1. AM Report 9/11/09 Prostate Cancer Julia Rauch

2. Disease Burden ~220,000 men were diagnosed with prostate cancer in 2007 ~1/6 men will receive the disagnosis during their lifetime ~28,000 men died from prostate cancer in 2006 w/ median age 80 yrs w/ 71% older than 75 yrs - Interestingly, autopsies of men done in their 70s show >90% w/ hyperplastic changes & >70% w/malignant changes

3. Anatomy & Physiology - Most cancers develop in peripheral zone which is area palpated by DRE. - >95% adenocarcinomas - Prostate cells express androgen receptors & depend on androgens for growth

4. Risk Factors 1) Age: Increased with increasing age 2) Race: African Americans have higher incidence & >twice cancer mortality rate when compared to Caucasians 3) Family history: Increased with family history with double the risk if one 1st degree relative is affected, and quadruple the risk if more than two 1st degree relatives are affected 4) Diet: Some thought that red meats, fatty diet increases risk, & cruciferous vegetables, lycopene (found in tomatoes), Vit E, and selenium offer protective effect

5. Typical Presentation Most commonly related to urinary tract obstruction including - urinary urgency, frequency, hesitancy - nocturia - new onset impotence - less firm penile erections - back pain - acute urinary retention - spinal cord compression -RARELY supraclavicular LAD, or hepatic abnormalities

6. Prostate Cancer Screening Remains controversial topic, with recent studies publishing opposing views: One reporting that PSA did not improve mortality and the other reporting that PSA screening did improve mortality. Current recommendations from US Preventive Services Task Force is 1) no recommendations regarding PSA screening in men <75 yrs due to insufficient evidence 2) in men 75 years & older, they do NOT recommend screening as benefits small to none

7. Prostate Cancer Screening Cont. Concerns regarding screening include 1) Harm to patient assoc w/ discomfort of biopsy and pyschological harm of false+ test 2) Morbidity associated with treatment including erectile dysfunction, urinary incontinence, bowel dysfunction. 3) Indolent vs Aggressive Cancer: Certain % of patients undergoing treatment for prostate cancer would never have had developed cancer symptoms in their lifetime

8. Diagnosis Established by TRUS-guided needle biopsy = gold standard Clinical evaluation may also include MRI of abdomen/pelvis help to evaluate visceral organs, urinary tract, para-aortic & pelvic adenopathy, CT scan often inaccurate Metastatic disease evaluation often involves bone scan in conjunction with plain radiographs for suspicious areas, especially if PSA >10, high Gleason grade

9. GLEASON GRADING SYSTEM - Core biopsies are measured for histologic aggressiveness using the above system, correlates w/prognosis = 5 histologic patterns, where the primary and secondary grades are measured then added together to make Gleason score 2-10, score <6 considered low grade

10. Staging Helps to guide treatment TNM System T1a-c Nonpalpalpable, detected based on abmornal PSA T2a-c Palpable but confined to gland T3a-c Palpable with extension beyond gland M1: distant mets Whitmore-Jewitt Stage A1-2 Well differentiated tumor B1-2 Palpable involving one or both lobes C1-2 Palpable with extension beyond capsule/seminal vesicles D: Metastatic disease

11. Management Localized Disease Options: (stages T1/2) 1) radical surgery 2) radiation therapy 3) watchful waiting No superiority of one treatment over another, plans based on symptoms, the chance that untreated cancer will adversely affect patient during their lifetime

12. Management Cont Metastatic Disease: -Hormonal therapy based on concept that male hormones/androgens cause prostate CA progression, elimination of androgens causes regression of disease 1) Bilateral orchiectomy 2) GNRH analogues act to lower testosterone levels 3) Androgen receptor blockade - Often double therapy for initial 2-4 weeks of therapy w/ GNRH analogue and antiandrogen agent. - Mets to bone Rx w/ radiation therapy

13. Follow -up Increasing levels of PSA after definitive radiotherapy for localized prostate cancer --> predict residual cancer & development of mets. PSA decline to normal after treatment, persistence of normal levels predicts favorable prolonged response to therapy

14. Summary -Prostate Cancer is a highly prevalent disease, however screening remains controversial. - Predicting clinically significant disease is difficult with many men remaining asymptomatic through the duration of their life.