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#1003 Prostate Cancer Update
October 5 to October 8
Robert R. Bahnson, MD
Louis Levy Professor of Surgery
Director, Division of Urology
The Ohio State University Medical Center &
The James Cancer Hospital and Solove Research Institute
Eric A. Klein, MD
Head, Section of the Urologic Oncology
Cleveland Clinic Foundation
Robert R. Bahnson, M.D.
Louis Levy Professor of Surgery
Director, Division of Urology
The Ohio State University Medical Center
The James Cancer Hospital and Solove
Research Institute, Columbus, Ohio
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Profile
Kevin
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42 year old white male
Father had prostate cancer
Healthy otherwise
Symptoms
- Weakening urination stream
- Frequent urination at night
- Hesitancy when urinating
- Dribbling of urination
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Profile
Kevin
• Evaluation
- Digital rectal exam
- Serum PSA determination
2A
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Prostate Cancer
• Most commonly diagnosed cancer in
adult men
• More than 179,300 men diagnosed in 1999
• Estimated 37,000 will die of disease
• Nearly 20 million males in U.S. forced to
make important decisions regarding early
detection
• Controversy has prompted early detection
guideline by the American Cancer Society
and the American Urologic Assoc. advising
a DRE and a serum PSA beginning at age 50
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Early Screening
• Opponents point out that randomized
trials have not demonstrated a survival
benefit in screened patients
• However, most agree that:
- Digital Rectal Exam and Serum PSA
have likely played a critical role in
the downward prostate cancer stage
migration seen in the last 10 years
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Guidelines
• Who are men at high risk?
- Those with a family history
- All African American men, they should
begin an early detection program at age 40
• Which men should undergo a biopsy?
- Men with a life expectancy exceeding
10 years and a palpable abnormality on
digital rectal exam
- Men with a PSA greater than 10ng per ml
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Guidelines
• In screening studies, nearly 3/4 of men
will have a normal DRE and a PSA of
less than 4 ng/ml
• Only 15% of this population will have
a cancer
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Recommendations
• Men with a normal DRE and a PSA
greater than 10ng per ml will harbor
cancer greater than 50% of the time
• Therefore, routine biopsy is suggested
for men with a 10 year life expectancy
if they have an abnormal DRE or a
PSA greater than 10ng per ml
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Prostate-Specific Antigen
• % Free PSA has emerged as the most
clinically useful with the potential to
provide:
- Improvements in early detection
- Staging
- And Monitoring of prostate cancer
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Biopsy Procedures
• Recent evidence suggests change in
biopsy technique is needed to increase
detection
• Systemic parasaggital sextant biopsies
are widely adopted as standard biopsy
procedure
• New literature suggests optimizing
transrectal ultrasound-guided biopsy
techniques
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Biopsy Procedures
• Increasing number of biopsies
increases likelihood of detecting
cancers
• Risk of finding cancer on repeat
biopsy with an initial benign biopsy
and an elevated serum PSA is 25%
• Report by Dr. McCullough shows
extended biopsy technique detects
more cancers than standard sextant
technique
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Summary
Kevin
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Serum PSA 1.5 ng/ml
Prostate slightly enlarged
No suspicious findings
Follow-Up:
- Due to family history, annual
prostate exam and testing is
recommended
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Eric A Klein, M.D.
Head, Section of Urologic Oncology
The Cleveland Clinic Foundation
Cleveland, Ohio
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Profile
Simmons Brothers
Brother #1
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50 year old man
Saw family physician one year ago
Prostate was normal upon exam
PSA was slightly elevated
Prostate biopsy revealed a pre-cancerous condition,
Prostatic Intra-epithelial Neoplasia or high-grade PIN
• Subsequent biopsy confirmed presence of cancer
• Underwent a radical prostectomy
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Profile
Simmons Brothers
Brother #2
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In family lounge, met twin brother
Recommended he be screened for prostate cancer
His biopsy showed high-grade PIN
Subsequent biopsy confirmed prostate cancer
Underwent a radical prostectomy
Genetic testing revealed brothers carried HPC1,
which holds a higher risk for development of
prostate cancer
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20A
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Genes And Prostate Cancer
• Susceptibility Genes
- Influence development of
cancer
• Phenotypic Genes
- Influence clinical behavior
of cancer
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Major Susceptibility Locus For
Prostate Cancer on Chromosome 1
Suggested By A Genome-Wide Search
• Susceptibility locus on long arm of
chromosome 1 in certain families
• Gene area designated as HPC1
• On-going intensive efforts to
identify gene association with
prostate cancer
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Prostate Cancer Susceptibility
Genes
• HPC1
- 1q24-35
- 9% of cases
- Early age of onset
- Many affected family members
- ? African Americans
- ? More advanced stage and grade
- Structure and function unknown
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Evidence For A Prostate Cancer
Susceptibility Locus On The
X Chromosome
• Three other reports that suggest three
additional areas that predispose
individuals to prostate cancer
• HPCX which appeared in Nature in 1998
• Epidemiologic observations suggest that
men with a brother affected with prostate
cancer are more likely to get prostate
cancer than those whose father was
only affected
• This suggests linkage with X chromosome
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Prostate Cancer Susceptibility
Genes
• HPCX
- Xq27-28
- 16% of cases
- Clinical features undescribed
- Structure and function unknown
- Not androgen receptor
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Predisposing Gene For
Early-Onset Prostate Cancer,
Localized On Chromosome 1q42.2-43
• French Study
- Has demonstrated another
susceptibility locus on
chromosome 1 also on the
long arm, but distal at Iq42
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Pcap Characteristics
• 1q42.2-43
• Associated with early age of
onset
• Phenotype unknown
• Structure and function
unknown
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Evidence For A Rare Prostate
Cancer-Susceptibility Locus
At Chromosome 1p36
• University of Washington
Study
- Has identified a 4th
susceptibility locus on
chromosome 1, on the
short arm at 1 p36
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CAPB Characteristics
• Chromosome 1p36
• Frequent LOH in CNS tumors
• Not linked to age of onset
• Linked to FH of CNS tumors
• Clinical behavior unknown
• Probably rare
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Genes And Prostate Cancer
• Susceptibility Genes
- HPC1
- HPCX
- Others likely - 4q, 5p, 7p, 13q
• Phenotypic Genes
- Androgen Receptor
- “Family history” gene
- Androgen metabolism genes
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NEXT WEEK
#1004 Evaluation & Management of Back Pain
October 12 to October 15
Brian Bowyer, MD
Associate Professor of Physical Medicine and Rehabilitation
Department of Physical Medicine and Rehabilitation
The Ohio State University Medical Center
Lawrence J. Mervis, M.D.
Clinical Associate Professor of Surgery
The Ohio State University Medical Center and
James Cancer Hospital and Solove Research Institute
Columbus, Ohio