A commentary notes that although this study does provide necessary safety data and also overall survival data suggesting a greater benefit from radium-223 with concomitant enzalutamide, abiraterone, or denosumab, compared with radium-223 monotherapy, these data alone are not sufficient to warrant the use of combination therapy in all patients, and randomised trials are required to confirm the potential efficacy suggested by these findings. It adds that if radium-223 could extend the benefit of these anti-androgens beyond the emergence of resistant androgen receptor subclones, it could favourably impact disease progression and overall survival, and given the disparate mechanisms of action, combining radium-223 and anti-androgens seems to be a rational strategy to contend with androgen receptor-resistance. It suggests that the potential of radium-223 appears unfulfilled, but perhaps the data from this study can provide the foundation for future therapeutic strategies employing this clinically active radiopharmaceutical.