Prostate Cancer PDF

Prostate Cancer DR. VAN DEN BERG ASSOCIATE PROFESSOR Objectives Discuss the risk factors and clinical presentation of prostate cancer Review national prostate cancer screening guidelines Describe the major signs and symptoms of tumor progression. Explain how Gleason’s score is determined and how it...

Prostate Cancer DR. VAN DEN BERG ASSOCIATE PROFESSOR Objectives Discuss the risk factors and clinical presentation of prostate cancer Review national prostate cancer screening guidelines Describe the major signs and symptoms of tumor progression. Explain how Gleason’s score is determined and how it is used in patient management 2 Cancer Statistics Estimated new cases in 2023: 288,300 Estimated deaths in 2023: 34,700 Median age of diagnosis: 66 years (65-74 yrs) Approximately 1 in 8 men will be diagnosed during his lifetime About 1 in 41 men will die of prostate cancer http://seer.cancer.gov/statfacts/html/prost.html https://www.cancer.org/cancer/prostate-cancer/about/key-statistics.html 3 Etiology Age Family History Risk Factors Nonmodifiable BPH Race Genetics 4 Etiology * Diet * * Smoking * * Mixed reports Risk Factors Modifiable STDs Occupation al Exposures Hormones 5 Risk factors Age Genetics: Men of African decent have highest rate worldwide African-American men are also more than twice as likely to die of prostate cancer as white men. Prostate cancer occurs less often in Asian-American and Hispanic/Latino men than in non-Hispanic whites. Family history: Familial predisposition responsible for 5-10% of prostate cancers ◦ Lynch Syndrome and BRCA1/BRCA2 mutations. ◦ First degree relative increases RR ≥2-fold. Hormones: Elevated levels of testosterone. Smoking increases risk of fatal prostate cancer but needs to be confirmed STIs: Increased risk with C. trachomatis IgA abs was restricted to blacks and requires confirmation. Modest risk associated with whites who have many STIs simultaneously. ◦ Could it all be related to “inflammation”? Cancer Epidemiol Biomarkers Prev. 2008 Sep; 17(9): 2374–2381. Cancer Net and others Effect of Age and Ethnicity on Prostate Cancer Risk http://www.medscape.org/viewarticle/710056 Screening No screening for men 50 yrs of age, average risk and >10 yrs life expectancy: Digital Rectal Exam (DRE) ◦ High specificity, ↓ cost, safety, ease of administration 8 Screening Prostate Specific Antigen (PSA) ◦ Prostate specific glycoprotein is produced in cytoplasm of benign and malignant prostate cells (t½ = 2-3 days) ◦ Useful in detecting cancer (early stage), predicting outcome, monitoring response ◦ Simple, but ↓ specificity ◦ Range ◦ 0-4 ng/mL: WNL ◦ > 4 ng/mL: further evaluation ◦ > 10 ng/mL: suspicious for malignancy ◦ 38%-48% of men with clinically significant prostate cancer will not have an elevated PSA 9 ACS Screening Recommendations PSA ± DRE annually ◦ Men ≥ 50 yrs of age and average risk ◦ Expected to live at least 10 more years ◦ Men ≥ 45 yrs and at high risk ◦ First degree relative, African American ◦ Males ≥ 40 and even higher risk ◦ More than 1 first degree relative If no cancer is found: ◦ PSA < 2.5 ng/mL: rescreen every 2 years ◦ PSA > 2.5 ng/mL: yearly screening Continual controversy regarding screening after age > 75 yrs and true benefit of screening < 75 years 10 Pathology Adenocarcinoma ◦ Most common (95% cases) Small cell neuroendocrine cancers, sarcomas, transitional cell carcinomas 11 Pathophysiology The prostate is a hormonally controlled organ ◦ Main androgens: ◦ Testosterone ◦ Dihydrotestosterone (DHT) ◦ Most androgen is made in the testes ◦ Adrenals also make a small amount of androgen 12 Pathophysiology Figure 128-2. Pharmacotherapy. 6th Ed., 13 Disease Spread Metastasis ◦ Pelvic and abdominal lymph node involvement are most common ◦ Bone ◦ Skeletal metastasis are most common sites of distant spread ◦ Lumbar spine, femurs, pelvis, thoracic spine, ribs, skull ◦ Lung, liver, brain, and adrenal glands are most commonly infiltrated organs 14 Clinical Presentation Signs and Symptoms Localized disease ◦ Asymptomatic Locally invasive disease ◦ Ureteral dysfunction, frequency, hesitancy, dribbling ◦ Impotence Advanced disease ◦ Back pain, cord compression, lower extremity edema, pathologic fractures, anemia, weight loss Traditionally diagnosed by symptoms, but implementation of screening methods diagnose cancer prior to symptom onset 15 Diagnosis DRE PSA Transrectal ultrasound (TRUS) ◦ If positive DRE or elevated PSA Biopsy ◦ Gleason score CBC, chem panel Bone Scan CT/MRI 16 Histological Grading Gleason Score ◦ 2 different specimens graded on a scale of 1-5 ◦ Add the scores: ◦ 2-4: well differentiated ◦ 5-6: moderately differentiated ◦ 7-10: poorly differentiated (poor prognosis) 17 Staging International Union Against Cancer, 1974 ◦ TNM staging American Urologic System (AUS) ◦ More commonly used in the US Stage Subcategory A: occult, non-palpable T1a-T1b* A1: focal A2: diffuse B: confined to prostate T2a-T2c* B1: single nodule in 1 lobe, < 1.5 cm B2:diffuse involvement of whole gland, > 1.5 cm C: localized to peri-prostatic area T3a-T4b* D: metastatic disease N1-3,M1a-M1c* C1: no seminal vesicle involvement, < 70 g C2: seminal vesicle involvement, > 70 g D1: pelvic lymph nodes or ureteral obstruction D2: bone, distant lymph node, organ, or soft tissue mets 19 Prognosis Histologic grade (Gleason Score) ◦ Most important, degree of differentiation (helps determine prognosis) Tumor size Local extent of primary tumor What are the 5-year survival rates for local and regional prostate cancer? Metastatic? 21 Five-year Relative Survival Rate by Stage at Diagnosis Cancer Stage Local Regional Distant Survival Rate > 99% > 99% 31% All stages combined: > 97% survival Cancer Facts 2017 22 Treatment Observation/Active surveillance Orchiectomy (bilateral) reduces circulating androgens (T and DHT) Endocrine therapy to reduce androgen synthesis or AR activity Chemotherapy for castration resistant disease or new FDA approved drugs. Immunotherapy 23