Why is a small retrospective study with radium-223 [1] important enough to warrant publication in this European Urology issue? To better understand the context, one needs to understand the actionable mutations in prostate cancer. In 2016, a seminal study [2] investigating the molecular genetics of prostate cancer in depth revealed a surprise. In addition to the widely known and appreciated importance of androgen receptors in advanced prostate cancer, there was also a remarkably frequent occurrence of DNA repair defects present in metastatic castrate-resistant prostate cancer (CRPC).