IS STATIN USE ASSOCIATED WITH PROSTATE CANCER AGGRESSIVENESS?

THE JOURNAL OF UROLOGY®

Vol. 181, No. 4, Supplement, Sunday, April 26, 2009

of prostate biopsy, prostate cancer, and exceeding age-specific PSA thresholds. Failure to exceed PSA thresholds may explain a reduction in risk of prostate biopsy and prostate cancer diagnosis. Alternatively, statin use may prevent development of prostate cancer. Source of Funding: Merck, NIH DK58859,AR30582, RR24150

575 ASSOCIATION BETWEEN STATINS, OBESITY AND PROSTATE TUMOR INFLAMMATORY INFILTRATE IN MEN UNDERGOING RADICAL PROSTATECTOMY Lionel L Bañez*, Jayakrishnan Jayachandran, Joseph C Klink, Amy L Lark, Leah Gerber, Robin T Vollmer, Stephen J. Freedland, Durham, NC INTRODUCTION AND OBJECTIVE: Emerging evidence suggests prostatic inflammation may contribute to both initiation and progression of prostate cancer (CaP). Indeed, we previously found inflammation around the tumor in radical prostatectomy (RP) samples correlated with more aggressive disease. Statins, which are reported to lower cancer risk, are known to have anti-inflammatory properties. Conversely, obesity, a known risk factor for aggressive CaP, is reported to promote an inflammatory state. However, whether statin use or obesity exerts their effects within prostate tumors is unknown. We investigated the relationship between statins, obesity, and prostate tumor inflammation among patients undergoing RP. METHODS: A total of 254 men who underwent RP at the Durham VA Medical Center from 1993 to 2004 with slides available for pathological review were included in the study. Cases were reviewed by a single pathologist blinded to clinical information and graded for inflammation within the index tumor as 0 (no inflammation), 1 (mild: a 10% tumor inflammation), and 2 (marked: > 10% tumor inflammation). Logistic regression was used to determine the association of body mass index (BMI) and statin-use with tumor inflammation (grade 0 vs. 1-2) controlling for age, race, pre-operative PSA, clinical stage, biopsy Gleason sum, year of surgery, pathological Gleason sum, surgical margins, extracapsular extension, seminal vesicle invasion, lymph node invasion and prostate specimen weight. RESULTS: Statin users were more likely to be either overweight (48%) or obese (31%; p<0.001). On multivariate analysis, statin use was significantly associated with lower risk for any intra-tumoral inflammation (OR=0.28; 95%CI=0.10-0.76; p=0.01). There was only a marginally significant association between increased BMI (q25 kg/m2) and marked tumor inflammation (OR=2.16; 95% CI=0.95-4.90; p=0.07) after adjusting for potential confounders including statin-use. CONCLUSIONS: Prior work from our group found inflammation in the tumor correlated with more advanced CaP. Thus, the fact that statin use in this study was associated with a significant 72% reduction in the risk for inflammation within the prostate tumor provides a potential mechanism for the purported anti-CaP properties of statins and supports continued exploration of statins for this cause. Furthermore, the fact that obesity may be associated with increased tumor inflammation provides another potential mechanism linking obesity with more aggressive CaP. Source of Funding: Duke Division of Urology, DoD, AUA/ Astellas

576 IS STATIN USE ASSOCIATED WITH PROSTATE CANCER AGGRESSIVENESS? Stacy Loeb*, Baltimore, MD; Donghui Kan, Brian T. Helfand, Sara N. Gashti, Robert B. Nadler, William J. Catalona, Chicago, IL INTRODUCTION AND OBJECTIVE: The association between statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) and prostate cancer risk is controversial. Some studies have suggested that statin use may reduce the risk of aggressive prostate cancer; whereas, others have shown no difference in treatment outcomes based upon statin use. The objective of our study was to further examine the

