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Background There is a considerable need to incorporate biomarkers of resistance to new antiandrogen agents in the management of castration-resistant prostate cancer (CRPC). Methods We conducted a phase II trial of enzalutamide in first-line chemo-naïve asymptomatic or minimally symptomatic mCRPC and analyzed the prognostic value of TMPRSS2-ERG and other biomarkers, including circulating tumor cells (CTCs), androgen receptor splice variant (AR-V7) in CTCs and plasma Androgen Receptor copy number gain (AR-gain). These biomarkers were correlated with treatment response and survival outcomes and developed a clinical–molecular prognostic model using penalized cox-proportional hazard model. This model was validated in an independent cohort. Results Ninety-eight patients were included. TMPRSS2-ERG fusion gene was detected in 32 patients with no differences observed in efficacy outcomes. CTC detection was associated with worse outcome and AR-V7 in CTCs was associated with increased rate of progression as best response. Plasma AR gain was strongly associated with an adverse outcome, with worse median prostate specific antigen (PSA)-PFS (4.2 vs. 14.7 m; p

96 Background: Radium-223 represents an option for symptomatic metastatic castration-resistant prostate cancer (mCRPC) after demonstrated an overall survival improvement in the ALSYMPCA trial. Radium-223 real-life experiences are scarce, particularly after the results of the ERA-223 trial. To describe Radium-223 outcomes in real life practice, and specifically those related with bone health, sequence of treatment, and prognostic factors. Methods: Multicenter retrospective study of a cohort of 143 patients with mCRPC treated with Radium-223 in either the second line or third line of therapy or beyond in the context of routine clinical practice between 11 March 2013 and 26 July 2022, in seven Galician hospitals. Survival estimates were calculated by the Kaplan-Meier method, and groups were compared with the log-rank test. The Cox proportional hazards regression model was used to evaluate factors independently associated with OS. Between March 11, 2013, and July 26, 2022, 143 patients were enrolled from 5 Galician hospitals. With a median follow-up of 9.68 months. All patients signed an informed consent form agreeing to participate in this observational study, that was approved by the Galician Ethics Committee, registration code 2018/282. Results: Baseline patient and disease characteristics are summarized. Median follow-up was 9.68 months. Median overall survival (OS) was 12 months (95% CI 9.7 – 16.0). Best OS outcomes were achieved in second and third line, 18 months (95% CI 12.0 – 26.0) and 9.4 months (95% CI 8.0 – 12.0) months, respectively. Among those baseline clinic-analytical factors analyzed, only alkaline phosphatase level >354 UI/L was correlated with a worse OS (HR 2.56 (95% CI 1.39 – 4.72; p=0.003) and the number of cycles of Radium-223 received (HR 0.63 (95% CI 0.54 – 0.73; p