The STAMPEDE (Systemic Therapy for Advanced or Metastatic Prostate cancer: Evaluation of Drug Efficacy) trial is a large randomized controlled phase 3 study that evaluated the addition of radiotherapy to standard systemic therapy for men with newly diagnosed metastatic prostate cancer. The primary outcome was overall survival, with failure-free survival, progression-free survival, and other secondary outcomes also assessed. The trial included 2061 patients from 117 hospitals in Switzerland and the UK. Patients were randomly assigned in a 1:1 ratio to standard of care (control group) or standard of care plus radiotherapy. Radiotherapy was delivered either daily (55 Gy in 20 fractions over 4 weeks) or weekly (36 Gy in six fractions over 6 weeks). The primary outcome analysis was by intention to treat. The median follow-up was 37 months. Radiotherapy did not improve overall survival (hazard ratio [HR] 0·92, 95% CI 0·80–1·06; p=0·266), but it improved failure-free survival (HR 0·76, 95% CI 0·68–0·84; p<0·0001). Subgroup analyses showed that radiotherapy improved overall survival in patients with a low metastatic burden (HR 0·68, 95% CI 0·52–0·90; p=0·007), but not in those with a high metastatic burden (HR 1·07, 95% CI 0·90–1·28; p=0·420). Adverse events were generally well tolerated, with a low incidence of grade 3 or 4 adverse events. In conclusion, radiotherapy to the prostate did not improve overall survival in unselected patients with newly diagnosed metastatic prostate cancer, but it may be beneficial in those with a low metastatic burden.The STAMPEDE (Systemic Therapy for Advanced or Metastatic Prostate cancer: Evaluation of Drug Efficacy) trial is a large randomized controlled phase 3 study that evaluated the addition of radiotherapy to standard systemic therapy for men with newly diagnosed metastatic prostate cancer. The primary outcome was overall survival, with failure-free survival, progression-free survival, and other secondary outcomes also assessed. The trial included 2061 patients from 117 hospitals in Switzerland and the UK. Patients were randomly assigned in a 1:1 ratio to standard of care (control group) or standard of care plus radiotherapy. Radiotherapy was delivered either daily (55 Gy in 20 fractions over 4 weeks) or weekly (36 Gy in six fractions over 6 weeks). The primary outcome analysis was by intention to treat. The median follow-up was 37 months. Radiotherapy did not improve overall survival (hazard ratio [HR] 0·92, 95% CI 0·80–1·06; p=0·266), but it improved failure-free survival (HR 0·76, 95% CI 0·68–0·84; p<0·0001). Subgroup analyses showed that radiotherapy improved overall survival in patients with a low metastatic burden (HR 0·68, 95% CI 0·52–0·90; p=0·007), but not in those with a high metastatic burden (HR 1·07, 95% CI 0·90–1·28; p=0·420). Adverse events were generally well tolerated, with a low incidence of grade 3 or 4 adverse events. In conclusion, radiotherapy to the prostate did not improve overall survival in unselected patients with newly diagnosed metastatic prostate cancer, but it may be beneficial in those with a low metastatic burden.