3RDS OF ENROLLEES HAD WHAT WERE CONSIDERED EITHER INTERMEDIATE OR HIGH RISK PATHOLOGY. A THREE PERSON UP COMMITTEE MINDED TO THE EXTENT POSSIBLE ASSESS CAUSE OF DETH. THAT'S THAT'S PROSTASTY CANCER OR PROBABLY DUE TO PROSTATE CANCER TREATMENT OR NOT PROSTATE CANCER EITHER DEFINITELY OR PROBABLY NOT DUE TO CANCER TREATMENT. AND I'D LIKE TO KNOW YOU KNOW THAT ASSESSING CAUSE OF DEATH IN THIS RANDOMIZED TRIAL WHILE RIGOROUSLY ATTEMPTED WAS EXTRAORDINARILY DIFFICULT. I URGE CAUTION IN ATTEMPTING TO DO THIS IN THIS STUDIES THAT DO NOT HAVE THIS DEGREE IN ASCERTAINMENT AND EVEN IN RANDOMIZED TRIALS IN ACCURATELY AND RELIABLE ASSESSING IT IS DIFFICULT. THE MEDIAN YEARS OF SEVEN TO 1012.6 YEARS. PROSTATE MORTALITY WAS INFREQUENT INCURRING BETWEEN 70.1% OF INDIVIDUALS. SO IT VARIED RANGING FROM 3.4%. MEN WITH LOW RISK DISEASE AND UP TO 13% IN MEN WITH HIGH RISK DISEASE. SIMILAR RANGES WERE ALSO SEEN BASED ON PSA VALUES. THIS SLIDE SHOWS THE RESULTS OF MORTALITY. 171 MEN ASSIGNED TO RADICAL PROSTATECTOMY, SEAN AND BRED, AND VERSES 183 MEN, 49.9% IN THE OBSERVATION GROUP SHOWED IN BLUE. THIS RESULTED IN AN ABSOLUTE RISK REDICTION OF 2.9% WHICH WAS NOT STATISTICALLY SIGNIFICANT. THE HAZARDS RATIO WAS 0.88. 12% RELATIVE RISK REDUCTION AND 0.22 INDICATING NO STATISTICAL DIFFERENCE, ANY DIFFERENCES, THERE ARE NO DIFFERENCES IN AT ANY OF THE TIME POINTS AND DIFFERENCES DECLINED OVER TIME. WE ASSESS THE POSSIBLE MODIFICATION IN SEVEN PREDEFINED PATIENT SUBGROUPS AS DETERMINED BY PATIENT AND TUMOR ATTRIBUTES. AGE, RACE, CHARLES TON SCORE, PERFORM AN STATUS AND PSA RISK CATEGORY AND GLEASON SCORE SCORES. WE FOUND NO DIFFERENCE BETWEEN SURGERY VERSES OBSERVATION IN ANY OF THE PATIENT ATTRIBUTES, AGE, LESS THAN VERSES GREATER OR EQUAL TO 65. RACE, WHITE, BLACK, OTHER, CHARLESTON SCORES OR PERFORMANCE STATUS AND NO DIFFERENCE BY GLEASON SCORES, SEVEN VERSES GREATER, LESS THAN SEVEN. YOU SEE THE P-VALUE ARE INTERACTION FOR GLEASON HISTOLOGY, INDICATING NO DIFFERENCE ACROSS THOSE„i GROUPS. IN CONTRAST, WE FOUND THAT THERE WAS AN EFFECT MODIFICATION ACCORDING TO PSA VALUES, WITH THEIR BEING A BENEFICIAL EFFECT IN MEN WITH PSAs GREATER THAN 10 AND NO BENEFIT IN THOSE WITH PSA'S LESS THAN OR EQUAL TO 10. THERE'S POREDDER LINE STATISTICAL SIGNATURES THAT I HAVE CANT EFFECT ACCORDING TO THE AMIC O RISK CATEGORIZATION AND I'LL SHOW THOSE SUBGROUPS NOW. FOR MEN USING LOCAL MORTALITY, THE HAZARD RATIO WAS 1.45, THE ABSOLUTE RISK DIFFERENCE WAS FINEUS 5.4. IT FAVORED OBSERVATION. THERE WERE FEWER DEATHS IN THE OBSERVATION GROUP THAN THE SURGERY GROUP. THIS WAS OUR PRIMARY OUTCOME. IN CONTRAST USING INTERMEDIATE RISK CLASSIFICATION AGAIN, LOCAL PATHOLOGY WOO SAW A 31% RELATIVE REDUCTION, 12.6% ABSOLUTE REDUCTION THAT DEBAN TO OCCUR FAIRLY EARLY ON AND ALSO INCREASED OVERTIME. HOWEVER, WHEN ASSESS THANKSGIVING USING ASSESSING THIS USING CENTRAL PATHOLOGY, THE ABSOLUTE DIFFERENCE WENT TO FOUR AND IT WAS NO LONGER STATISTICALLY SIGNIFICANT. THEREFORE I URGE CAUTION IN USING THIS INTERMEDIATE RISK CATEGOR TOW DETERMINE TREATMENT DIFFERENCES. OUR RESULTS WERE MOST ROBUST AT 10 VALUES, REGUARDLESS OF HISTOLOGIC GRADE OR TUMOR STAGE. THE HADS ARD RATE WAS 1.03, AND ABSOLUTE RISK REDUCTIONU 2.7 AGAIN FAVORING OBSERVATION. YOU CAN SEE THE CURVES ARE VIRTUALLY SUPER IMPOSABLE THROUGHOUT EVERY 15 YEARS. IN CONTRAST, THE MEN WITH PSA VALUES GREATER THAN 10, WE AGAIN FOUND A 33% RELATIVE REDUCTION, 13% ABSOLUTE REDUCTION, WITH SMALL DIFFERENCES, THROUGH ABOUT EIGHT YEARS AND THEN THE CURVES BEGIN TO SEPARATE FURTHER AT ABOUT 10 YEARS. THESE RESULTS REMAIN WHEN WE LOOKED AT SEBTERAL VERSES LOCAL PSA DATA. PASTATE CANCER MORTALITY SHOWN ON THIS SLIDE, AS I INDICATED PROSTASTY CANCER MODEL CITIZENTALLITY OCCURRED IN 31 MEN AND OBSERVATION GROUP AND 21 IN THE RADICAL PROSTATECTOMY GROUP. THE ABSOLUTE REDUXES WAS 2.7% AND WAS NOT STATISTICALLY SIGNIFICANT. THERE IS A 37 RELATIVE RISK REDUCTION AND THOSE ARE SUPER IMPOSABLE ON EACH OTHER AND IT BEGINS TO BE A LITTLE SEPARATION BETWEEN 12 YEARS AND AGAIN FEW PATIENTS OUT HERE, BUT AGAIN CROSS UP HERE. IN THE 2/3RDS OF MEN DIED IT WAS DEFINITELY DUE TO PROSTATE CANCER, THE ABSOLUTE DIFFERENCE WAS LESS THAN ONE%. 0.5%. AGAIN URGING CAUTION AND THE USE OF PROSTATE CANCER MORTALITY AND DETERMINING TREATMENT EFFECTIVENESS. SIMILAR TO ALL CAUSE MORTALITY, WE LOOK FOR POSITIVE EFFECT BY PATIENT ATTRIBUTES AND TUMOR ATTRIBUTES ATTRIBUTES AND SIMILAR TO ALL CAUSE MORTALITY WE FOUND THAT THE EFFECT WAS NOT MODIFIED BY AGE, RACE, CHACIALTZ STONE SCORE, PERFORMANCE STATUS OR GLEASON SCORE. AGAIN A P-VALUE FOR INTERACTION OF OF GLEASON SCORES. WE SAW EVIDENCE FOR INTERACTION BY PSA AND TUMOR RISK CATEGOR ESTIMATE ESTIMATE THADS WHERE P-VALUE AND AGAIN PROBABLILY LOW POOR TO DETECT INTERACTION. ANOTHER CORDING TO THE LOW RISK PATHOLOGY, USING LOCAL PATHOLOGY, RADICAL PROSTATECTOMY DID NOT REDUCE PROSTASTY CANCER MORTALITY COMPARED TO OBSERVATION. THAT'S DUE TO PROSTATE CANCER WERE AWARE IN THIS GROUP, OCCURRING IN ONLY ABOUT THREE% AND AS YOU CAN SEE, THE ABSOLUTE RISK REDUCTION FAVORED OBSERVATION BY ABOUT 1.5%. THE CURVES AREENTIOUS SENTIALLY SUPERIMPOSABLE THROUGHOUT 13-14 YEARS. RADICAL PROSTATECTOMY DID NOT REDUCE MORTALITY COMPARED TO OBSERVATION IN MEN WITH LOW RISK TUMORS. IN CONTRAST, THERE WAS A 60% RELATIVE 8.4% ABSOLUTE RISK REDUCTION THAT WAS STATISTICALLY SIGNIFICANT. YOU SEE THE CURVES SEPARATE HERE AT ABOUT SEVEN YEARS AND GET LARGE. WHEN USING CENTRAL PATHOLOGY, THE RATES DECREASE TO 5 PERCENT AND DO NOT BECOME STATISTICALLY SIGNIFICANT. LOOKING AT IRPT MEET YAID PATHOLOGY, THEY'RE NOT SIGNIFICANT WHEN USING SEBTERAL PATHOLOGY. AGAIN, CAUTIONING THE USE OF HISTOPATHOLOGY AS BEING A DRIVE AND TREATMENT DECISIONS. AGAIN, AS WITH ALL CAUSE MORTALITY. PSA WAS MOST ARE BUST IN DETERMINING TREATMENT EFFECTIVENESS IN MEN WITH PSA VALUES LESS THAN OR EQUAL TO 10. THERE WAS NO STATISTICAL DIFFERENCE WITH AN ABSOLUTE RISK REDUCTION OF 0.3%, AGAIN THE CURVES ARE VIRTUALLY SUPER IMPOSABLE ON EACH OTHER. THAT'S DUE TO PROSTATE CANCER, WE'RE RARE IN THIS GROUP AND NO DIFFERENCE OVER THE COURSE ALL THE WAY OUT TO ABOUT 15 YEARS. IN CONTRAST, IN MEN WITH PSA VALUES ABOVE 10, WE FIND A 67% RELATIVE, SEVEN PASSPORT TWO% ABSOLUTE RERISKRIA DUCKS, WITH CURVES BEGINNING TO SEPARATE AT ABOUT SEVEN YEARS. AND AGAIN RESULTS WERE CONSISTENT WITH WHEN WE LOOK AT CENTRAL VERSES LOCAL PATHOHISTOLOGY. A REPORT NOW, THE RESULTS ON ADVERSE EFFECTS, HEALTH STATUS, URINARY AND BOWEL OUTCOMES. COMPLICATIONS OCCUR INDEED ABOUT 27% OF INDIVIDUALS AND DEATH OCCURRING IN ZERO PUBLICITY 14%. AND THIS SLIDE SHOWN ADVERSE EFFECTS THAT OCCUR INDEED ONE% OF INDIVIDUALS. WITH WOUND INFECTION BEING THE MOST COMMON OCCURRING IN 4.3%. AND YOU CAN SEE A LIST OF THE OTHERS OCCURRING AT ABOUT ONE TO TWO%. THERE ARE NO DIFFERENCE IN HEALTH STATUS AS MEASURED BY THE SF 12 PHYSICAL COMPONENT SCALE BETWEEN RADICAL PROSTATECTOMY AND OBSERVATION. NO STATISTICAL DIFFERENCE, THE ABSOLUTE DIFFERENCES WERE QUITE SMALL IN BOTH GROUPS IT DECLINED OVERTIME. SIMILARLY IN THE MENTAL COMPONENT SCALE, THERE ARE NO DIFFERENCES BETWEEN OBSERVATION AND CADICAL PROSTATECTOMY OUT THROUGH 10 YEARS. ADVERSE EVENTS TYPICALLY WERE GREATER IN THE SURGERY GROUP THAN OBSERVATION AND GREATEST EARLY ON AND DECLINED AT DIFFERENCES, DECLINED OVERTIME, I SHOW YOU JUST THE RESULTS OF TWO YEARS FOR CLARITY'S STEAK BUT AS YOU CAN SEE HERE, URINARY INKOBTINENT, ERECTILE DYSFUNCTION AND SEXUAL DISSATISFACTION BUT NOT BOWEL DYSFUNCTION WERE GREATER IN THE SURGERY COMPARED TO THE OBSERVATION GROUP. BOTHER ABOUT PROSTASTY CANCER TREATMENT WAS ACTUALLY SLIGHTLY BETTER IN THE OBSERVATION GROUP THAN IN THE RADICAL PROSTATECTOMY. HERE IT'S SHOWN AS A PERCENT REPORTING AS NO BOTHER AND YOU CAN SEE THAT THROUGHOUT THE COURSE ACCIDENT IT IS PERCENT OF OF THESE INDIVIDUALS REPOREDDING NO BEEFS WAS SLIGHTLY GREATER IN THE OBSERVATION GROUP THAN IN THE RADICAL PROSTATECTOMY GROUPS AND SOME OF THESE ARE STATISTICALLY SIGNIFICANT. I AM JUST IN THE PROCESS OF BEGINNING TO ANALYZE THESE SO THE EFFECT SIDES ARE GOOD. I'M JUST PROFESS OF DETERMINING THE LEVEL OF STATISTICAL SIGNIFICANCE ON THESE. SIMILARLY, FOR WORRY ABOUT PROSTASTY CONSER, THEY REFLECT THE FINDINGS THAT DR. HOLMBERG SHOWED PRIOR TO THIS, THE RESULTS WERE SIMILAR AGAIN, THE PERCENT SHOWING NO WORRY ABOUT PROSTASTY CANCER. AGAIN ALMOST IDENTICAL ABOUT THREE YEARS, SMALL DIFFERENCES AT ABOUT FIVE YEARS AND 13% DIFFERENCE AT 10 YEARS FOR NO BOTHER. BUT IF YOU COLLAPSE TWO CATEGORIES OF LITTLE OR NO WORRY, ABOUT 3-QUARTERS OF MEN HAD LITTLE OR NO WOR SCHETHERE'S ABSOLUTELY NO DIFFERENCE ON THAT MAGNITUDE WAS LIKE A HALF% DIFFERENCE. SO THIS IS JUST KIND OF A SUMMARY OF OVERALL OF THE MORTALITY EFFECT OF RADICAL PROSTATECTOMY VERSES OBSERVATION FOR EVERY 100 MEN TREATED WITH R. P. COMPARED TO OBSERVATION THREE FEWER MEN BUT NOT STATISTICALLY DIFFERENT BUT WOULD DIE, AND PSA ARE EQUAL TO THEN OR THREE MORE BUT NOT STATISTICALLY SIGNIFICANT. AND FEWER. AND MEN WITH LOW RISK DISEASE, FIVE MORE MEN WOULD DIE IN SURGERY VERSES OBSERVATION. WHEN MEN WITH INTERMEDIATE OR HIGH RISK DISEASE THAT RANGES FROM FOUR THORS 13% AND SOME OF THOSE ARE NOT STATISTICALLY SIGNIFICANT. DEATH DUE TO PROSTASTY, WAS NOT SIGNIFICANT AND PSAS 10 OR LESS, ONE FEWER OR NOT SIGNIFICANT. GREATER THAN 10, IT WAS SEVEN FEWER SO PEOPLE CAN ESTIMATE THE NUMBER NEEDED TO TREAT THAT AT ABOUT 10 TO 12 YEARS AND IN LOW RISK DISEASE, ZERO TO THREE FEWER, NOT SIGNIFICANT, FOR ONE FOR INTERMEDIATE OR HIGH RISK DISEASE, ONE MORE TO EIGHT FEWER DEPENDING ON WHETHER USING LOCAL OR CENTRAL HISTOPATHOLOGY TO DETERMINE RISK CATEGORIES. THE BIGGEST DRIVER IN DETERMINING DIFFERENCES WAS PSA CATEGORY IN OUR PREDOMINANTLY SCREENED POPULATION WHICH MAY EXPLAIN THE SPGC-FOUR STUDY. WITH REGUARD TO HARMS, THERE WAS MORE ERECTILE DYSFUNCTION AT TWO AND FIVE YEARS AS WELL AS SEXUAL DISSATISFACTION. URINARY INCONTINENCE WAS GREATER THAT THE TO YEARS AND SLIGHTLY BUT NOT STATISTICALLY GREATER AT FIVE YEARS AND NO DIFFERENCE IN BOWEL DISFUNCTION, HEALTH STATUS, BOTHER AND WORRY WERE SIMILAR TO MEN TREAT WIDE OBSERVATION COMPARED TO SURGERY. IT'S UNLIKELY THAT ACTIVE SURVEILLANCE WOULD HAVE BETTER OUTCOMES THAN OBSERVATION IN SUMMARY, AMONG MEN WITH LOCALIZED PROSTATE CANCER DETECT INDEED THE LOCAL P SA ERA AND IT WAS LESS THAN 10% T. VARIED LITTLE BY RACE, AGE, AND HEALTH STATUS, BUT IT VARIED CONSIDERABLY BY TUMOR FACTORS AND LOW PSA, LOW STAGE AND LOW RISK DISEASE, IT WAS LESS THAN SIX% IN A POST HOC SUBGROUP ANALYSIS, AND PSAs LESS THAN 10. THAT IS THE PREDOMINANT TYPE OF MAN BEING DIAGNOSED WITH PROSTATE CANCER IN THE UNITED STATES, THE RISK OF PROSTATE CANCER MODEL CITIZENTALLITY WAS LESS THAN FIVE% AND NO DIFFERENCE IN MORTALITY. THE ABSOLUTE DIFFERENCE IN MORTALITY WAS ABOUT 0.5% AND FAVORED OBSERVATION IN THAT GROUP. T-1 CPSALESS THAN 10. THE GROUP BEING DIAGNOSED IN THE UNITED STATES TODAY. AND MEN WITH HIGHER PSA AND RISK DISEASE, IT WAS ABOUT 10 TO 20% BUT WE REALLY WANT TO ASK OURSELVES WILL EARLY INTERVENTION IMPROVE THAT OUTCOME. AND PARTICULARLY THERE'S SUGGEST THAT IT MAY. PHYSICAL AND MENTAL HEALTH STATUS DID NOT BOTHERS IN MEN. ERECTILE DISDISFUNCTION AND URINARY INCONTINENT WAS GREATER WITH RP VERSES OBSERVATION THROUGH TWO YEARS FUTURE RESEARCH NEEDS DR. DONOVAN NOTED HER STUDY, BACK TO SURVEILLANCE VERSES EARLY INTERVENTION FOR SCREEN DETECTING CANCER AND I URGE THIS ASSESSMENT OF BENEFITS AND ARM OF SURVEILLANCE VERSES EARLY INTERVENTION AND HIGHER RISK OR PSA DISEASE, OUR DATA SUPPORT THAT OBSERVATION IS A PREFERRED TREATMENT IN MEN WITH LOW RISK DISEASE. DEVELOP AND TEST INCREASE AND ACTIVE SURVEILLANCE AND IMPLEMENT STRATEGIES TO REDUCE OVERDIAGNOSIS AND OVERTREATMENT AND THESE MAY INCLUDE REDUCE PTS TESTING AND PREVENTIVE SERVICE TASK FORCE AND INCLUDED STUDIES TO MEN BEING DIAGNOSE DIAGNOSED AND TREATED IN THE UNITED STATES TO WHOM SCREEN SUGGEST RELEVANT TOO OR RAISE PSA THRESH HOLDS. NO BENEFIT FROM TREATMENT. WE COULD MARKEDLY REDUCE HARM BY NOT HAVING TO DIAGNOSE AND TREAT THOSE PATIENTS. MODIFY THE NAMING OF INDOLENT DISEASE AND DISSEMINATE ACTIVE SURVEILLANCE STUDIES AND CONSIDER USING PERFORMANCE METRICS TO ENHANCE ENHANCED OBSERVATION AND ACTIVE SURVEILLANCE. IN CONCLUSION, THE MEN WITH LOCALIZED PROSTASTY CANCER DETECTED DURING THE EARLY P SA ERA AND RADICAL PROSTATECTOMY DID NOT SIGNIFICANTLY REDUCE ALL CAUSE IN PROSTATE CANCER MORTAILITY. ABSOLUTE DIFFERENCES THROUGH 12 YEARS WERE LESS THAN THREE%. WHILE SURGERY DID NOT REDUCE MORTALITY MORE THAN OBSERVATION WITH MEN AND LOW RISK PSA OR CANCER OUR RESULT SUGGESTS A POTENTIAL PORTALLITY BENEFIT FROM SURGERY MAY EXIST AND IN MEN WITH HIGHER PSA AND POSSIBLY HIGHER RISK DISEASE. BUT MEN CURRENTLY BEING DIAGNOSED HAVE LOWER VOLUME, LOWER PSAs AND THE LOWER RISK OF OVERTREATMENT WITH TIME TO ANY BENEFIT SHOULD IT EXIST IS LIKELY LARGER THAN AS SEEN IN OUR STUDIES. THANK YOU. [ APPLAUSE ] >> THANK YOU DR. WILT. OUR NEXT SPEAKER IS DR. MARK, PROFESSOR OF UROLOGY AND CHAIR OF THE DEPARTMENT OF UROLOGY AT THE DAVE--DAVID GEFFEN SCHOOL OF MEDICINE AT THE UNIVERSITY OF CALIFORNIA AND HE WILL SPEAK ON IMPACT OF DIFFERENT MANAGEMENT STRATEGY O SINGLE THE QUALITY OF LIFE IN LOCALED PROSTATE CANCER. >> THANK YOU VERY MUCH DR. GANNAS AND HONORED PANEL MEMBERS I WAS TOLD I WOULD NOT BE ABLE TO SPEAK WITH SLIDES BECAUSE THERE WAS A PROBLEM SO I'M PLEASED TO SEE THEM HERE ALTHOUGH PREPARED TO SPEAK WITHOUT SLIDES. WHAT YOU HAVE HEARD FROM THE PRIOR SPEAKER AND SPEAKERS IS THAT MORTALITY RATES FOR MEN WITH LOWER PROSTATE CANCER ARE NO DIFFERENT WHETHER THEY'RE TREATED OR NOT WHICH BRINGS US TO REALLY THE TRUCKS OF THE ISSUE WHICH I WILL ARGUE TODAY IS MY 20 MINUTE SYSTEM THE MAIN THING WE AUGHT TO THINK ABOUT WHICH IS THE QUALITY OF LIFE BECAUSE THAT IN FACT ENDSS UP BEING THE DECIDING FACTOR. OUTCOMES OF CARE CAN BE THOUGHT OF IN TERMS OF MORTALITY, MORBIDITY COMPLICATIONS SOME OF THE THINGS THAT WE'RE MORE FAMILIAR WITH MEASURING SUCH AS OBJECTIVE VARIABLES OR IN TERMS OF PATIENT CENTERED OUTCOMES. MOST WELL COMMONLY THOSE YOU SEE LISTED HERE AND THE MOST STUDIED IS HEALTH RELATED QUALITY OF LIFE THOSE DATE BACK TO THE MIDDLE OF THE LAST CENTURY WHEN THE WORLD HEALTH ORGANIZATION WAS CHART AND THE IN THAT DOCUMENT IT STATES THAT HEALTH IS NOT MERE LEER THE ABSENCE OF DISEASE BUT A STATE OF COMPLETE PHYSICAL EEMOTIONAL AND SOCIAL WELL BEING. SOMEONE EVEN ARGUED THAT SPIRITUAL OUGHT TO BE INCLUDED AND THAT UNDERLIES THE WAY WE THINK ABOUT MEASURING AND FOR MEASURING QUALITY OF LIFE IN USING IT TO INFORM DECISION MAKINGS. SO THE PURPOSE OF ANY MANAGEMENT OPTION IS TO MAXIMIZE NOT ONLY THE QUANTITY OR LENGTH OF LIFE BUT ALSO THE QUALITY OR THE BREDTH OF THAT LIFE, CONTENT OF THAT LIFE AND THAT'S REALLY WHAT WE OUGHT TO BE FOCUSING ON. THE RESEARCH IN THE LITERATURE THAT I SUBSCRIBE TO AND MANY OTHERS DO AS WELL IS WHEN LOOKING AT TREATMENT OPTIONS FOR PROSTASTY CANCER TO ASSESS NOT ONLY TREATMENT EFFICACY, NOT ONLY TO HELP DETERMINE WHETHER THE SPECIFIC TREATMENT GOAL VS BEEN THAT, BUT TO INFORM MEDICAL DECISION MAKING AND AGAIN I WOULD CONTENTS IF THE MANAGEMENT OPTIONS ARE EQUIV LEAPT WHICH WE HEARD SINCE YESTERDAY MORNING THEY ARE FOR LOW RISK PROSTASTY CANCER. --PROSTATE CANCER. ONE SLIDE TO SUMMARIZE THEY USE TO TEACH IN THE SCHOOL OF PUBLIC HEALTH WHICH WAS DESIGNED BY DR. GANNAS AND NOW PASSED ON TO ME AND OTHERS, AND THIS SUMMARIZES WHAT WE TEACH IN A WHOLE 10 WEEK COURSE. A MEASUREMENT OF PROSTATE, OF QUALITY OF OF LIFE IS DONE WITH SURVEYS WHICH WE REFER TO AS TRIEWMENTS THAT ARE MADE UP OF QUESTIONS, ALSO GONE AS ITEM WHICH IS WE COLLAPSE TOGETHER INTO SCALES. IN THE INDUSTRY DOMAINS AND THAT ARE ULTIMATELY SCORED, OFTEN BUT NOT ALWAYS ON HUNDRED POINTS RANCHES AND INSTRUMENTS MUST HAVE CERTAIN PSYCHOMETRIC PROPERTIES AND THEY MUST BE RELIABLE AND THEY MUST BE VALID AND RESPONSIVE TO CHANGE OVERTIME. IN ANY--THE SOME THE ASSESSMENT OF QUALITY OF LIFE IN ANY DISEASE WE LOOK AT DOMAINS IN THE GENERAL AND DISEASE TARGETED AND WHAT THE GENERAL DOMAINS ARE AND WHAT SOME OF THE DISEASE TARGETED DOMAINS ARE IN CANCER AND IN PROSTATE CANCER IN PARTICULAR AND THEN ULTIMATELY WE HAVE TO LOOK NOT ONLY AT FUNCTION OR DYSFUNCTION BUT ALSO AS YOU'VE HEARD JUST NOW AT DISSTRESS OR BOTHER AND IT MARYS WELL WITH CLINICAL EXPERIENCE IN THAT SOME MEN MAY HAVE A LITTLE BIT OF URINARY LEAKAGE AND BE HORRIBLY BOTHERED BY IT, OTHERS MAY HAVE MORE SIGNIFICANT URINARY LEAKAGE AND NOT BE BOTHERED BY IT AND IT HAS TO DO WITH THE WAY THAT PATIENTS AND INDIVIDUALS IN GENERAL PERCEIVE THEIR OWN LIFE, THEIR OWN EXPERIENCE AND JUST SORT OF HOW THEY--HOW IT STACKS UP AGAINST THE OTHER ISSUES IN THEIR LIVES. IS IT HAS A FAIRLY LIMITED SET OF INSTRUMENTATION, THE GENERAL DOMAINS ARE SFTHERE HE GOES OR 12 WHICH HAS THESE DOMAINS HERE YOU SEE IN CANCER IN GENERAL CROSS ALL DIFFERENT HUMAN CANCERS WE TEND TO USE SOME OF THESE TRIEWMENTS THAT YOU SEE BRIEFIATED HERE, THE MEASURE OF PHYSICAL EMOTIONAL, TOLL OF CANCER AS WELL AS SPECIFIC CANCERRER DOMAINS, THE CARES, THE LAST ONE HERE, DEVELOPED BY DR. GANNAS. SEWE USE SOME OF THE INSTRUMENTS YOU SEE HERE, THIS IS NOT A COMPLETE LIST BUT SOME OF THE MORE POPULAR ONES TO AGAIN MEASURE BOTH FUNCTION AND BOTHER IN THESE DOMAINS OF SEXUAL, URINARY AND BOWEHU(X„ HEALTH. A COUPLE MORE SLIDES ABOUT MEASUREMENT, AND THE AUDIENCE IS JEFFREY SAN WHO IS A URLOGICAL FELLOW IN UCLA AND WHEN HE WAS A STANFORD, THEY CAPTURE THD DATA AND IF YOU LOOK CLOSELY YOU'LL SEE THE BLUE BARS ARE PHYSICIANS REPORT OF WHETHER PATIENTS HAVE IMPAIRMENT QUALITY OF LIFE DOMAINS. AND THE ORANGE, PINK BARS ARE THE ACTUAL PATIENT'S REPORT OF WHETHER THERE'S IMPAIRMENT IN THESE DOMAINS. THIS IS A REPEAT THAT HAD BEEN DONE 10 YEARS EARLIER TO SEE IF WE'RE DOING BETTER THESE DAYS AS PHYSICIANS IN REPORTING OR BEING AWARE OF IMPAIRMENT. WE'RE NOT. THIS IS FROM A STUDY PUBLISHED BY STACIE KREPSKY, AND I JUST PICKED ONE TABLE FROM HER PAPER ON HOW THE VARIATIONS AND DEFINITIONS OF IMP POTENCE OR INCONTINENCE REALLY HAS AN IMPACT ON WHETHER WE CALL SOMEONE DYSFUNCTIONAL. SO ALONG THE FAR LEFT COLUMN, YOU SEE THESE QUINTILES OF SEXUAL FUNCTION COMPOSSITY AS A COMPOSITE SCORE ZERO TO A HUNDRED AND THEN ACROSS THE OTHER COMUMKCS, YOU SEE HOW THOSE COMPOSITE SCORES PLAY OUT IN TERMS OF SPECIFIC QUESTIONS SO JUST LOOK AT SOMETHING LIKE THE TOP ROW. IF YOU SCORE 80 TO A HUNDRED WHICH MOST PEOPLE„i WOULD–r SAY IS PRETTY GOOD IN TERMS OF SEXUAL FUNCTION AS A COMPOSITE OF MULTIPLE ITEMS, WELL THE SPECIFIC ITEMS, THE SPECIFIC QUESTIONS WHICH I WON'T TAKE TIME TO READ, BUT YOU CAN SEE, VERY FAIRLY SIGNIFICANTLY EVEN WITHIN THAT TOP HIGHLY PERFORMING CATEGORY SO–Ri THE DEFINITIONAL ASPECT OF ALL THESE ISSUE SYSTEM QUITE IMPORTANT AS L. SO TO SUMMARIZE THE PRINCIPLES OF MEASUREMENT WE WE MEASURE THOSE WITHIN THE GENERAL AND DISEASE TARGETED DOMAINS, WE ASSESS THEIR BASELINE AS AN INTERNAL CONTROL AND THEN TRACK THEIR TRENDS OVERTIME AS YOU'VE SEEN IN OTHER PRESENTATIONS AND THEN ULTIMATELY, WHAT YOU WANT TO DO, I WOULD ARGUE IS HO TO ASSESS PATIENTS RETURN TO THEIR OWN PERSONAL BASELINE. THIS IS THE ROCK MONITORRA OFF QUESTION, THE PATIENT WHO ASKS THE DOCTOR PROPRIETORSHIP TO CARP WILL TUNNEL SURGERY WILL I BE ABLE TO PLAY AFTER MY SURGERY DOCTOR AND THE ANSWER OF COURSE IS, IT DEPENDS IF YOU CAN PLAY IT NOW. AND THE QUESTION IS PERTINENT AS WELL TO MEN WHO ASK, WILL I BE ABLE TO HAVE EREEKSS AFTER MY SURGERY? AND WHAT YOU SEE IN SOME OF MY SUBSEQUENT SLIDE SYSTEM THAT NOT EVERYONE BRINGS THE SAME THING TO THE TABLE IN TERMS OF LEVEL OF FUNCTION. I ARGUE THAT IT'S OXIOM ATTIC--AXIOMATIC THAT PATIENTS BE MEASURED BY SELF-ASSESSMENT AND NOT THAT OF A PROKES SCHETHEN RIGOROUS SCIENTIFIC METHODS BE USED. SO NOW ON TO DATA. THERE IS A LIMITED AMOUNT OF DATA IN THE QUALITY OF LIFE OUTCOMES IN MEN WITH WATCHFUL WAITING OR ACTIVE SURVEILLANCE BUT NOT A WHOLE LOT SO MY TASK IS TO TALK ABOUT QUALITY OF LIFE ACROSS THE DIFFERENT TREATMENTS FOR MEN WITH PROSTATE CANCER AND SO I'LL GIVE YOU A BIT OF A HIGHLIGHT. TODAY THERE'S A INDUSTRY IN THE LITERATURE. THIS IS AN EARLY STUDY IN ONE OF THE FIRST TO LOOK AT LONGITUDINAL CHANGES IN QUALITY OF LIFE AND JUST PICKED A COUPLE OF GRAFFS FROM EACH OF SEVERAL STUDIES, THIS ONE MEASURES SEXUAL FUNCTION WITH THE PROSTASTY CANCER INDEX. HIGHER IS BETTER ON THIS SCALE. ZERO-100. AND IT STARTS AT BASELINE. THIS STARTS AT A POST TREATMENT BASELINE AND COMPARING PATIENTS WHO HAVE XRT WITH NERVING BEARING RADICAL PROSTATECTOMY AND YOU NOTICE SEVERAL THINGTHIS SLIDE THAT WILL BE ECHOES THROUGHOUT A NUMBER OF THE OTHER CHARTS THAT I SHOWN ONE IS THAT THE CURVES ARE SIMILAR AND THEY'RE NOT ALL THAT DIFFERENT, YOU KNOW THAT AT LEAST IN THIS PARTICULAR MEASURE OF SEXUAL FUNCTION, THEY DID BETTER BUT NAY DIDN'T DO BETERAL ALL TIME POINTS SO WHEN A PATIENT SAYS WHICH TREATMENT DOCTOR, RADIATION OR SURGERY OR IN PARENTHESES, ACTIVE SURVEILLANCE YIELD BETTER SEXUAL FUNCTIONS, WELL IT DEPENDS ON WHEN YOU DO THE MEASUREMENT. AT SIX MONTHS OUT, IT'S DIFFERENT THAN IT IS AT 24 MONTHS OUT AND THE FINAL OBSERVATION THAT I MAKE ON THIS SLIDE IS LOOK WHAT PEOPLE ARE BRINGING TO THE TABLE. THEY'RE NOT STARTING OUT AT A HELPED. OORKTD SIMILAR GROUP IN WHICH WE LOOK AT URINARY FUNCTION AND ALSO URINARY BOTHER SO YOU'VE HAD ABOUT SEXUAL AND BIG THING IN PROSTASTY CANCER THAT'S LOOKEDDA THE IS URINARY AND YOU SEE HOW THESE OUTCOMES TREND OUT OVER TIME. --LIFE IN THESE AREAS DOESN'T GET BETTER, IT GETS WORSE OVERTIME. WHAT ABOUT BACK IT TO THEIR OWN BASELINE? WELL THIS, IS AN EXAMINATION OR PRESENTATION OF SINGLE INSTITUTION SERIES OF DATA LOOKING AT MEN GETTING BACK TO SURGERY OR RADIATION IN--PARTON ME AFTER SURGERY IN THE PHYSICAL DOMAIN, THIS IS FROM THE IT AND IN THE MENTAL DOMAIN. YOU SEE THAT GET BACK PRETTY FAST IN THE GENERAL DOMAINS OF QUALITY OF LIFE AND THIS IS REFLECTED BOO BY MANY OTHER IS IT THES. WHAT ABOUT BASELINE AFTER SURGERY FOR PROSTATE CANCER. WELL, SUEY FUNCTION AND YOU SEE BOTHER, NOT BAD, BUT IN GENERAL MEN DID NOT GET BACK TO THEIR OWN BASELINE EVEN BY 36 MONTHS OUT AND THERE'S SUBSEQUENT DATA THAT I'LL SHOW THAT BY 48 MONTHS OUT AND FURTHER ALONG, PEOPLE AS A GROUP DON'T ALL MAKE IT BACK TO THEIR OWN PERSONAL BASELINE. ISLE SHOW YOU--I'LL SHOW YOU THREE SLIDES IN THIS STUDY FROM THE NEW ENGLAND JOURNAL. YELLOW IS THE SURGERY PATIENTS AND BLUE IS THE WATCHFUL WAITING PATIENTS. I PUT THEY STAR THERE BECAUSE THEY'RE DIFFERENT IN ALL THESE AND SO AT THE TIME POINT THEY MEASURED PATIENTS AT, FOR THIS THIS REPORT, INADEQUATE EREEKS ARES INFREQUENT INTERCOURSE AND DISSTRESS FROM ALL OF THIS WAS MORE COMMON IN THE PATIENT WHO IS UNDERWENT SURGERY THIS, IS NOT OTHER THAN INTUITIVE BASED ON WHAT WE KNOW ABOUT PROSTASTY CANCER OUTCOMES. WHAT ABOUT URINARY FUNCTION, WELL, BASICALLY THE SAME THING IN THE FIRST THIRD AND FOURTH PAIR OF BARS HERE BUT IN THE SECOND PAIR OF BARS, THE IPSF WHICH IS THE INTERNATIONAL PROSTASTY SYMPTOM SCORE TWEPPED WITH THE NIDDK, WHICH IS IN THE AUDIENCE TODAY, SHOWS THAT PATIENTS WHO HAD RADICAL PROSTATECTOMY IN GENERAL, TENDED TO DO WORSE. OR BETTER BECAUSE THEY HAD A LOWER SCORE. THE LOWER YOU ARE, THE BETTER YOU AND THAT INTUITIVE BECAUSE PATIENT WHO IS HAD THEIR PROSTASTY GRAND REMOVED, IT'S NO LONGER BLOCKING THEM UP AND THEY URINATE MORE FREELY SO THERE'S A BENEFIT IN TERMS OF URINARY FUNCTION THAT'S NOT INCONTINENCE BUT IT'S ACTUALLY IMPROVEDDED OUTFLOW AND THEN FINALLY, IN GOVERNOR QUALITY OF LIFE THIS, IS ALSO BEARS OUT A NUMBER OF DIFFERENT STUDIES IS THAT NO MATTER WHAT TWO TREATMENTS YOU LOOK AT, SURGERY RADIATION, BRACHYTHERAPY, ACTIVE SURVEILLANCE, ACTIVE STUDIES THE GENTLEMEN DOMAINS OF QUALITY OF LIFE TEND TO BE INN CYSTENT THROUGH DIFFERENT TREATMENT OPTIONS. THIS IS A FOLLOW UP STUDY AS WELL FROM THE SCANDINAVIAN TRIAL WHICH IS A LITTLE BIT LONGER TERM THAN THE ONE I SHOWED EARLIER FROM DR. STEINAC, AND JUST TAKE A MOMENT TO ORIENT YOURSELF TO THE WAY THE SLIDES ARE SET, THE FIRST PAIRS OF BARS IF YOU LOOK AT THE BOTTOM IS THAT FOUR YEARS OUT, FOR RANDOMIZATION AND A SECOND PAIR OF BEAR FIST YOU LOOK AT THE BOTTOM IS AT 12 YEARS OUT SO THESE ARE LONG-TERM OUTCOMES. IF YOU LOOK AT THE TOP ONE, GENERAL QUALITY OF LIFE. PINK RADICAL PROSTATECTOMY, BLUE WATCHFUL WAITING AND FOUR YEARS OUT, IT'S THE SAME. AT 12 YEARS OUT YOU'RE BEGINNING TO SEE A DIFFERENCE IN THE PATIENTS ARE REPORTING BETTER OVER ALL QUALITY OF LIFE. BUT THEY'RE LIKELY TO HAVE A HIGH QUALITY OF LIFE. THEN YOU LOOK DOWN AT ERECTILE DYSFUNCTION, URINARY OUTCOMES, AS WELL AND THEN THE HASH MARKS THERE HAVE BOTHER FROM DYSFUNCTION. THE HASH MASHS ARE SHORTSER THAN --ARE SHORTER THAN THE BAR BUT THEY'RE NOT BOTHERED BY THEIR DYSFUNCTION. IT'S WORTH TO LOOK AT THOSE AND MAKE A MENTAL NOTE TO GLANCE AT THESE CHARTS AND THEY'RE INTERESTING AND INFORMATIVE. THIS IS AN EXAMPLE OF FROM MARTY'S PAPER FROM THE NEW ENGLAND JOURNAL OF MEDICINE, FROM A COUPLE YEARS BACK WHICH MAY BE ONE OF THE--HAS BECOME ONE EVER THE STANDARDS OR GOLD STANDARDS NOW IN THIS LOOKING AT LONGITUDINAL STUDY OF LIFE T. INCLUDED A NUMBER OF ACTEMDICK MEDICAL CENTERS AROUND--ACADEMIC STUDIES AROUND THE COUNTRY WHEN YOU LOOK AT ALL THE FINE DETAIL OF THESE CHARTS YOU CAN SEE FROM THE BACK OF THE MEZZANINE UP THERE IS S THAT A COUPLE OF THINGS THAT YOU SEE ON WHETHER YOU LOOK AT SEXUAL, URINARY OR BOWEL IS THAT NUMBER ONE THEY START OUT WITH A SCORE THAT YOU WOULD EXPECT FOR 67 OR 57 OR 72 YEAR-OLD MEN. NUMBER TWO, THE CURVES DO SPLIT FROM EACH OTHER DEPENDING ON IF YOU LOOK AT SURGERY, PATIENTS WITH OR WITHOUT NERVES AT RADIATION PATIENTS WITH OR WITHOUT NHT WHICH ISNYEE ADJUVANT AND YOU SEE THAT OVERTIME OVERTHE FIRST YEAR OR SO, THE PATIENTS DO CONTINUE TO EVOLVE IN MOST OF THESE DOMAINS BUT IN THE AFTER A ABOUT A YEAR AND CERTAINLY AFTER TWO YEARS AS I'LL SHOW NUCLEOTIDES--YOU IN A MINUTE. THAT'S ALL YOU'LL GET. R YOU SEE THE DARK, SOLID LINE IS THE SURGICAL PATIENTS HERE I'M NOT SURE IF YOU CAN READ THE KEY BACK THERE, RP, RADICAL PROSTATECTOMY. PHYSICAL FUNCTION, YOU XEKD IN THE FIRST MONTH OR TWO AFTER A MAJOR ENCOURAGEN ROBOTIC OR OTHER WISE, THEY'LL TAKE A HIT, AND THEY DO, AND NOT BECAUSE THEY GETTER, OR BECAUSE OF SURGERY MAKES THEM BETTER BUT BECAUSE THEY STARTED OUT BETTER. YOU SEE THEY STARTED OUT AT A HIGHER SCORE THAN THOSE WHO GOT TREATED WITH EITHER FORM OF THE RADIATION. THE MENTAL COMPOSITE. THE CURVES ARE SIMILAR TO EACH OTHER. URINARY CONTROL, BOWEL, FUNCTION, SEXUAL FUNCTION, BOTTOM RIGHT, YOU SEE THESE THINGS FLIT OUT OVER TIME, THEY DON'T START AT A PERFECT SCORE. BUT THEY DO SPLIT OUT AGAIN. THIS IS WITHOUT ACTIVE SURVEYANCE YET. RETURN TO BASELINE. THE SIMILAR THEME OF FINDINGS IS THAT OVERTIME MOST PATIENTS GET BACK TO BASELINE IN THINGS LIKE URINARY CONTROL, BOWEL FUNCTION, CERTAINLY NOT IN SEXUAL FUNCTION SO THAT DOES TAKE A HIT. SIGNIFICANT BOTHER, THE AGENDA BOOK AND YOU CAN LOOK AT THEM AND SPEND MORE TIME IF YOU CARE TO BUT THE SEXUAL DOMAIN IS THE ONE THAT TENDS TO END UP WITH THE MOST BOTHER FOR PATIENTS. AND OUT TO 48 MONTHS IS PAPER BY JOHN GORE WHO IS AT THE UNIVERSITY OF WASHINGTON DEPARTMENT OF UROLOGY SHOWS SIMILAR FINDINGS ONCE YOU TRACK THEM OUT. AFTER ABOUT TWO YEARS YOU DON'T SEE MUCH CHANGE IN MOST OF THESE DOMAINS. SAME THING WITH SEXUAL FUNCTION AND WITH BOWEL FUNCTION. ONE INTERESTING OBSERVATION FROM THE PRA STUDY THAT'S BEEN MENTIONED SO FOR, IT'S A TODAY STATE REGULATOR DOES HAVE A QUALITY OF LIFE COMPONENT LOOKING AT MEN ON ACTIVE SURVEILLANCE. WHAT YOU SEE HERE IS THE BLUE IS AT THE TIME OF RANDOMIZATION OR INCLUSION, THE PINK OR THE RED BARS ARE WHAT THEY CALL FOLLOW UP AND THIS IS--YOU KNOW CERTAIN POINT AFTERWARDS AND THEN YELLOW IS THE STANDARD POPULATION SCORE, AND IT'S INTERESTING, WHAT'S INTERESTING TO ME, IN LOOKING AT THIS IS THAT AT EVERY ONE OF THESE DOMAINS, AND THESE ARE THE DOMAINS OF THE SF36 WHICH YOU'LL RECOGNIZE THESE LITTLE APREVIATIONS HERE IF YOU'RE FAMILIAR WITH IT BUT THE DOMAINS OF GENERAL QUALITY OF LIFE. THE PATIENTS WHO ARE UNDERGOING ACTIVE SURVEILLANCE SCORED BETTER THAN THE GENTLEMEN POPULATION, I DON'T KNOW WHY. EVERYONE SHOULD HAVE PROSTASTY CANCER AND YOU'LL DO BETTER. WE HAVE TO LOOK AT M. H. OR MENTAL EXPHELGT LOOK AT SEE IF IT PLAYS IDENTITY OVER TIME OR NOT. SO WHAT ARE THE LESSONS. THE LESSONS ARE IN TOTAL THAT PHYSICAL AND MEBT AT HEALTH SEEM TO RECOVER SIMILARLY. THE IRRITATIVE AND OBJECTIVE URINARY SYMPTOMS PERSIST AFTER BRACHYTHERAPY. URINARY BOTHER FROM THE BLADDER SIS FUNCTION TENDS TO BE WORSE, EVEN THOUGH SURGERY PATIENTS END UP WITH MORE INCONTINENCE, THE BOWEL DISTONKS AS IT DOES PERSIST FOR A BIT AFTER BREAKY THERAPY AND AMONG MEN WHO ARE POTENT AT BASELINE, SEXUAL FUNCTION ACTUALLY IS NOT SO DIFFERENT ACROSS ANY OF THESE DIFFERENT TREATMENTS ALTHOUGH AFTER BRACHYTHERAPY IT DOES TEND TO TAKE A NOSE DIVE AND THAT'S A DOMAINATION OF AGE AND THE OOH CUMULATIVE EFFECT OF RADIATION, I THINK WE NEED MORE STUDIES OF ANXIETY OR TREATMENT DECISION MAKING REGRET AND SOME OF THE DOMAINS IN THAT AREA FOR MEN ON ACTIVE SURVEILLANCE. WORRY ABOUT CANCER RECURRENCE. QUALITY OF LIFE DOMAINS ARE I BELIEVE ARE CRITICAL IN MEDICAL DECISION MAKING FOR MEN AND WE HAVE TO INTERPRET OUTCOMES IN THE CONTEXT OF EACH INDIVIDUALS OWN BASELINE. WE HAVE TO USE VALIDATE TED INSTRUMENTS AND WE HAVE TO ASK THE PATIENT EXPHIMS NOT A PROXY AND WITH ALL OF THAT, WITH THOSE METRICS AND WITH THAT--WITH THOSE RESULTS, THE ULTIMATE GOAL SHOULD BE NOT ONLY TO ADD YEARS TO LIFE, BUT ALSO TO ADD LIFE TO YEARS. THANK YOU. >> THANK YOU DR. LITWIN, OUR NEXT SPEAKER IS DR. DONEIELA PERLROTH, AND SHE'S RESEARCH ASSOCIATE CENTER FOR HEALTH POLICY, CENTER FOR PRIMARY CARE ASK OUTCOMES RESEARCH STANFORD UNIVERSITY. AND HER TALK IS: ECONOMIC ANALYSIS OF DIFFERENT MANAGEMENT STRATEGIES FOR LOCALIZED PROSTASTY CANCER. --PROSTATE. >> HI, O I'M DELATED TO BE HERE TODAY. I WANT TO THANK DR. GANNAS AND THE ORGANIZATION FOR THE TIEWPT TO SPEAK TO YOU TODAY. OIME HERE TO PRESENT MY WORK ON THE ECONOMIC IMPLICATIONS OF MEN WITH CHOICE, AND LOCALIZED PROSTASTY CANCER AND WITH THE PARTICULAR FOCUS ON ESTIMATING POTENTIAL LONG-TERM SAVINGS THAT MIGHT BE ACHIEVE WIDE INCREASED USE OF ACTIVE SURVEILLANCE. SO HOW DO I--I'M SORRY HOW DO I ADVANCE. >> OH, OKAY. OKAY, SO I FIRST WANT TO PRESENT TO YOU WHICH TREATMENTS ARE ACTUALLY BEING UTILIZED IN THE COMMUNITY. THIS SLIDE HERE SHOWS INITIAL TREATMENTS FOR NEWLY DIAGNOSED PATIENTS BASED ON IDENTIFYING PATIENTS IN THE SEER DATA WITH LOCALIZED PROSTASTY CANCER AND THEN, USING CLAIMS FOR REIMBURSEMENT TO SAY WHAT TREATMENTS WERE PROVIDED. AND THE YEAR OF DIAGNOSIS OF PROSTATE CANCER, LOCALIZED DISEASE OLDSMOBILE IS SHOWN ON THE HORIZONTAL HERE AND THIS IS ALMOST AN ANALYSIS OF ALMOST 50,000 PATIENTS. AND I WANT TO POINT OUT A COUPLE OF THINGS. FIRST OF ALL, THE USE OF PRIMARY ANTIGEN DEPRIVATION THERAPY WHICH HAS BEEN A QUESTIONABLE VALUE IN THIS LOCALIZED DISEASE POPULATION HAS MENTION TED BEFORE COME DOWN QUITE A BIT IN THIS TIME PERIOD, SO IT'S ACTUALLY FROM THE EARLY 2000S, PEEKED AROUND 2001, 2002 OVER HEREOF OVER 20% OF THE GROUP AND IT HAS COME DOWN NOW TO 11.5%. NTHIS IS THE CONFORMAL TECHNOLOGY, THIS IS SEVEN% NOW, DOWN TO 1.2%, LARGERY RELACED I WOULD IMAGINE BY IMRT WHICH WAS ADVANCING DURING THIS TIME PERIOD, THE MAJOR CHANGE HAS BEEN THAT THE USE OF IMRT EITHER ALONE OR IN COMBINATION WITH BRACHYTHERAPY HAS INKEYS CREASE FRIDAY 19.7 OF PATIENTS TO ALMOST 40% OF PATIENTS FOR INITIAL MANAGEMENT THIS INITIAL PERIOD I MUST POINT OUT IS ACCOMPANY ON ANNIEED AT THE INITIAL NINE MONTHS AFTER DIAGNOSIS. DESPITE HYPE IN THE MEDIA THERE WAS LITTLE GROWTH OF PROTON BEAMS DOWN HERE. SO THE RESEARCH FRAMEWORK THAT I'M GOING TO SET UP TODAY IS, GIVEN THAT THE WEIGHT OF EVIDENCE SUGGESTS THAT MOST MEN DIAGNOSED TODAY WITH LOCALIZED PROSTASTY CANCER, DON'T DO WORSE IN TERMS OF MORTALITY. IT MIGHT DO BETTER IN TERMS OF MORBIDITY. BETWEEN INITIAL TREATMENT ALTERNATIVE, WHAT WOULD BE THE COST DIFFERENCES AND POTENTIAL FOR SAVINGS BY USING CONSERVATIVE MANAGEMENT STRATEGIES AS INITIAL MAGMENT. SO IN ORDER TO ANALYZE THIS QUESTION, WE'RE USING OBSERVATIONAL DATA, REAL WORLD DATA AND WHAT'S HAPPENING OUT THERE AND WE'RE GOING TO DO THIS AND FIRST IT'S A SPECIALLY INSURED POPULATION AND THE SECOND IS A SEER MEDICARE DATA ANALYSIS AND AND FOR THAT, I'M GOING TO SHOW YOU SOME SUBSET ANALYSIS AND REALLY SPEND THE BULK OF THE TIME ON A SUBSET ANALYSIS BY RISK OF DISEASE. ACTUALLY I'M SORRY, IT'S NOT SUBSET, IT'S STRATIFIED. SO, THE WAY THIS METHODOLOGY WORKS IS THAT WE CATEGORIZE PATIENTS INTO THE INITIAL MANAGEMENT STRATEGIES. I LOOKED AT BOTH SIX MONTHS AND NINE MONTHS OF PERIODS AND IT REALLY MATTERS VERY LITTLE. NOT AT ALL IN CONCLUSIONS SO GIVEN THE PLETHORA, THAT ARE OUT THERE, I'M GIVING THEM NINE MONTHS TO DECIDE OR TO HAVE REFLECTED IN THE CLAIMS DATA WHAT THEIR ACTUAL CHOICES WERE: AND WE DO THIS BASED ON PRESENCE OF PROCEDURE CODES AND THE PLAIN STATE VERSES TREATMENT SERVICES THAT WERE PROVIDED. AND THEN USING THAT TIME PERIOD TO IDENTIFY THAT STRATEGY WE FOLLOW THE PATIENTS FORWARD AND ESTIMATE TOTAL HEALTH EXPENDITURES FOR FIVE YEARS FOLLOWING THE INITIAL DIAGNOSIS. OVER THE 5-YARD PERIOD OF TIME TO ESTIMATE WHAT TOTAL COSTS WERE FOR EACH GROUP. USING THAT DATA WE POPULATE A U.S. ANNUAL COHORT MODEL OF NEWLY DIAGNOSED PROSTASTY CANCER CASES, VISIT LOCALIZED DISEASE AGAIN AND ESTIMATE SAVINGS FROM SHIFTING THE MIX OF TODAY'S ACTIVE TREATMENTS TOWARDS THE CONSERVATIVE MANAGEMENT GROUP. SO I'M GOING TO GO HOVER THE COMMERCIAL DATA JUST RELATIVELY QUICKLY. WHAT YOU'LL FIND IN THE DESCRIPTIVE STATISTICS IS THAT RADICAL PROSTATECTOMY IS BEING DONE IN THE YOUNGER POPULATIONS. I. M. R. T. IN THE OLDER, THERE IS A REGIONAL DIFFERENCE IN USE OF TREATMENTS AND THEN IN ANALYSIS OF THE CO-MORBIDITY SHOWS THAT THOSE GETTING PRIMARY ANDROGEN DEPRIVATION HAVE PROBABLY THE GREATEST SET OF ADDITIONAL OTHER MEDICAL CONDITIONS AND THOSE WITH BRACHYTHERAPY AND THEN E. B. R. T. ALSO RADICAL PROSTATECTOMY HERE ARE THE HEALTHIER PATIENTS. THE NEXT SLIDE IS A RUSSIAN OUTPUT MODEL RESULT FOR EACH YEAR. THIS IS NOT CUMULATIVE. IT MIGHT HAVE BEEN EASIER TO UNDERSTAND COUPE RADIFLY. SO THIS IS FOUR YEAR TWO AND ONE. SHOWING THAT THE SIGNIFICANT DIFFERENCE IN THIS CORS AND THE IN DATA WAS IN YEAR ONE AS YOU MIGHT EXPECT BASED ON TREATMENT COSTS. THESE ARE INCREMENTAL COSTS TO CONSERVATIVE MANAGEMENT THIS IS NOT THE TOLTAL COST. THIS IS A PATIENT IN THE DATA SET WHO GOT RADICAL PROSTATECTOMY, IN THE FIRST YEAR, THE EXPENDITURE WERE $15,002,000 GREATER--$15,200 GREATER AND THAT WAS CONTROLLED FOR JUST A SET OF THE EXPLANATORY VARIABLES CONTROLLED FOR BUT IT WAS ESEBTIALLY SOCIO DEMOGRAPHICS AGE, YEEJION, MARKERS IN THE DATA FOR INCOME, RACE, CORMORBIDITY RACE, INDEX AS WELL AS 15 COMORBID CONDITIONS THAT THAT WERE ALSO USED WITH ANDROGEN DEPRIVATION THERAPY AND ACTIVITIES AND PROJECTS CHE IS ALSO EXTREMELY ALSO USE INDEED MEAS POPULATIONS I'LL TALK ABOUT THAT MORE IN A FEW SLIDES. SO THE OTHER THING TO NOTE IS THAT THE PRIMARY THERAPY GROUP THIS IS TRUE FOR EVERY SET OF OF DATA THAT I'VE SEEN THAT ASKS THIS QUESTIONS. THE COST FOR THIS GROUP ACTUALLY EXTEND OUT AS FAR AS THE DATA SET GOES. AT STATISTICALLY SIGNIFICANT GREATER COSTS EACH YEAR AFTER THAT, THAT INITIAL SOME OF THAT IS GOING TO BE THAT THESE FOLKS ARE TREATED FOR SEVERAL YEARS BUT THEN EVEN AFTER THAT THE INITIAL DIRECT TREATMENT COSTS THEY MAINTAIN HIGHER COSTS THROUGH THE TIME OF THE DATA. SO USING THESE DIFFERENTIAL COST ESTIMATES SO THE TREATMENT GROUPS WE CAN LOOK AT A POPULATION MODEL DIAGNOSED EACH YEAR IN THE UNITED STATES AND ASSUME THAT WE SHIFT FORMS FROM BASICALLY LOCAL TREATMENTS TO CONSERVATIVE MANAGEMENT AND THE THE CONCLUSION HERE IS THAT IF YOU SHIFTtćV BASICALLY SHIFT THESE TO A LOCAL PROGRESSIVE IT DEMONSTRATES POTENTIAL AND I'M SURE CAPTURING A HUNDRED% OF THAT IS NOT POSSIBLE BUT IT WILL REPRESENT FIVE YEAR ESTIMATED COST FOR THIS CO HORDE OR 2.9 BILLION DOLLARS OUT OF ESTIMATED JUST OVER NINE BILLION OF TREATMENT CARE FOR THIS GROUP. SO, BECAUSE YOU'RE ALL PROBABLY SITTING THERE THINKING, WELL, LET'S NOT RISK STRATIFIED AND I WANT TO KNOW ABOUT THE LOW RISK GROUPS I'M ALSO GOING TO SPEND MORE TIME ON LOOKING AT THE SEER MEDICARE DATA WHICH DOES HAVE THIS RISK STRATIFICATION WITH YOU SOY THIS NOW MOVING TO ALMOST 50,000 PATIENTS IN SEER MEDICARE FILES, WE USE THE NCCN DEFINITION OF RISK OF DISEASE AND THAT IS ACROSS THE TOP HERE, SO IT'S LOW RISK, INTERMEDIATE RISK AND HIGH RISK. AND THIS IS ALL PATIENTS DIAGNOSED BETWEEN 2003 TO 2007 WITH THE FIVE YEAR--WHICH IS--WHICH IS GOING TO BE LINKED TO FIVE YEAR FOLLOW UP OF THEIR CLAIMS DATA. SO, A COUPLE OF THINGS THAT I WOULD LIKE YOU TO NOTE HERE, I HAVE THE GLEASON SCORES, THE PKSA AND THE STAGE LISTED HERE SO WE CAN ALL FEEL COMFORTABLE THIS WAS LOW RISK AND IT'S VERY LOW RISK BECAUSE THE GLEASON SCORE HERE IS TWO TO FOUR WITH A PSA$ PATIENTS IN IN LOW RISK GROUP. AND AND THE PSA IS LESS THAN 20. NOW I WANT TO TALK ABOUT THE AGE GROUP, YOU'VE HEARD FROM THE EVIDENCE AND RANDOMIZED TRIALS ABOUT A BIT ABOUT WHO WAS INCLUDED IN THOUGH TRIALS. I WANT TO POINT IDENTITY THAT NONE OF THEM INCLUDED THE POPULATION OVERTHE AGE OF 75. DOWN HERE YOU'LL SEE THAT 34% OF THE LOW RISK DISEASE WAS IN THAT POPULATION AND THEN 40% WAS INTERMEDIATE RISK DISEASE WAS IN THAT POPULATION, 75 AND OLDER. 60% OF THE HIGH RISK DISEASE WAS IN THAT POPULATION. SO, I JUST--I JUST WANT TO POINT THAT OUT BECAUSE THAT POPULATION'S NOT ADDRESSED IN TERMS OF CERTAINLY IN TERMS OF WHAT THEIR OPTIMAL MANAGEMENT STRATEGIES MIGHT BE AND THEY'RE IN AGE GROUPS WHERE THEY'RE COMPETING RISKS OF DEATH ARE EXTREMELY HIGH. SO WITH THIS DATA, I FIRST WANT STOCK EXCHANGE SHOW YOU THE TREATMENT YOU DID VARY BY RISK OF DISEASE, WHICH I GUESS IS GOOD NEWS. THERE WAS CLEARLY LESS CONSERVATIVE MANAGEMENT HAPPENING AT HIGHER RISK. AND MORE PRIMARY ANDROGEN DEPRIVATION THERAPY. THERE WAS LESS USE OF BRACHYTHERAPY WHICH IS MOVING TO MORE CONKORT ANDROGEN WITH--CONCORDANT WITH GUIDELINES. THERE WAS EQUIVALENT USE OF I. M. R. T. WITH GROUPS HERE AND PRETTY MUCH EIGHT-13--I LITTLE MORE I. M. R. T. PLUS BREAKY THR ACTIVITIES AND PROJECTS NEUROECTODERMAL IN GROUP HERE AND THEN PROTONE THERAPY WAS LOW BUT USED IN COMBINATIONS. THIS REFERS TO COMBINATIONS OF TREATMENTS OTHER THAN THE I. M. R. T. PLUS BRACHYTHERAPY GROUP AND THOSE DID INCREASE WITH RISK. WHY AM I NOT ABLE TO ADVANCE. OKAY, SO NOW WHAT I'M GOING TO SHOW YOU IS, ON THE--THE ACCESS OVER HERE, THE VERTICAL ACCESS, THIS IS ESEBTIALLY TOTAL HEALTH EXPENDITURES AND THIS IS A COST FUNCTION OVERTIME BASED ON EACH INITIAL TREATMENT GROUP. IN THE SERUM MEDICARE DATA, FOUR JUST THE LOW RISK PROSTATE CANCER GROUP. AND WHAT YOU SEE HERE IS THAT, THE YEAR FROM DIAGNOSIS, THERE IS RAMP UP IN THE INCREASE IN THE SLOW PEER OF COURSE FOR CONSERVATIVE MANAGEMENT AND ALL OTHER ACTIVE TREATMENT STRATEGIES HAVE FIVE YEAR COSTS GOING OUT THAT ARE GREATER THAN CONSERVATIVE MANAGEMENT. THE ONES THAT ARE ACTUALLY THE GREATEST UP HERE ARE PROTON B'S NOT VERY PRESENT IN THE DATA FOLLOWED BY THE COMBINATION OF IM. R. T. AND BRACHYTHERAPY AND I. M. R. T. ALONE. AFTER CONSERVATIVE MANAGEMENT, THE LEAST COSTLY. NOW IF YOU'RE THINK THANKSGIVING IS NOT THE RIGHT TIME FRAME FOR ANALYSIS AND THESE GO OUT MUCH LONGER THEN I INVITE TO YOU LOOK AT THIS GRAPH, CAREFULLY AND THINK ABOUT THIS BEING THE CUMULATIVE COST FUNCTION AND THIS DOWN HERE BEING THE YEARS OF DIAGNOSIS AND CARRY THESE SLOPES OUT FORWARD INTO THE 10 TO 15 YEAR TIME FRAME OUT HERE TO THINK ABOUT WHEN THIS LINE HERE MIGHT CROSS SOME OF THE OTHERS AND THAT POINT AT WHICH IT CROSSED IT WOULD NEED TO GUY HIGHER BEFORE A COST EQUIVALENCY OR NEUTRALITY ASSOCIATED WITH THE FINDINGS THAT CONSERVATIVE MANAGEMENT IS ASSOCIATED WITH LOWER COSTS. THIS NEXT SLIDE HERE HAS NOW BEEN SHIFTED FOR INTERMETEDIATE RISK PROSTASTY CANCER PATIENTS AND SO AGAIN, THE FINDINGS ARE SIMILAR, I. M. R. T. EITHER ALONE OR IN COMBINATION OF BRACHYTHERAPY, PROTON BEAM IS THE TOP, BUT THAT'S ACTUALLY AGAIN, ALSO NOT YET, UTILIZED, THAT MAY BE CHANGING NOT YET UTILIZED GREATLY AND THEN SURGERY AGAIN IS THE NEXT LEAST COSTLY ALTERNATIVE. THE LAST IS A HIGH RISK CATEGORY AND HIGH RISK OF DISEASE AND IT'S ESEBTIALLY THE FINDINGS.„i AND IN PARTICULAR, I'M GOING TO FECUS ON MEDICARE. MEDICARE FINANCES PRIMARY CARE FOR THIS GROUP. 75% OF ALL MEN FOR PROSTATE CANCER ARE OVER THE AGE OF 65. SO, THE MAJORITY OF THEM HAVE LOW RISK DISEASE, SO, LOOKING AT MEDICARE SAVINGS BY SHIFTING FOLKS FROM ACTIVE TREATMENT TO CONSERVATIVE MANAGEMENT BY RISK GROUP, THE RISK GROUPS ARE RIGHT HERE ON THE VERTICAL AND THEN, THE COLORS SHOWS WHAT THE SHIFT FROM CURRENT ACTIVE MANAGEMENT TO CONSERVATIVE MANAGEMENT MIGHT BRING IN ALL OF THOSE PATIENTS WERE SHIFTED. YOU KNOW WHICH MAY BE THAT'S UNREASONABLE BUT YOU CAN--IF YOU THINK 50%, CAN YOU CUT THAT IN HALF. SO, AGAIN, WE HAVE I. M. R. T. WHERE YOU WHICH WOULD ENCOMPASS THE LARGEST SAVINGS. I. M. R. T. PLUS BREAKY THERAPY IS ALSO LARGE. PRIMARY ANDROGEN DEPRIVATION THERAPY AND THEN OTHER TREATMENT COMBINATIONS. DOING IT THIS WAY, I'M LOOKING AT A FIVE YEAR NETPRESSENT SO I'VE FIVE YEARS IN DISCOUNTING ALL OF THAT, $2010 WE HAVE FOR THE ENTIRE COHORT, WE HAVE 1.5 BILLION DOLLARS OF POTENTIAL SAVINGS FOR PEOPLE FROM TREATMENT TO CONSERVATIVE MANAGEMENT IN THIS PATIENT POPULATION. OKAY, SO I--I WANT TO POINT OUT TO YOU THAT IN THIS REAL WORLD DATA, THE MINORITY ACTUALLY RECEIVED CONSERVATIVE MANAGEMENT THAT THERE WAS A A HIGHLY--MANY DIFFERENT--MANY ACTIVE TREATMENT OPTIONS THAT ARE BEING USED AND THAT WERE BEING USED IN THE MAJORITY OF PATIENTS. THAT SUBSTANDIAL SAVINGS WOULD BE POSSIBLE BY INCRETESSING THE USE OF CONSERVATIVE MANAGEMENT STRATEGIES WITH THE LOCALIZED PROSTASTY CANCER PARTICULARLY OVER THE AGE OF 65 AND FOR THE MEDICARE PROGRAM, THE OTHER THING I MIGHT POINT OUT THAT IF YOU LOOK AT MEMBER--KHIHIGH DIDN'T PRESENT UP HERE BUT I WILL THROW OUT THERE IF YOU LOOK AT COST SAVINGS PER PATIENT GOING FROM I. M. R. T. TO CONSERVATIVE MANAGEMENT, AGAIN, THIS IS A COST ANALYZED AFTER FIVE YEARS IT'S ABOUT 27 AND HALF PER PATIENT. NA'S THE LEAST COSTLY COMBINATION THAT IS PERPATIENT FOR THE FIVE YEAR COST THAT WOULD BE SHIFTED TO CONSERVATIVE MANAGEMENT. SO IN TERMS OF MAGNITUDE FOR THE OPPORTUNITY, PROTON BEAM IS TALKED ABOUT IN THE MEDIA BECAUSE IT'S NOT AT LEAST AS OF 2007, IT'S NOT AGGRESSIVELY USED, THE OPPORTUNITY REALLY IS AN I. M. R. T. AND I. M. R. T. PLUS BRACHYTHERAPY USE INDEED COMBINATION AND PRIMARY ANDROGEN DEPRIVATION THERAPY AND ACTIVITIES AND PROJECTS CHE IS ASSOCIATED OVER THE LONG-TERM WITH HIGHER COSTS AS FAR AS THE DAT CAN--AS WE CAN SEE. AND AGAIN, THE POTENTIAL SAVINGS HERE IS INAURUABLY QUITE LARGE. THIS IS ONE YEAR OF COHORT, ALMOST ONE BILLION DOLLARS AND THAT'S WHERE THE LOW AND INTERMEDIATE RISK POPULATIONS THAT ARE CURRENTLY BEING RECEIVING THEIR CARE BY MEDICARE. SO I WANT TO ALSO POINT OUT SOME LIMITATIONS FOR PEOPLE CAN SAY INACERACY OF CODING AND PROCEDURES IN CLAIMS TEND TO BE FAIRLY ACCURATE BECAUSE SOME OF THEM HAVE TO BE PAID FOR AND THOSE IDENTIFICATION OF THOSE PROCEDURES OVER THAT TIME PERIOD IS--IS I THINK BEING DONE WELL IN THESE DATA SETS, OBSERVATIONAL DATA SO UNOBSERVABLE CONFOUNDERS, THE TIME FRAME OF THE ANALYSIS, I WOULD ASK YOU TO CONSIDER THE SLOPE OF THOSE MEDICARE COSTS AND CURVES AND HOW FAR OUT THEY WOULD HAVE TO GO TO REALIZE COST EQUIVALENTS QUITE FAR. AND THEN, IT DOESN'T OF COURSE ADDRESS HOW SAVINGS CAN BE, HOW THESE SAVINGS COULD ACTUALLY POTENTIALLY BE ACHIEVED FOR MEDICARE, PROGRAM, WHICH AS WE ALL KNOW IS A MAJOR CONCERN FOR THE OVERALL PHYSICAL HEALTH OF THE U.S. AND U.S. GOVERNMENT. AND D YOU KNOW CERTAINLY MOST PEOPLE BELIEVE THAT A SHIFT AWAY FROM FEE FOR SERVICE ISSUES PAYMENTS WOULD BE BE A GOOD START. WELL, AND THAT POLICIES THAT MATCH MORE WITH OVERALLZ THAT MATCH PRICE WITH UP TO OVERALL VALUE WOULD BE HIGHLY USEFUL IN THIS AREA. SO ANYWAY, I WOULD LIKE TO ACAGE MY MENTORS IN IN RESEARCH. ALL MY COLLEAGUES AT IN THE UNIVERSITIES AT CALIFORNIA AND MANY PEOPLE WHO WORKED ON ARKINAL SIS WITH ME,--ANALYSIS WITH ME AND THE NIH AND THE FUNDING FOR THE RESEARCH. THANK YOU. >> THANK YOU VERY MUCH AND OUR LAST SPEAKER WILL BE FROM THE EVIDENCE BASED PRACTICE CENTER MADE RON. DR. MEISPACE CHUNG, EVIDENCE BASED PRACTICE CENTER, AND TUSTS MEDICAL CENTER HAD--TUFTS, MEDICAL CENTER, THIS IS EVIDENCE-BASED PRACTICE CENTER PRESENTATION III, COMPARATIVE EFFECTIVENESS OF ACTIVE SURVEILLANCE VERSUS RADICAL PROSTATECTOMY. >> THANK YOU. >> THANK YOU FOR THE OPPORTUNITY TO PRESENT OUR WORK, THIS IS A CONTINUE FROM YESTERDAY'S PRECEPTATION ABOUT OUR REPORT. I AM HERE TO PRESENT KEY QUESTION FOUR WHICH IS COMPARATIVE EFFECTIVENESS OF ACTIVE SURVEILLANCE VERSES RADICAL PROSTATECTOMY OR RADIATION THERAPY IN MEN WITH LOCALIZED PROSTATE CANCER. SO, FOR THESE KEY QUESTION WE CONDUCT A SYSTEMATIC REVIEW OF STUDY THAT COMPARE THE EFFECTIVENESS OF ACTIVE SURVEILLANCE WITH ACTIVE TREATMENT IN TERMS OF CLINICAL OUTCOMES AND COST. --SUPPLEMENTED WITH TWO PREVIOUSLY COMPLETED EVIDENCE REPORT ON TREATMENT FOR LOCALIZED PROSTASTY CANCER AND--PROSTATE CANCER ANDEC NATIONAL LIBRARY OF MEDICINIC VERYIATION OF ACTIVE SURVEILLANCE. THE DESIGNS OF INTEREST WERE MULTICENTER COMPARATIVE STUDY OR COMPARISON OR CONTROL GROUP. WE DID NOT INCLUDE NONCOMPARATIVE COHORT STUDY: OUR POPULATIONS OF INTEREST ARE MEN WITH LOCALIZED PROSTATE CANCER WITHOUT KNOWN LYMPHNODES OR METASTASIS. OUR COMPARISONS OF INTEREST INCLUDE OBSERVATIONAL MANAGEMENT STRATEGY WITHOUT A. D. T. VERSES ACTIVE TREATMENT WITH OR WITHOUT A. D. T., A. D. T. MONOTHERAPY WAS NOT CONSIDERED A TREATMENT OF THE CURRENT REVIEW. THIS DECISION WAS MADE IN CONSULTATION WITH OUR TECHNICAL EXPERT PANEL. OUR OUTCOMES OF INTEREST INCLUDE PROSTASTY CANCER SPECIFIC MORTALITY, [INDISCERNIBLE] MORTALITY, MOBILITY OF PROSTATE TREATMENT, METASTATIC DISEASE AND GENERAL AND DISEASE [INDISCERNIBLE] CAUSE FOR TREATMENT INCLUDING PRIMARY COST STUDY AND MODEL BASED ECONOMIC VARIATION. WE USE STANDARD E. P. C. METHODOLOGY TO ASSESS METHOD LOGICAL QUALITY OR RECENT STUDIES. THIS IS A GENERAL THREE CAD GORY GRADING SYSTEM, AB, B, AND C. GRADE A INDICATE LOW REGIONAL BIAS, GRADE B IS MODERATE, GRADE C IS HIGH RISK OF BIOS. OLDSMOBILE RANDOMIZED TRIAL AUTOMATICKIZED--OHM RANDOMIZED CONTROL TRIALS AND THE STUDY CAN RECEIVE AGGRADE, BUT IT DOESN'T MEAN THAT THEY AUTOMATICALLY RECEIVE THE GRADE A. SO FOR OUR KEY QUESTION OF INTEREST, WE DID NOT IDENTIFY ANY STUDY REPORT, REPORED PORTING CLINICAL OUTCOMES SPECIFICALLY FOR ACTIVE SURVEILLANCE VERSES IMMEDIATE TREATMENT. THEREFORE, THE STRENGTH OR QUALITY OF EVIDENCE WAS VERY INSUFFICIENT FOR THESE KEY QUESTION. SO FURTHER ELUCIDATE THIS TOPIC, WE EXPANDED THE SCOPE TO INCLUDE STUDIES THAT COMPARE WATCHFUL WAITING WITH IMMEDIATE TREATMENT. WE FIRST REALIZED ON TWO PREVIOUSLY COMPLETED HRQ REPORTS ON TREATMENTS FOR LOCALIZED PROSTATE CANCER, IN THESE TWO REPORTS, BOTH RANDOMIZED TRIAL AUTOMATICKIZED CONTROL TRIAL AND OBSERVATIONAL STUDY, COMPARING DIFFERENT TREATMENTS WERE INCLUDED WHICH INCLUDING ALL OF THE RANDOMIZED CONTROL TRIAL ALREADY PRECEPTED BY DR. ROACH EARLY EARLY IN THIS MORNING AND MANY OF THESE STUDIES INCLUDED MEN RECEIVING HOMOTHERAPY, THEREFORE, THEY WERE NOT QUALIFIED TO BE INCLUDED IN OUR UPDATE. NEVERTHELESS, WE INCLUDED PREVIOUS TOO A BROADER SCOPE, HRQ EVIDENCE REPORT. FOR OUR UPDATE WE INCLUDED TWO RANDOMIZED TRIAL AUTOMATICKIZE CONTROL TRIAL, COMPARE WATCHFUL WAITING TREATMENT, THESE TOOLS TRIALS ARE THE UPDATE, LONGER TERM FOLLOW UP OF THE SPC G TRIAL AND THE SWEDEN TRIAL. WE ALSO INCLUDED THREE PERSPECTIVE COHORT STUDY, 10, COHORT STUDY FOR CLINICAL OUTCOMES. FOR THE TREATMENT COST OUTCOMES WE INCLUDED FOUR PRIMARY COHORT STUDY, TO WHICH WE HOPE USING U.S. DATA AND ONE USE SWEDISH DATA AND WE ALSO INCLUDED THREE MODEL BASED CODE ESTIMATES OF ACTIVE SURVEILLANCE. SO FAR THE PURPOSE OF MY PRESENTATION, I WOULD LIKE TO FOCUS ON THE ELIGIBLE STUDIES UPDATE, MENTION PREVIOUSLY, WE INCLUDED TWO RANDOMIZED TRIAL AUTOMATICKIZED CONTROL TRIAL COMPARED SURGERY WITH WATCHFUL WAITING ONE IS RANDOMIZED TRIAL AUTOMATICKIZED CONTROL TRIAL COMPARED TO RADIATION THERAPY AND ACTIVITIES AND PROJECTS WEB CONNECTED WATCHFUL WAITING. WE ALSO INCLUDED OBSERVATIONAL STUDY REPORTING DATA FOR ANY OF THE FOLLOWING COMPARISON OF INTEREST. THIS SLIDE, SUMMARIZE THE VERY BRIEF FINDINGS FROM TWO RANDOMIZED TRIAL AUTOMATICKIZED CONTROL TRIAL COMPARING SURGERY WITH WATCHFUL WAITING. IT SHOULD BE NOTED THAT ALL PATIENTS IN THE VA TRIAL WHICH IS THE FIRST TRIAL, OLDER TRIAL WERE NOT PSA DETECTED CASES. AND 95% OF PATIENT IN THE SPC 34 TRIAL WERE NOT PSA DETECTED CASES.MY THEREFORE, THE COMPARISON OF THESE TWO TRIALS THROUGH THE CURRENT U.S. PRACTICE ARE LIMITED. THE OLDER TRIAL WHICH IS THE VA TRIAL FOLLOW 142 MEN FOR 23 YEARS AND FOUND SO SIGNIFICANT DIFFERENCE IN MORTALITY BETWEEN SURGERY AND WATCHFUL WAITING GROUPS. THE SPC IT 34 TRIAL WHICH WAS PRESENTED IN MUCH MORE DETAIL BY DR. HOLMBERG EARLIER, SO THIS IS VERY BRIEF SUMMARY OF THE RESULT AND THE SPC G-34 TRIAL FOLLOW 695 PATIENTS FOR AVERAGE OF 12.8 YEARS AND THEY FOUND THAT SURGERY REDUCE RISK FOR DISEASE IN ALL CAUSE OF MORTALITY IN DISTANT METASTASIS SURGERY INCREASE THE RISK FOR TREATMENT RELATED MODEL MOBILITY INCLUDING ERECTILE DISDISPUNKZ URINARY INCONTINENCE IN THE EARLIER FOLLOW?4A[ UP TIME POINT. AND AS WAS MENTIONED EARLIER RINGS SEVERAL ANALYSIS WERE PERFORMED AND ONE OF THE ANALYSIS TOLD THAT THE FAVORABLE EFFECT OF SURGERY WAS PRESENT--PRESENT OHM AMONG MEN LESS THAN 65 YEARS OLD BUT IT WAS MENTIONED EARLY EARLY THERE ARE SEVERAL LIMITATIONS OF SUPPLEMENTAL ANALYSIS SHOULD BE NOTED. >> RECHIEFMENT BOTH OF WATCHFUL WAITING AND QUALITY OF LIFE OUTCOME IN RANDOMIZED CONFLICT TRIAL. TWO ANCILLARY INVESTIGATION OF SPGB TRIAL AND THE SWEDEN TRIAL WERE INCLUDED. SO, THE--IT SHOULD BE NOTED THAT DIFFERENT QUALITY OF LIFE MEASUREMENT TOOL WERE USED. BOTH THEY DID NOT FIND STATISTICALLY SIGNIFICANT DIFFERENCE WITH THE LONG-TERM FOLLOW UP. MOVING ON TO THE OBSERVATIONAL STUDY IN OUR UPDATE, WE INCLUDED A TOTAL OF 13 OBLIGATIONS OBSERVATIONAL STUDY--OBSERVATIONAL STUDIES MOSTLY FOR THE COMPARISON BETWEEN SURGERY AND WATCHFUL WAITING AND WITHIN SITE COULD REPORT DATA FOR MORE THAN ONE COMPARISON OF INTEREST. THE SIMPLE SIZES RANGE FROM 113 TO [INDISCERNIBLE] 44,000, FOLLOW UP DURATION RANGE FROM ONE YEAR TO 12 YEARS AND EIGHT OUT OF 13 OBSERVATION AT STUDY WERE RATED QUALITY B AND FIVE WERE RATED QUALITY. SO OBSERVATIONAL STUDYING OF OUR UPDATE SHOWED THAT ACTIVE TREATMENT WAS ASSOCIATED WITH A REDUCED RISK FOR DISEASE SPECIFIC MORTALITY OUTCOME, THIS OBSERVATIONAL STUDY DIFFERENT NATIONAL PRESENTED DATABASEIS, SHOWN IN THE THIRD COLUMN IN THIS TABLE, BUT THEY ARE POTENTIALLY LARGE OVERLAPS IN PATIENT POPULATION ACROSS STUDY. THIS IS JUST ONE EXAMPLE OF MANY STUDIES THAT WE ARE INCLUDING OUR REPORT TO SHOW THAT TYPICAL DATA ANALYSIS WERE DONE IN THE OBSERVATIONAL STUDY, THE GRAPH REPRESENT THE PROBABILITY OF PROSTASTY SPECIFIC MORTALITY FOR PATIENT WHO WERE TREATED WITH WATCHFUL WAITING OR ACTIVE TREATMENT. I WOULD LIKE TO DRAW YOUR ATTENTION TO THE RED CURVE WHICH WOULD REPRESENT THE WATCHFUL WAITING GROUP, WATCHFUL WAITING GROIP THIS HIGHER DISEASE SPECIFIC MORTALITY ACTIVE TREATMENT GROUP. THE DIFFERENCES BETWEEN GAPS WERE MORE APPARENT AROUND PATIENT WITH INTERMEDIATE RISK OF DISEASE THAN IN PATIENT WITH LOW RISK OF DISEASE. THESE SLIDE SUMMARIZE THE ALL CAUSE MORTALITY OUTCOME IN THE OBSERVATIONAL STUDY IN OUR UPDATE SIMILARLY, OBSERVATIONAL STUDY SHOWED THAT ACTIVE TREATMENT WAS ASSOCIATED WITH A REDUCED RISK FOR ALL-CAUSE MORTALITY OUTCOME. IN TWO, MOBILITY AND METASTATIC DISEASE OUTCOMES, OBSERVATIONAL STUDY IN OUR UPDATE SHOW THAD SURGERY AND RADIATION THERAPY WERE ASSOCIATED WITH AN INCREASED RISK FOR UREIGHTERAL PROCEDURE SURGERY ALSO ASSOCIATE WIDE INCREASED RISK FOR BLADDER IRRIGATION BUT REDUCED RISK FOR UREIGHTERAL DILATION COMPARED WITH WATCHFUL WAITING. MOVING ON TO OUTCOME, IN THE OBSERVATIONAL STUDIES, THE RESULTS WERE MIXED. HOWEVER, DIFFERENT QUALITY OF LIFE WERE USED ACROSS STUDY, THAT COULD MAYBE EXPLAIN THE DIFFERENCES IN FINDINGS. SO FOR EXAMPLE, FOR GENERAL QUALITY OF LIFE OUTCOME, ONCE THEY SHOWED THAT PATIENTS WHO RECEIVED ACTIVE TREATMENT HAD BETTER SOCIAL FUNCTION QUALITY OF LIFE, THAN THOSE PATIENTS WATCHFUL WAITING, BUT OTHER STUDIES DID NOT FIND THE SAME RESULT FOR DISEASE SPECIFIC QUALITY OF LIFE, THEY SHOWED THAT PATIENT WHO RECEIVED SURGERY HAD MORE [INDISCERNIBLE] AND SEXUAL FUNCTION THAN THOSE WHO WERE WATCHFUL WAITING. BUT THIS RESULT WAS NOT SHOWN IN OUR STUDY. FOR THE COURSE OUTCOMES. WE INCLUDED THE PRIMARY STUDY, WE RECORDED THAT THE COURSE OF WATCHFUL WAITING WAS GENERALLY LOWER THAN THE ACTIVE TREATMENT WITH CAVEAT THAT COURSE CALCULATION WOULD PERFORM„i USING THE RETROSPECTIVE DATA WITH DIFFERENT METHOD AND AT DIFFERENT FOLLOW OBSERVATIONS. WE ALSO INCLUDESSED COST MODELS USING YOU U.S. DAT A. WE INCLUDED TOOLS, MODEL BASE ESTIMATE, OF SURVEILLANCE COSTS. SO JUST TO THAT, 10 TO 15 YEARS OF DIAGNOSIS SURVEILLANCE MAY BE LESS COSTLY COMPARED TO ACTIVE TREATMENT, ONE MODEL INDICATED THAT LONG-TERM FOLLOW UP, THE COST OF AFFECTIVE SURVEILLANCE EXCEEDS THE COSTS OF OF SURGERY AND BRACHYTHERAPY BUT MAY BE LOWER IN THE COST OF [INDISCERNIBLE] IS RADIATION THERAPY. THIS MODEL USED DIFFERENT MODELING ASSUMPTIONS SO THAT MAY EXPLAIN THE DIFFERENCES IN THEIR FINDINGS. SO FROM A CLINICAL TRIAL .GOV REGISTRY WE HAVE THREE ONGOING STUDIES. THE FIRST STUDY PITTED 30 OF THE PRELIMINARY RESULTS ALREADY PRESENTED EARLIER THIS MORNING THE SECOND TRIAL WHICH IS THE STAR TRIAL WAS TERMINATED EARLY DUE TO DIFFICULTY IN THE PATIENT RECOMBINANT. AND IN THE THIRD TRIAL, PROTECT TRIAL IS CURRENTLY IN THE FOLLOW UP PHASE. I WOULD LIKE TO MENTION SOME OF THE LIMITATION OF OUR REPORT. WE INCLUDED TWO PREVIOUS RANDOMIZED CONTROL TRIALS, PRIMARILY NONPSA SCREENING DETECTED CASES. AND THEY ARE INHERENT LIMITATION OF DATA OBTAINED FROM THE OBSERVATIONAL STUDY PRIMARY RESIDUAL CONFOUNDING. WE WERE UNABLE TO PERFORM QUANTITATIVE SYNTHESISSISM E. META-ANALYSIS DUE TO OVERAGE STUDIES IN THE RESPECTIVE COHORT STUDY. IN CONCLUSION, THERE'S NO PUBLISHED STUDY COMPARED TO ACTIVE SURVEILLANCE WITH IMMEDIATE ACTIVE TREATMENT, RANDOMIZED CONTROL TRIAL AND RETROTECTIVE OBSERVATIONAL STUDIES SUGGEST THAT ACTIVE TREATMENT MAY BE MORE AFFECTED THAN WATCHFUL WAITING FOR REDUCING ALL COST AND SPECIFIC MORTALITY. SIDUAL CONFOUNDING IS LIKELY IN OBSERVATIONAL STUDIES USING ILLUSTRATED DATA. THANK YOU. [ APPLAUSE ] >> IF ALL OF THE SPEAKERS FROM THE SESSIONS COULD COME UP TO THE STAGE AND JOIN ME HERE. ALL RIGHT, I HAVE ONE QUESTION FOR THE PANELISTS: GIVEN THAT OUR FOCUS HAS BEEN ON THE LOW RISK PATIENT AND THE VERY LOW RISK PATIENT, ARE WE READY NOW TO MOVE BEYOND A RANDOMIZED TRIAL BETWEEN AS ACTIVE SURVEILLANCE AND IMMEDIATE TREATMENT AND RATHER SHOULD WE--CAN WE FOCUS INSTEAD ON WHAT ACTIVE SURVEILLANCE WE OUGHT TO BE DOING FOR THESE LOW RISK AND VERY LOW RISK PATIENTS, UNDERSTANDING THAT ACTIVE SURVEILLANCE MEANS DEFERRED THERAPY. THERAPY IF YOU NEED IT? THAT'S MY QUESTION. >> WELL I'LL START AND OTHERS WILL CHIME IN. THE PIVOT STUDY WOULD SUPPORT THE FACT THAT OBSERVATION IS PREFERRED OVER EARLY INTERVENTION WITH RADICAL PROSTATECTOMY FOR LOW INDIVIDUALS. I THINK THE PIVOT STUDY DATA WOULD SUPPORT THE ROLE OF ACTIVE SURVEILLANCE PROGRAMS HOWEVER OTHERS IN THE AUDIENCE MIGHT DESCRIBE FOR HIGHER RISK DISEASE, PARTICULAR LOW IT'S DEFINED BEST IN THE PIVOT STUDY BY PSA VALUES GREATER THAN 10. AGAIN, THERE WAS NO DIFFERENCE IN OVERALL„i OR PROSTATE CANCER MORTALITY AND NO DIFFERENCE IN HEALTH STATUS OR QUALITY OF LIFE BUT MORE HARMS IN THE LOW RISK, LOW PSA PATIENTS WITH OBSERVATION PIVOT. >> I HAVE I QUESTION RELATED TO THAT, CAN YOU TELL US WHAT YOU DID IN THE OBSERVATION ARMS BECAUSE THAT WOULD SEEM THAT DOING EVEN ANYTHING THAT WOULD LEAD SOMEBODY TO GO INTO SURGERY WITH ACTIVE SURVEILLANCE MIGHT BE HARMFUL. >> WELL, I BELIEVE IN BOTH OUR STUDY IS THE SPG-FOUR STUDY, THERE WAS NO ACTIVE MONITORING VIS A VIS BIOPSIES OR PSAs TO TRIGGER FACTORS. INTERVENTION IN THE PIVOT STUDY WAS TO RELIEVE BOTHERSOME SYMPTOMS. IT WAS NOT DIRECTED AT PSA OR AATISM TOMATIC PROGRESSION. WHAT WAS CONSIDERED A BREECH OF PROTOCOL WAS SOME TYPE OF DEFINITIVE THERAPY BE IT SURGERY, EXTERNAL BEAM RADIATION, DESIGNED FOR CURIAATIVE IPT GREATER TENT. THERE ARE NO PERIODIC BIOPSIES OR PSAs THAT WOULD TRIGGER THINGS. CERTAINLY PATIENTS WE DON'T HAVE THAT DATA AVAILABLE BUT WE MEASURED THE VALUES DURING THE COURSE OF THE STUDY BUT IT DIDN'T TRIGGER ANY AATIONAL--ADDITIONAL-- >> DEPARTMENT YOU SAY 10% OF YOUR PATIENTS IN THE OBSERVATION ARM WEPT ON TO RADICAL PROSTATECTOMY. >> THAT'S CORRECT. CONSISTENT WITH OTHER-- >> AND PATIENTS MAY BE UNCOMFORTABLE WITH THE STRATEGY THAT YOU TOOK, BUT COULD A MINIMALIST ACTIVE SURVEILLANCE PROGRAM BE JUSTIFIED BASED RATHER THAN ON THE AGGRESSIVE ONES DESCRIBED BY THE PRESENTERS PRECEPTED TODAY. >> IT WOULD STRONGLY SUPPORT A MINIMALISTIC APPROACH GIVEN THE RESULTS FROM OBSERVATION SHOWED NO DIFFERENT WITH THE CAVEATS DESCRIBED WITH NO DIFFERENCE OR OVERALL DISEASE SPECIFIC MORTALITY. SO IT WOULD BE UNLIKELY THAT ACTIVE SURVEILLANCE WOULD HAVE A BETTER OUTCOME WITH THAT AND YOU COULD MINIMIZE HARMS RELATED TO BIOPSYS AND ANXIOUS FROM PSA. >> FROM CLARITY YOU WOULD AGREE THAT RANDOMIZED TRIAL FROM ACTIVE SURVEILLANCE WHICH IS ACTIVE VERSES OBSERVATION LIKE YOU DID MIGHT BE A VERY REASONABLE RANDOMIZED STUDY FOR THIS GROUP OF PATIENTS. >> RATHER DIFFERENT STRATEGIES OF OBSERVATIONAL FOLLOW UP WITH DIFFERENT INTENSITIES IF SOMEBODY BELIEVED IN A MORE INTENSIVE REGIMEN. >> FOR LOW RISK DISEASE? >> I'M GOING TO PUSH THAT THE DATA SUPPORTED FOR HIGHER RISK DISEASE. OUR STUDIES SHOWS NO DIFFERENCE IN OVERALL DISEASE OR SPECIFIC MORTALITY WITH OBSERVATION. >> I GUESS THE OTHER THING IS, IS THE SUBGROUP OF PATIENTS WITH A PSA LESS THAN 10 AND T-ONE-C SUFFICIENT TO BE ABSOLUTELY CONFIDENT ABOUT THAT? IT'S A SUBGROUP ANALYSIS. >> COULD I CHIME IN I'M WAS IN AGREEMENT WITH WHAT YOU SAID ABOUT LOW RISK PATIENTS IN GENERAL. I THINK THE QUESTION, MY ANSWER TO YOUR QUESTION WOULD BE YES. IT WOULD BE A GOOD STUDY TO TAKE LOW RISK PATIENTS AND DO SOMETHING CALLED ACTIVE SURVEILLANCE AND SOMETHING THAT WAS MORE LIKE WATCHFUL WAITING TO LOOK AT WHETHER OR NOT THERE'S ANY DIFFERENCE IN THE--I MEAN THAT--I'M NOT TALKING ABOUT TREATMENT, I'M TALKING ABOUT FOLLOWING THE PATIENTS TO FIGURE OPTIMAL--WE DON'T KNOW WHAT ACTIVE SURVEILLANCE REALLY IS. BUT THE COMMENT ABOUT HIGHER RISK PATIENTS I WOULD ABSOLUTELY DISAGREE WITH. THE PIVOT STUDY, THE SAMPLE SIZES ARE WAY TO SMALL AND THE FOLLOW UP WAY TOO SHORT TO USE THE PIVOT STUDY TO MAKE ANY COMMENTS ABOUT INTERMEDIATE AND HIGH RISK PATIENTS. THERE ARE A NUMBER OF CONCLUSIONS THAT ARE REACHED THAT ARE TOTALLY INCONSISTENT WITH THE DATA WE KNOW FROM LARGE PHASE THREE ABDOMEN ORDER OF MICRONSIZED TRIALS FOR EXAMPLE, PSA OVER10, IS REALLY IMPORTANT IN THE PIVOT STUDY. IN FACT, IN LARGE STUDIES, MULTIPLE STUDIES HAVE BEEN DONE TO LOOK AT PREDICTORS OF DEATH FROM PROSTATE CANCER, DINGLE MOST PREDICTER OF DEATH FROM PROSTATE CANCER AND GLEASON SCORE. IF YOU LOOK AT PSA, IT'S IMPORTANT BUT NOT AS IMPORTANT AS GLEASON SCORE AND NOT AS IMPORTANT AS T-STAGE AND THAT THING. SO IT'S GOOD DATA, IT'S EXACTLY WHEY WOULD EXPECT TO SEE, THE LOW RISK PATIENTS SHOW LITTLE OR NO BENEFIT FROM TREATMENT, BUT THE PATIENTS WITH INTERMEDIATE AND HIGH RISK DISEASE, WE KNOW WAY MORE ABOUT THOSE PEOPLE BASED ON THE TREATMENT TRIALS THAT WE'VE CONCLUDED, THAN WE GET FROM A VERY SMALL SHORT FOLLOW UP SAMPLE SIZE FROM THE PIVOT STUDY. >> 12 YEARS IS NOT SHORT FOLLOW UP AND I AGREE WITH YOU THAT PSA, GLEASON SCORE AND RISK CATEGORY DESCRIBE INCREASE RISK OF OVERALL AND DISEASE SPECIFIC MORTALITY WHAT YOU OUGHT TO LOOK AT IS THE TREATMENT EFFECT MODIFIED BY THOSE AND WE DID NOT SEE THAT CONSIST EPTLY BY RISK CATEGORY DID NOT SEE IT AT ALL BY GREASEON. IT WAS PSA. >> DR.? >> WHATEVER YOU DECIDE TO DO? THE ABILITIES TO ACTUALLY DO A VERY FORMAL PROSSPECTIVE COHORT STUDY WHERE IT LIMITS THE KIND OF RECURRENCE OR DEPTH I WOULD ACCEPT TO BE REASONABLE THUNDER PROT COLBUT I THINK THE MAIN QUESTION IS THAT WE HAVE BEEN DISCUSSING A LOT WHO IS IT THAT WE'RE GOING TO SUCH STUDIES, I THINK WE MUST ALSO DISCUSS WHAT IS REALLY THE INTERVENTION? WHAT IS ACTIVE SURVEILLANCE, IT IS ABSOLUTELY IMPOSSIBLE TO ESAMUATE WHEN YOU DON'T KNOW WHAT ACTUAL SURVEILLANCE WHAT THE INTERVENTION IS, NO THE INTERVENTION NEEDS TO CAREFULLY DEFINE THAT AND DESIGN IT. >> IN THIS WHOLE DISCUSSION, I THINK WE HAVE TO BE VERY CAREFUL ABOUT STRATIFYING PATIENTS AND MAKING SURE THAT THE MEN WHOM WE SAY CAN GO ON ACTIVE SURVEILLANCE OR OBSERVATION OR HOWEVER WE'RE GOING TO DEFINE IT, IN FACT, HAVE LOW RISK OR VERY LOW RISK DISEASE. THE AND WE HEARD YESTERDAY, AND THERE'S A LOT OF EVIDENCE IN THE LITERATURE ABOUT, IS THAT MEN HAVE TO BE ASSESSED CORRECTLY. SO IF SOMEONE COMES IN WITH A FOUR CORE BIOPSY SHOWING A LITTLE BIT OF GLEASON SIX, HE IS TO BE REASSESSED PROPERLY WITH THE PROPER IMAGES AND INVOLVE HIGH-TECH IMAGES LIKE MR OR MR FUSION, AS SOME CENTERS ARE DOING AND TARGETED REBIOPSIES TO MAKE SURE THAT WE'RE NOT DEALING WITH SOMEONE WHOSE GOT A SMALL ANTERIOR GLEASON EIGHT TUMOR WHO IS NOT SERVED BY ANY GLEASON PROTOCOL BUT ONCE WE'RE SATISFIED THAT THE ELIGIBLE IS TRULY LOW RISK, THEN THE SEFDZ PRETTY CLEAR THAT HE OUGHT TO BE MANAGED BY SOME FORM OF OBSERVATION. >> AGAIN SUBGROUP DATA BUT WE TRY TO ADDRESS THAT QUESTION WITHIN PIVOT WHICH IS A RANDOMIZED CONTROL TRIAL ALBEIT SUBGROUP DATA. WE LOOK AT INDIVIDUALS WITH PSAs LESS THAN 10 WHO HAD HIGH AND INTERMEDIATE RISK. I'M SORRY, HIGH GLEASON SCORES, SEVEN OR GREATER. TO SPECIFICALLY GET AT THAT ISSUE. ARE WE MISSING SOME INDIVIDUALS BY JUST LUMPING IN ALL THE LOW RISK PATIENTS INTO THAT LOW PSA CATEGORY. THERE WAS NO DIFFERENCE IN ALL CAUSE MORTALITY LESS THAN TWO%. THE DIFFERENCE IN PROSTATE CANCER MORTALITY, NOT SIGNIFICANT, LESS THAN FIVE%, I AGREE, IT'S A SUBGROUP. WE HAVE ESTIMATES FOR THAT, IT SHOULD GIVE US SOME LEVEL OF CONFIDENCE BETTER THAN THE OBSERVATION STUDIES, IT'S RANDOMIZED SUBGROUP SO NO STATISTICAL DIFFERENCE AT DISEASE SPECIFIC AND OVERALL MORTALITY IN THE HIGH GLEASON SCORES, LOW PSAs AND LOW ABSOLUTE DIFFERENCES. >> COMPLETELY UNRELIABLE DATA, THE SAMPLE SIZE FOR THOSE GROUPS OF PATIENT SYSTEM WAY TOO SMALL. IT TOOK US 2000 PATIENTS TO SHOW A 10 YEAR SURVIVAL RATE. >> BUT THAT'S PART OF THE ANSWER. >> THE NUMBER NEEDED TO TREAT WAS SMALL. 2000 PATIENTS--IT DEPENDS ON HOW YOU VALUE WHAT'S AN IMPORTANT OUTCOME. THIS IS OVERALL SURVEYAL. I ONLY TALK ABOUT DATA FROM RANDOMIZED TRIAL. I CAN'T TAKE THE NUMBER OF PATIENTS AND 12 YEARS AND NOT A LONG FOLLOW UP FOR SURVIVAL. YOU NEED HIGHER STUDIES THAN THAT. DON'T OVERREAD THE PIVOT DAT. >> WHEN WILL BE PUBLISHED? >> WE HAVE IT READY TO PUBLISH. >> THANK YOU. >> EVEN AT UNIVERSITY OF MICHIGAN BUT AFTER INTENSE COUNSELING, DIFFERENT TYPES OF WERE NEAR TO DILUTED AND ONE OF THE THINGS I'M VERY INTERESTED IN IF WE ARE GOING TO DO ANY SORT OF RANDOMIZED TRIAL, COMPARING DIFFERENT TYPES OF ACTIVE MONITORING, WHATEVEY TO DISTINGUISH IT.Ť—yq9/ >> CAN'T RULE IT OUT BASED ON THAT DATA AND THANK YOU FOR A COMMENT. I THINK THAT ACTUALLY THAT WOULD BE AN INTERESTING SORT OF NEXT STEP TO LOOK INTO TO SEE WHAT THOSE RATES OF SUBSEQUENT TREATMENT IN THAT GROUP FALL OUT TO BE AND WHETHER THEY GO OUT TO YEAR FOUR AND FIVE, EVEN. >> BI YOUR DATA ARE--BUT YOUR DATA ARE FROM REAL CLAIMS, NOT HERISTIC, YOU AND I MAY THINK WE KNOW WHAT GOES ON IN THE REAL WORLD BUT IN FACT, PAIBTS MAY FALL OFF OF ANDROGEN DEPRIVATION THERAPY, OUTSIDE OF DR. TOWERS. >> BUT IN FACT, I SEE THESE PATIENTS ALL THE TIME AND THREE YEAR SYSTEM STILL FORT FOLLOW UP. SOME MEN ARE ON AND OFF ANDROGEN DEPRIVATION THERAPY FOR FIVE OR SIX YEARS AND THEN DECIDE THEY'RE TIRED OF IT AND WANT TO GO FOR TREATMENT. AND THEN THE OTHER THING, NOW THERE ARE THREE RANDOMIZED TRIALS THAT SHOW THAT ANDROGEN„i DEPRIVATION THERAPY ALONE IS NOT GOOD PLUS RADIATION. NOW THERE ILL BE PEOPLE WHO EVALUATE THE THERAPY ALONE SO THERE SEE SOME SELECTION BIAS AND SO FOR, THERE WERE SOME PEOPLE WHO THOUGHT RADIO THERAPY IS NOT THE THING. >> I'M SORRY, I HAVE WITH YOU. >> ALL OF THIS IS INCIDENTAL TO THE TOPIC OF THIS CONFERENCE, WHICH IS ACTIVE SURVEILLANCE WHICH IS NOT TREATING PATIENTS AT ALL, RIGHT? >> SO TO GET BACK TO MY QUESTION, SORE YOUR EXNATIONAL LIBRARY OF MEDICINIC MODEL INCLUDES ACTIVE SURVEILLANCE AND WATCHFUL WAITING. THAT IS THE MOST ACCURATE, THE IMPERICAL DATA IS FROM OBSERVATIOBUT YOU DON'T KNOW WHETHER THEY'RE IN THAT NO TREATMENT, NO PLAN GROUP THAT WAS REFERRED TO EARLIER OR INACTIVE SURVEILLANCE WITH INCURRAATIVE INTENT. >> THAT'S CORRECT. I'M SOMEWHAT REASSURED BY THE PREVIOUS COMMENTS THAT EVEN IF THEY WERE ALL UNDER OBSERVATION, IT'S STILL A ROBUST FRAMEWORK FOR ANALYSIS. ONE OF OURMATION SYSTEM TO LOOK ADHERENCE TO AN ACTIVE SURVEILLANCE PROTOCOL, CAN STUDIED WATCHFUL WAITING, THE PATIENTS WHO CHOSE NOT TO BE ON WATCHFUL WAITING AND WENT TO RADICAL PROSTATECTOMY, DO YOU HAVE OBSERVATION ABOUT THOSE GROUPS. ANY IDEA WHY THEY DID IT, INTERVIEWS, QUESTIONNAIRES, ANYTHING THAT YOU MIGHT COMMENT ON WHY PATIENTS CHOSE NOT TO BE IN WATCHFUL WAITING. >> I DON'T THINK SBC FOUR HAVE SPECIFIC INFORMATION ABOUT THOSE. YOU MAY CORRECT ME IF I'M WRONG HERE BUT I DON'T THINK WE HAVE SPECIFIC QUESTIONS ABOUT WHY ANY STUDY WENT FROM WATCHFUL WAITING TO CURIAATIVE TREATMENT. >> I THINK THE MAJORITY WAS FROM [INDISCERNIBLE]--SO AFTER THAT-- >> BUT IF I UNDERSTAND IT, THESE ARE PEOPLE WHO AGREED TO BE RANDOMIZED RANDOMIZED AND THEN ONCE RANDOMIZED DECIDED NOT TO PURSUE THE RANDOMIZATION. SO THEY DID COMPLY IN THE BEGINNING BUT THEN THEY MADE A DECISION AT THAT POINT, NOT TOO. >> [INDISCERNIBLE] OF COURSE, WHEN YOU RETHINK YOUR DECISION TO TAKE PART IN THIS STUDY. >> NOT SO MUCH CRITICIZING AS TRYING TO LEARN WHAT THE CAUSES OF THOSE THINGS WERE. >> YEAH, SO I DON'T HAVE THE ACTUAL DATA THERE BUT I CAN TELL YOU AT LEAST FROM THE TIME FRAME, INDIVIDUALS WHO ARE WATCHFUL WAITING GROUP PONDER RADICAL PROSTATECTOMY. MOST OF THOSE DID IT RELATIVELY SOON AFTER SURGERY. OTHER FORMS OF DEFINITIVE THERAPY WERE TYPICALLY FAR OUT DOWN STREAM, SUGGESTING THERE MIGHT BE DIFFERENCES IN THE REASONING BEHIND THE OTHER TREATMENT DECISIONS BUT WE HAVEN'T ACTUALLY LOOKED AT IT. WE HAVE DATA FROM OTHER THINGS LIKE OTHER IS ITS UP THERE AS TO WHY PEOPLE WOULD CHOOSE RANDOMIZATION AND OTHER THINGS LIKE THAT BUT IT WAS MOSTLY PROVIDER OR FAMILY DRIVEN THAT THEY DIDN'T WANT TO BE RANDOMIZED. >> YEAH, I VALID QUESTION FOR MARK, TOORKS SINCE BLACKS SEEM TO BE DISPROPORTIONATELY AFFECTED, DO YOU HAVE QUALITY OF LIFE INFORMATION FROM BLACKS SEPARATE FROM WHITES AND IS YOUR--I ASSUME YOUR SURVEY IS VALIDATED FOR BLACKS? >> YEAH, THEERATOR DIFFERENCE IS IN QUALITY OF LIFE, THE ONE ANSWER TO THE QUESTION, BARRY, IS IT'S THE SAME, BASICALLY AND THERE ARE CULTURAL DIFFERENCES AND YOU KNOW CROSS NATIONALLY LINGUISTIC DIFFERENCES AND PERCEPTIVE DIFFERENTS AND HERISTIC DIFFERENCES IN ALL THIS, BUT BY AND LARGE, IT'S SIMILAR. >> DR. LYNCH AND THEN I'LL GO TO THE BACK MICROPHONES. >> I HAVE A QUESTION FROM DR. WILT ABOUT THE PIVOT STUDY. YOU HAD MENTIONED IN YOUR PRESENTATION ABOUT CAUSE OF DEATH ASCERTAINMENT BEING VERY DIFFICULT. YOU DIDN'T ELABORATEOT DETAILS FOR THAT BUT COULD YOU TELL US SOMETHING ABOUT THE AGREEMENT OF THE CONSENSUS WAS WHAT WAS RECOROFFICE OF DIVERSITY THE DEATH CERTIFICATE AND THEN HOW THAT RELATED TO TIME, PROGRESSINOSEIS OF PROSTATE CANCER. >> IT WAS A THREE POINT COMMIT THAT'S TO THE EXTENT POSSIBLE, THE DEATH CERTIFICATES CORRESPONDING MEDICAL INFORMATION AND A NOTE FROM THE PHYSICIAN WERE COMPILED BY STUDY COORDINATOR AND WENT THROUGH TO TRY AND SCRUB ANYTHING RELATED TO SPECIFIC TREATMENTS, IT WAS RP IN THE OBSERVATION GROUP OR FAILURE TO HAVE RP IN THE RADICAL PROSTATECTOMY GROUP. THAT COMMITTEE WOULD THEN DETERMINE WHETHER DEATH WAS DEFINITELY PROBABLY DUE TOO PROSTATE CONSER TREATMENT OR NOT, DEFINITELY NOT DUE. THEY ALSO HAD CATEGORIES THAT LOOKED AT STRONGLY AGREE AND AGREE WITH THAT. THERE WAS TYPICALLY DISAGREEMENTS OCCUR TED BETWEEN ONE OUT OF THREE WHERE THEY WOULD HAVE KIND OF DIFFERENCES BETWEEN HOW STRONGLY THEY FELT IT WAS DEFINITE VERSES PROBE DEVELOPMENTABLY, THERE WAS ALSO GREAT DIFFICULTY IN ACTUALLY BLINDING THE TYPE OF TREATMENTS BECAUSE THE DATA USED TO ASSESS CAUSE OF DEATH OFTEN WOULD BE SOMETHING, LET'S SAY LIKE A PSA VALUE AND YOU COULD SEE WHERE IT ALL OF A SUDDEN DROPPED OFF AND GRADUALLY CAME AND THINGS LIKE THAT. SO THEY WERE ABLE TO PREDICT TREATMENT BY ABOUT 70, ROUGHLY--DON'T QUOTE ME ON THE NUMBERS BECAUSE I DON'T HAVE IT RIGHT WITH ME. AND THAT IN GENERAL THAT THERE WAS AGREEMENT BUT THAT THEY WOULD OFTEN HAVE A DETAILED CONFERENCE TO TRY AND GET TOGETHER TO HAVE UNAMITY AND FINALLY I WANT TO DESCRIBE TO YOU THAT 2/3RDS OF THE DEATHS WERE DEDEFINED AS DEFINITELY DUE TO PROSTATE CANCER. IN THAT 2/3RDS, THE DIFFERENCE BETWEEN SURGERY AND OBSERVATION WAS LESS THAN ONE%. ALL THE DIFFERENCE IN PROSTATE CANCER MORTALITY THAT I SHOWED IN THE 37 PERCENT RELATIVE REDUCTION IS DUE TO PROBE DEVELOPMENTABLY. HOW CERTAIN WE FEEL ABOUT THAT, I JUST DON'T KNOW, BUT ANECDOTEALLY TALKS WITH THE END POINT COMMITTEE MEMBERS I WANT TO BE DISTANT FROM THAT]I„ WHICH SUGGEST THAD THEY WOULD INFORM ME IT WAS DIFFICULT TO ASKER TAN AND IT'S NOT CLEAR THAT A DEATH DUE TO PROSTATE CANCER IS MUCH WORSE THAN OTHER CAUSES OF DEATH [CHECK] WE DECIDED AS ALL CAUSE MORTALITY AND THE PRIMARY OUTCOME, WE WANT TO LOOK TO SEE WHETHER SURGERY HELPED MAKE THEM LIVE LONGER RATHER THAN TRANSFER THE TYPE OR CAUSES OF DEATH BUT WE ALSO FELT THAT PROSTATE MORTALITY WAS AN IMPORTANT OUTCOME. >> WE DON'T HAVE THIS TYPE OF EXPERIENCE IN THE SBCG-FOUR TODAY, AND IT MAY HAVE TO DO IN OUR HEALTHCARE SYSTEMS IT'S VERY EASY TO FIND THE INFORMATION SO WE HAVE A VERY COMPLETE MEDICAL RECORD OF ALL THOSE AND WE HAVE ABOUT 140 DEATHS FROM PROSTATE CANCER AS THEY WERE COULD YOU RECOLLECT TED IN OUR STUDY. WE HAD A SIMILAR PROCEDURE WITH THE BLINDED COMMITTEE INDEPENDENT FROM THE FINALISTS AND IT TURNED OUT THAT OF THOSE, ABOUT 140 PATIENTS IT WAS ONLY ONE THAT'S DIED OF PROSTASTY CANCER WITHOUT PROLONGED HISTORY OF OCCURRENCE TREATMENT FOR DIFFERENT REOCCURRENCES SO ACTUALLY GIVEN THAT THE NATURE OF THE DISEASE AND OFTEN SUCH THAT HAVE YOU A LONG HISTORY WHERE YOU CAN--WHERE YOU TREAT THE DISEASE EVEN IN THE METASTATIC POSITION, MAKES THE DETERMINANT OF CAUSE OF DEATH EASIER, I THINK. >> I WOULD JUST SAY THAT COLLECTION OF DATA WAS NOT A MAJOR FACTOR IN THE VAST MAJORITY OF CAUSE OF DEATH. >> BACK MICROPHONE, GIVEN THE FACT THAT 220,000 MEN ARE DIAGNOSED WITH PROSTATE CANCER ANNUALLY, GIVEN ACCORDING TO MOST OF THE PRESENTATIONS MOST OF THESE ARE EARLY STAGE RELATIVELY LOW RISK CANCER PATIENTS, DOES ANYBODY HAVE A PROBLEM WITH THE FACT THAT THERE REALLY ARE NO RANDOMIZED CONTROL TRIALS THAT HAVE LOOKED AT ACTIVE SURVEILLANCEERALITY O RADICAL PROSTATECTOMY VERSES STATE-OF-THE-ART RADIATION THERAPY TO COME TO A DEFINITIVE CONCLUSION AS TO REALLY WHAT THE RESULTS WOULD BE. VERY MUCH IN THE WAY THAT WOMEN UNDER WENT STUDIES FOR THE MANAGEMENT OF BREAST CANCER IN THE LEVELLECTOMY, LUMPECTOMY AND MAST ECTOMYOSINMATION AND RADIATION ERA. I JUST HAVE A PROBLEM WITH US COMING UP TO CONSENSUS STATEMENT WHEN THE RANDOMIZED TRIALS REALLY HAVE BEEN DONE. WE HAVE--WE HAVE TRIALS OF RADICAL PROSTATECTOMY VERSES HORMONAL THERAPY AND ADJUVANT RADIATION THERAPY, ET CETERA, BUT THERE REALLY ARE NO RANDOMIZED CONTROL TRIALS THAT STRATIFIED PATIENTS THAT LOOK ACROSS DIFFERENT TREATMENT TECHNIQUES TO TEALLY DETERMINE ARE THERE BENEFITS, ARE THERE PROBLEMS, WHAT THE QUALITY OF LIFE IS, AND WHAT THE OUTCOMES ARE. JUST AN OBSERVATION. >> LET ME JUST RESILIENCE SPOND TO THAT. THERE ARE THREE TRIALS THAT I AM AWARE OF THAT THAT ATTEMPT IS MADE AND MEN WOULD NOT GO ON THE STUDIES AND UROLOGYST AND RADIATION WOULD NOT PARTICIPATE WITH AND I WOULD AUGUST THAT MEN UNDERSTAND THAT THE TREATMENTS ARE ROUGHLY EQUAL AND NOW, MEN ARE USING INFORMED DECISIONS TO DECIDE WHICH SET OF SIDE EFFECTS THEY MIGHT WANT. SO, MEN DON'T NECESSARILY WANT TO BE RANDOMIZED TO SURGERY OR RADIATION. SOME MEN WANT SURGERY AND SOME MEN WANT RADIATION. THE POP OOLOGIES BASED STUDIES IN THE RETROSPECTIVE STUDIES HAVE ALREADY BEEN DONE. WE HAVE TONS OF LITERATURE WE HAVE MANY QUALITY OF LIFE STUDIES. I DON'T THINK IT'S A GOOD USE OF RESOURCES SOPHISTICATED TAKE MEN, THEY'VE ALREADY DEMONSTRATED THREE TIMES THAT THEY DON'T WANT TO BE RANDOMIZED BETWEEN THESE TWO EFFECTIVE TREATMENTS, SO I DON'T ACTUALLY THINK THAT THAT'S AN IMPORTANT ISSUE RIGHT NOW. >> BUT IS THAT NOT ALSO SOME DEPENDENT AS HAS BEEN DEMONSTRATED BY A NUMBER OF THE DISCUSSIONS THAT THAT'S HOW PATIENTS ARE COUNSELED PRIOR TO MAKING THEIR DECISION PROCESS. THAT ONCE, IF PATIENTS ARE COUNSELED, IN A WAY THAT PREVENTS THINGS IN A MORE--YOU KNOW EQUAL WAY, THAT THEY--THEY ARE MORE WILLING TO PARTICIPATE THAN IF THE SURGEON TELLS THEM THAT SURGERY IS YOUR BEST CHOICE OR THE RADIATION ONCOLOGIST SAYS, RADIATION IS YOUR BEST CHOICE? >> BUT THE IS SHE WHAT IS THE UPSIDE, WHAT ARE YOU GOING TO FIND OUT IN THE STUDY? IN THE CASE OF BREAST CANCER WOMEN WERE RANDOMIZED BETWEEN MASTECTOMY, LUMPECTOMY AND RADIATION BECAUSE THE WOMEN WANTED TO GET TO A PLACE WHERE THEY HAD BREAST CONSERVATION AS AN END POINT. WITH RESPECT TO RADIATION AND SURGERY, IF WE WERE GOING TO USE OVERALL SURVIVAL AS A PRIMARY END POINT FOR THE STUDY, WE WOULD NEED A VERY LARGE NUMBER OF MEN BECAUSE OF THE EFFECTIVENESS MUCH THE TREATMENT--OF THE TROAMENT. SO WITH SURVIVAL RATE AND HORMONES, SURVIVAL IS 90% DEPENDING ON SELECTION AND SO FORTH. SO THE QUESTION IS DO WE WANT TO SPEND MILLIONS OF DOLLARS RANDOMIZING 3000 MEN TO RADIATION SORE SURGICAL TREATMENTS FOR HIGH RISK DISEASE TO BE ABLE TO SHOW A VERY SMALL DIFFERENCE IN OUTCOME WHEN MEN MAY STILL CHOOSE TO PICK A TREATMENT BASED ON THE TOXICITY PROFILE BECAUSE THE ISSUE IS WHAT ARE YOU GOING TO GET FROM THE TRIAL THAT'S GOING TO CHANGE WHAT PEOPLE DECIDE TO DO. AND I THINK RIGHT NOW PEOPLE UNDERSTAND THAT THE DIFFERENCES IN THE OUTCOME ARE RIELATIVELY SMALL AND THEY CHAZ THEIR TREATMENTS BASED ON THE LITERATURE IN TERMS OF OF SIDE EFFECT. >> DR. BARRY? DR. WILT, JUST FOR PURPOSES OF DISCUSSION, LET'S USE THE LOW DMRE FOR,--DO YOU THINK THERE'S ANY ROLE FOR THERAPY FOR LOW RISK PATIENTS? >> YEAH. >> FOR CURIAATIVE TREATMENT? >> I THINK THE PIVOT DATA DEMONSTRATE THERE'S NO DIFFERENCE IN OVERALL OR DISEASE SPECIFIC MORTALITY UP THROUGH 12 YEARS AND ACTUALLY THE HAZARD RATES SLIGHTLY FAVOR OBSERVATION WITH VERY LOW DISEASE SPECIFIC MORTALITY, LESS THAN 5 PERCENT, NO DIFFERENCE IN QUALITY OF LIFE, WORRY OR BOTHER. AND FEWER ADVERSE EFFECTS. >> I'LL TAKE THAT AS A NO. DR. HOLMBERG. >> FROM OUR DATA, I THINK IT'S--IT'S NOT EASY TO KNOW HOW GENTLEMENNIZEABLE OUR DATA ARE TO--GENERALIZABLE OUR DATA IS FROM THE MODEL. I THINK IT IS AN OVERRICISM LIAISON FIELD SIMPLIFICATION TO SAY THAT WE ADD 10 OR 12 YEARS OF LEAD TIME TO OUR DATA AND THEE WILL WIPE OUT ALL THE DIFFERENCES, IT MAY BE THAT THERE'S STILL IRRELEVANT SUBGROUPS WHERE YOU WOULD HAVE A BENEFIT FROM- PROSTATECTOMY BECAUSE I THINK THAT AT THE BASELINE IT ALTERS THE NATURAL HISTORY OF THE DISEASE BUT THE TROUBLE IS THAT AS WE ARE NOW, WE HAVE ONE--WE HAVE NO WAY TO FIND THOSE IN THIS BIG LOW RISK POOL OF PATIENTS AND TWO, I ALSO NEED AS I SAID B EFORE, IF WE ARE GOING TO DO ANY SORT OF STUDY PERSPECTIVE FOR THAT, WE NEED A VERY STRONG AND CLEAR DEFINITION OF WHAT AN ACTIVE SURVEILLANCE OR COMPARATIVE REALLY IS. >> I WANT TO MAKE ONE OTHER COMMENT ALONG THOSE LINES. THAT ENROLL AT A TIME PHASE BETWEEN SPC G-FOUR AND WHAT WE'RE CURRENTLY AT. OUTCOMES RELATED TO PROSTATE CONSER ARE LIKELY TO BE MUCH BETTER WITHOUT OBSERVATION BECAUSE WE PICK THE DISEASE UP EARLIER AT LOWER PSA LEVELS AND SMALLER VOLUMES AND REPEAT BI OPPOSITE SCHEBECAUSE OF HISTOLOGIC UPGRADING. ANY CANCER MORTAL SIT LIKELY, BE LESS AND TAKE A LONGER TERM AND THE NEED THEREFORE TO SHOW ANY KIND OF IMPROVEMENT IN OUTCOMES WOULD REQUIRE LARGER SAMPLE SIZE AND LONGER FOLLOW UP DURATION AND I THINK THE SAME WOULD BE SAID ABOUT ANY INTERMEDIATE OR HIGHER RISK CASES ISSUES BECAUSE THEY MAY BE DEFINED BY HISTOLOGIC RATE BUT HAVE MUCH SMALLER VOLUME TUMORS AND MUCH LOWER PSAs. >> OKAY, CAN I MAKE THAT THE--ONE ADDITIONAL COMMENT, I THINK THAT ONE OF THE THINGS THAT WE DO TODAY, WHICH I THINK IS A PROBLEM IS THAT WE TAKE A LOT OF DECISIONS OR DISCUSS DECISIONS ABOUT TREATMENT ACCORDING TO RISK. NOW, RISK IS NOT A VERY GOOD CONCEPT IF YOU WANT TO CLALSZIFY PERSONS, YOU ARE THE ONE THAT WOULD NEED TREATMENT, YOU ARE NOT THE ONE THAT WOULD NEED TREATMENT. BECAUSE IF YOU WANT TO MAKE DISTINCTION BETWEEN GROUPS LIKE, YOU MAKE RISKS OF 15, 20 IN TERMS OF RELATIVE RISKS SO IF YOU LOOK AT AN ROC CURVE, A RELATIVE RISK OF TWO AND HALF OR THREE, IT'S CLOSE TO USELESS. SO I MEAN, WE HAVE A GREAT PROBLEM IN THE SENSE THAT WE HAVE NOT EITHER ANALYZED ALL OUR DATA IN TERMS OF DECISION MAKING TOOLS, WHICH I THINK WE NEED TO DO MORE. >> ONE EXPOINT THAT IS-- >> I WAS GOING TO ASK YOU NEXT. >> SO I WAS GOING TO GO PROBABLY NO, MAYBE, DR. ROCKY--COULD ROACH? >> I THINK 12 YEARS OF FOLLOW UP IS WAY TOO SHORT. IF YOU ARE A 50 YEAR-OLD MAN WITH LOW RISK PROSTATE CONS CANCER BUT THE DEFINITION OF LOW RISK THAT WAS ALLUDED TO TO DIMICO, FOR MEN, I SEE MEN WHO HAVE 12 OUT OF 15 BIOPSIES POSITIVE. THOSE PATIENTS CAN BE CLASSIFIED AS LOW RISK, BUT THOSE PATIENTS HAVE A VERY UNFAVORABLE PROGNOSIS. SO IT'S SIMPLISTIC, THERE'S A LOORNLG NUMBER OF MEN WHO DON'T BENEFIT FROM TREATMENT. I THINK THAT'S PRETTY CLEAR, I THINK THE DATA PRESENTED ARE EXCELLENT DAT BAH I DON'T THINK THAT 12 YEARS OF FOLLOW UP IS ADEQUATE FOR A 50 YEAR-OLD MAN WHO'S BEEN DIAGNOSED WITH PROSTASTY CANCER, THAT MAN IS BEING GOING TO BE INTERESTED IN 20 AND 30 YEAR RESULTS AND THOSE DATA DON'T ANSWER THE QUESTION. >> YES FROM YOU? NOW YOU MENTIONED REAL WORLD BEFORE AND IT'S BEEN BROUGHT UP BEFORE BUT IT SEEMS TO ME THAT WE DO AN ARBITRARY NUMBER OF BIOPSIES IN A PROSTATE REGUARDLESS OF THE SIZE OF THE GLAND. IS THERE SOME MOVE TOWARDS BIOPSY PER GRAM OF TISSUE FOR INSTANCE SO A HUNDRED GRAM PROSTASTY MAKE IT 20 NEEDLES, 30-GRAM--WHAT IS IT? >> SO UPON THE TREND IS TOWARD 12 OR 15 CORE. NOT DONE PER GRAM, BUT THE TREND WAS BACK IN THE EARLY DAYS, PEOPLE DID ONE BIOPSIES OF WHAT THEY COULD FEEL AND THEN THEY WENT TO BIOPSIES OF THE LOBE AND THEN SIX-10 BIOPSIES. SOME PLACES ARE USING SIX BUT THE TREND IS GOING FOR INCREASING NUMBER OF BIOPSIES BUT NOT EXACTLY BASED ON PERGRAM OF TISSUE. >> MAY I ADD SOMETHING TO THAT? IT'S NOT ABOUT HOW MANY BIOPSIES OLDSMOBILE, IT'S ABOUT TARGETING THE BIOPSIES ACCURATELY IN THE PROSTATE AND WHAT WE WILL SEE OVER THE NEXT COUPLE THREE YEARS IS A SIGNIFICANT INCREASE IN THE INCLUSION OF MR AND OTHER FORMS OF REALLY, REALLY ACCURATE IMAGES TO GUIDE THESE BIOPSIES. ANYONE WHOSE DONE A PROSTASTY BIOPSY UNDER GUIDANCE KNOWS IT'S NOT THAT MUCH AND MR BIOPSIES MAY END UP CHANGES THE FACE OF ALL THIS BECAUSE YOU CAN YOU ONLY NEED ONE BIOPSIES TO HIT A HOT SPOT ON MR. >> SO YOU THINK THERE WILL BE FEWER IF WE USE MORE. >> THEY NEED TO BE ACCURATE. >> OKAY. ANOTHER REAL WORLD QUESTION, COUPLE PROBLEMS THAT HAPPENED WITH PROSTATE BIOPSIES OR ONE IS PAIN AND THE OTHER CALL IT DISCOMFORT AND THE OTHER IS INFECTION RELATED COMPLICATIONS AND A DENTIST WAITS IT SEEMS TO BE TO BE SURE AND NUMB BEFORE HE WORKS ON MY TEETH AND HOW LONG A UROLOGYST IN A REAL WORLD WAIT BEFORE HE PUTS IN THE BLOCK THE OR BEFORE HE DOES THE 10 TO 12 NEW BIOPSY SYMPATHETIC NERVOUS SYSTEM. >> SINCE I'M NOT A UROLOGYST I DON'T KNOW THE ANSWER TO THAT. >> THEN I'LL EXCLUDE YOU, DR. LITMAN? >> WELL, I GO TO THE SAME DENTIST THAT YOU DO AND I LIKE TO WAIT TILL THE TOOTH IS NUMB BEFORE THE CAVITY IS--THE CROWN IS PLACED. SO I INJECT THE LIDOCAINE ON EITHER SIDE AND WAIT TELL I THINK THE PATIENT IS NUMBER AND I TELL THAT BY POKING THE NEEDLE IN HIS PROSTATE AND SAYING DO YOU FEEL THE A-PICKAL CORE IS THE-- >> THE A-PICKAL CORE IS THE FARTHER AWAY FROM THE INJECTION SO THAT'S THE ONE THAT HURTS THE MOST. >> PERHAP FIST WE WAIT LONGER IT WILL BE RHUMB. >> I DO THINK IF YOU WAIT LONGER IT WILL BE NUMB. >> HOW ABOUT IN SCANDINAVIA. >> WELL I'M NOT A UROLOGYST BUT THERE'S MODEST REDUCTION IN THE STRATEGIES, BUT ONE OF THE BIGGER ISSUE SYSTEM THE RISK OF INFECTION, PARTICULARLY HOSPITALIZATION-- >> I WAS COMING TO THAT, SO I WOULD LIKE TO COMMENT ABOUT REPEAT BIOPSIES WHERE WE ARE NOW RECLASSIFYING PEOPLE BASED ON THEIR NEW BIOPSY READING. LET'S SAY THEY WERE A FIVE AND A REPEAT BIOPSY GETS THEM AT SEVEN. I DON'T KNOW HOW TO INTERPRET THAT, VIS A VIS THE PIVOT DATA YOU BUT I WOULD SUGGEST THOSE PEOPLE WOULD BE RESTARTED BACK AT WHAT THE PIVOT DATA WOULD SHOW. SO YOU WOULD HAVE TO LOOK AT THE NATURAL HISTORY OF A NEWLY DIAGNOSED SEVEN, TO FIGURE OUT WHAT THEIR NATURAL HISTORY WOULD BE. >> AND I THINK WE'VE AUTOMATICALLY ASSUMED THAT ONCE THEY WERE A FIVE AND NOW A SEVEN, THAT THEY'RE NOW FIVE YEARS INTO THEIR DISEASE. >> BASED ON PIVOT DATA WE DON'T KNOW WHAT THAT NEW SEVEN IS. WAS IT A MISSED SEVEN FROM THE FIRST ONE AND ARE THOSE THE SAME PEOPLE WHO WERE MISSED IN THE PIVOT GROUP? >> I WANT TO GO BACK TO REAL WORLD AGAIN WITH INFECTION AFTER PROSTASTY BI OPTSYS--BIOPSIES, THE RISK OF PUTTING ONE NEEDLE IN THE RECTUM THROUGH INTO THE PROSTASTY WOULD GIVE YOU A RISK OF ONE WHATEVER THAT IS WITH RESPECT TO INFECTION, SO PUT 12 IN THAT,'S 12 TIMES THAT RISK AND I'M AWARE OF STUDIES ENEMAS VERSES NO ENEMAS BUT I'VE SEEN NO STUDIES OF STOOL ON THE GLOVE OR STOOL STOOL NOT ON THE GLOVE BEFORE THE BIOPSIES ARE DONE. >> IF YOU PUT ONE NEEDLE IN THE PROSTASTY THAT INCREASES THE RISK, BUT PUTTING 12 NEEDLE INTO'S THE PROSTASTY DOESN'T MAKE IT MULTIPLICCAATIVE, THE MARGINAL INCREASE IS LESS, THE DIG 95ICABILITY IS GOING FROM NO PROSTASTY BIOPSY--PROSTATE INTO TWO, BUT THERE'S A POINT ON THE, A SECTION ON THE CURVE WHERE DOING SIX OR 10 OR 12 DOESN'T ADD SIGNIFICANTLY TO THE RISK, THE RELATIVE RISK OF INFECTION IN THE MEANINGFUL WAY. AND THEN THERE'S PROBABLY I ANOTHER INFLECTION POINT ABOVE WHICH DOING 20 OR 40 OR 60 BIOPSIES DOES ADD MEANINGFULLY TO IT. SO I WOULD DISAGREE THAT 12 NEEDLE CORES IS A 12 FOLD INCREASE IN RISK INFECTION. >> WELL, IT'S COMFORTING. DOES THE UROLOGYST LOOK AT HIS FINGER TO BE SURE THERE'S NO STOOL BEFORE HE DOES THE BIOPSIES. >> DOES THE UROLOGYST EXAMINE THE PROSTASTY AT THE TIME OF THE BIOPSY, GENERALLY NOT IF THEY'VE DONE AN EXAMINATION IN THE OFFICE PREVIOUSLY. THE UROLOGYST SHOULD DO THE EXAMINATION OF THE PROSTASTY BEFORE HE DOES THE BIOPSY. >> WE HAVE A FEW MORE QUESTIONS. >> YEAH, I'M OLSON, FROM NEW YORK AND I'VE BEEN FOLLOW THANKSGIVING CONFERENCE FOR AND DAY AND A HALF AND IT'S WARMFUL TO SEE ALL THE HEROES OF ACTIVE SURVEILLANCE PRESENT IN THE SAME ROOM AT THE SAME TIME. AND THEY WERE HEROS TO BECAUSE TO HAVE THOUGHT OF NOT TREATING A PATIENT PROSTASTY WITH PROSTATE CANCER SOME 10 YEARS AGO, WOULD HAVE BEEN VERY, VERY, BRAVE TO EXPERIENCE THE UPROAR FROM THE COMMUNITY WHETHER IT BE A URY LOGIC COMMUNITY, AND HOW CAN YOU SPOBLLY DO THAT? SO THEY DID A WONDERFUL JOB AND THEY DID A GREAT SERVICE TO US BUT I'M A LITTLE BIT CONCERNED THAT WE HAVEN'T TALKED ABOUT THE POTENTIAL ADVERSE ASPECTS OF ACTIVE SURVEILLANCE A LITTLE BIT MORE FULLY. REGUARDING THE KEY NOTE SPEECH FROM UNDER LIP TON WHO SAID UNDER NO CIRCUMSTANCES WOULD I DO ACTIVE SURVEILLANCE EACH NOW, WHICH I THOUGHT WAS REFRESHING BUT AT THE SAME TIME HEARING FROM PEOPLE IN THE AUDIENCE WHO HAVE BEEN ON ACTIVE SURVEILLANCE AND ENTHUSIASTIC ABOUT IT MAKES YOU FEEL GOOD. BUT KEEP IN MIND, PLEASE, EVERYBODY AND THE PANELISTS SHOULD DO THIS MORE THAN ANYBODY ELSE, THAT THIS IS A JUVENILE--AT LEAST YOUTHFUL SCIENCE. THE DATA IS NOT SUPPORTED AS YET. I MEAN EVERYBODY THINKS THAT IT'S GOING TO BE THE RIGHT THING TO DO BUT WE DON'T HAVE THE ACTUAL DATA. THERE'S NO CATEGORY ONE MEDICAL EVIDENCE THAT WILL PROOF THAT THIS IS THE RIGHT THING TO DO THIS AS THEY TEND TO DO. I THINK IF YOU LOOK AT THE STATISTICS THAT WERE PRESENTED YESTERDAY BY LARRY KLUNTZ, MARVELOUS STATISTICS. THEY TALK ABOUT LESS THAN 10 GROUPS REPORT O GBA JUST OVER 2000 PATIENTS, WITH MEAN [INDISCERNIBLE] AS LOW AS FOUR YEARS AND MAXIMUM FOLLOW UPS JUST BARELY GETTING BEYOND THE EIGHT YEAR INTERVAL. KEEP IN MIND THAT IT TOOK EIGHT YEARS--WELL, IT TOOK NINE YEARS FOR THE ERSPC TO SHOW A DIFFERENCE IN PURVIVAL WEAN THE--SURVIVAL BETWEEN THE PATIENT WHO WAS SCREENED VERSES THE PATIENT WHO WASN'T SCREENED. IT'S SIMILAR TO WHAT YOU WOULD EXPECT TO SAY, WHAT LENGTH OF TIME WILL IT TAKE FOR A PERSON WHO IS ACTIVELY SURVEILLED VERSES THE PERSON'S WHO'S ACTIVELY TREATED TO FIBBED A DIFFERENCE. IT'LL BE ABOUT THAT. >> DO HAVE YOU A QUESTION FOR THE PANEL? >> WELL, I HAVE ONE QUESTION, AND I TRAVELED TO PRESENT AS WELL-- >> THERE ARE PEOPLE BEHIND AND YOU PEOPLE FROM THE PANEL WHO HAVE QUESTIONS. >> WELL, OKAY. SO I JUST--I JUST ASK YOU TO KEEP IN MIND, I THINK THE THINGS THAT THE PANEL SHOULD FOCUS ON ARE MORE, WHAT ARE7. FOR MAKING A PERSON A CANDIDATE, HOW SHOULD ACTIVE SURVEILLANCE BE TRULY DONE AND IF WE CAN ANSWER THOSE TWO QUESTIONS AND DO THE ACTUAL ACTIVE PROCESS OF ACTIVE SURVEILLANCE IN THE FORMAL FASHION, WE WOULD BE MUCH BETTER OFF. I HAVE ONE QUESTION TONOTE THAT REALLY DISTURBED ME WITH HER DATA. AND THIS IS SOMETHING THAT'S PROBABLY I'M GOING TO BE ACCUSED OF SEXISM, BUT YOU ACTUALLY PRESENTED THE CONCERN THAT WOULDN'T IT BE NICE TO SAVE MONEY FROM PROSTATE CANCER THERAPY IN THIS FASHION JUST BY SIMPLY PUTTING EVERYBODY INTO AN ACTIVE SURVEILLANCE THING? I WONDER, COULD YOU EVER HAVE PRECEPTED THAT TO THE AMERICAN FEMALE POPULATION ABOUT BREAST CASTER? I MEAN THE 65 YEAR-OLD LADY WHO HAS BREAST TO BE LOOKED AT BY OUR NEW HEALTHCARE SYSTEM AS A POTENTIAL SIGHT OF SAVINGS AS YOUR PRESENTATION SEEMS TO HAVE DONE. >> I'M A BREAST CANCER ONCOLOGIST AND THOSE ANALYSIS HAVE BEEN PRECEPTED AT OUR MEETINGS AND IN FACT THERE'S BEEN A DISCONTINUATION OF RADIATION IN OLDER WOMEN WITH BREAST CANCER, BASED ON THE LACK OF BENEFIT AND THE INCREASED COST. >> WELL IF THERE'S A LACK OF BENEFIT I WOULD LIKE TO ASK THE DOCTOR, IS SHE PROPOSING THAT WE SAVE MONEY ON THE BACKS OF THESE 65 YEAR-OLD MEN WHO HAVE PROSTATE CANCER? >> YEAH, SO EACH DISEASE SNEEDS SNEEDS--NEEDS TO BE EVALUATE TED DIFFERENTLY AND BREAST CANCER AND RESEARCHED DIFFERENTLY THAN PROSTASTY CANCER, FOR LOW, LOW, TO INTERMEDIATE RISK DISEASE, MAYBE EVEN FOR THE HIGHER RISK LOCALIZED DISEASES BUT CERTAINLY FOR LOW TO INTERMEDIATE THERE, IS NOT A CORRELARY IN BRAFORT CANCER WHERE AN ACTIVE SURVEILLANCE OPTION AS AS MUCH SUPPORT OR DATA AS WHAT WE'RE TALKING ABOUT STUDY. NOW I WANT TO MAKE ANOTHER DMEANT WHEN I PRECEPT THIS DATA I FREQUENTLY GET SIMILAR COMMENTS AND I--I JUST FIND IT RATHER INAPPETIZING. AND THIRDLY I WANT TO SAY THAT RATHER THAN THINKING WE'RE GOING TO GET SAVINGS ON THE BACKS OF THE ELDER LEE, MAYBE WE SHOULD THINK ABOUT IT AS BEING, OH, GHEE, MAYBE WE COULD ACTUALLY PREVEPT THE ELDERLY FROM CARRYING THE BURDEN BEING OVERTREATED FOR A CONDITION FOR WHICH ACTIVE SURVEILLANCE IS JUST AS GOOD TO PAD THE PAYCHECKS OR POCKETS OF SOME THEIR PHYSICIANS. >> DR. TU? >> YES, I HAVE A QUESTION ABOUT THE DIFFERENCES IN THE SUBGROUP ANALYSIS BETWEEN THE PIVOT STUDY AND THE SCANDINAVIAN TRIAL. IN PARTICULAR I'M INTERESTED IN THE DIFFERENCES BY AGE, AGE SUBGROUP ANALYSIS AND I CAN THINK OF A NUMBER OF REASON YES THEY MIGHT BE DIFFERENT BUT I'D LIKE TO HEAR FROM BOTH OF YOU ABOUT WHY YOU THINK THEY'RE DIFFERENT AND THEN AS A FOLLOW UP TO THAT, THE ROLE OF ACTIVE AGE AND SURVEILLANCE AND WATCHFUL WAIT. >> SO I'M LIKE YOU, I CAN SPECULATE, BUT OUR DATA WOULD SAY THAT WE'RE ABLE TO NOT FIND INTERACTION BY ANY OF THE PATIENT ATTRIBUTES. WHEN I LOOK AT THE RELATIVE EFFECT SIZES, THE RELATIVE EFFECT ON PROSTATE CANCER MORTALITY IS SIMILAR TO THE RELATIVE EFFECT THAT WE--FROM THE SCANDINAVIAN TRIAL. THE RELATIVE EFFECT IN ALL CAUSE MORTALITY WAS LESS THAN PIVOT THAN IT WAS IN THE SPGB-FOUR, THE ABSOLUTE EFFECT SIZE WAS LESS THAN A HALF OF OF THAT IN PIVOT COMPARED TO SBCG-FOUR. MY BELIEF IS THAT IT IS PREDOMINANTLY DUE TO THE FACT THAT WE HAD PSA DETECTED CANCERS WHICH ARE MUCH LONGER TIED TO ANY PROBLEMS. WHEN I LOOK AT OTHER FACTORS LIKE CO-MORBIDITY, AGE, THINGS LIKE THAT, ALL CAUSE SURVIVAL IS PRETTY SIMILAR TO THEIRS SO I DON'T THINK THAT'S THE BIG DRIVERRING FORCE SO I REALLY THINK IT'S MOST LIKELY TO BE THE TYPE OF TUMORS DETECTED, I DON'T THINK IT'S THE QUALITY OF THE SURGERY, I DON'T THINK IT IS THE CROSS OVER RATES BETWEEN THE TWO, THEY APPEAR TO BE PRETTY COMMON BUT AGAIN IT'S SPECULATION. >> THERE ARE SUBGROUP ANALYSIS AND THEY SHOULDN'T BE TAKEN TOO FAR IN INTERPRETATION BECAUSE YOU RUN MANY RISKS FOR POSITIVES AS WELL AS FOR SUBGROUP ANALYSIS, WHAT'S LESS OFTEN DISCUSS SIDE ALSO FALSE NEGFIVES, IT'S DIFFICULT IN SMALL SUBSETS TO EXCLUDE THE DIFFERENCE SO WE SHOULD BE REALLY CAREFUL WHEN WE LOOK AT THE SUBSET ANALYSIS IN BOTH OUR STUDIES ACTUALLY AND I HOPE WE TRY TO CURVE THAT, THAT THAT IS THE CASE. SO, I WOULDN'T OVER SPECULATE ABOUT THE DEFICIENCYS BUT THERE IS SO, THAT IT'S REALLY FIVE TIMES MORE SCREENING DETECTED PATIENTS IN THE STUDY OPPOSE TO THE SPGCD, SO EVEN IF WE LOOK AT AGE WE MIGHT BE LOOKING AT DIFFERENT AGE RELATION TO THE TIME OF DIAGNOSIS IN THE TWO STUDIES BECAUSE THE LEAD TIMES ARE AT AN AVERAGE BETWEEN--SOMEWHERE BETWEEN SIX OR SEVEN OR EVEN UP TO 15 YEARS IN SOME ESTIMAGINATIONS. SO--ESTIMATIONS. SO AGE MIGHT HAVE DIFFERENT MEANING IN THE TWO STUDIES WITH CHARACTERIDESSATIONS. >> I THINK THE ONE THING WE SEE DIFFERENT FROM THE SPGC, VERSES OUR PIVOT STUDY WHEN CLASSIFIED BY LOW RISK DISEASE, IT'S CLEAR THAT PROSTATE CANCER MORTALITY AND LOW RISK DISEASE IS MUCH, MUCH, HIGHER AND IT'S BASICALLY THE SAME AS WHAT IS WAS IN OUR HIGH RISK GROUP. I BELIEVE IT'S LIKELY DUE TO THE FACT THAT MOST OF THE PEOPLE WHO HAVE LOW PSA, LOW GLEESON HISTOLOGY, PROBABLY HAD HIGHER VOLUME TUMORS. >> THEY HAD T-TWO PAPPABLE DISEASE ISSUES THAT WAS NOT THE CASE IN THE PIVOT STUDY. >> DO YOU WANT TO GO? >> I'M FROM THE CPC, WE DON'T DO CLINICAL RECOMMENDATIONS IN OUR REPORT. BUT SUMMARIZING THE TWO PREVIOUS DAYS, I SEE TWO ROADS, ONIS WE NEED A NEW TRIAL OF AS, THE OTHER IS IMPLEMENTING THE A. S. SO MY QUESTION IS BOTH FOR THOSE ADVOCATING FOR TRIAL AND THOSE ADVOCATING FOR CLINICAL IMPLEMENTATION. FOR THE CLINICAL PART, WHICH SPECIFIC PROTOCOL, HOW ARE YOU PLANNING TO DETERMINE THE ONE SPECIFIC A. S. PROTOCOL THAT WILL BE APPLIED? FOR THE IT'S BIGGER TALENT. EACH SO WITH SIMULATION OR ANALYTICALLY IF YOU ARE INTERESTED IN DIFFERENT THRESHOLDS FOR PSA, LET'S SAY, DIFFERENT PSA KINETIC MEASUREMENTS, COMBINATIONS OF THOSE, BIOPSY, DIFFERENT BIOPSY REGIMENS, INCLUDING FREQUENTY NUMBER OF COURSE IS SO ON. IT'S TRIVIAL TO SHOW, THE SAMPLE SIZES REQUIRED GIVEN THE LOW ONE, EASILY WITH THE 10S OF THOUSANDS OF PATIENTS SO HOW IF YOU ARE PROPOSING A TRIAL, HOW IS THE OPTIMAL TRIAL REGIMEN GOING TO BE CHOSEN? >> WOULD THIS BE MOSTLY FOR THE INTERMEDIATE AND HIGH RISK OR--BECAUSE I THINK THE LOW RISK IT'S JUST IMPOSSIBLE IN TERMS OF THE NUMBERS OTHER THAN TO PERHAPS STUDY DIFFERENT STRATEGIES. BUT YOU KNOW TO COMPARE TO AN ACTIVE TREATMENT WOULD BE HARD. >> SO I DIDN'T WANT TO GET INTO THE APPLICABLE POPULATION, WHICH POPULATION SHOULD BE USED FOR ITS DESIGNS, THE TRIAL OR THE CLINICAL APPROACH, BUT THIS IS ANOTHER QUESTION. HOW ARE YOU GOING TO DETERMINE THE OPTIMAL [INDISCERNIBLE] FOR THE OPTIMAL POPULATION? >> I DON'T THINK WE HAVE THE DATA YET TO SAY WHAT THE FOLLOW UP REGIMEN SHOULD BE. I THINK THE MOST IMPORTANT OUTCOME OF THIS MEETING AND PANEL RECOMMENDATION SYSTEM SIMPLY THE EMPHASIS THAT ACTIVE SURVEILLANCE IS IN FACT, A VIABLE MANAGEMENT OLYMPIC TERNATIVE FOR CERTAIN MEN WITH NEWLY DIAGNOSED PROSTASTY CANCER AND BEYOND THAT, THERE ARE MANY QUESTIONS TO BE ANSWERED. , AND IF A TRIAL WAS DONE OF ACTIVE SURVEILLANCE VERSES WATCHFUL WAITING I THINK YOU WOULD HAVE TO PICK AN IMPACT BIKE QUALITY OF LIFE, AND SHOWS SORTS OF THINGS, AN OVERALL SURVIVAL ADVANTAGE IS SHOWN. IF YOU'VE DONE THE POPULATION BASED DATA TELLS US THE EVENT DATA WILL BE LOW SO THE QUESTION IS, IS IT BETTER FOR PEOPLE, BETTER QUALITY OF LIFE AND SO FORTH TO BE SEEN IN CLINIC LESS FREQUENTLY OR SEEN IN CLINIC MORE FREE RADICALS WENTLY AND WE CAN STUDIANCEULARY TECHNOLOGIES WITH MRI WITH SPECROSCOPY AND MULTIPARAMETTIC IMAGES TO SAY IF YOU HAVE AN MRI ONCE A YEAR, MAYBE YOU'LL NEED TOW HAVE A BIOPSY ANYMORE TO. DO ACTIVE SURVEILLANCE. >> IT'S NICE TO HEAR DR. ROACH SAY THAT THE EFFECT DEFICIENCYS WOULD LIKELY BE VERY SMALL AT VERY LONG TIME PERIODS AND THAT ANY RANDOMIZED TRIAL WOULD HAVE TO BE LUGELY LARGE SUGGESTING THAT ANY INTERVENTION IS UNLIKELY TO HAVE A BIG EFFECT AND THAT THE TREATMENT WITH THE FEWEST ADVERSE EFFECTS IS OBSERVATION. RAISING PSA THRESHOLDS BEFORE TRYING TO DETECT DISEASE WOULD MARKETEDLY REDIAGNOSE OF INDOLENT DISEASE THAT HAS EXTRAORDINARILY GOOD 20 YEAR OUTCOMES THAT IS THE LONGEST FOLLOW UP OF ANY DISEASE THAT I KNOW ABOUT AND COULD MARKEDLY REDUCE THE ARMS, ANXIOUS AND COST ASSOCIATED WITH HOW WE CURRENTLY DIAGNOSE AND MANAGE PROSTASTY CANCER. >> HUNTER? >> I THINK DR. HOLMBERG ALREADY ANSWERED THIS, BUT DR. WILT, WHEN YOU DID THE SUBGROUP ANALYSIS WERE THOSE PREDEFINED AND COULD YOU EXPLAIN THE POWER THAT YOU HAD TO DRAW ON THOSE. I'M NOT QUITE CLEAR. >> SO THE SUBGROUPS THAT I SHOWED IN THE FORCE PLOT WERE ALL PREDEFINED. THEY WERE REFINED DURING THE COURSE OF THE STUDY, LIKE THE DEAMIC O CLASSIFICATION STUDY RISK DID NOT EXIST IN 1993, BUT THEY WERE BASED ON WHAT WE FELT WERE CLINICALLY VALID CRITERIA. SOME WERE TRYING TO REAFFIRM OR REFUTE THE DATA FROM DR. HOLMBERG STUDY AND DONE IN THE ABSENCE OF LOOKING AT DATA. YOU ARE ABSOLUTELY DIRECT THAT THERE IS INSUFFICIENT POWER TO DETECT THAT, THAT'S ONE OF THE REASON YES WE USED AN INTERACTION TERM TO LOOK FOR THAT. THAT WAS A LITTLE MORE LENIENT, .11. WE SAID THERE WAS SOME EVIDENCE OF INTERACTION. I SHOW YOU THE POINT ESTIMATES, I SHOW WHAT THE CONFIDENT INTERVALLINGS ARE WE DISCUSS THESE AT GREAT LENGTH WITH THE DATA AND SAFETY MONITORING BOARD. WE DID SENSITIVITY ANALYSIS TO DETERMINE WHETHER THE RESULTS WERE CONSISTENT WHEN LOOKING AT THINGS THIS WAY, THAT WAY, ET CETERA. OVERWHELMING THREE, PSA WAS MOST ROBUST WAY OF LOOKING AT THAT TIME AND OBVIOUSLY IT'S INCORPORATE INDEED THE DEAMICO CATEGORIZATION, THAT'S WHAT'S DRIVE TAG DIFFERENCE IF WE BELIEVE THERE'S A DIFFERENCE IN THAT AND FURTHER MORE GLEASON HISTOLOGY THERE WAS NOT A TESTIFY OF INTERACTION, AGREEABLY, LOW VALUE, P-FIVE, THE SLIDES SHOW YOU THE POINT ESTIMATES IN INTERVALS, AND WHEN YOU USE SEBTERAL HISTOPATHOLOGY, I'M NOT SURE WHY THEY LOOKED AT THE SAME SLIDE SET MAYBE IT'S HISTOLOGIC UPGREATING THOSE DIFFERENCES ALMOST ALWAYS GOT SMALLER AND ANY STATISTICAL DIG 95 CANC DISAPPEARED IN SOME CASES OF FAVORING THE OBSERVATION SO DATA PROVIDE MUCH LESS CONFIDENCE, I'M TRYING NOT TO OVERSTATE IT, BUT THE DATA, MUCH LESS CONFIDENCE OF THE USE OF HISTOLOGY AND THAT INCORPORATION OF HISTOLOGIC CLASSIFICATIONS AND MAKING TREATMENT DECISIONS. >> IT APPEARS ONE OF THE MAIN FEETS OR KEY ISSUES HERE IS GRADING THE DISEASE, TRYING TO PREDICT THE PROBABLE PROGRESSION AND PEOPLE LOOKING AT PSA AND GLEESON FOR THAT, NOW 20 YEARS AGO, CARDIOLOGISTS LOOKED AT TOTAL CHOLESTEROL TO TRY TO DETERMINE THE RISK OF HEART ATTACK. TODAY WE KNOW THE HDL, LDL RADIO IS WHAT MATTERS, I UNDERSTAND THE AUTHORITY KNOWN THAT THE RATIO BETWEEN FREE AND BOUND PSA IN THE BLOOD SEEMS TO HAVE MORE PREDICTIVE VALUES AND TOTAL PSA. HAS ANYBODY GOT DATA ON THAT? IS THERE ENOUGH TISSUE REMAINING FROM OTHER STUDIES TO DO A RETROSPECTIVE? >> THERE ARE TONS OF STUDY O SINGLE PSA AND I BELIEVE THE PIVOT DATA BUT IF YOU LOOK AT THE PREPONDERANCE OF LITERATURE, GLEASON SCORE IS FAR MORE IMPORTANT THAN PSA. BUT TO YOUR QUESTION, PSA HAS BEEN SLICED AND DICES AND MANY THING VS BEEN DONE WITH IT. IT HAS PROGNOSTIC SIGNIFICANT, THE TOTAL PSA IS PARTLY EFFECTIVE BY BPh A PATIENT HAS BUT THE END OF THE DAY IF YOU LOOK AT MODELS, THERE ARE A NUMBER OF OF NOMAL GRAHAMS THAT PREDICT THE DEATH AND PROSTASTY CANCER AND PSA BECOMES RELATIVELY INSIGNIFICANT. THE DAT FROM HOPKINS BY ECEATER AND ALL, THEY HAVE A 15 YEAR NOMA GRAM THAT PREDICTS THE LIKELIHOOD OF DYING FROM PROSTASTY--PROSTATE CANCER FROM HOPKINS, AND PSA FALLS OUT AS HAVING VERY LITTLE PROGNOSTIC SIGNIFICANT. >> THAT'S TOTAL-- >> IT DOESN'T MATTER. >> PSA WHETHER IT'S TOTAL, SLICED AND DECKED IT DOESN'T--DICED IT DOESN'T MATTER THAT MUCH. >> I DON'T DOUBT THAT GLEASON HAS PROGNOSTIC SIGNIFICANT, THE QUESTION IS DOES IT HAVE MODIFICATION OF TREATMENT, THE DATA DEMONSTRATE, NO? >> WITHIN THE TRIAL. >> WE HAVE ONE MORE QUESTION FROM A PANELISTS, DR.? >> DR. CAROL YESTERDAY SPOKE ABOUT DISPARITYS AND POPULATIONS FROM WEALTHY AND EDUCATED PEOPLE TO LOWER SOCIOECONOMIC GROUPS AND I KNOW MARK YOU HAVE A LOT OF EXPERIENCE WITH UNINSURED PEOPLE WITH PROSTATE CANCER IN CALIFORNIA. ARE THEY CANDIDATES-- >> MAYBE UNINSURED WILL GO AWAY WITH HEALTH REFORM BUT PROBABLY NOT. ARE POOR SOCIOECONOMIC PATIENTS GOOD CANDIDATES, BAD CANT DADS APPROPRIATE FOR ACTIVE SURVEILLANCE? >> MEN FROM UNDERSERVED POP EULOGISTSS, THE DID THEA SUG--THE DATA SUGGEST HEY TEND TO HAVE WORST OUTCOMES BUT MOSTLY BECAUSE THEY DON'T ACCESS CARE IN THE SAME WAY THAT PEOPLE FROM MORE AFFLUENT BACKGROUNDS DO. SO IF YOU CONTROL FOR THAT DIFFERENTIAL ACCESS TO KEEP THEM THERE, THE PRESUMPTION IS THAT THEY WOULD HAVE SIMILAR OUTCOMES. >> I GUESS IT DEPENDS ON HOW YOU DEFINE ACTIVE SURVEILLANCE AND HOW MUCH INTERVENTION THERE IS, BUT WOULD YOU SAY THEN A BENEFIT FOR AN ACUTE CURIAATIVE TREATMENT WHERE THEY DON'T NEED A LOT OF FOLLOW UP VERSES ACTIVE SURVEILLANCE WHERE THEY DO NEED TOO BE FOLLOWED UP. >> WELL, AGAIN, IF SOMEONE HAS DIFFICULTY ACCESSING CARE BECAUSE HE IS KIND EVER SKATING ALONG THE EDGES OF BEING ABLE TO, YOU KNOW ACCESS THE HEALTHCARE SYSTEM THAT WE HAVE TODAY, THEN ACTIVE SURVEILLANCE MAY BE MORE CHALLENGING IN THAT INDIVIDUAL, IF WE TRULY FEEL THAT MEN ON ACTIVE SURVEILLANCE NEED TO BE SURVEYED AND NOT JUST IGNORED AND "OBSERVED OR NOT OBSERVED" BUT THE DIFFERENT BIOLOGIC OUTCOMES ARE NOT AS GENETIC AS ONCE BELIEVED TO BE PARTICULARLY WITH AFRICAN-AMERICAN MEN. AND 33 WORK OF UNDERSERVED POPULATIONS BUT ALSO IN THE VA DATABASE, THE RESEARCH DATABASE, AND FROM COLLEAGUES AT DUKE THAT WHEN THERE'S FINANCIAL ACCESS IN THE VA SYSTEM, THAT THESE RACIAL ETHNIC DIFFERENCES THAT WE'VE SEEN SO ROBUSTLY, DISAPPEAR. AND AGAIN, WE DID NOT SEE ANY DIFFERENCES IN OUTCOMES IN THE PIVOT DATA SET WITH ABOUT ONE-THIRD OF MEN BEING OF AFRICAN AMERICAN. >> I THINK THE ONLY OTHER CAVEAT THERE IS YOUR MEN WERE IN A CLINICAL TRIAL AND WE THAN THE QUALITY OF CARE WITHIN A CLINICAL TRIAL, EVEN IF IT WAS OBSERVATION IS LIKELY TO BE BETTER THAN THE UNDERSERVED POPULATION THAT MARK IS REFERRING TO WHO WILL NOT GET INTO THE HEALTHCARE SYSTEM EASILY IF THEY HAVE A PROBLEM. >> AND THERE ARE EXAMPLES FOR EXAMPLE, IN THE KISER STUDY THAT SUGGESTS THAT AFRICAN-AMERICAN MEN DO WORSE IN THE KISER EVEN THOUGH THEY HAVE THE SAME HEALTHCARE SYSTEM AFTER YOU ADJUST FOR CERTAIN THINGS SO IT'S A SLIPPERY SLOPE. >> ONE MORE QUESTION FROM THE PANEL AND THEN WE ARE HAVING TO GO. >> HI, SO I THINK WHAT I HEARD TODAY WAS WE HAVE A VERY COMPELLING CASE FOR MEN WHO HAVE VERY LOW STAGE DISEASE AT ACTIVE SURVEILLANCE APPEARS NOT ONLY TO BE SAFE, POSSIBLY PREFERABLE, HOWEVER THE CAVEAT FROM YESTERDAY'S TALK AND LITERATURE IS THAT THERE IS THIS PROBLEM WITH MISCLASSIFICATION BECAUSE OF WHERE YOU PUT THE NEED WILL. AND YOU ARTICULARLY SAID WE HAVE THESE NEW TECHNOLOGIES AND THERE ARE WAY WHAT'SY CAN INSURE, I'M JUST WORRY BECAUSE IN THIS CLASSIFICATION THAT SEEMS TO BE A RANDOM PROCESS, NOT RELATED TO THE QUALITY OF YOUR PATHOLOGIST BUT WHERE THE NEEDLE GOES, HOW MANY CORES– CAN LEAD TO 20-30% MISCLASSIFICATION AND UPSTAGING SO THEORETICALLY THE RISK AND THE OLDSMOBILE RISK I'M SEEING HERE, THE ONLY SIGNIFICANT RISK IS THAT THERE'S A 30% CHANCE THAT SOMEBODY WHO WOULD POTENTIALLY BENEFIT FROM TREATMENT IS PUT INTO AN ACTIVE SURVEILLANCE PROTOCOL. YOU MENTIONED THAT THERE ARE WAYS OF DEALING WITH THIS, NOW THE QUESTION IS, HOW REALISTIC IS IT IN TODAY'S--THE WAY THE, HEALTHCARE SYSTEM IS TODAY RECOGNIZING THE VARIETY OF PATIENTS WE HAVE SEEN, THE VARIETY OF CARE, ACADEMIC VERSES COMMUNITY CENTERS, PATIENT WITHIN THE HEALTHCARE SYSTEM, PATIENTS OPERATE O GBA THE FRINGE ARE NOT WITH ACCESS TO HEALTHCARE WHA.'S THE LIKELIHOOD OF US BEING ABLE TO ACRIGHT--ACCURATELY IDENTIFY THIS DEC BEFORE PUTTING THEM ON ACTIVE SURVEILLANCE. >> AS WITH ACCESSING THE HEALTHY INDIVIDUALS, THE BEHAVIOR OF OUR SPECIALTIES IN MEDICINE CAN BE IMPACTED BY A VARIETY OF FORCES. SOME OF THEM SCIENTIFICALLY AND EVIDENCE BASED AND OTHERS NOT FOR EXAMPLE, THE ADOPTION OF ROBOTIC ASSISTED RADICAL PROSTATECTOMY OVER STANDARD PROSTATECTOMY, HAPPENED OVER A PERIOD OF A FEW YEARS FROM ZERO TO SOMETHING LIKE 70% NOW, IN A COMPLETE ABSENCE OF EVIDENCE. AND WHY THERE WAS A MOTIVATION TO CHANGE. NOW IT MAY OR MAY NOT BE BETTER OR THE SAME, IN THE STUDIES BEING DONE NOW BUT IT HAPPEN INDEED AN ABSENCE OF EVIDENCE BECAUSE THERE WAS MOTIVATION TO CHANGE. SO TO YOUR DIRECT QUESTION, HOW CAN WE DO A BETTER JOB WITH PERHAPS NEW TECHNOLOGIES IN MORE ACCURATELY STRATIFYING MEN WHO WOULD IN FACT BE BEST SERVED BY ACTIVE SURVEILLANCE IF THE TECHNOLOGY IS AVAILABLE AND THERE'S REASON TO BELIEVE THAT IT IS OR AT LEAST BEGINNING AND THEN I BELIEVE THAT THAT--IF THERE'S A ROLE FOR IT, THEN IT WILL BE ADOPTED. >> I GUESS IS IT BEING USED NOW--IS IT AVAILABLE NOW FOR PATIENTS AND HOW WIDELY? >> IT IS AVAILABLE, IMAGE GUIDED ADVANCES IN PROSTATE BIOPSIES ARE AVAILABLE NOW, BUT IT'S NOT WIDELY USED BECAUSE WE'RE AT THE BEGINNING OF THE CURVE. >> AND AGAIN THIS TO ME IS NO DIFFERENT THAN LOOKING AT PSA VERSES ARE DIGITAL RECTAL IT'S A PROGNOSTIC VARIABLE BUT WE WANT TO KNOW DO TREATMENT OUTCOMES VARY BY THAT AND TO BE HONEST WE'VE BEEN IN THIS ARGUMENT NOW FOR 20 YEARS BECAUSE WE HAVEN'T DONE THE RANDOMIZED TRIAL. >> WE NEED TO DO A RANDOMIZED TRIAL OR SOME FORM OF HIGHLY CONTROLLED TRIAL SO WE GET CLONING TERM CLINICAL OUTCOMES TO SEE IF THEY MAN WITH THESE KIND OF THINGS AND YOU ADD ON A NEW PROD NOVELTYIC VARIABLE, BE IT AN MRI, BE IT TO ACTIVE SURVEILLANCE OR WHATEVER, I HAVE NO DOUBT THESE WILL IMPROVE MOG NOVELTYICATION, THEY'RE ALL THERE BUT DO THEY EFFECT THE TREATMENT O SINGLE OUTCOME. >> I ASK A BASIC QUESTION, IS THAT, THERE IS--FROM WHAT WE KNOW, THERE'S A--20-30% CHANCE RIGHT NOW THAT WE WILL BE PUTTING MEN THAT ARE NOT IN THIS LOW RISK CATEGORY INTO WHAT WE THINK IS A GOOD PROTOCOL FOR LOW RISK MEN. SO THERE WILL BE MEN WHO WILL BE STARTING ON THIS PROTOCOL AND WHO PERHAPS DEPENDING ON WHAT THE SURVEILLANCE PROTOCOL MIGHT BE MAY NEVER ACTUALLY BE REVEALED THAT THEY--THAT THE ACTUAL TRUE STAGE IS ACTUALLY HIGHER THAN WHAT WE THOUGHT IT WAS. >> IS THAT A REAL RISK OR NOT? AND ARE THERE WAYS THAT IF WE'RE THINKING ABOUT DO THANKSGIVING, WE CAN MITIGATE THIS, AGAIN GIVEN THE REALITIES OF NOT GOING THERE IN FUTURE BUT HOW WOULD WE DO THIS-MARKED FOR IDENTIFICATION. >> LET ME ANSWER THIS IS IN A DIFFERENT WAY, THE LOW RISK PATIENTS ARE BEING UNDERTREATED IF THEY REALLY HAVE MORE AGGRESSIVE DISEASE THAN EVEN IF THEY GET TREATED, THEY'RE BEING UNDER TREATED AND WE FIND OUT THEY HAVE BAD PATHOLOGY, SO THESE PATIENTS. --I UNDERSTAND YOUR UNDERSTAND OF 20-30% BUT IF THEY'RE ACTIVELY SURVEYED, YOU WILL FIND OUT THEY HAVE MORE DISEASE IF THEY GET TREATED, THEY GET PATHOLOGY, THAT SHOWS THEY HAVE MORE DISEASE THAN YOU THOUGHT THEY HAD AND THE TECHNOLOGY IS E VOLVING SO I THINK THE PIVOT STUDY IS A VERY IMPORTANT STUDY AND IT SHOWS THAT EVEN ś WE'RE MISCLASSIFYING PEOPLE IN SOME PERCENTAGE OF THE TIME WE CAN CATCH UP WITH SOME OF THOSE PEOPLE LATER. THE OVERALL EFFECTIVE SIZE IS VERY SMALL EVEN IF PEOPLE WE KNOW HAVE EXPENSIVE DISEASE, THE 10 YEAR SURVIVAL RATE IS 90%, SO IT'S A CONCERN THAT'S A REAL CONCERN BUT THE OVERALL IMPACT TELEVISION IS RELATIVELY SMALL. >> WE HAVE TO ACTUALLY GO RIGHT NOW. WE HAVE TO CLOSE THE MEETING. >> SO I REALLY WANT TO THANK EVERYONE, THOSE OF YOU WHO HAVE HUNG IN THERE TILL THE END FROM THE PARTICIPANTS IN THE AUDIENCE WHO CAME FORWARD AND TOLD US SOME OF THEIR STORIES AND TO ALL OF THE SPEAKERS AND WE ACTUALLY--YES, WE'RE GOIN HERE--PARIS IS REMINDING ME, PLEASE STAY TUNED AND COME BACK TOMORROWMORNING AT NINE WHEN WE WILL BE READING OUR RECOMMENDATIONS FROM OUR STATEMENT. [ APPLAUSE ]