2225 INFLUENCE OF METABOLIC SYNDROME ON PROSTATE VOLUME AND PROSTATE SPECIFIC ANTIGEN

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71.1% ERG⫹) compared to the older patient cohort (⬎55 years, N⫽162, 43.8% ERG⫹, p⫽0.001). In the younger age group ERG⫹ patients had a significant lower median serum PSA of 4.0 ng/ml compared to 6.0 ng/ml in ERG⫺ patients (p⫽0.011). The older patient cohort showed no significant differences in PSA values (ERG⫹ 5.6 ng/ml, ERG⫺ 6.3 ng/ml, p⫽0.079). No associations of ERG status with other clinical and histopathological parameters were found. CONCLUSIONS: In our PSA screening PCa cohort ERG overexpression is significantly more frequent in tumors detected at a lower age than in tumors diagnosed in older patients. This indicates an acceleration of tumor development by ERG overexpression. Furthermore, ERG overexpression seems to lower PSA sequestration into the circulation. This could reflect a lower production of androgen regulated genes like the PSA gene caused by interactions of ERG and androgen receptor. Source of Funding: None

2224 PROSTATE CANCER RISK ALLELES ARE ASSOCIATED WITH PROSTATE CANCER TUMOR VOLUME BUT NOT PROSTATE SIZE Stacy Loeb*, New York, NY; Brian T. Helfand, Barry B. McGuire, Qiaoyan Hu, Phillip R. Cooper, Matthias D. Hofer, William J. Catalona, Chicago, IL INTRODUCTION AND OBJECTIVES: An increasing number of single nucleotide polymorphisms (SNPs) have been identified that are associated with prostate cancer risk. Less is known about the association of these genetic variants with prostatic enlargement and tumor volume. METHODS: From 2003 to 2011, 1321 Caucasian men underwent radical prostatectomy at our institution and were genotyped for 38 prostate cancer risk alleles. Prostate size was determined from the weight of the prostatectomy specimen, tumor volume was calculated by visual (microscopic) estimation, and the best-fit genetic model was established for each variant. We also examined the relationship between prostate cancer risk alleles with prostate size as compared to tumor volume. Multivariate analyses adjusted for multiple comparisons. RESULTS: On univariate analysis, carriers of the rs9364554 and rs11067228 risk alleles had a significantly smaller prostate volume. One SNP, rs10788160, was associated with a larger prostate volume on univariate analysis; however, on multivariable analysis, none of the SNPs maintained a significant association with prostate volume. By contrast, 6 SNPs were significantly associated with tumor volume on univariate analysis. Of these, rs16901979 (p⫽0.01) and rs6983267 (p⫽0.02) were significantly associated with higher tumor volume on multivariate analysis. These SNPs previously have been associated with tumor aggressiveness. In contrast, rs17632542 (p⫽0.01) was associated with lower tumor volume. CONCLUSIONS: Among 38 SNPs previously associated with prostate cancer risk, there was no significant association with prostate volume on multivariable analysis. By contrast, several prostate cancer risk SNPs were associated with tumor volume, suggesting a possible future role in clinical prognostication.

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).

2225 INFLUENCE OF METABOLIC SYNDROME ON PROSTATE VOLUME AND PROSTATE SPECIFIC ANTIGEN Woo Suk Choi*, Gangwon-do, Korea, Republic of; Nam Ju Heo, Sung Yong Cho, Seung Bae Lee, Soo Woong Kim, Jae-seung Paick, Hwancheol Son, Seoul, Korea, Republic of INTRODUCTION AND OBJECTIVES: There is increasing evidence that benign prostate hyperplasia and lower urinary tract symptom are related with metabolic syndrome (MS). Recent findings also suggested that the level of prostate specific antigen (PSA) is influenced by MS, but there is some controversy. We investigated the influence of MS on prostate volume and PSA. METHODS: We retrospectively analyzed 26,245 men who underwent routine check-ups. Transrectal ultrasonography was performed on 2934 of these men. We compared prostate volumes and PSA levels in subjects with MS (Group MS) and without MS (Group C; control). The definition of MS was based on the International Diabetes Federation (IDF) 2005 criteria.

