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Prostate2013 130412164034-phpapp01
- 1.
- 2. Cancer Cases in2013
- 3. Cancer Deaths in2013
- 4. Life time riskof developing cancer 2007 - 2009 Site Men Women All sites 44% 38% Breast 12.4% Colorectal 5.17% 4.78% Lung 7.8% 6.4% Melanoma 2.9% 1.9% Prostate 16.2%
- 5. Life time riskof dying of cancer Site Men Women All sites 23.5% 19.9% Breast 2.9% Colorectal 2.3% 2.2% Lung 7.8% 4.9% Melanoma 0.35% 0.20% Prostate 2.97%
- 6. Prostate Cancer Incidence Peaked Duringthe Clinton Years
- 7. Male Cancer Incidence Rates1975 to 2009 Prostate Peak year 1992
- 8. Male Cancer MortalityRates 1930 to 2009 prostate colorectal stomach lung
- 9. Median Age atDiagnosis and Death
- 10. 60 62 64 66 68 70 72 74 76 78 80 Lung Colon AllBreast Prostate Diagnosis Death Median Age at Diagnosis and Death 13 year age gap
- 11. Leading Cause ofCancer Death in 2009
- 12. Time Period SurvivalRate 1975-1977 68% 1987-1989 83% 2002-2008 100% Trends in Relative 5 Year Survival Rate
- 13. Prostate Cancer…more men diewith it than of it 80% found at autopsy 16% diagnosed during their lifetime 3% will die of it
- 14. Risk Factors forProstate Cancer Age Family History Hormones Race Dietary Fat Multivitamin use Dairy and Calcium Intake Cadmium Exposure (-) Dioxin Exposure (-)
- 15. Can you Prevent ProstateCancer? Based on solid evidence, chemoprevention with finasteride and dutasteride reduces the incidence of prostate cancer, but the evidence is inadequate to determine whether chemoprevention with reduces mortality from prostate cancer.
- 16. •(PCPT) Prostate CancerPrevention Trial the 24.8% reduction of prostate cancer prevalence over a 7-year period in those men taking the 5alpha-reductase inhibitor, finasteride (Proscar 5mg per day) •REDUCE study using dutasteride (Avodart) (-23%) •CombAT Trial (Avodart + Tamsulosin (Flomax) (-40% and no increase in high grade cancers) •SELECT study using vitamin E and selenium (worse, Viy E increased prostate cancer by 17%) •Physicians Health Study (PHSII) beta-carotene, Vit E, C or multivitamins (no benefit) Prostate Cancer Prevention Trials
- 17. Vitamins E andC in the Prevention of Prostate and Total Cancer in Men The Physicians' Health Study II Randomized Controlled Trial JAMA. 2009;301(1):52-62
- 18. Should you screenfor prostate cancer?
- 19. Age Distribution ofMen Diagnosed with Prostate Cancer 2000-2010 0% 5% 10% 15% 20% 25% 30% 35% 40% 30 40 50 60 70 80 90 Age 3% 22% 39% 28% 7% 1%
- 20. The evidence isinsufficient to determine whether screening for prostate cancer with prostate-specific antigen (PSA) or digital rectal exam (DRE) reduces mortality from prostate cancer.
- 21. Men who haveat least a 10-y life expectancy should have an opportunity to make an informed decision with their health care provider about whether to be screened for prostate cancer. Asymptomatic men who have less than a 10-year life expectancy based on age and health status should not be offered prostate cancer screening.
