Prostate Cancer Overview

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Prostate Cancer Overview

  1. 1. Prostate Cancer: Overview Alan J. Wein, MD, PhD (hon) Professor and Chair, Urology University of Pennsylvania School of Medicine Chief of Urology University of Pennsylvania Health System
  2. 2. The Future • “It’s hard to make predictions, especially about the future.” -Yogi Berra • “For every problem there is a solution that is simple, neat and wrong.” -H L Mencken
  3. 3. Who Gets Prostate Cancer and Why (1) • Man, Dog: only species • Both possess genes for PSA and hKZ (?related)
  4. 4. Who Gets Prostate Cancer and Why (2) • Hormones • Age • Genetic component • Race • Ethnicity • Diet (nutrition) • Geography (?climate, soil) • Inflammation (at molecular level) • Toxins
  5. 5. New Cancer Cases CA Cancer J Clin 2007;57:43-66.
  6. 6. Cancer Deaths CA Cancer J Clin 2007;57:43-66.
  7. 7. Lifetime Risk of Developing or Dying of Prostate Cancer for a 50-Year-Old Man in the United States Lifetime Risk of Risk (%) Risk Ratio Proportional Developing Risk Developing 42 11.7 100 Incidental Cancer Developing 16.7 4.4 38 Clinical Cancer Dying of Prostate 3.6 1 8.6 Cancer For every 100 men who develop cancer cells in their prostate during their lifetime, For every 100 men who develop cancer cells in their prostate during their lifetime, only 38 of them will ever be diagnosed with prostate cancer by biopsy, and only only 38 of them will ever be diagnosed with prostate cancer by biopsy, and only 8.6 are at risk of dying of prostate cancer. 8.6 are at risk of dying of prostate cancer.
  8. 8. Incidental vs. Clinical Cancer • 8-10 % grow, develop capacity to turn lethal and spread Scardino, PT. The Prostate Book, Penguin Group, NYC, 2005
  9. 9. Probability of Developing Significant Prostate Cancer, US, 2000 0-39 yr 40-59 yr 60-69 yr ≥70 yr 0-? 1/10149 1/38 1/14 1/7 1/6 National Cancer Institute, 2005
  10. 10. Genetics • 1 First Degree Relative 2.5X • 2 First Degree Relatives 5-10X • 3 First Degree Relatives 11X
  11. 11. Genetics • 9 separate genes that appear to have some correlation with PCa but only ~4-5% have an inherited form of the disease
  12. 12. Toxins • Dioxin (Agent Orange byproduct)
  13. 13. Diet (Nutrition) • Fat (↑) • Red Meat (↑) • Soy (↓) • Cruciferous Greens (broccoli, cabbage) (↓) (?) • Native Japanese vs 3rd Generation in US
  14. 14. Additives • Selenium • Lycopene • Vitamin E • Green tea
  15. 15. The PCPT • Long term finasteride ↓ incidence 25% (24.4 to 18%) compared with placebo • Control incidence in the study 24.4%, much higher than expected (6%) • Those with tumor had higher grade/score, but… in play now
  16. 16. Prostate Cancer: Factoids • 75% of all and 90% of serious cases arise in PZ • 20 % eventual mortality
  17. 17. Doubling Time • Early: 2-4 yr • Later: Growth rate ↑, DT ↓
  18. 18. Untreated: Factoids • 10-12 yr to metastases • 15-17 yr to death • Large, locally advanced 8-12 yr to death • Gross LN involvement 6-8 yr to death • Bone metastases 5-6 yr to death
  19. 19. Detection, Diagnosis
  20. 20. Digital Rectal Exam
  21. 21. PSA • A glycoprotein enzyme found in ejaculate
  22. 22. Normal Range of PSA Levels for Men in Each Age Group Age Range (Yr) PSA Normal Range (mg/ml) 40-49 0-2.5 50-59 2.6-3.5 60-69 3.6-4.5 70-79 4.6-6.5
  23. 23. Probability of Finding Cancer on Biopsy According to a Man’s DRE Result and PSA Level PSA 2-4 PSA 4-10 PSA >10 Normal DRE 15% 25% 50% Abnormal DRE 20% 45% >75%
  24. 24. PSA: Factors • Absolute number • Age • Density <0.07; 0.07-0.15; >0.15 • Velocity 0.75 units or 20% per year • Free % (from BPH) <10-13; >25 • Complexed (~bound) (?)
