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. 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. Who Gets Prostate Cancer and Why (1)
• Man, Dog: only species
• Both possess genes for PSA and hKZ (?related)
4. Who Gets Prostate Cancer and Why (2)
• Hormones
• Age
• Genetic component
• Race
• Ethnicity
• Diet (nutrition)
• Geography (?climate, soil)
• Inflammation (at molecular level)
• Toxins
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. Incidental vs. Clinical Cancer
• 8-10 % grow, develop capacity to turn lethal
and spread
Scardino, PT. The Prostate Book, Penguin Group, NYC, 2005
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.
11. Genetics
• 1 First Degree Relative 2.5X
• 2 First Degree Relatives 5-10X
• 3 First Degree Relatives 11X
12. Genetics
• 9 separate genes that appear to have some
correlation with PCa but only ~4-5% have
an inherited form of the disease
14. Diet (Nutrition)
• Fat (↑)
• Red Meat (↑)
• Soy (↓)
• Cruciferous Greens (broccoli, cabbage) (↓) (?)
• Native Japanese vs 3rd Generation in US
15. Additives
• Selenium
• Lycopene
• Vitamin E
• Green tea
16. 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
19. 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
23. 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
24. 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%
25. 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) (?)
27. 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
30. Factors in Choosing Treatment
• Gleason Score and Stage
• Life-expectancy without prostate
cancer: overall medical health
• Knowledge and acceptance of risks for
selected treatment
48. Surgery
• PSA goes to zero
– easy to follow
• Recurrence detected early
– curative treatment possible (XRT)
• Psychological
• Lower longer term biochemical recurrence rate
• Longer survival
49. Surgery
• Time from work
• Hospitalization
• Anesthesia
• General risks
• Specific risks
50. Factors in Choosing Treatment
• Gleason Score and Stage
• Life-expectancy without prostate
cancer: overall medical health
• Knowledge and acceptance of risks for
selected treatment
51. Risks of All Types of Surgery
Must be individualized for each patient
52. 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%
55. 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
56. 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
59. 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
60. 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
63. 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%
65. 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?
66. Androgen Blockade - Side
Effects
• Vasomotor hot flashes
• Loss of libido
• Loss of lean muscle mass
• Anemia
• Osteopenia - Osteoporosis
• Fatigue
• Memory Loss
67. 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
68. Newer Developments
• Vaccine Therapies
– Dendritic Cells
– Viral Vector antigens and costimulants
– DNA vaccines
• Chemotherapy
– Taxanes and Estramustine
• Photodynamic Therapy
– Phase One investigations
