#1003 Prostate Cancer Update

October 5 to October 8

Robert R. Bahnson, MDLouis Levy Professor of SurgeryDirector, Division of UrologyThe Ohio State University Medical Center & The James Cancer Hospital and Solove Research Institute

Eric A. Klein, MDHead, Section of the Urologic OncologyCleveland Clinic Foundation

Robert R. Bahnson, M.D.Louis Levy Professor of Surgery

Director, Division of UrologyThe Ohio State University Medical CenterThe James Cancer Hospital and Solove

Research Institute, Columbus, Ohio 1

Profile Profile

Kevin• 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

Kevin• 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 Profile

Kevin

• Evaluation - Digital rectal exam - Serum PSA determination

Kevin

• Evaluation - Digital rectal exam - Serum PSA determination

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Prostate Cancer 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

• 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 4

Early Screening 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

• 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 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

• 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 6

Guidelines 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

• 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 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

• 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 AntigenProstate-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

• % 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 ProceduresBiopsy 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

• 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 13

Biopsy ProceduresBiopsy 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

• 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 Summary

Kevin

• 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

Kevin

• 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 FoundationCleveland, Ohio

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Profile Profile

Simmons Brothers

Brother #1• 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

Simmons Brothers

Brother #1• 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 Profile

Simmons Brothers

Brother #2• 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

Simmons Brothers

Brother #2• 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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Genes And Prostate CancerGenes And Prostate Cancer

• Susceptibility Genes - Influence development of cancer

• Phenotypic Genes - Influence clinical behavior of cancer

• Susceptibility Genes - Influence development of cancer

• Phenotypic Genes - Influence clinical behavior of cancer

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Major Susceptibility Locus ForProstate Cancer on Chromosome 1

Suggested By A Genome-Wide Search

Major Susceptibility Locus ForProstate 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

• 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

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

• 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 25

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Evidence For A Prostate CancerSusceptibility Locus On The

X Chromosome

Evidence For A Prostate CancerSusceptibility 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

• 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 27

Prostate Cancer Susceptibility Genes

Prostate Cancer Susceptibility Genes

• HPCX - Xq27-28 - 16% of cases - Clinical features undescribed

- Structure and function unknown - Not androgen receptor

• HPCX - Xq27-28 - 16% of cases - Clinical features undescribed

- Structure and function unknown - Not androgen receptor

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Predisposing Gene ForEarly-Onset Prostate Cancer,

Localized On Chromosome 1q42.2-43

Predisposing Gene ForEarly-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

• French Study - Has demonstrated another susceptibility locus on chromosome 1 also on the long arm, but distal at Iq42

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Pcap CharacteristicsPcap Characteristics

• 1q42.2-43

• Associated with early age of onset

• Phenotype unknown

• Structure and function unknown

• 1q42.2-43

• Associated with early age of onset

• Phenotype unknown

• Structure and function unknown

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Evidence For A Rare ProstateCancer-Susceptibility Locus

At Chromosome 1p36

Evidence For A Rare ProstateCancer-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

• 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 CharacteristicsCAPB 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

• Chromosome 1p36

• Frequent LOH in CNS tumors

• Not linked to age of onset

• Linked to FH of CNS tumors

• Clinical behavior unknown

• Probably rare 32

Genes And Prostate CancerGenes And Prostate Cancer

• Susceptibility Genes - HPC1 - HPCX - Others likely - 4q, 5p, 7p, 13q• Phenotypic Genes - Androgen Receptor - “Family history” gene - Androgen metabolism genes

• Susceptibility Genes - HPC1 - HPCX - Others likely - 4q, 5p, 7p, 13q• Phenotypic Genes - Androgen Receptor - “Family history” gene - Androgen metabolism genes

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#1004 Evaluation & Management of Back Pain

October 12 to October 15

Brian Bowyer, MDAssociate Professor of Physical Medicine and RehabilitationDepartment of Physical Medicine and RehabilitationThe Ohio State University Medical Center

Lawrence J. Mervis, M.D.Clinical Associate Professor of SurgeryThe Ohio State University Medical Center andJames Cancer Hospital and Solove Research InstituteColumbus, Ohio

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