  25. 25. PSA Screening
  26. 26. Screening PRO CON ↓ Death rate • # of unnecessary • ↑ Lower Stage Disease biopsies • • Incidental Ca • Diagnosis at younger age detected – • Less Progression to unnecessary to treat Metastases
  27. 27. Prostate Needle Biopsies
  28. 28. Treatment Algorithm
  29. 29. Factors in Choosing Treatment • Gleason Score and Stage • Life-expectancy without prostate cancer: overall medical health • Knowledge and acceptance of risks for selected treatment
  30. 30. Gleason Score
  31. 31. TNM Staging System for Prostate Cancer
  32. 32. Staging Metastatic Disease: lymphatic and venous
  33. 33. Staging Simplified • Confined, clinically localized • Locally extensive – Minimal – Gross • Widespread, metastatic
  34. 34. Treatment Algorithm
  35. 35. Treatment Options • Active Surveillance (watchful waiting) • Surgery – Retropubic – Retropubic – Perineal – Perineal – Laparoscopic – Laparoscopic – Robotic Assisted Laparoscopic – Robotic Assisted Laparoscopic • Radiotherapy – External Beam – External Beam – IMRT – IMRT – Brachytherapy – Brachytherapy – Brachytherapy + External Beam/IMRT – Brachytherapy + External Beam/IMRT • Cryotherapy • High Intensity Focused Ultrasound
  36. 36. Relative 5 Yr Survival Rate (%), US, Prostate Cancer: Adjusted for Normal Life Expectancy 1974-1976 1983-1985 1995-2001 Prostate 67% 75% 100% Lung 12% 14% 15% Pancreas 3% 3% 5% Colon 50% 58% 64% Breast 75% 78% 88% Ries, Lag, et al., Seer Cancer Statistics Review, 1975-2002, 2005
  37. 37. Surgery for Prostate Cancer Cure
  38. 38. Radical Retropubic Prostatectomy
  39. 39. Perineal Prostatectomy
  40. 40. Laparoscopic Prostatectomy
  41. 41. Robotic Prostatectomy
  42. 42. External Beam Radiation
  43. 43. External Beam Radiotherapy
  44. 44. Radiation Therapy
  45. 45. Brachytherapy
  46. 46. Brachytherapy
  47. 47. Surgery • PSA goes to zero – easy to follow • Recurrence detected early – curative treatment possible (XRT) • Psychological • Lower longer term biochemical recurrence rate • Longer survival
  48. 48. Surgery • Time from work • Hospitalization • Anesthesia • General risks • Specific risks
  49. 49. Factors in Choosing Treatment • Gleason Score and Stage • Life-expectancy without prostate cancer: overall medical health • Knowledge and acceptance of risks for selected treatment
  50. 50. Risks of All Types of Surgery Must be individualized for each patient
  51. 51. Risks of All Types of Surgery • Incontinence 2-15% • Erectile Dysfunction 25-90% • Rectal Injury 1% • Temporary Colostomy 0.1% • Bladder Neck Contracture (requiring treatment) 3% • Ureteral Injury 0.2% • Lymphocele (requiring treatment) 0.4%
  52. 52. Surgery Outcomes
  53. 53. Surgery Outcomes -Stratified
  54. 54. EBRT Outcomes for T1-2 Disease Institution No. FU Gy Prog Group 5yr BRFS Harvard 1765 4.1 69.4 I 81 II 69 III 47 MSKCC 743 3 75.4 Fav. 85 Inter 65 Unfav 35 Cleveland Clin 628 4.3 70.2 Fav 90 Unfav 59
  55. 55. XRT value of dose escalation • Doses above 70 Gy may benefit patients • Data from MD Anderson 70% vs 60% BRFS p=0.03 • Rectal complications higher (26 v. 12 percent) • IMRT provides improved conformality with lower symptoms
