Goals Objectives Prostate Cancer The goal of the session is to briefly review the incidence and epidemiology signs and symptoms diagnosis and staging of prostate cancer The majority of the session will deal with the management of the disease Please review pages 1 7 prior to class Most of class time will concentrate on material that begins on page 8 Objectives At the conclusion of the session those in attendance should be able to 1 discuss the incidence and epidemiology of prostate cancer 2 present the major risk factors for development of prostate cancer 3 describe the signs and symptoms of prostate cancer 4 describe the diagnosis and screening procedures employed and explain why the latest guidelines state that screening should be offered 5 explain the staging and grading systems 6 summarize the basic principles of the management of prostate cancer including the roles of active surveillance vs observation radiation therapy radical prostatectomy androgen deprivation therapy ADT castration resistant prostate cancer CRPC chemotherapy 7 describe the mechanisms of action of the hormonal and chemotherapy agents used in the management of advanced disease 8 analyze the clinical activity and place in therapy for systemic agents used in patients with CRPC 9 describe the major monitoring parameters and adverse effects associated with the hormonal and chemotherapies employed in advanced prostate cancer 1Prostate Cancer I Anatomy Physiology A Anatomy Figure 1 B Physiology 1 Purpose prostate gland II Epidemiology Etiology A Incidence and function of the The most common cancer in men Incidence increases with age 28 of new male cancers 220 800 new cases in 2015 10 of male cancer deaths 27 540 annually 2015 Deaths 100 000 1990 38 56 2007 2011 22 3 Chance of eventually being diagnosed with prostate cancer 1 in 6 Mass 5 420 Mass 570 2 1 Age median age at diagnosis 66 years rare before age 40 B Etiology risks at dx have some disease diagnosed in Peak age 65 74 3 4 of men 80 evidence of 2 3 of cases men 65 2 Race more common among African Americans than whites less common among Asians Race African American White Hispanic Asian Incidence 224 100 000 140 100 000 122 100 000 79 100 000 3 High serum testosterone levels may increase risk 4 Agricultural workers nitrate fertilizers cadmium workers 5 Genetic risk SEER data from 2007 2011 6 Migration factor men who move from a country with a low incidence to a country with a high incidence from Japan to US 7 Diet a diet with a lot of red meat or high fat dairy products slightly higher risk These men tend to eat fewer fruits and vegetables it is uncertain as to which of these factors increases the risk 8 No consistent relation to smoking venereal disease sexual habits III Signs Symptoms A Symptoms 1 Localized disease often asymptomatic Urological symptoms weak interrupted stream incomplete emptying painful burning on urination 2 Distant disease bone pain back legs hips IV Patterns of spread A Direct extension bladder urethra pelvis 3 difficulty starting stopping stream erectile dysfunction 3 seminal vesicles local nodes Figure B Hematogenous lymphatic pelvic nodes bones liver lungs V Diagnosis Screening A Screening 1 Definition purpose 2 Screening recommendations ACS a Both the PSA and the DRE should be offered annually beginning at age 50 to asymptomatic men who have at least a 10 year life expectancy Why should screening be offered Information should be provided to all men about what is known and what is uncertain about the benefits limitations and harms of early detection and treatment of prostate cancer so that they can make an informed decision about testing b Men at high risk African Americans and men with a family history of one or more first degree relatives diagnosed before age 65 should have the discussion at age 45 c Men at higher risk due to multiple first degree relatives affected before age 65 should have the discussion at age 40 d 4 If a man is unable to decide if testing is right for him the screening decision can be made by his health care provider who should take into account the patient s general health preferences and values e After the discussion men who want to be screened should be tested with the PSA blood test The digital rectal exam DRE may also be done as a part of screening f Not offering testing is not appropriate g Men with a PSA of 2 5 ng ml may be screened every 2 years B Digital rectal examination palpate for size configuration a mass and consistency C Prostate specific antigen a glycoprotein released from the prostate gland elevations prostate cancer prostatitis BPH can be decreased by finasteride dutasteride LHRH agonists anti androgens results Traditional view PSA level Significance 0 4 ng dL normal 4 1 10 elevated needs evaluation 10 highly elevated suspicious for malignancy 2 trials of men with PSA of 2 5 4 0 demonstrated CA in 22 and 24 5 NCCN guidelines Consider biopsy for PSA 2 6 4 D Other PSA considerations 1 PSA density PSA gland volume 0 15 ng cm3 limited clinical acceptance 2 PSA velocity 5 a evaluation should be based on 3 consecutive measurements over 18 24 months 3 PSA by age and race age specific reference ranges initially created to increase cancer detection in younger men by lowering their PSA cutoff values and to reduce unnecessary biopsies in older men by increasing the PSA cutoffs clinical studies inconclusive exact role uncertain 4 Free PSA PSA binding FDA approved for use in men with PSA of 4 10 ng mL 25 free PSA associated with cancer free PSA probability of cancer 0 10 15 20 25 56 20 8 F Transrectal ultrasound TRUS G Additional Diagnostic tests Biopsy for definitive diagnosis Radiology x rays CT scans bone scans VI Grading Staging A Purpose 1 to determine extent of disease 2 to plan appropriate management 3 to assess prognosis B Grading to evaluate the prostate tissue for cell development and differentiation 1 The two most predominant growth patterns in the specimen are graded on a score of 1 5 2 The numbers are added together for a final Gleason score of 2 10 3 Final score 6 well differentiated 7 moderately Figure 4 differentiated 8 10 poorly differentiated X can t be processed 6 C Staging to determine the extent of the disease Table 1 Staging system for prostate cancer Description Occult non palpable Confined to gland palpable Local spread beyond capsule Metastatic disease Stage I II III IV 81 combined incidence of stages I II disease 81 81 12 4 Incidence at diagnosis Figure 5 Illustration of