- 22. Median Life Expectancyin Men by Health (poor, average or excellent)
- 24. ? Proven Benefitfrom PSA Screening ERSPC European Randomized Screening for Prostate Cancer (ERSPC) Trial, 182,000 men age 50-74y, PSA yearly for 4 years Median follow up of 11 years Screen No Screen Diagnosis of prostate cancer 7.4% 5.1% Deaths from prostate cancer 299 462 Death risk prostate cancer 0.79 1.00 Conclusion: screen lowers the death rate by 21%, but you would need to screen 1,055 men and treat 37 to prevent one death
- 25. Mortality results fromthe Göteborg randomized population-based prostate-cancer screening trial. University of Göteborg, Sweden. Lancet Oncol. 2010 Aug;11(8):725-32. Epub 2010 Jul 2. 20,000 men, age 50 to 64, half PSA every 2 years 14 year follow up Screen Control prostate cancer 12.7% (1.64) 8.2% prostate death 0.5% (0.56X) 0.9%Screening had 44% lower prostate death rate so had to screen 293 and treat an additional 12 to save 1
- 26. ? Proven Benefitfrom PSA Screening PLCO Study Prostate, Lung, Colorectal, Ovary US Study, n = 76,693 , annual PSA for 6 years and DRE 4 years, with 13 years follow up Screen No Screen Incidence cancer 1.22 1 prostate cancer death 50 44 mortality rate/100,000 2 1.7
- 27. Prostate, Lung, Colorectal,and Ovarian (PLCO) Cancer Screening Trial on prostate-cancer mortality. NEJM.org March 18, 2009 76,693 men at 10 U.S. study centers, Men in the screening group were offered annual PSA testing for 6 years and digital rectal examination for 4 years. Incidence 22% higher Mortality was 13% higher (not lower)
- 28. Long Term PLCOTrial • Those who had 2 or more early PSA screenings had 25% lower prostate cancer mortality • Those with minimal comorbidities had a 44% reduction in prostate cancer mortality. Treat an additional 5 to save 1 JCO February 1, 2011 vol. 29no. 4 355-361 Prostate Cancer Mortality screen No screen
- 29. Prostate Cancer Screening Mata-analysisof 6 trials ( n = 387,286) • Odds of diagnosing prostate cancer = increased by 46% • Odds of being in stage I = increased by 95% • Impact on prostate cancer mortality = none • Impact on overall survival = none BMJ. 2010 Sep 14;341:c4543
- 30. Favor Screening FavorControl Prostate Cancer Screening Mata-analysis of 6 trials ( n = 387,286) BMJ. 2010 Sep 14;341:c4543
- 31. Check for abaseline PSA at age 40 and if 1 or over go to annual (if less than 1 start screening at 50) Median PSA for Men age 40 – 49 median 0.5 to 0.7 75th percentile is 0.7 to 0.9
- 32. • If PSAis > 2.5 or higher or velocity is 0.35/y consider biopsy or check Free-PSA • If PSA 4-10 get biopsy or at least free-PSA • If over 10 get biopsy
- 33. % Free PSAAge 50 - 64y Age 65 - 75y 0 - 10% 56% 55% 10.1 - 15% 24% 35% 15.1 - 20% 17% 23% 20.1 - 25% 10% 20% > 25% 5% 9% Probability of finding cancer in men with clinically normal prostate glands but PSA between 4 – 10 using Free PSA PSA Cancer 0.5 6.60% .6-1 10% 1.1-2 17% 2.1-3 24% 3.1-4 27% 4-10 25-30% >10 42-64%
- 34.
- 35. Prostate Cancer BiopsyPredictor
- 36. Prostate Cancer BiopsyPredictor
- 37. Positive Biopsy basedon PSA and Family History
- 38. 0% 10% 20% 30% 40% 50% 60% 70% 80% 2.5 4 1020 50 W55 W70 B55 B70 Positive Biopsy by Age, Race and PSA
- 39. 0% 10% 20% 30% 40% 50% 60% 70% 80% 2.5 4 1020 50 W55 W70 B55 B70 Positive High Grade Biopsy by Age, Race and PSA
- 40. Radical Prostatectomy versus Observationfor Localized Prostate Cancer Prostate Cancer Intervention versus Observation Trial (PIVOT). From November 1994 through January 2002, we randomly assigned 731 men with localized prostate cancer (mean age, 67 years; median PSA value, 7.8 ng per milliliter) to radical prostatectomy or observation and followed them through January 2010. Patients had to be medically fit for radical prostatectomy and to have histologically 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, an age of 75 years or less, negative results on a bone scan for metastatic disease, and a life expectancy of at least 10 years from the time of randomization. NEJM 2012; 367:203
- 41. During the medianfollow- 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 to radical prostatectomy, 5.8% died from prostate cancer or treatment, as compared with 8.4% assigned to observation absolute risk reduction, 2.6 percentage points NEJM 2012; 367:203 Death from Any Cause Death from Prostate Cancer
- 42.