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RESULTS: The prevalence of MS was 20.8%. Between the groups there were significant differences in mean age (50.0¡3⁄49.7yr (MS) vs. 48.9¡3⁄49.4yr (C), p⬍0.001), prostate volume (33.0¡3⁄49.9cm3 (MS) vs. 30.4¡3⁄49.6cm3 (C), p⬍0.001) and PSA (1.004¡3⁄40.727ng/ml (MS) vs. 1.037¡3⁄40.753ng/ml (C), p⫽0.004). The mean difference in PSA between groups was ⫺0.33ng/ml. After adjusting for age, prostate volume was still significantly larger in group MS than group C (difference (D) ⫽ 2.21cm3, p⬍0.001), and the difference in PSA between groups increased to -0.047 ng/ml (CI⫽⫺0.069⬃⫺0.025, p⬍0.001). Group MS had lower age-adjusted PSA density than group C (difference⫽⫺0.0061ng/ml/cm3 (CI⫽⫺0.0085⬃⫺0.0037)). On linear regression analysis, age, prostate volume and MS were significant independent factors that influence PSA level. PSA increased with age (0.009ng/ml/yr CI⫽0.005⬃0.009) and prostate volume (0.030ng/ml/cc CI⫽0.026⬃0.033), but decreased with MS (difference⫽⫺0.180ng/ml, CI⫽⫺0.260⬃⫺0.101). CONCLUSIONS: Patients with MS have larger prostate volumes and lower PSA levels than patients without MS. Larger prostate volumes in patients with MS hide the PSA lowering effect of MS. These results may be helpful for consultation of PSA results on patients with MS. Source of Funding: None

2226 LET-7B IS DOWN-REGULATED IN HIGH RISK PROSTATE CANCER AND AN INDEPENDENT PREDICTOR FOR CLINICAL FAILURE Maria Schubert*, Burkhard Kneitz, Susanne Kneitz, Claus Juergen Scholz, Wuerzburg, Germany; Steven Joniau, Hein van Poppel, Leuven, Belgium; Pia Bader, Detlef Frohneberg, Karlsruhe, Germany; Hubertus Riedmiller, Martin Spahn, Wuerzburg, Germany INTRODUCTION AND OBJECTIVES: MicroRNA (miRNA) expression profiles have been linked to clinical and pathological features of several cancers. The miRNA family let-7 plays a pivotal role in the pathogenesis of some solid tumours, e.g. lung cancer, its expression being down-regulated. However its role in prostate cancer (PCa), especially high risk PCa remains largely unknown. This study aimed to evaluate the expression and clinical significance of let-7 in a large cohort of patients with high risk disease. METHODS: The study included 98 patients of the EMPAcT tumorbank with high risk cancer features (PSA⬎20ng/ml ⫾ cⱖT3 ⫾ bx Gleasonⱖ8) treated with radical prostatectomy. All patients had preoperative data as well as post-operative pathological information. We analyzed expression of the let-7 family in paraffin-embedded high risk PCa and compared it to benign hyperplastic prostate tissue (BPH) and low risk disease by microarray experiments. We further performed qRT-PCR in 42 samples of frozen PCa and corresponding benign tissue. We analyzed let-7b expression by qRT-PCR in our study cohort to validate associations between expression, various clinico-pathologic factors and patient survival. RESULTS: Microarray analysis of the let-7 family in high risk PCa revealed significant down-regulation compared to BPH. Hierarchical clustering for the let-7 family showed a clear distinction between malignant and benign prostatic tissue. Similar results were seen in the array analysis of low vs. high risk PCa. RT-PCR analyses of additional samples (98 high risk, 42 pairs of frozen PCa, 7 BPH) confirmed these findings. For the 98 high risk patients Kaplan Meier and Cox proportional hazard models showed that let-7b expression was linked to poor pathological characteristics like high Gleason Score, clinical failure (CF) or cancer related death (CRD). The 10 yr recurrence free survival rate was 90% and 55% for high and low let-7b expression respectively (p⫽0.003). In the multivariable model dichotomized let-7b was confirmed as an independent predictor for CF p⫽0.02, HR 0.29 (95% CI 0.10 to 0.83). CONCLUSIONS: The majority of the let-7 family members is significantly reduced in high risk cancer compared to low risk PCa and BPH. In our study cohort of 98 high risk PCa patients down-regulation

