Probing Your Prostate Health:

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Probing Your Prostate Health  What Every Man
Should KnowProstate Cancer

• Douglas S. Scherr, M.D.
• Clinical Director, Urologic Oncology
• Weill Medical College of Cornell University

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What is the Prostate?
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Problems of the Prostate

• Prostatitis
• Benign Prostatic Hyperplasia (BPH)
• Prostate Cancer
• Infection
• Urinary Retention
• Urinary Bleeding

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What Causes the Prostate To Grow?

• Testosterone
• Dihydrotestosterone (DHT)

Testosterone
DHT
Finasteride (Proscar)
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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

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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

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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

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Prevalence of Prostate Cancer
Men With PIN Or CaP
Decade
Sakr et al., J Urol, 150 379, 1993
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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

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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
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Why the Differences?

• Lack of screening programs in Asia
• Socioeconomic Status
• Cultural barriers to medical care
• Biological Explanation?
• Birthplace?

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Policies of Prostate Cancer Screening
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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

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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

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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

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High Risk Prostate Cancer

• Single treatments often not effective
• Surgery does have a role
• Quality of life can be maintained

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The Problem
Low Risk
High Risk
100
100
90
90
80
80
70
70
60
60
PSASurvival()
PSASurvival()
50
50
40
40
30
30
20
164 147 117 83 55 36 109 77 42 17 4 2
10 8 5 2 1 0 6 4 3 3
2 1
20
239 158 102 47 26 11 309 218 99 38 12 0
23 14 3 0 0 0 19 13 4 0 0 0
10
10
0
0
0
1
2
3
4
5
0
1
2
3
4
5
Time (Years)
Time (Years)
RP External Beam Radiation Therapy
Implant and Neoadjuvant Hormonal Therapy Implant
DAmico AV, et al. JAMA. 1998280969-974.
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Prostate Cancer Risk Stratification
Cooperberg et al, J Urol 170 S21-7, 2003.
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Why is high-risk disease bad?

• Primary therapy inadequate -positive surgical
  margins -unrecognized node positive disease
• Early tumor dissemination

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Occult Node-Positive Disease

• 231 patients PSA lt 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

Schumacher et al, Eur Urol, 2006
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Recurrence in NED Patients

• Recurrence PSA 0.4 ng/ml or salvage radiation
  Rx

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Why is high-risk disease bad?

• Early tumor dissemination
• Circulating tumor cell data

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Improved Cancer Detection Through
ImagingEndorectal MRI/Spectroscopy

• Potential improvement over ultrasound
• Biochemical gradients to decipher cancer from
  benign
• Possible role in high risk patients

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Image 8 I 54.44 mm
Image 9 I 57.56 mm
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H
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H
H H
H
H
H
H H
H H
H H
H H
vc
sc vc
H H H H H
H H
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Treatment Stratifications

• Allow for improvement in patient understanding
• More objective in guiding treatment decisions
• Less physician bias

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Preoperative Nomogram for Prostate Cancer
Recurrence
Points
PSA
20
4
0.1
1
2
3
6
8
9
10
12
16
30
45
70
110
7
T2a
T2c
T3a
Clinical Stage
T1c
T1ab
T2b
? 23
? 4?
3 ? 2
Biopsy Gleason Grade
? 2 ? 2
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? 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
Instructions for Physician Locate the patients
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 patients
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 ltpredicted percentage from nomogram -
10gt and ltpredicted percentage 10gt 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. Scardino

Kattan MW et al JNCI 1998 90766-771.
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Palm Pilot Nomogram Software

• Includes pretreatment and postoperative
  predictions.
• Uses published nomograms in prostate cancer.

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Postoperative Nomogram for Prostate Cancer
Recurrence
10
3,

• ? 1998 Michael W. Kattan and Peter T. Scardino

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PSA Kinetics

• PSA Velocity (PSAV) in year preceding diagnosis1
• 1095 pts, clinically localized CaP undergoing RP
• PSAV gt 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 lt 3 months associated with cancer-specific
  mortality (HR 19.6, 12.5-30.9, plt0.001)

1DAmico, NEJM 351125, 2004 2DAmico, JNCI
951376, 2003
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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

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Robotic Prostatectomy
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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

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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
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Adjuvant RT vs Observation for pT3 CaP

• Bolla, Lancet, 2005
• Thompson, JAMA, 2006

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Progression-Free Probability After Salvage RT
Pre-RT PSA
0.5
0.51-1.00
1.01-1.50
gt 1.5
Stephenson et al, J Clin Onc, 2007
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Neoadjuvant Therapy in High-risk Localized
Prostate Cancer CALGB 90203
Docetaxel 70 mg/m2 IV day (6 cycles) ADT X 4
months
Q 21 days
Radical prostatectomy
RANDOMIZE
Radical prostatectomy
Entry Criteria cT1-3aNXM0 and nomogram
probability of lt60 PFS at 5 yrs. N 750
patients Outcome 5-yr bPFS (45 mo. to 60 mo.) HR
1.35
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VA Cooperative Studies 553 Adjuvant Therapy in
High Risk Disease
Docetaxel (6 cycles) prednisone
Patients post-RP pT3, G7-10, N0 Kattan nomogram

RANDOMIZE
Surveillance
Primary endpoint PSA progression Secondary
endpoints OS, CSS, mets-free
survival
Docetaxel 75mg/m2 q 3wks x 6 cycles n 700
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RTOG 0521 Adjuvant Docetaxel

• Gleason 9, PSA 150, any T category
• Gleason 8, PSA lt 20, T2
• Gleason 7-8, PSA 20-150, any T category

RT Hormonal therapy (2 yrs)

RANDOMIZE
RT Hormonal therapy (2 yrs) 6 cycles adjuvant
docetaxel (starting 1 mo after RT)
Docetaxel 75mg/m2 q 3wks x 6 cycles n 600
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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

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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

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Prostate Cancer in the USA Radical Prostatectomy
-M. Eisenberger, JHU