Abstract Background: Ten years following the 9/11/2001 attacks on the World Trade Center (WTC), an increased incidence of prostate cancer was reported in two separate cohorts of WTC rescue and recovery workers. Whether this increase is due to WTC-related exposures or increased surveillance is uncertain. Methods: Prostate cancer cases and Gleason scores diagnosed after 9/11 from 2002 to 2014 were obtained from the WTC Health Program (n = 180). Differences in proportions of Gleason scores 7+ (moderate to high-grade cancer) in WTC respondents and New York State were calculated based on the NYS Cancer Registry (NYSCR). An age-adjusted rate for Gleason scores of ≥7 was calculated using the indirect method based on NYSCR. Age- and race-matched prostate cancer non-WTC respondent controls (n = 253) were obtained from Mount Sinai Hospital. We evaluated the effects of WTC-respondent status, exposure level, age, race, prostate-specific antigen (PSA) concentrations, and clinical stage on Gleason scores using log-linear regression. WTC exposure was analyzed by four categorical levels and continuously using a relative rank of potential carcinogen-related post-9/11 exposures. Differences in mean numbers of PSA screening visits were assessed using Student's t-test. Results: The age-adjusted rate for a Gleason score ≥7 was 1.15 for WTC respondents (95% Confidence Interval (CI): 0.94, 1.36) compared to the NYSCR. WTC respondents < 40 years old had an 8-time higher proportion of aggressive cancers than expected based on NYSCR age-specific rates. The proportion of Gleason scores ≥7 was 0.33 (95% CI: -0.06, 0.12) higher in WTC respondents than NYSCR. WTC respondents had lower Gleason scores (Odds Ratio (OR): 0.90 (95% CI: 0.82, 0.99)), PSA values (OR: 0.79; 95% CI: 0.71, 0.89), but higher clinical stage (OR: 1.04; 95% CI: 0.92, 1.16) than controls. When Gleason score was adjusted for PSA and clinical stage, the OR for PSA testing was 1.04; 95% CI: 0.88, 1.23 and clinical stage was lower (OR: 0.82; 95% CI: 0.69, 0.98) in WTC-respondent cases. The mean numbers of PSA-screening visits were not different between WTC respondents and controls (t = 0.64; P = 0.52) and were not associated with Gleason scores ≥7 (OR: 1.0; 95% CI: 0.88, 1.13). Four-level exposure categories (OR: 0.99; 95% CI: 0.99, 1.00) and continuous rank (OR: 0.88; 95% CI: 0.73, 1.06) showed no associations with Gleason scores. Days spent at WTC (OR: 1.00; 95% CI: 1.00, 1.03) and working on the WTC debris pile (OR: 0.95; 95% CI: 0.86, 1.05) showed similar results. Conclusions: Young WTC respondents had higher Gleason scores than the NYSCR. Number of PSA screening visits did not significantly differ between WTC respondents and controls and PSA values of WTC respondents were lower than controls. Aggressive prostate cancer was not associated with WTC exposure levels. Considering the high grade of prostate cancer in younger men and the long latency for prostate cancer development, continued monitoring is needed to determine alternative causes of elevated prostate cancer in the WTC population. Citation Format: Dana Hashim, Paolo Boffetta, William Oh, Sylvain Wallenstein, Matthew Galsky, Emanuela Taioli. Prostate cancer in WTC respondents. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3435.