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of let-7b was associated with poor clinico-pathological parameters, including Gleason Score, CF and CRD during follow-up. We identified let-7b as an independent predictor for CF. This miRNA may therefore serve as predictive marker in high risk PCa in the future. Source of Funding: * Supported by a Ferdinand Eisenberger grant of the Deutsche Gesellschaft fu¨r Urologie (German Society of Urology), grant ID ScM1/FE-11 * Supported by the interdisciplinary center for clinical research, University Wuerzburg, grant ID Z-3/14

2227 SERUM ISOFORM [ⴚ2]PROPSA (P2PSA) AND ITS DERIVATES, %P2PSA AND PHI (PROSTATE HEALTH INDEX), ARE MORE ACCURATE OF REFERENCE STANDARD TEST (PSA) IN MEN SCHEDULED FOR REPEAT BIOPSY Massimo Lazzeri*, Giovanni Lughezzani, Vincenzo Scattoni, Milan, Italy; Vittorio Bini, Perugia, Italy; Alessandro Larcher, Andrea Cestari, Giulio Maria Gadda, Tommaso Maga, Patrizio Rigatti, Francesco Montorsi, Giorgio Guazzoni, Milan, Italy INTRODUCTION AND OBJECTIVES: The aim of this study is to determine the performance characteristics and clinical utility of the isoform [⫺2]proPSA and its derivates in detecting PCa in men scheduled for repeat biopsy. METHODS: This study was an observational prospective evaluation of a cohort of men with one or two previous negative prostate biopsies, with persistent suspicion of PCa (suspected DRE, elevated tPSA and or low f/tPSA) who were scheduled for repeat biopsy. Men receiving medical therapy known to affect serum PSA (dutasteride and finasteride), suffering from prostatitis and having had invasive treatment for benign prostatic hyperplasia (BPH), were excluded. Serum p2PSA, and it derivates, namely %p2PSA {([⫺2]proPSA/10)/fPSA)} and Beckman Coulter phi (prostate health index) {[[⫺2]proPSA/fPSA] x squart PSA} were considered the index tests and compared with the standard referenced test (tPSA, fPSA and f/tPSA). All the patients underwent ambulatory repeated TRUS-guided 18 core prostate biopsies. The primary outcome was to evaluate the accuracy of p2PSA and its derivates in detecting PCa at repeat biopsy. RESULTS: From June 2010 and June 2011, 222 men underwent repeated biopsy. PCa cancer was found in 71/222 (31.9%) subjects. p2PSA, %p2PSA and phi values were significantly higher (p⬍0.0001), and %fPSA values significantly lower (p⬍0.0001) in patients with PCa. At univariate accuracy analysis, %p2PSA (AUC: 72.5%) and phi (AUC: 67.2%) were the most accurate predictors and significantly outperformed tPSA (AUC: 51.8%). %p2PSA significantly outperformed %fPSA (AUC: 60.2%) in the prediction of PCa (pⱕ0.001), but not PHI (p⫽0.136). At 90% of sensitivity, the cut-off of %p2PSA and PHI were respectively of 1.23 and 28.8 with a specificity of 40.4 and 25.2%. At a %p2PSA cut-off of 1.23 a total of 153 (68.9%) biopsies could be avoided; an overall of 6 PCa patients would have been missed but only 1 (5%) patient with a Gleason score of 7 or greater would have been missed. At a PHI cut-off of 28.8 a total of 116 (52.25%) biopsies could be avoided; an overall of 6 PCa patients would have been missed but no patients with a Gleason score of 7 or greater would have been missed. CONCLUSIONS: %p2PSA and PHI are more accurate than standard reference tests (tPSA, fPSA and f/tPSA) in predicting repeat prostate biopsy outcome and may be indicative of cancer aggressiveness. Source of Funding: Beckman Coulter Italy