Michael G. Oefelein

SKELETAL FRACTURES NEGATIVELY CORRELATE WITH OVERALL SURVIVAL IN MEN WITH PROSTATE CANCER.

PURPOSE We assessed the correlation of skeletal fracture with survival in men with prostate cancer on chronic androgen suppressive therapy. MATERIALS AND METHODS A total of 195 consecutive patients on chronic androgen suppression for prostate cancer were evaluated for the history and type of skeletal fracture. Correlation with overall survival was performed via multivariate analysis. RESULTS Of these 195 men 24 reported skeletal fracture since the diagnosis of prostate cancer. Median overall survival was 121 and 160 months in men without and with a history of skeletal fracture since the diagnosis of prostate cancer, respectively (p = 0.04). A history of skeletal fracture was retained as a negative predictor of survival on forward stepwise regression analysis (RR = 7.4, p = 0.007). CONCLUSIONS Our results suggest that skeletal fracture in patients with prostate cancer is an independent and adverse predictor of survival. Consideration for screening men at greatest risk via bone mineral density measurements and initiating empirical skeletal therapies (bisphosphonates, estrogens and so forth) may be warranted. This recommendation awaits validation through prospective randomized trials.

SKELETAL FRACTURE ASSOCIATED WITH ANDROGEN SUPPRESSION INDUCED OSTEOPOROSIS: THE CLINICAL INCIDENCE AND RISK FACTORS FOR PATIENTS WITH PROSTATE CANCER

PURPOSE Limited information exists regarding the long-term risk of skeletal fracture in men on androgen suppression for prostate cancer. In addition, the clinical risk factors predisposing them to skeletal fracture are incompletely defined. We define the long-term risk and clinical risk factors for skeletal fracture in patients with prostate cancer on chronic androgen suppression. MATERIALS AND METHODS A total of 181 consecutive patients with prostate cancer on androgen suppression therapy were evaluated. The primary end point was skeletal fracture. Comprehensive demographic information was gathered, and univariate and multivariate analyses were performed to identify associations with skeletal fracture. RESULTS The proportion of patients who had survived fracture-free at 5 and 10 years on androgen suppression therapy was 96% and 80%, respectively. The black race (p = 0.009) and increased body mass index (p = 0.024) were identified as protective against androgen suppression associated skeletal fractures. A significant correlation was identified between the duration of androgen suppression and risk of skeletal fracture (p = 0.003). CONCLUSIONS Patients with prostate cancer treated with androgen suppression are at risk for skeletal fracture, and risk increases with the duration of therapy. Slender white men are at greatest risk. Conversely, black men and those with body mass indexes greater than normal (greater than 25 kg/m(2)) are at minimal risk despite a prolonged duration (10 years) of androgen suppression.

FAILURE TO ACHIEVE CASTRATE LEVELS OF TESTOSTERONE DURING LUTEINIZING HORMONE RELEASING HORMONE AGONIST THERAPY: THE CASE FOR MONITORING SERUM TESTOSTERONE AND A TREATMENT DECISION ALGORITHM

PURPOSE We report the failure to achieve a castrate level of testosterone associated with 3-month depot luteinizing hormone releasing hormone (LH-RH) agonist therapy, which to our knowledge is a previously unrecognized outcome. MATERIALS AND METHODS We prospectively enrolled in our study 38 men with prostate cancer on 3-month depot LH-RH agonist therapy. We monitored total serum testosterone and prostate specific antigen every 28 days beginning 90 days after the last depot LH-RH agonist injection. Data were analyzed with castrate testosterone defined as less than 50 and 20 ng./dl. or less. RESULTS Using the 50 and 20 ng./dl. definitions of castrate testosterone 2 (5%) and 5 (13%) of the 38 men, respectively, failed to achieve castrate testosterone. A patient with a nadir testosterone of 70 ng./dl. subsequently underwent orchiectomy and testosterone decreased to 10 ng./dl. thereafter. CONCLUSIONS A small but potentially important subgroup of men on depot LH-RH agonist therapy fail to achieve a castrate level of testosterone. Our findings support monitoring testicular response when LH-RH agonist therapy is initiated.

The accuracy of the increased prostate specific antigen level (greater than or equal to 20 ng./ml.) in predicting prostate cancer: Is biopsy always required?

PURPOSE Urologists are often referred patients who initially present with an extremely high serum prostate specific antigen (PSA) level. Despite a presumptive diagnosis of prostate cancer, many of these men undergo biopsy to obtain a tissue diagnosis before treatment with androgen ablative therapy. We examined a data base of men undergoing prostate biopsy to determine the accuracy of high PSA levels (greater than or equal to 20 ng./ml.) in predicting prostate cancer. MATERIALS AND METHODS We reviewed the records of 1,250 consecutive patients undergoing transrectal ultrasound guided prostate biopsy at 1 institution. From this data base we identified all patients with PSA greater than or equal to 20 ng./ml. at the time of prostate biopsy. The accuracy of PSA in predicting cancer was determined by calculating positive predictive values for PSA ranges and PSA cutoffs. RESULTS We identified 187 men (15%) presenting with PSA greater than or equal to 20 ng./ml. Of these 187 men 157 (84.0%) were diagnosed with prostate cancer on initial biopsy. Due to a negative initial biopsy, yet a high suspicion of cancer, 12 (6.4%) patients underwent at least 1 repeat biopsy. Of these 12 men 6 (50%) were diagnosed with cancer on repeat biopsy. Overall, 163 of the 187 men (87.2%) were diagnosed with prostate cancer by biopsy. Stratified by PSA ranges, positive predictive values were 73.6% for 20 to 29.9, 90.3% for 30 to 39.9, 93.8% for 40 to 49.9, 100% for 50 to 99.9, 95% for 100 to 199.9 and 100% for greater than or equal to 200 ng./ml. Using PSA cutoffs positive predictive values were 95.7% for PSA greater than or equal to 30, 97.6% for PSA greater than or equal to 40 and 98.5% for PSA greater than or equal to 50 ng./ml. CONCLUSIONS Serum PSA, when increased above 50 ng./ml., is 98.5% accurate in predicting the presence of prostate cancer on tissue biopsy. Nonetheless, since transrectal prostate biopsy has a low complication rate and is relatively well tolerated, we recommend continuing to biopsy most patients with high PSA levels. However, carefully selected elderly patients on chronic anticoagulation, with severe co-morbidities or presenting with spinal cord compression may not require biopsy before androgen ablative therapy since PSA is highly accurate in diagnosing prostate cancer at levels greater than 50 ng./ml.

Urologic manifestations of nonurologic diseases Gastrointestinal disorders

A variety of common, gastrointestinal diseases result in significant genitourinary tract pathology. In general, knowledge of these associated disease processes permit rapid and accurate diagnosis and treatment. The underlying thread is the recognition of one pathophysiological process to explain patterns of a single disease.

Re: Determining Dosing Intervals for LHRH Agonists Based on Serum Testosterone Levels: A Prospective Study

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Androgen suppression therapy and prostate cancer: balancing the harms and the benefits.

ome 65 years after the landmark discovery by Huggins thatprostate tissue is androgen regulated, androgen suppressiontherapy (AST) remains the primary treatment for advanced stagecarcinoma of the prostate (CaP). Since this significant discovery,refinement and validation of the efficacy of AST in a variety of clini-cal situations has occurred. Despite these advances, the adverseevents associated with AST have become an important clinical con-cern to physicians treating men with carcinoma of the prostate.Specifically, reports regarding cancer treatment-induced bone loss(CTIBL, eg, osteoporosis),