Background: Treatments and outcomes of men with nmCRPC in routine care are poorly described. We assessed the cumulative impact of new therapies in men who transition through nmCRPC using a single-institution database. Methods: We conducted a retrospective study of consecutive nmCRPC pts enrolled into a hospital-based registry at Dana-Farber Cancer Institute. Pts were analyzed by era of diagnosis of nmCRPC: 2000-2009 (when docetaxel was the only life prolonging metastatic CRPC therapy) (cohort A) and 2010-2018 (when new systemic therapies were approved for mCRPC or in trials for nmCRPC) (cohort B). We collected pt, treatment, metastasis-free survival (MFS) and overall survival (OS) data. Results: 230 men were included: 148 in cohort A and 62 in cohort B. Despite only 39% of cohort B pts receiving new hormonal therapies for nmCRPC, there was no difference in median MFS between both eras: 2.7 yrs (2.1-3.2) in cohort A and 2.2 yrs (1.4-3.3) in cohort B. 30% of pts in cohort A and 53% of pts in cohort B had two or more life prolonging mCRPC therapies at any time (Table). No difference in 3-year OS was seen but 4-year OS was numerically higher in cohort B, with a trend towards improved OS in the new era. Conclusions: In an era with access to more than one life prolonging therapy for mCRPC, greater use of these agents in pts who transition through nmCRPC to mCRPC did not improve 3-year OS but may impact longer term OS.

* Evaluable N=134 (cohort A) and 59 (cohort B); life prolonging mCRPC therapies: docetaxel, cabazitaxel, enzalutamide, abiraterone, sipuleucel-T, radium **Follow-up was truncated at 4 years. Multivariable model is adjusted for Gleason (≤7 vs >7), log(PSA) and PSA doubling time (≥ 6 vs < 6 mos).