Ajay Nehra, Jennifer St. Sauver, Laureano Rangel, Rachel Carlson,. R. Jeffrey Karnes, Eric Bergstralh, Rochester, MN. INTRODUCTION AND OBJECTIVES: ...
e188
THE JOURNAL OF UROLOGY姞
461 FREE AND BIOAVAILABLE SERUM TESTOSTERONE WERE ELEVATED BY DECREASING SEX HORMONE BINDING GLOBULIN IN PROSTATE CANCER Jongwon Kim*, Cheryn Song, Jun Hyuk Hong, Choung-Soo Kim, Hanjong Ahn, Seoul, Korea, Republic of INTRODUCTION AND OBJECTIVES: We aimed to identify the relationship between the serum testosterone (TS) axis and the prostate cancer and its association with clinicopathological features. METHODS: Between May 2006 and October 2009, 741 patients (mean age, 64.6⫾6.7 years) with prostate cancer undergoing RP without hormonal therapy or chemotherapy and age-matched 741 men (mean age, 64.6⫾7.2 years) who had visited health promotion center for routine health exam were enrolled prospectively. Total serum TS, sex hormone binding globulin (SHBG) and albumin were measured at 8 AM after midnight fasting. In the cancer group, we followed the hormone levels after RP. Between the two groups, we compared total serum TS, TS-derivatives and SHBG. In the cancer group, further subgroup analysis was done between the preoperative hormone levels and the perioperative changes in relationship with various clinicopathological characteristics. RESULTS: Lower levels of SHBG (53.8⫾21.5 vs. 59.0⫾23.9 nmol/L, p⬍0.001), total TS (4.09⫾1.54 vs. 4.31⫾1.64 ng/ml, p⬍0.001), higher levels of free TS (70.2⫾24.7 vs. 63.4⫾28.6 pg/ml, p⫽0.012), bioavailable TS (1.54⫾0.55 vs. 1.39⫾0.59 ng/ml, p⫽0.016), and free TS index (FTI) (8.98⫾3.46 vs. 7.97⫾3.45, p⬍0.001) were observed in the cancer group compared to the control group. Preoperative SHBG was an independent predictor for high pathologic Gleason score (ⱖ7) (p⫽0.013, HR 1.540). After RP, both SHBG and total TS significantly increased from 53.8⫾21.5 to 59.0⫾22.9 nmol/L and from 4.09⫾1.54 to 4.30⫾1.22 ng/ml, respectively (both, p⬍0.001). Subsequently free TS was reduced from 70.2⫾24.7 to 64.26⫾18.01 pg/ml, bioavailable TS reduced from 1.54⫾0.55 to 1.42⫾0.40 ng/ml, and FTI from 8.98⫾3.46 to 7.89⫾3.15 (all, p⬍0.001). CONCLUSIONS: We have demonstrated that patients with prostate cancer have increased TS bioactivity compared to agematched controls. SHBG was an independent predictor of cancer differentiation. Following RP, enhanced TS bioactivity normalized and consequently preoperative low TS rebounded to the level comparable to the control group, which was mainly attributable to the postoperatively elevating SHBG, mechanism of which remains to be elucidated. Source of Funding: None
462 TREATMENT WITH 5-ALPHA REDUCTASE INHIBITORS AND PROSTATE CANCER SURVIVAL Anders Kjellman*, Stockholm, Sweden; So¨ren Friis, Copenhagen, Denmark; Fredrik Granath, Ove Gustafsson, Stockholm, Sweden; Henrik Toft So¨rensen, Copenhagen, Denmark; Olof Akre, Stockholm, Sweden INTRODUCTION AND OBJECTIVES: In prevention trials 5-alpha-reductase inhibitors such as finasteride have been found to reduce the risk of a subsequent prostate cancer (PC) diagnosis. Paradoxically, this medication also has been associated with increased risk of more aggressive tumours. At present, there is no data on long-term survival of PC patients treated with 5-alpha-reductase inhibitors. We therefore compared survival after diagnosis of prostate cancer in men previously treated with 5-alpha-reductase inhibitors, in men previously treated with alpha-adrenoceptor antagonists, and in men who had received neither type of medication before diagnosis of prostate cancer. METHODS: We conducted the study within the population of Northern Denmark. We used the region’s prescription database to identify all men prescribed 5-alpha-reductase inhibitors and alphaadrenoceptor antagonists and those who had received neither medication. We then evaluated their risk of a subsequent PC diagnosis, risk of metastasised disease and risk of death from PC. The odds ratio for
