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5085 Background: Historically, the use of testosterone replacement therapy (TRT) has not been recommended in men with a history of prostate cancer (PC). However, low testosterone levels are significantly associated with metabolic complications, decreased sexual function, and (more recently) high-grade PC. In 2009, in hopes of improving sexual function outcomes in men following radical prostatectomy (RP), we began treating low-risk patients with TRT. The current study examines the impact of TRT on biochemical recurrence (BCR). Methods: Between December 2009 and June 2018, a cohort of 850 patients underwent RP by a single surgeon. 152 (18%) men were postoperatively placed on TRT for recovery of sexual function. All data was prospectively collected and retrospectively analyzed. TRT patients were proportionately matched to 419 control patients by pathologic Gleason Grade Group (GGG) and stage. Univariate and multivariate comparisons were used to compare rates and time to BCR (two consecutive PSAs ≥ 0.2 ng/dl); Cox regression modeling was used to generate a survival function at the mean of covariates. Results: There were no statistically significant differences in preoperative PSA, age, prostate weight, pathologic GGG and stage between the control versus TRT groups. Median follow-up time was 3 years in both groups. 7/152 (4.6%) and 39/419 (9.3%) patients experienced BCR in the TRT versus control groups, respectively (unadjusted, p=0.068). In adjusted time to-analysis, TRT was an independent predictor of recurrence-free survival, after controlling for GGG, p-stage, preoperative FT and PSA. A patient on TRT was approximately 53% less likely to experience a BCR (OR: 0.534, 95%CI: 0.288-0.993). Conclusions: After accounting for pathologic GGG, stage, and other significant covariates, the use of TRT independently reduced recurrence post-RP. These results suggest the need for a multi-center randomized control trial.

e16570 Background: The role of testosterone in prostate growth and the development of prostate cancer is a controversial topic. Most current data suggest that lower testosterone leads to higher grade conversion, whereas higher testosterone may serve a protective role in preventing both development and recurrence. We seek to analyze whether free testosterone (FT) values can predict aggressiveness in prostate cancers. Methods: We retrospectively reviewed 830 patients who presented to a single surgeon for evaluation and management of prostate cancer. Total Testosterone (TT) and FT values were obtained on each patient at initial visit. All patients underwent radical prostatectomy and samples from surgery were sent for grading and staging. Patients were stratified by FT quartile (25th [≤ 4.42 ng/dL], 50th [4.43 – 5.60 ng/dL], 75th [5.61 – 6.95 ng/dL], and 100th [≥ 6.96 ng/dL]). Results: Of 830 patients, 168 (22.2%), 330 (39.8%), 188 (22.7%), 46 (5.5%), and 98 (11.8%) had GS 3+3, 3+4, 4+3, 4+4, and ≥4+5, respectively. Mean FT values for each Gleason grade group (GGG) were significantly different (p = 0.008). Mean FT was also lower in patients with higher stage disease (p = 0.01). In contrast, TT did not differ significantly among GGG (p = 0.489) or stage (p = 0.670). Patients who had a FT level in the lowest quartile (≤ 4.42 ng/dL) had a higher proportion of GGG 5 (15.6%) than patients in the highest quartile (≥ 6.96 ng/dL) (6.2%) (p = 0.002). After adjusting for age, prostate specific antigen (PSA), and body mass index (BMI) in multivariate analysis, lower FT was a significant predictor of high-risk score 9-10 (OR: 0.912, 95% CI: 0.836-0.994, p = 0.036). These trends showed strong correlation in pathologic stage (p = 0.057), but larger numbers are needed to gauge effect size. Conclusions: Based on our data, biochemically low FT may be a risk factor for high grade and high stage cancer. These results have implications for the current recommendations for testosterone therapy, which is contraindicated in men with prostate cancer. [Table: see text]