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Probing Your Prostate Health: What Every Man Should Know
Prostate Cancer
Douglas S. Scherr, M.D. Clinical Director, Urologic Oncology
Weill Medical College of Cornell University
What is the Prostate?
Problems of the Prostate
• Prostatitis
• Benign Prostatic Hyperplasia (BPH)
• Prostate Cancer
• Infection
• Urinary Retention
• Urinary Bleeding
What Causes the Prostate To Grow?
• Testosterone
• Dihydrotestosterone (DHT)
Testosterone DHT
Finasteride (Proscar)
PROSTATE CANCERHighest in Incidence and Second in Cause of Death
from Cancer in American Males
Incidence Cause of DeathMelanoma of Skin 5%
Lung & Bronchus 14%
Oral Cavity & Pharynx 3%
Pancreas 2%
Colon & Rectum 11%
Kidney 3%
Prostate 30%Urinary Bladder 7%
Leukemia 3%
Non-Hodgkin’s Lymphoma 4%
All Sites 637,500All Sites 637,500
189,000 New Cases
3% Esophagus
31% Lung & Bronchus
5% Pancreas
3% Kidney
3% Liver
10% Colon & Rectum
11% Prostate3% Urinary Bladder 4% Leukemia
5% Non-Hodgkin’s Lymphoma
288,200 All Sites 288,200 All Sites
30,200 Death2002 Estimates
Prostate Cancer
• In 2007, 225,000 new cases of prostate cancer
• 28,900 men will die from prostate cancer
• Highest death rates in Caribbean and African American Men
• 1 in 6 men in the U.S. will development prostate cancer
Prostate Cancer in African American Men
• 275.3 per 100,000 men
• Incidence in African American men is 60% higher than among white men
• Between 1992-1999 the death rate from prostate cancer was 2.3 times higher than white men and 3.3 times higher than Hispanic men
• More men present with metastatic disease in the African American population
Prostate Cancer in African American Men
• 5 year survival rates have improved over the last 3 decades for African American men
• 40% of prostate cancers occurring in men under age 55 have a hereditary basis
• Risk of developing prostate cancer doubles for men with a father or brother with prostate cancer
Prevalence of Prostate Cancer
0
5
10
15
20
25
30
35
40
45
2nd 3rd 4th 5th
PIN
Prosate Cancer
Decade
% Men With PIN Or CaP
Sakr et al., J Urol, 150: 379, 1993
Myths of Prostate Cancer in Asian Men
• Asian men do not get prostate cancer
• Asian men have small prostates that do not cause problems
• Not important to check PSA levels in Asian Men
Prostate Cancer in Asian- American Men
• Higher % of foreign born Asian Americans are diagnosed with distant disease at presentation (controlled for socioeconomic status and co-morbidities)
• Distribution of Stage for North American-born Asian Americans is similar to whitesand both groups are diagnosed at the same age
• Foreign-born Asian Americans are diagnosed at older ages
• Death rates higher for foreign-born Asian Americans but no difference for North American-born Asian Americans
Oakley-Girvan et al. Am J Pub Health, Vol 93(10): 1753, 2003
Why the Differences?
• Lack of screening programs in Asia
• Socioeconomic Status
• Cultural barriers to medical care
• Biological Explanation?
• Birthplace?
Policies of Prostate Cancer Screening
Group Policy Statement Recommendations
AUA Screen annually at age 50
Take personal decision after consultation
ACS Screen annually at age 50
Provide risk and benefit information
AMA Mass screening is premature
Allow “well informed” decision
ACP Routine PSA is “inappropriate”
Counsel patient
EU Introduction as policy is premature
Provide risk and benefit, await randomized trials
Evidence for the Effectiveness of Screening
• PSA screening initiated in 1989
• A decrease in prostate cancer mortality has been demonstrated in the U.S. by 4.4%/year from 1994-97
• Total decrease in mortality of 17.6%
Does Screening for Prostate Cancer Help?
• Mortality decreased by 27% between 1991-1997 in white men and by 17% in African American men
• Less men present with advanced disease and thus potential for cure increases
Diet and Prostate Cancer
• Saturated fat intake is associated with prostate cancer
• High red meat intake may increase risk of prostate cancer
• High soy intake may have a protective effect
• Vitamin E, Selenium, Lycopene
High Risk Prostate Cancer
• Single treatments often not effective
• Surgery does have a role
• Quality of life can be maintained
The Problem
Low Risk High Risk
D’Amico AV, et al. JAMA. 1998;280:969-974.