- 43. Incidence of deathfrom prostate cancer in a randomized trial that compared radical prostatectomy with watchful waiting. Only the young men (< 65 years) did poorly without active treatment Death from Prostate Cancer
- 44. Dysfunction Surgery Observation Urinary Incontinence 17.1%6.3% Erectile Dysfunction 81.1% 44.1% Bowel Dysfunction 12.2% 11.3% Patient Reported Dysfunction at 2 Years NEJM 2012; 367:203
- 45. Treating prostate cancer Surgery? Radiation? OrWatchful Waiting?
- 46. 0 20 40 60 80 100 120 18-64 65-74 75-85 Surgery Radiation WatchfulWaiting Prostate Cancer Treatment in 2008 from NCDB
- 47. Choices with ProstateCancer 1. Depending on the man’s 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?
- 48. Watchful Waiting orActive Surveillance NCCN appropriate for: 1. Very low risk cancers and life expectancy < 20 y 2. Low Risk and life expectancy < 10 y
- 49. Very Low RecurrenceRisk 1. Stage T1c 2. Gleason 6 or lower 3. 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)
- 50. Low Recurrence Risk 1.Stage T1 – T2a 2. Gleason 6 or lower 3. PSA < 10
- 51. Median Life Expectancyin Men by Health (poor, average or excellent)
- 52. Age Expectancy 50 29 5525 60 21 65 17 70 14 75 11 80 7.9 85 5.7 Life Tables for Men in the US (2007 data)
- 53. Watchful Waiting? Mortality ifUntreated Gleason Score Death by 15 Years 2 – 4 4 – 7% 5 6 – 11% 6 18 – 30% 7 42 – 70% 8 – 10 60 – 87%
- 54. Mortality with NoActive Therapy
- 56. Watchful Waiting, theodds that untreated prostate cancer would cause death related to the age and the Gleason Score
- 57. Active Surveillance • Limitedto men with low risk cancer and shorter life expectancy • PSA every 3 to 6 months • DRE every 6 to12 months • Repeat biopsy may be considered every 12 months up to 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)
- 59. Partin Tables: calculatethe risk that the cancer is already outside the capsule prior to therapy
- 60. Laparoscopic Prostate Surgery Thesurgeon tries to dissect the prostate away from the rectum, bladder, the neurovascular bundle (nerves) and penile urethra
- 61. Radiation Fields withProstate Cancer A 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
- 62. Radiation Fields withProstate Cancer A High Dose Large Area (Phase 2) The final, high dose radiation target will be focused very precisely only on the prostate gland
- 63.
- 66. Prostate Cancer RiskGroups combine all 3 things, the stage, the PSA level and the Gleason score •Low risk: (T1c, T2a Gleason 6, PSA <10) •Intermediate risk: (T2b, T2c, Gleason 7, PSA 10-20) •High risk: (T3, Gleason 8-10 or PSA > 20)
- 72. Cure Rates withRadiation versus Surgery for Early Stage Prostate Cancer are the same from the Cleveland Clinic. Kupelian. JCO Aug 15 2002: 3376-3385
- 73. 10 Year CureRates for Patients with High Risk Prostate Cancer (PSA >20 or Gleason 8-10 or T3) Mayo Clinic Study (Cancer Jan 10, 2011) Treatment Number Cure Rate Radical Prostatectomy 1,238 92% Radiation/Hormones 344 92% Radiation 265 88%
- 74. Long-Term Functional Outcomesafter 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 5 years but the same by 15 years • Erectile Dysfunction: worse with surgery at 2 and 5 years but the same by 15 years • Bowel Urgency: worse with radiation at 2 and 5 years' but by 15 years' the same N Engl J Med 2013; 368:436-445
- 75. Sexual Function after Radiotherapyor Surgery N Engl J Med 2013; 368:436-445
- 76. Quality of Life/ Medicare Survey Prostate Cancer Patients Symptom Surgery Radiation Wear Pads 30% 7% Potent (< 70y) 11% 33% Potent (>70y) 12% 27% More frequent bowel movements 3% 10% J Clin Oncol 14 (8): 2258-65, 1996
