The results of the ALSYMPCA international phase III clinical study, published online July 17 in the New England Journal of Medicine, showed that radium 223 prolonged overall survival by nearly four months and reduced the risk of death by 30 percent in patients with debulking refractory bone metastases from prostate cancer (N. Engl. J. Med. 2013 July 17 [doi: 10.1056/ NEJMoa1213755]). In this study, Christopher Parker, MD, of the Royal Marsden Hospital in Sutton, England, and colleagues enrolled 921 male patients with progressive decompensated refractory prostate cancer with ≥2 symptomatic bone metastases and no visceral metastases from 136 study centers in 19 countries. All patients required conventional analgesic medications or other treatments to relieve cancer-related bone pain. Patients were stratified according to whether they had been treated with doxorubicin or diphosphonates and according to baseline alkaline phosphatase levels, and then randomized to 614 patients in the radium 223 group and 307 patients in the matched placebo group for 6 monthly intravenous injections. All patients received the best available standard of care, including local external beam radiation therapy, glucocorticoids, antiandrogens, ketoconazole, or estrogen, concurrently at their respective treatment centers. Therefore, the results of the study should be extrapolated to routine clinical practice. The results showed that the median overall survival (primary endpoint) in the radium 223 group was 14.9 months, significantly longer than the 11.3 months in the placebo group. A total of 528 patients in the intention-to-treat population died; the mortality rates were 54% and 64% in the radium 223 and placebo groups, respectively. Mortality from any cause was 30% lower in the radium 223 group than in the placebo group. These overall survival differences were consistent across all subgroups of patients, regardless of baseline alkaline phosphatase levels, current bisphosphonate application, prior doxorubicin therapy, any opioid application, and extent of underlying cancer. Radium 223 significantly prolonged the time to first symptomatic skeletal event compared to the placebo group (15.6 months vs. 9.8 months). In addition, radium 223 also prolonged the time to increased total alkaline phosphatase levels and PSA levels.FACT-P scores showed that a significantly higher proportion of patients in the radium 223 group had a meaningful improvement in quality of life compared to the placebo group (25% vs. 16%). The overall incidence of adverse events, serious adverse events, grade 3 or 4 adverse events, and hematologic adverse events was lower in the radium 223 group than in the placebo group. The number of discontinued patients in the radium 223 group was less than in the placebo group. This favorable safety profile of radium 223 can be attributed to its highly targeted effect, i.e., it minimizes myelosuppression while having little effect on normal tissues. The study included an important subgroup of patients who were denied or unsuitable for treatment with doxorubicin. Currently, many patients with desmoid-refractory prostate cancer with bone metastases are not treated with doxorubicin because they are frail, have comorbidities that prohibit the drug, or refuse chemotherapy. Therefore, this study addresses an important need in this population of patients who are not receiving current treatment. The investigators said that prostate cancer treatment has evolved since the study began, and new data on cabazitaxel, abiraterone, and enzalutamide have now been accumulated. Future studies should assess the suitability of radium 223 for sequential application or combination with these drugs. Algeta and Bayer Healthcare Pharmaceuticals funded and co-designed and conducted the ALSYMPCA study with the investigators, and Dr. Parker and colleagues declare an affiliation with several companies, including Amgen.