RP
External Beam Radiation Therapy
Implant and Neoadjuvant Hormonal Therapy
Implant
100
90
80
70
60
50
40
30
20
10
0
PSASurvival
(%)
0 1 2 3 4 5
Time (Years)
164 147 117 83 55 36109 77 42 17 4 2 10 8 5 2 1 0 6 4 3 3 2 1
100
90
80
70
60
50
40
30
20
10
0
PSASurvival
(%)
0 1 2 3 4 5
Time (Years)
239 158 102 47 26 11309 218 99 38 12 0 23 14 3 0 0 0 19 13 4 0 0 0
Prostate Cancer Risk Stratification
Cooperberg et al, J Urol 170: S21-7, 2003.
Why is high-risk disease “bad”?
• Primary therapy inadequate-positive surgical margins-unrecognized node positive
disease
• Early tumor dissemination
Occult Node-Positive Disease
Schumacher et al, Eur Urol, 2006
• 231 patients: PSA < 10, RP + PLND (extended)
• Positive nodes:
• 11% overall
• 25% in men with Gl ≥ 7
• Distribution:
• 23% obturator only
• 31% internal only
• 73% with some internal involvement
Recurrence in NED Patients
12/14
44/84
0
20
40
60
80
100
Pat
ient
s with
DTC (%
)
Recurrence No recurrence
Recurrence in all NED patients after RRP
* p<0.01
Recurrence: PSA ≥ 0.4 ng/ml or salvage Recurrence: PSA ≥ 0.4 ng/ml or salvage radiation Rxradiation Rx
• Early tumor dissemination
– Circulating tumor cell data
Why is high-risk disease “bad”?
Improved Cancer Detection Through Imaging
Endorectal MRI/Spectroscopy• Potential improvement over ultrasound
• Biochemical gradients to decipher cancer from benign
• Possible role in high risk patients
Image 8 I 54.44 mm Image 9 I 57.56 mm
H
H H
H H H
H H H H
H H H
H H
H H
H H H H
H H H H H
* * *
sc vc vc
Treatment Stratifications
• Allow for improvement in patient understanding
• More objective in guiding treatment decisions
• Less physician bias
Biopsy Gleason Grade 2+ 2 3+3 3+ 4
2+3 4+
Total Points 0 20 40 60 80 100 120 140 160 180 200
60 Month Rec. Free Prob. .96 .93 .9 .85 .8 .7 .6 .5 .4 .3 .2 .1 .05
3+ 2
Clinical Stage T1c T1ab
T2a T2c T3a
T2b
Points 0 10 20 30 40 50 60 70 80 90 100
PSA 0.1 1 2 3 6 8 9 10 12 16 30 45 70 1107 204
Preoperative Nomogram for Prostate Cancer RecurrencePreoperative Nomogram for Prostate Cancer Recurrence
Instructions for Physician: Locate the patient’s PSA on the PSA axis. Draw a line straight upwards to the Points axis to determine how many points towards recurrence the patient receives for his PSA. Repeat this process for the Clinical Stage and Biopsy Gleason Sum axes, each time drawing straight upward to the Points axis. Sum the points achieved for each predictor and locate this sum on the Total Points axis. Draw a line straight down to find the patient’s probability of remaining recurrence free for 60 months assuming he does not die of another cause first.
Note: This nomogram is not applicable to a man who is not otherwise a candidate for radical prostatectomy. You can use this only on a man who has already selected radical prostatectomy as treatment for his prostate cancer.
Instruction to Patient: “Mr. X, if we had 100 men exactly like you, we would expect between <predicted percentage from nomogram - 10%> and <predicted percentage + 10%> to remain free of their disease at 5 years following radical prostatectomy, and recurrence after 5 years is very rare.”
1997 Michael W. Kattan and Peter T. ScardinoKattan MW et al: JNCI 1998; 90:766-771.
Palm Pilot Nomogram Software
• Includes pretreatment and postoperative predictions.
• Uses published nomograms in prostate cancer.