- 77. Potency Rates afterProstate Cancer Treatment Treatment Probability Range Seeds 80% 64 – 96% Seeds + External 69% 51 – 86% External 68% 51 – 95% Radical Prostatectomy Nerve Sparing 22% 0 – 53% Standard 16% 0 – 37% Cryotherapy 11% 0 - 53% IJROBP 2002:54:1063
- 78. Potency Rates afterSurgery can range from 2% to 70%) Did they have a ‘nerve sparing’ prostatectomy? Hold old is the man? How high was the PSA? How good was their sexual function before? JAMA. 2011;306(11):1205-1214
- 79. Did theyget hormone therapy along with the radiation? How high was the PSA prior to radiation? How good was their sexual function before? Potency Results after External Radiation can range from 16% to 92%
- 80. Responded to Viagra Surgery: 43% Radiation:70 – 91% General Population: 80% from other studies in the literature
- 81. Choosing Treatment ProstateCancer Urologist with experience and a good outcome with the procedure Experienced Radiation Oncologist with Modern Technology (IGIMRT) and good outcome data
- 82. The experience ofthe surgeon is a critical factor associated with a successful outcome Open prostatectomy the learning curve did not plateau until a surgeon had performed at least 250 retropubic radical prostatectomies The probability of biochemical recurrence at five years was significantly lower (10.7 versus 17.9 percent)
- 83. Minimally invasive prostatectomy– In a series of 4,702 men who were managed with laparoscopic prostatectomy by one of 29 surgeons at seven centers, the five-year risk of recurrence progressively decreased with increasing experience (17, 16, and 9 percent with 10, 250, and 750 prior laparoscopic procedures)
- 84.
- 85. Using the properdose of radiation “It may be a bit over-exposed”
- 86. External beam >72Gy External beam < 72Gy Surgery or Seeds Prostate Cures Rates by Treatment, The Radiation Dose is Critical Months IJROBP 2004; 58:25
- 87. Best results with highdose external Cure Rate (PSA cure) in 2991 Men By Therapy
- 88. Years Prostate Cancer RelapseRate by Radiation Dose < 72Gy 72 - 82Gy 82Gy Kupelian. IJROBP 2008:71:16
- 89. bladder Radiation zone prostate rectum Goal =radiation zone precisely around the prostate cancer with small margin
- 90. IMRT (intensity modulated radiation therapy) using7 different beams to target the prostate The computer can determine the optimal number of beams to deliver the radiation dose to hit the target and avoid other structures
- 91. After IMRT wasestablished then IGRT (image guided) was introduced
- 92. Lower Risk ofSide Effects with Image Guided IMRT compared to IMRT
- 93. Better Cure Rateswith Image Guided IMRT compared to IMRT for Prostate Intermediate Risk High Risk
- 94. Combine a CTscan and linear accelerator to ultimate in targeting (IGRT) and ultimate in delivery (dynamic, helical IMRT) ability to daily adjust the beam (ART or adaptive radiotherapy) The most sophisticated technique for image guided IMRT is Tomotherapy.
- 95. There is significantmovement of the prostate gland based on daily gas in rectum Planned target Rectal gas No Rectal gas Planned target, missed badly if rectal gas pushes the prostate forward
- 96.
- 97. Non Isocentric Deliverywith CK Beams
- 98. SBRT Prostate Cancer/ Naples-Tampa Experience 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
- 99. PSA Response toCyberKnife 97% biochemical control at 30 months median follow-up Mean PSAi 6.8ng/ml Mean PSAp 0.78ng/ml
- 100. Cure Rate afterCyberknife N = 515, Alan Katz in New York
- 101. PSA Response afterCyberknife Follow-up median 54 months (range, 7 - 78) Median PSA ◦ 36 m 0.20 ng/ml ◦ 60 m 0.10 ng/ml By 48 months ◦ 290 of 329 pts PSA < 0.5 0 12 24 36 48 60 72 0 1 2 3 4 5 6 7 35 Gy 36.25 Gy Months PSAng/ml
- 102.