Vol. 185, No. 4S, Supplement, Sunday, May 15, 2011
the risk of being diagnosed with disseminated PC was calculated using conditional logistic regression. Hazard ratios for mortality were estimated using Cox proportional hazard regression and used to compare exposed and unexposed patients. RESULTS: A total of 3 791 men were evaluated. The risk of being diagnosed with metastasised disease was increased for men taking 5-alpha-reductase inhibitors with an odds ratio (OR) of 1.14 (95% CI 1.01–1.29) per 100 defined daily doses (DDD). Treatment with alpha-adrenoceptor antagonists was inversely associated with risk of disseminated disease (OR 0.89 (0.81– 0.98) per 100 DDD). The hazard ratio (HR) for death from PC after treatment with 5-alpha-reductase inhibitors was 0.93 (95% CI 0.76 –1.14). Treatment with alpha-adrenoceptor antagonists significantly reduced the risk of PC-death (HR 0.78 (95% CI 0.67– 0.90)). CONCLUSIONS: Treatment with 5-alpha-reductase inhibitors before diagnosis of PC did not affect survival, but increased the risk of being diagnosed with metastasised disease. Treatment with alphaadrenoceptor antagonists was associated with better survival and lower risk of metastasised disease. Source of Funding: None
463 THE ASSOCIATION BETWEEN ANDROGEN DEPRIVATION AND CARDIOVASCULAR EVENTS IN A POPULATION BASED COHORT WITH LONG TERM FOLLOW-UP Rodney Breau*, Ottawa, Canada; Brant Inman, Durham, NC; Ajay Nehra, Jennifer St. Sauver, Laureano Rangel, Rachel Carlson, R. Jeffrey Karnes, Eric Bergstralh, Rochester, MN INTRODUCTION AND OBJECTIVES: The purpose of this study was to determine the association between androgen deprivation and selected cardiovascular events in men with prostate cancer. METHODS: Using the Rochester Epidemiology Project record linkage system, all men with pathologically confirmed prostate cancer between 1983 and 1997 were identified. In 2009, all medical records were reviewed for use of androgen deprivation (LHRH agonists or orchiectomy) and incidence of myocardial infarction (MI), cerebrovascular accident (CVA), congestive heart failure (CHF) or cardiovascular death. Androgen deprivation was analyzed as a time dependent covariate and all associations presented are adjusted for age, diabetes, hypertension, hyperlipidemia, obesity, chronic kidney disease and tobacco use. RESULTS: During the study period, 869 men were diagnosed with prostate cancer and 311 (36%) were treated with androgen deprivation at a median follow-up of 10.4 years. The incidence of events was: 121 MI, 178 CVA, 211 CHF and 132 cardiovascular deaths. The adjusted associations between androgen deprivation and cardiovascular events are shown in the table below. CONCLUSIONS: Androgen deprivation was associated with a modest increased risk of CHF, but not MI, CVA, or cardiovascular death. These data support the continued use of androgen deprivation in prostate cancer patients when clinically indicated. Associations between androgen deprivation and cardiovascular events Outcome LHRH Agonist Orchiectomy Myocardial infarction 0.61 (0.28,1.32) 1.08 (0.68,1.71) Cerebrovascular accident
0.77 (0.44,1.38)
0.86 (0.58,1.27)
Congestive heart failure
1.66 (1.08,2.57)
1.38 (0.99,1.93)
Cardiovascular death
0.51 (0.23,1.10)
0.86 (0.55,1.33)
Adjusted HR (95% Confidence Interval)
Source of Funding: None