Points 0 10 20 30 40 50 60 70 80 90 100
Preop PSA0.1 0.2 0.3 0.5 0.7 1 2 3 4 6 8 100
Gleason Sum5 7 9
4 6 8 10
Extraprostatic Ext.None Focal
Inv.Capsule Established
Surgical MarginsNeg
Pos
Seminal Ves. InvasionNo
Yes
Lymph NodesNeg
Pos
Total Points 0 40 80 120 160 200 240 280
84-Month Rec. Free Prob.0.010.10.30.50.70.80.90.950.980.99
10
3,
Postoperative Nomogram for Prostate Cancer Recurrence
19981998 Michael W. Kattan and Peter T. ScardinoMichael W. Kattan and Peter T. Scardino
PSA Kinetics
• PSA Velocity (PSAV) in year preceding diagnosis1
– 1095 pts, clinically localized CaP undergoing RP– PSAV > 2 ng/ml/yr predicted disease-free, cancer-
specific, and overall survival
• PSA Doubling Time (PSADT) at recurrence2
– 8,669 pts treated by RP or XRT for localized CaP– PSADT < 3 months associated with cancer-specific
mortality (HR 19.6, 12.5-30.9, p<0.001)
1D’Amico, NEJM 351:125, 2004
2D’Amico, JNCI 95:1376, 2003
Technical Improvements in SurgeryNerve Grafts
• Cavernosal nerves necessary for post-operative erectile functions
• In advanced disease, nerves may need to be resected to obtain a negative margin
• Sural nerve or genitofemoral nerve serve as sources of nerve grafts in this setting
Robotic Prostatectomy
Conclusion
• Prostate Cancer is a common disease
• Family history is important
• Screening can lead to earlier diagnosis
• Treatment strategies have improved and quality of life concerns are addressed
Adjuvant Radiation after RP
Two completed, randomized studies:
SWOG 87941 and EORTC 229112
• Patients with pT3/T4, +/- pos margins
• Adjuvant RT (prostatic fossa) vs. Observation
• Primary endpoint – metastasis free survival
1. Thompson, JAMA, 2006
2. Bolla, Lancet, 2005
Adjuvant RT vs Observation for pT3+ CaP
1. Bolla, Lancet, 20052. Thompson, JAMA, 2006
EORTC1 SWOG2
(RT vs. Obs) (RT vs. Obs)
Number 1005 473
Median F/U 5 yrs 10 yrs
PSA failure 26% vs 44% 35% vs. 64%
(HR 0.48, 0.37-0.62) (HR 0.43, 0.31-0.58)
Metastasis-free survival NR NS
(HR 0.75, 0.55-1.02)
Overall survival NS NS
(HR 1.09, 0.67-1.79) (HR 0.80, 0.58-1.09)
Stephenson et al, J Clin Onc, 2007
Progression-Free Probability After Salvage RT
≤ 0.5
1.01-1.50
0.51-1.00
> 1.5
Pre-RT PSA
Neoadjuvant Therapy in High-risk Localized Prostate Cancer: CALGB 90203
RA
ND
OM
IZE
RA
ND
OM
IZE
Docetaxel 70 mg/m2 IV day(6 cycles)ADT X 4 months
Q 21 days Radical prostatectomy
Entry Criteria: cT1-3aNXM0 and nomogram probability of <60% PFS at 5 yrs.N: 750 patientsOutcome: 5-yr bPFS (45 mo. to 60 mo.) HR 1.35
Radical prostatectomy
Patients post-RP
pT3, G7-10, N0Kattan
nomogram
Docetaxel (6 cycles) + prednisone
SurveillanceRA
ND
OM
IZE
RA
ND
OM
IZE
VA Cooperative Studies # 553: Adjuvant Therapy in High Risk Disease
Primary endpoint: PSA progression
Secondary endpoints: OS, CSS, mets-free survival
Docetaxel 75mg/m2 q 3wks x 6 cycles
n = 700
•Gleason ≥ 9, PSA ≤ 150, any T category
•Gleason 8, PSA < 20, ≥ T2
•Gleason 7-8, PSA 20-150, any T category
RT + Hormonal therapy (2 yrs)
RT + Hormonal therapy (2 yrs) + 6 cycles adjuvant docetaxel (starting 1 mo after RT)
RA
ND
OM
IZE
RA
ND
OM
IZE
RTOG 0521: Adjuvant Docetaxel
Docetaxel 75mg/m2 q 3wks x 6 cycles
n ~ 600
Take Home Points
• High-risk disease difficult– Inadequate primary therapy, early tumor
dissemination, tumor biology
• Predictive models with improved ability to identify high-risk patients– Biopsy information– Tertiary grade– PSA kinetics – Emerging biomarkers
Take Home Points
• Adjuvant therapy– RT : Efficacy in subset with positive margin,
undetectable PSA, low/int Gleason– ADT: in N+ disease– Substantial side effects
• Future– Neoadjuvant or adjuvant chemo/chemohormonal
therapy in high-risk disease– Await RCTs
200(1%)
Clinical
trials
20,000/yearHigh Risk
100,000/yearHave surgery
~230,000/year
Prostate Cancer in the USARadical Prostatectomy
-M. Eisenberger, JHU