Radium-223 use and survival by line of treatment in metastatic castration-resistant prostate cancer: a nationwide population-based register study.

BACKGROUND: The role and optimal sequencing of radium-223 in the treatment of metastatic castration-resistant prostate cancer (mCRPC) remain debated. In Europe, radium-223 is restricted to third line treatment or later for chemotherapy-eligible men, although studies suggest greater benefit with earlier use. In this nationwide, population-based study, we investigated radium-223 use in Sweden and analyzed the association between line of treatment and overall survival. METHODS: Men with mCRPC who started radium-223 in 2014-2020 were identified in national registers. The Kaplan-Meier method was used to estimate survival. The association between line of treatment and survival was analyzed with Cox regression and presented as adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs). A subgroup with at least three mCRPC treatment lines was similarly analyzed. RESULTS: 1,133 men were included. Median overall survival was 13.9 months (95% CI 13.0-14.5). Later line of radium-223 treatment was associated with shorter survival; with first line as reference, aHR for death for second line was 1.34 (95% CI 1.12-1.59) and for third line 1.55 (1.29-1.87). The opposite was observed for 596 men with at least three lines of mCRPC treatment: aHR for second line was 0.80 (0.59-1.08) and for third line 0.78 (0.59-1.03). INTERPRETATION: Survival after start of radium-223 in Sweden was comparable to pivotal trials, suggesting effective use. Our overall results do not suggest a better effect of radium-223 in first versus later mCRPC treatment lines but rather emphasize the value of a randomized controlled trial to more definitely determine the optimal timing of radium-223 treatment.