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PROSTATE CANCER (Module 3 of Renal/Prostate Disease) Bill Lyons, M.D. UNMC Geriatrics & Gerontology PROSTATE CANCER: LEARNING OBJECTIVES Epidemiology and General Principles Treatment Approaches, Vigorous vs. Frail Androgen Deprivation Therapy: Benefits and Burdens BACKGROUND Most common non-skin cancer in men Second-most-common cause of cancer mortality in American men Lifetime risk of prostate cancer: 16% Risk of dying of the disease 3.4% BACKGROUND, cont. Many/most elderly men die with, not of, prostate cancer Hence controversy regarding screening for and treating early-stage disease Damage done to normal tissue by treatment (radiation, surgery) may exceed that from untreated indolent cancer BACKGROUND, cont. Prostate cancer diagnosed Elevated PSA TURP pathology Local urologic symptoms Metastatic symptoms (esp. bone) NATURAL HISTORY OF EARLY PROSTATE CANCER Johansson et al: population-based cohort Mean observation period 21 years N = 223 men Early stage: T0-T2 NX M0 Most early-stage tumors have indolent course Local progression, metastatic disease can arise over longer term “Findings early radical treatment, notably among patients with estimated LE > 15 yr” OVERALL APPROACH TO TREATMENT Mortimer & McElhaney’s Schema Approach depends on function, co-morbidity GENERAL SCHEMA: CANCER CONFINED TO GLAND Good Function, Low Comorbidity: Prostatectomy vs. radiation treatment Poor Function, High Comorbidity: Consider watchful waiting GENERAL SCHEMA: LOCAL EXTENSION OF DISEASE To capsule, seminal vesicle, bladder, rectum, or pelvic nodes Good Function, Low Comorbidity: Radiation + GnRH agonist Poor Function, High Comorbidity: Consider GnRH agonist alone GENERAL SCHEMA: DISEASE OUTSIDE THE PELVIS Initial approach: Good Function, Low Comorbidity: Castration (androgen deprivation therapy) + antiandrogen (eg, flutamide) AKA “Combined androgen blockade” Poor Function, High Comorbidity: Same GENERAL SCHEMA: DISEASE OUTSIDE THE PELVIS If disease has progressed: Good Function, Low Comorbidity: Stop antiandrogen treatment Poor Function, High Comorbidity: Same GENERAL SCHEMA: DISEASE OUTSIDE THE PELVIS If disease progresses still further: Good Function, Low Comorbidity Consider chemotherapy Poor Function, High Comorbidity Symptomatic management RISING PSA AFTER LOCAL TREATMENT After RRP, typically check PSA q 3 mo Rising PSA, short doubling time predict disease progression After radiation treatment, PSA declines Typically nadir < 1.0 ng/mL reached Three consecutive increases from nadir signifies biochemical failure ANDROGEN DEPRIVATION THERAPY Generally first-line therapy for advanced prostate cancer, also used as adjuvant for local treatment of highrisk disease Medical now more common than orchiectomy, outcomes similar ANDROGEN DEPRIVATION THERAPY, cont. GnRH agonists – leuprolide, goserelin Depot injections, subcutaneous implants Decrease pituitary release of LH Castration levels of testosterone w/in 3 wks Initial testosterone surge Flare of metastatic disease, bone pain Some start androgen receptor blocker beforehand ANDROGEN DEPRIVATION THERAPY: BENEFITS In advanced prostate cancer: Reduced bone pain Fewer pathologic fractures Reduced incidence of spinal cord compression Reduced incidence of ureteral obstruction Survival? Unclear ANDROGEN DEPRIVATION THERAPY: ADVERSE EFFECTS Decreased libido and erectile dysfunction Hot flashes in up to 80% Osteoporosis with increased risk of fracture Mood and cognitive effects Body composition: lean fat Increased fasting glucose, cholesterol Anemia Gynecomastia ANDROGEN DEPRIVATION THERAPY: ADVERSE EFFECTS Check BMD at baseline; start Ca + D Bisphosphonates Osteoporosis Bony metastases of androgen-independent prostate cancer ADVANCED PROSTATE CANCER …almost always becomes androgen- independent after some time on ADT Duration of ADT response in metastatic disease typically 14-20 months Options: Hormone receptor blockers (flutamide, bicalutamide, nilutamide) Ketoconazole – decreases adrenal androgen synthesis REFERENCES AND READINGS Baum N. Clinical Geriatrics 2005;13(5):23- 26. Johansson JE et al. JAMA 2004; 291:27132719 Mortimer JE, McElhaney J. Cancers in the Geriatric Population. Chapter 30 in: Landefeld CS et al. Current Geriatric Diagnosis and Treatment, 2004, McGraw-Hill. REFERENCES AND READINGS Sharif N et al. JAMA 2005;294:238-244. Stoller ML, Carroll PR. Urology. Chapter 23 in: Tierney LM Jr, McPhee SJ, Papadakis MA, Current Medical Diagnosis & Treatment, 2004, McGraw-Hill. Post test 1 An 82-year-old patient of yours is diagnosed with prostate cancer, and pelvic imaging strongly suggests he has extensive involvement of pelvic lymph nodes. Because of his functional dependence (he requires assistance for bathing and dressing, and he ambulates with a walker) and comorbidity (he has poorly-controlled diabetes mellitus, advanced heart failure, and mild dementia), he is started on leuprolide injections as sole therapy. All of the following statements regarding his androgen deprivation therapy (ADT) are true EXCEPT: All of the following statements regarding his androgen deprivation therapy (ADT) are true EXCEPT: (a) Flutamide should be started before the GnRH agonist, leuprolide. (b) ADT is expected to reduce his risk of pathologic fractures. (c) ADT is expected to prolong his survival. (d) ADT may exacerbate his cognitive problems. (e) His bone mineral density should be checked before treatment begins, and he should be considered for treatment with a bisphosphonate. Correct Answer: (c) ADT is expected to prolong his survival. Feedback:(c) is not necessarily a true statement (and therefore is the correct answer); it is not yet clear that ADT prolongs survival in men with prostate cancer, although it does reduce the risk of many complications. Statement (a) is true, because androgen blockers reduce the odds of GnRH-induced flares. Statement (b) is true pathologic fractures are one complication that occur less frequently when GnRH agonists are employed. Statement (d) is true, and should be remembered in the care of patients like this one who already have cognitive deficits. Finally, statement (e) is true, because ADT places patients at risk of treatment-induced osteoporosis.