205

association between statins with pathological tumor features and shortterm treatment outcomes in a large radical prostatectomy population. METHODS: From 2003 to 2008, 1282 men with data on preoperative statin use underwent radical prostatectomy by a single surgeon. Statistical analysis was used to compare clinico-pathological features between 480 statin users and 802 non-users. RESULTS: Statin users were significantly older and had a higher mean body mass index (BMI) than non-users (Table 1). Preoperative PSA, tumor volume, and percentage of cancer in the radical prostatectomy specimen were significantly lower in patients taking statins. Overall, statin users tended to have a lower proportion of adverse tumor features, including a significantly lower risk of positive surgical margins. CONCLUSIONS: Our results suggest that the use of statins may be associated with more favorable pathological features at radical prostatectomy. The long-term disease-specific outcomes and the underlying link between statins and prostate cancer require additional investigation. Radical prostatectomy features stratified by preoperative statin use. Statin use No statins p-value Mean tumor volume (cc) 5.06 5.81 0.035 Mean percentage cancer 10.6% 12.0% 0.048 Organ-confined 81.3% 79.7% 0.51 Positive surgical margins 13.6% 18.2% 0.035 Extracapsular extension 17.4% 19.5% 0.37 Seminal vesicle invasion 3.1% 5.1% 0.12 Lymph node metastases 0.2% 0.9% 0.27 Gleason score 7-10 46.5% 49.1% 0.035

Source of Funding: Supported in part by the Urological Research Foundation, Prostate SPORE grant (P50 CA9038605S2) and the Robert H. Lurie Comprehensive Cancer Center grant (P30 CA60553)

577 DIABETES AND OUTCOMES AFTER RADICAL PROSTATECTOMY - ARE RESULTS AFFECTED BY OBESITY AND RACE? RESULTS FROM THE SHARED EQUAL ACCESS REGIONAL CANCER HOSPITAL (SEARCH) DATABASE Jayakrishnan Jayachandran*, Durham, NC; William J Aronson, Los Angeles, CA; Martha K. Terris, Augusta, GA; Jospeh C. Presti, Jr, Palo Alto, CA; Christopher L Amling, Birmingham, AL; Christopher J. Kane, San Diego, CA; Stephen J. Freedland, Durham, NC INTRODUCTION AND OBJECTIVE: Diabetes (DM) is associated with lower prostate cancer (PC) risk. One study of mostly Caucasian men (CM) found DM was not associated with biochemical recurrence (BCR) after radical prostatectomy (RP). Alternatively, obesity is associated with both BCR and DM. Race appears to be interlinked as well with AfricanAmerican men (AAM) being more likely to have DM, PC, and obesity. We hypothesized the association between DM and outcome after RP may vary by race and obesity. METHODS: We performed a retrospective analysis of 1725 men treated with RP in the SEARCH Database. Adjusting for preoperative features, we used proportional hazards and linear regression, respectively, to assess the influence of DM on BCR and PSADT at the time of BCR. Obesity was defined as a BMI > 30 kg/m2. Data were examined as a whole and stratified by race and obesity. The differential effect of obesity and race on the association between DM and outcomes was assessed by including interaction terms in the multivariate models. RESULTS: DM was more prevalent among AAM (21% vs. 13%, p<0.001) and obese men (27% vs. 16%, p<0.001). DM was not significantly associated with overall BCR risk (HR 0.91, p=0.45) nor PSADT at the time of BCR (p=0.16). Among AAM, DM was associated with a lower risk of BCR (HR 0.75, p=0.09) and a longer PSADT (26.0 vs. 15.7 months, p=0.045). These results were generally similar among both obese and non-obese AAM. In contrast, among CM, DM was not associated with either BCR (HR 1.24, p=0.28) or PSADT (18.7 vs. 16.4 months, p=0.71). The interaction between DM and race for predicting BCR was borderline significant (p-interaction=0.06). When CM were stratified by obesity, DM was strongly associated with increased BCR risk among obese men (HR