Parker CC, et al. - In this randomized controlled phase 3 trial performed at 117 hospitals in Switzerland and the UK, researchers investigated whether radiotherapy to the prostate would improve overall survival in men with metastatic prostate cancer and, in patients with a low metastatic burden, if the benefit would be greatest. For this purpose, they compared the standard of care, with and without radiotherapy, for metastatic prostate cancer. Outcomes suggested that, for unselected patients with newly diagnosed metastatic prostate cancer, no improvement in overall survival was achieved administering radiotherapy to the prostate.

Methods

• At 117 hospitals in Switzerland and the UK, researchers performed a randomized controlled phase 3 trial including patients who had newly diagnosed metastatic prostate cancer.
• Patients were randomly (1:1) allocated to standard of care (control group) or standard of care and radiotherapy (radiotherapy group).
• They performed stratification of randomization by hospital, age at randomization, nodal involvement, WHO performance status, planned androgen deprivation therapy, planned docetaxel use (from December 2015), and regular aspirin or non-steroidal anti-inflammatory drug use.
• Lifelong androgen deprivation therapy, with up-front docetaxel permitted from December 2015, comprised the standard of care.
• Before randomization, men allocated radiotherapy were nominated to receive either a daily (55 Gy in 20 fractions over 4 weeks) or weekly (36 Gy in six fractions over 6 weeks) schedule.
• Overall survival, measured as the number of deaths, was assessed as the primary outcome; this analysis had 90% power with a one-sided α of 2.5% for a hazard ratio (HR) of 0.75.
• Failure-free survival, progression-free survival, metastatic progression-free survival, prostate cancer-specific survival, and symptomatic local event-free survival were assessed as the secondary outcomes.
• Cox proportional hazards and flexible parametric models, adjusted for stratification factors, were used for analyses.
• Intention to treat analysis was performed for the primary outcome.
• They performed two prespecified subgroup analyses to determine the effects of prostate radiotherapy by baseline metastatic burden and radiotherapy schedule.

Results

• Randomization was performed for 2,061 men between January 22, 2013 and September 2, 2016; 1,029 were allocated the control and 1,032 radiotherapy.
• Allocated groups were balanced; median age was 68 years (IQR 63–73) and median amount of prostate-specific antigen was 97 ng/mL (33–315).
• