1.Prostate Cancer 2013Still an

2. Cancer Cases in 2013 3. Cancer Deaths in 2013 4. Life time risk of developing cancer 2007 - 2009 Site MenWomen All sites44%38% Breast12.4% Colorectal 5.17%4.78% Lung 7.8% 6.4% Melanoma 2.9% 1.9% Prostate 16.2% 5. Life time risk of dying ofcancerSiteMen WomenAll sites 23.5% 19.9%Breast2.9%Colorectal 2.3% 2.2%Lung7.8%4.9%Melanoma 0.35%0.20%Prostate2.97% 6. Prostate CancerIncidence PeakedDuring the ClintonYears 7. Male Cancer Incidence Rates 1975 to 2009Prostate Peak year 1992 8. Male Cancer Mortality Rates 1930 to 2009 lung stomachprostate colorectal 9. Median Age at Diagnosis and Death 10. Median Age at Diagnosis and Death 80Diagnosis 78Death 76 13 74 year 72 age 70 gap 68 66 64 62 60Lung ColonAll Breast Prostate 11. Leading Cause of Cancer Death in 2009 12. Trends in Relative 5 Year Survival RateTime PeriodSurvival Rate1975-197768%1987-198983%2002-2008 100% 13. Prostate Cancermore men die with it than of it 80%found at autopsy 16% diagnosed during theirlifetime 3% will die of it 14. Risk Factors for Prostate CancerAgeFamily HistoryHormonesRaceDietary FatMultivitamin useDairy and Calcium IntakeCadmium Exposure (-)Dioxin Exposure (-) 15. Can you PreventProstate Cancer?Based on solid evidence, chemoprevention withfinasteride and dutasteride reduces the incidenceof prostate cancer, but the evidence is inadequateto determine whether chemoprevention withreduces mortality from prostate cancer. 16. Prostate CancerPreventionTrials(PCPT) Prostate Cancer Prevention Trial the 24.8% reduction ofprostate cancer prevalence over a 7-year period in those mentaking the 5alpha-reductase inhibitor, finasteride (Proscar 5mg perday)REDUCE study using dutasteride (Avodart) (-23%)CombAT Trial (Avodart + Tamsulosin (Flomax) (-40% and noincrease in high grade cancers)SELECT study using vitamin E and selenium (worse, Viy Eincreased prostate cancer by 17%)Physicians Health Study (PHSII) beta-carotene, Vit E, C ormultivitamins (no benefit) 17. Vitamins E and C in the Prevention of Prostate and Total Cancer in Men ThePhysicians Health Study II RandomizedControlled Trial JAMA. 2009;301(1):52-62 18. Should you screen forprostate cancer? 19. Age Distribution of Men Diagnosed withProstate Cancer 2000-201039%40%35%28%30%22%25%20%15%7%10% 3%5% 1%0%30 40 50607080 90 Age 20. The evidence is insufficient to determinewhether screening for prostate cancerwith prostate-specific antigen (PSA) ordigital rectal exam (DRE) reducesmortality from prostate cancer. 21. Men who have at least a 10-y life expectancyshould have an opportunity to make aninformed decision with their health careprovider about whether to be screened forprostate cancer. Asymptomatic men whohave less than a 10-year life expectancybased on age and health status should not beoffered prostate cancer screening. 22. Median Life Expectancy in Men by Health (poor, average or excellent) 23. ? Proven Benefit fromPSA Screening ERSPCEuropean Randomized Screening for Prostate Cancer (ERSPC)Trial, 182,000 men age 50-74y, PSA yearly for 4 yearsMedian follow up of 11 years ScreenNo ScreenDiagnosis of prostate cancer 7.4%5.1%Deaths from prostate cancer299 462Death risk prostate cancer 0.791.00Conclusion: screen lowers the death rate by 21%, butyou would need to screen 1,055 men and treat 37 toprevent one death 24. Mortality results from the Gteborgrandomized population-basedprostate-cancer screening trial.University of Gteborg, Sweden.Lancet Oncol. 2010 Aug;11(8):725-32. Epub 2010 Jul 2. 20,000 men, age 50 to 64, half PSA every 2years 14 year follow upScreenControlprostate cancer 12.7% (1.64) 8.2%Screening had 44% lower 0.5% (0.56X) rate so hadprostate deathprostate death0.9%to screen 293 and treat an additional 12 to save 1 25. ? Proven Benefit from PSAScreening PLCO StudyProstate, Lung, Colorectal, Ovary US Study, n =76,693 , annual PSA for 6 years and DRE 4 years, with 13 years follow up ScreenNo ScreenIncidence cancer1.22 1prostate cancer death 50 44mortality rate/100,00021.7 26. Prostate, Lung, Colorectal, and Ovarian (PLCO) CancerScreening Trial on prostate-cancer mortality. NEJM.org March 18, 200976,693 men at 10 U.S. study centers, Men in the screening group wereoffered annual PSA testing for 6 years and digital rectal examination for 4years.Incidence 22% higherMortality was 13% higher (notlower) 27. Long Term PLCO Trial Those who had 2 or more early PSA screenings had 25% lowerprostate cancer mortality Those with minimal comorbidities had a 44% reduction in prostatecancer mortality. Treat an additional 5 to save 1 Prostate Cancer MortalityNo screen screenJCO February 1, 2011 vol. 29no. 4 355-361 28. Prostate Cancer ScreeningMata-analysis of 6 trials ( n = 387,286) Odds of diagnosing prostate cancer= increased by 46% Odds of being in stage I = increasedby 95% Impact on prostate cancer mortality= none Impact on overall survival = none BMJ. 2010 Sep 14;341:c4543 29. Prostate Cancer ScreeningMata-analysis of 6 trials ( n = 387,286) Favor Screening Favor Control BMJ. 2010 Sep 14;341:c4543 30. Check for a baseline PSA at age 40 and if 1 orover go to annual (if less than 1 start screeningat 50) Median PSA for Men age 40 49median0.5 to 0.775th percentile is 0.7 to 0.9 31. If PSA is > 2.5 or higher or velocity is 0.35/yconsider biopsy or check Free-PSA If PSA 4-10 get biopsy or at least free-PSA If over 10 get biopsy 32. Probability of finding cancer in men withclinically normal prostate glands but PSAbetween 4 10 using Free PSAPSA Cancer % Free PSA Age 50 - 64y Age 65 - 75y0.5 6.60%0 - 10%56%55%.6-1 10% 10.1 - 15%24%35%1.1-217% 15.1 - 20%17%23%2.1-324% 20.1 - 25%10%20%3.1-427% > 25%5% 9%4-1025-30%>10 42-64% 33. Prostate Cancer Biopsy Predictor http://www.aboutcancer.com/prostate_calc_main_page.htm 34. Prostate Cancer Biopsy Predictor 35. Prostate Cancer Biopsy Predictor 36. Positive Biopsy based on PSA andFamily History 37. Positive Biopsy by Age, Race andPSA 80% 70% 60% 50% W55 40% W70 30% B55 B70 20% 10% 0% 2.5 4 10 20 50 38. Positive High Grade Biopsy by Age, Race and PSA80%70%60%50%W5540%W7030%B55 B7020%10%0%2.5 4102050 39. Radical Prostatectomy versus Observation for Localized ProstateCancerProstate Cancer Intervention versus Observation Trial (PIVOT).From November 1994 through January 2002, we randomly assigned 731men with localized prostate cancer (mean age, 67 years; median PSAvalue, 7.8 ng per milliliter) to radical prostatectomy or observation andfollowed them through January 2010.Patients had to be medically fit for radical prostatectomy and to havehistologically confirmed, clinically localized prostate cancer (stage T1-T2NxM0) of any grade diagnosed within the previous 12 months.Patients also had to have a PSA value of less than 50 ng per milliliter, anage of 75 years or less, negative results on a bone scan for metastaticdisease, and a life expectancy of at least 10 years from the time ofrandomization.NEJM 2012; 367:203 40. Death from Any Cause During the median follow- up of 10.0 years, 47.0% assigned to radical prostatectomy died, as compared with 49.9% assigned to observation absolute risk reduction, 2.9 percentage points). Among men assigned toDeath from Prostate Cancer radical prostatectomy, 5.8% died from prostate cancer or treatment, as compared with 8.4% assigned to observation absolute risk reduction, 2.6 percentage pointsNEJM 2012; 367:203 41. NEJM 2012; 367:203 42. Incidence of death from prostate cancer in a randomized trial thatcompared radical prostatectomy with watchful waiting.Only the young men (< 65 years) did poorly without activetreatmentDeath from Prostate Cancer 43. Patient Reported Dysfunctionat 2 YearsDysfunctionSurgeryObservationUrinary 17.1%6.3%IncontinenceErectile81.1% 44.1%DysfunctionBowel 12.2% 11.3%Dysfunction NEJM 2012; 367:203 44. Treating prostate cancer Surgery?Radiation?Or Watchful Waiting? 45. Prostate Cancer Treatment120 in 2008 from NCDB100 80Surgery 60RadiationWatchful Waiting 40 20018-64 65-74 75-85 46. Choices with Prostate Cancer1. Depending on the mans life expectancy and the nature of the specific cancer (Gleason score) is treatment necessary?2. If treatment is appropriate how to choose between surgery or radiation? 47. Watchful Waiting or Active SurveillanceNCCN appropriate for:1. Very low risk cancersand life expectancy < 20 y2. Low Risk and lifeexpectancy < 10 y 48. Very Low Recurrence Risk1. Stage T1c2. Gleason 6 or lower3. Less than 3 cores positive and none over 50%4. PSA density < 0.15 (so PSA was 5 and volume 35g then density would be 0.14 or 5/35) 49. Low Recurrence Risk 1. Stage T1 T2a 2. Gleason 6 or lower 3. PSA < 10 50. Median Life Expectancy in Men by Health (poor, average or excellent) 51. Life Tables for Men in the US (2007 data) Age Expectancy50 2955 2560 2165 1770 1475 11807.9855.7 52. Watchful Waiting?Mortality if UntreatedGleason Score Death by 15 Years 244 7% 5 6 11% 618 30% 742 70% 8 10 60 87% 53. Mortality with No Active Therapy 54. Watchful Waiting, the odds that untreated prostatecancer would cause death related to the age and the GleasonScore 55. Active Surveillance Limited to men with low risk cancer and shorter lifeexpectancy PSA every 3 to 6 months DRE every 6 to12 months Repeat biopsy may be considered every 12 months upto the age of 75 Repeat biopsy if increased PSA or PSA velocity Considered Disease Progression and Reason to Initiate Therapy If Gleason Grade 4 or 5 is found on repeat biopsy If prostate volume increase (number of + biopsies or the extent of the cancer) 56. Partin Tables: calculate the risk that thecancer is already outside the capsuleprior to therapy 57. Laparoscopic Prostate Surgery The surgeon tries to dissect the prostate away from the rectum, bladde r, the neurovascular bundle (nerves) and penile urethra 58. Radiation Fields with Prostate CancerA Low Dose Large Area (Phase 1) With radiation it is possible to include a wider area around the prostate to cover any cells that may have escaped After the highest safe dose is reached, the radiation target will be made smaller 59. Radiation Fields with Prostate CancerA High Dose Large Area (Phase 2)The final, highdose radiationtarget will befocused veryprecisely onlyon the prostategland 60. NCCN.org 61. Prostate Cancer Risk Groupscombine all 3 things, thestage, the PSA level and the Gleason scoreLow risk: (T1c, T2a Gleason 6, PSA 20) 62. Cure Rates with Radiation versus Surgery forEarly Stage Prostate Cancer are the same from the Cleveland Clinic.Kupelian. JCO Aug 15 2002: 3376-3385 63. 10 Year Cure Rates for Patients with High RiskProstate Cancer (PSA >20 or Gleason 8-10 or T3)Treatment Number Cure RateRadical Prostatectomy 1,238 92%Radiation/Hormones 34492%Radiation26588%Mayo Clinic Study (Cancer Jan 10, 2011) 64. Long-Term Functional Outcomes after Treatment for Localized Prostate Cancer The Prostate Cancer Outcomes Study (PCOS), comprised 1655 men in whom localized prostate cancer had been diagnosed between the ages of 55 and 74 years and who had undergone either surgery (1164 men) or radiotherapy (491 men). Functional status was assessed at baseline and at 2, 5, and 15 years after diagnosis Urinary Incontinence: worse with surgery at 2 and 5years but the same by 15 years Erectile Dysfunction: worse with surgery at 2 and 5years but the same by 15 years Bowel Urgency: worse with radiation at 2 and 5 yearsbut by 15 years the sameN Engl J Med 2013; 368:436-445 65. Sexual Function afterRadiotherapy orSurgery N Engl J Med 2013; 368:436-445 66. Quality of Life / Medicare Survey Prostate Cancer PatientsSymptom Surgery RadiationWear Pads 30%7%Potent (< 70y)11% 33%Potent (>70y) 12% 27%More frequent bowel3% 10%movements J Clin Oncol 14 (8): 2258-65, 1996 67. Potency Rates after Prostate Cancer TreatmentTreatmentProbabilityRangeSeeds 80%64 96%Seeds + External69%51 86%External68%51 95%Radical Prostatectomy Nerve Sparing22%0 53% Standard 16%0 37%Cryotherapy 11%0 - 53%IJROBP 2002:54:1063 68. Potency Rates after Surgerycan range from 2% to70%) Did they have a nerve sparingprostatectomy? Hold old is the man? How high was the PSA? How good was their sexual functionbefore?JAMA. 2011;306(11):1205-1214 69. Potency Results after ExternalRadiation can range from 16% to 92% Did they get hormone therapy alongwith the radiation? How high was the PSA prior toradiation? How good was their sexual functionbefore? 70. Responded to ViagraSurgery: 43%Radiation:70 91%General Population: 80% from other studies in the literature 71. Choosing Treatment Prostate CancerUrologist withexperience and a goodoutcome with theprocedureExperienced RadiationOncologist withModern Technology(IGIMRT) and goodoutcome data 72. The experience of the surgeon is a criticalfactor associated with a successful outcomeOpen prostatectomy the learning curve did notplateau until a surgeon had performed at least250 retropubic radical prostatectomies Theprobability of biochemical recurrence at fiveyears was significantly lower (10.7 versus 17.9percent) 73. Minimally invasive prostatectomy In aseries of 4,702 men who were managed withlaparoscopic prostatectomy by one of 29surgeons at seven centers,the five-year risk of recurrence progressivelydecreased with increasing experience (17, 16,and 9 percent with 10, 250, and 750 priorlaparoscopic procedures) 74. Evolving RadiationTechnology 75. Using the proper dose ofradiation It may be a bit over-exposed 76. Prostate Cures Rates by Treatment,The Radiation Dose is Critical External beam > 72Gy Surgery or SeedsExternal beam < 72Gy IJROBP 2004; 58:25Months 77. Cure Rate (PSA cure) in 2991Men By Therapy Best results with high dose external 78. Prostate Cancer Relapse Rate by Radiation Dose< 72Gy72 - 82Gy 82GyYearsKupelian. IJROBP 2008:71:16 79. Goal = radiation zone precisely aroundthe prostate cancer with small margin bladderprostateRadiation zone rectum 80. IMRT (intensitymodulatedradiation therapy) using 7 different beamsto target the prostateThe computer candetermine the optimalnumber of beams todeliver the radiationdose to hit the target andavoid other structures 81. After IMRT was established then IGRT(image guided) was introduced 82. Lower Risk of Side Effects with ImageGuided IMRT compared to IMRT 83. Better Cure Rates with Image Guided IMRT compared to IMRT for ProstateIntermediate RiskHigh Risk 84. The most sophisticated technique forimage guided IMRT is Tomotherapy.Combine a CT scan and linear accelerator to ultimate intargeting (IGRT) and ultimate in delivery (dynamic, helicalIMRT) ability to daily adjust the beam (ART or adaptiveradiotherapy) 85. There is significant movement of the prostate gland based on daily gas in rectumPlannedtarget No Rectal gasPlanned target,missed badly ifrectal gas pushesthe prostateRectal gasforward 86. Cyberknife Radiosurgery 87. Non Isocentric Delivery with CKBeams 88. SBRT Prostate Cancer / Naples-TampaExperience Feb 2005 Apr 2008 (Naples, FL) 164 monotherapy, 35 Gy 168 monotherapy, 36.25 Gy 59 EBRT + CK boost Jul 2008 Dec 2011 (Tampa, FL) 121 monotherapy, 36.25 Gy 10 monotherapy, 38 GY 12 EBRT + CK boost 89. PSA Response to CyberKnifeMean PSAi 6.8ng/mlMean PSAp 0.78ng/ml97% biochemical control at 30 months median follow-up 90. Cure Rate after Cyberknife N = 515, Alan Katz in New York 91. PSA Response after Cyberknife Follow-up median 54 months (range, 7 -78) Median PSA 7 35 Gy 36 m 0.20 ng/ml 636.25 Gy5 60 m 0.10 ng/ml PSA ng/ml 4 By 48 months3 290 of 329 pts21 PSA < 0.500 12 24 36 48 60 72Months 92. New MedicalTreatmentsfor ProstateCancer 93. Clinical development of novel therapeuticsfor castrationresistant prostate cancer 94. New Drugs for Prostate Cancer 95. New Drugs for Advanced Prostate CancerDrugFDA Approval CostProvenge (sipuleucal) immunoRx4/2010 $93,000Jevtana(cabazitaxel) chemoRx6/2010 $8.000 q3wXgeva (denosumab) skeletal11/201$1,600 doseZytiga (abiraterone) hormone Lupron (1985) LHRH agonist4/2011 $5,000/mos Bicalutamide (Casodex, 1995) anti-androgenXtandi (enzalutamide) hormone 8/2012 Degarelix/ Firmagon(2008) GnRH antagonist $7,450/mos Abiraterone androgen synthesis inhibitor Enzalutamide androgen receptor blocker 96. Expose the patients activated T cells to cancer antigen targetsThen re-infuse thepatients activated cells(atcs) back into themwhich will attack prostatecancer cells 97. FDA Approval 4.29.10median OS of 25.8 months compared to 21.7months for patients who received the controltreatment There was no difference in time-to-progression.The total cost for three courses of treatmentwith Sipuleucel-T is $93,297.60 98. Phase 3 TROPIC clinical study involving 755 patients with mHRPC previously treated with a docetaxel-containingMedian overall survival in the patients receiving JEVANA + prednisone was 15.1 months compared to 12.7 monthstumor response rates were 14.4% and 4.4% forcabazitaxel-treated and mitoxantrone-treatedpatients respectively, FDA Approval 6.18.10 99. Xgeva the first and only RANK Ligand inhibitor toprevent SRE (skeletal related events in cancer)FDA Approval 11.19.10 100. Xgeva RANK Ligand inhibitor 101. Recent advances have demonstrated thatandrogen-based pathways continue to have aclinically significant role in the progression ofcastrate-resistant prostate cancer. In addition to androgen production by theadrenal gland and testis, several of the enzymesinvolved in the synthesis of testosterone anddihydrotestosterone, including CYP17, are highlyexpressed in tumor tissue 102. ZYTIGA is an oral androgenbiosynthesis inhibitor that worksby inhibiting the CYP17 enzymecomplex, which is required forthe production of androgens atthese three sources.FDA Approval 4.28.11 103. Zytiga and prednisone combination had a median overall survival of 14.8 months compared to 10.9 months for patients receiving the placebo and prednisone combination. 104. August 2012In clinical trials, men who received the drug, which waspreviously known as MDV3100, lived a median of 18.4months, nearly five months longer than the median of13.6 months for those who received a placebo. Before2004, the only drug shown to prolong the survival of menwith advanced prostate cancer wasthe chemotherapy drug docetaxel. Now there are fourothers on the market Jevtana, Provenge, Zytiga and 105. Enzalutamide (marketed as Xtandi and formerly known as MDV3100) is asecond generation androgen receptor antagonist drug for the treatment ofmetastatic castration-resistant prostate cancer.Enzalutamide has approximately fivefold higher binding affinity for theandrogen receptor (AR) compared to the antiandrogen bicalutamide(Casodex) 106. www.aboutcancer.comCancer InformationCancer VideosTomotherapyCyberknifeOther TopicsDr. Miller 107. www.aboutcancer.comCancer InformationBasic Cancer InformationGeneral Cancer StatisticsMost Common Cancers* brain* breast* colon/rectum* gynecologic* lung* prostateOther Specific CancersRadiation or ChemotherapyAll Other Cancer TopicsOther TopicsBest Web Sites 108. Robert Miller MD Medical Channelbone metastasesbrain metastasesbreast cancer:understanding the disease, treatment decisionshead and neck cancer (mouth, throat, larynxunderstanding the disease, radiation treatmentlung cancer:understanding lung cancer, radiation treatmentsprostate cancer:understanding the disease, treatmentdecisions, radiation therapyskin canceruterine (endometrial cancer) aboutcancer.com/you_tube_videos