  56. 56. Brachytherapy Outcomes Author No. PSA FU BRFS Grado 392 7.3 30 76 Blasko 230 7.3 41.5 83.5 Ragde 147 8.8 93 66 Zelefsky 248 7.0 48 71 Brachmn 695 ---- 51 64
  57. 57. Biochemical Failure - Treatment Options Observation • Androgen Blockade • Radiation Therapy • Cytoreductive Chemotherapy • Immunomodulation (Vaccines) •
  58. 58. Salvage XRT for Post Prostatectomy PSA Elevation • Review of 501 patients at 5 academic centers [median FU 45 months] – Stephenson et al JAMA 291:1325, 2004 – Stephenson et al JAMA 291:1325, 2004 • Overall 50% disease progression If no adverse features 77% bNED at 4 years • • Adverse features include – Gleason 8-10 – Gleason 8-10 – SV involvement – SV involvement – Negative surgical margins – Negative surgical margins – PSADT of < 10 months – PSADT of < 10 months – Treatment after PSA >2.0 – Treatment after PSA >2.0
  59. 59. Post RRP Radiation • General take home message: – Delay in therapy until recurrence biopsy proven is deleterious – Multiple series suggest that treating before the PSA is greater than 1 or 2 has the best impact
  60. 60. PSA Failure - Salvage Prostatectomy Study Pts FU Organ Confined% DFS% Link 14 9 35 33 Pontes 43 12-120 30 28 Rogers 40 39 20 47 Lerner 132* 64 30 52 Moul 12* 49 25 33 Garzotto 29 65 28 79
  61. 61. PSA Failure - Salvage Prostatectomy Study Pts Rectal BNC Incont Link 16 0 7 55 Ahlering 11 0 64 64 Pontes 35 6 11 30 Lerner 79 6 27 41 Garzotto 97 0 22 67 Gheirler 30 3 16 50*
  62. 62. Salvage Cryosurgery- Response Study # FU mo Pos Bx mo Pisters 150 13.5 (1.2-32.2) 23% Lee 43 3 mo 15% 12mo 35% Miller 33 17.1 (4.1-34.3) 27.3% Katz 43 21.9 (1.2-54) 37% 6 mo 79% 12mo 66%
  63. 63. Androgen Blockade • Finasteride alone • Oral Antiandrogen Alone (Casodex) • Finasteride plus oral antiandrogen • LHRH agonist • Total Androgen Blockade • Tertiary Androgen Blockade
  64. 64. Androgen Blockade • Can androgen blockade improve survival in recurrent/ advanced prostate cancer? • Arguments for early vs. late hormonal therapy mixed • Medical Research Council study was positive but flawed. • ECOG [Messing] trial in D1 patients positive, but can it be applied to PSA only failures?
  65. 65. Androgen Blockade - Side Effects • Vasomotor hot flashes • Loss of libido • Loss of lean muscle mass • Anemia • Osteopenia - Osteoporosis • Fatigue • Memory Loss
  66. 66. PSA Failure -Summary • One of the largest and fastest growing group of prostate cancer patients • Diagnosis of PSA failure has heterogeneous outcomes • No consensus on BEST treatment for post surgery or post radiation patients • Radiation or androgen blockade are the principle treatments • Adjuvant therapy for intermediate and high risk patients? • Novel therapies on the horizon
  67. 67. Newer Developments • Vaccine Therapies – Dendritic Cells – Viral Vector antigens and costimulants – DNA vaccines • Chemotherapy – Taxanes and Estramustine • Photodynamic Therapy – Phase One investigations

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