- 103. Clinical development ofnovel therapeutics for castration‐resistant prostate cancer
- 104. New Drugs forProstate Cancer
- 105. New Drugs forAdvanced Prostate Cancer Drug FDA Approval Cost Provenge (sipuleucal) immunoRx 4/2010 $93,000 Jevtana(cabazitaxel) chemoRx 6/2010 $8.000 q3w Xgeva (denosumab) skeletal 11/201 $1,600 dose Zytiga (abiraterone) hormone 4/2011 $5,000/mos Xtandi (enzalutamide) hormone 8/2012 $7,450/mos Lupron (1985) LHRH agonist Bicalutamide (Casodex, 1995) anti-androgen Degarelix/ Firmagon(2008) GnRH antagonist Abiraterone androgen synthesis inhibitor Enzalutamide androgen receptor blocker
- 107. Expose the patient’s activatedT cells to cancer antigen targets Then re-infuse the patient’s activated cells (atc’s) back into them which will attack prostate cancer cells
- 108. FDA Approval 4.29.10 medianOS of 25.8 months compared to 21.7 months for patients who received the control treatment There was no difference in time-to- progression. The total cost for three courses of treatment with Sipuleucel-T is $93,297.60
- 109. Phase 3 TROPICclinical study involving 755 patients with mHRPC previously treated with a docetaxel-containing Median overall survival in the patients receiving JEVANA + prednisone was 15.1 months compared to 12.7 months tumor response rates were 14.4% and 4.4% for cabazitaxel-treated and mitoxantrone-treated patients respectively, FDA Approval 6.18.10
- 110. Xgeva the firstand only RANK Ligand inhibitor to prevent SRE (skeletal related events in cancer) FDA Approval 11.19.10
- 111. Xgeva RANK Ligandinhibitor
- 112. Recent advances havedemonstrated that androgen-based pathways continue to have a clinically significant role in the progression of castrate-resistant prostate cancer. In addition to androgen production by the adrenal gland and testis, several of the enzymes involved in the synthesis of testosterone and dihydrotestosterone, including CYP17, are highly expressed in tumor tissue
- 113. FDA Approval 4.28.11 ZYTIGAis an oral androgen biosynthesis inhibitor that works by inhibiting the CYP17 enzyme complex, which is required for the production of androgens at these three sources.
- 114. Zytiga and prednisonecombination had a median overall survival of 14.8 months compared to 10.9 months for patients receiving the placebo and prednisone combination.
- 116. August 2012 In clinicaltrials, men who received the drug, which was previously known as MDV3100, lived a median of 18.4 months, nearly five months longer than the median of 13.6 months for those who received a placebo. Before 2004, the only drug shown to prolong the survival of men with advanced prostate cancer was the chemotherapy drug docetaxel. Now there are four others on the market — Jevtana, Provenge, Zytiga and
- 117. Enzalutamide (marketed asXtandi and formerly known as MDV3100) is a second generation androgen receptor antagonist drug for the treatment of metastatic castration-resistant prostate cancer. Enzalutamide has approximately fivefold higher binding affinity for the androgen receptor (AR) compared to the antiandrogen bicalutamide (Casodex)
- 118. Cancer Information Cancer Videos Tomotherapy Cyberknife OtherTopics Dr. Miller www.aboutcancer.com
- 119. Cancer Information •Basic CancerInformation •General Cancer Statistics •Most Common Cancers * brain * breast * colon/rectum * gynecologic * lung * prostate •Other Specific Cancers Radiation or Chemotherapy •All Other Cancer Topics •Other Topics •Best Web Sites www.aboutcancer.com
- 120. Robert Miller MDMedical Channel bone metastases brain metastases breast cancer: understanding the disease, treatment decisions head and neck cancer (mouth, throat, larynx understanding the disease, radiation treatment lung cancer: understanding lung cancer, radiation treatments prostate cancer: understanding the disease, treatment decisions, radiation therapy skin cancer uterine (endometrial cancer) aboutcancer.com/you_tube_videos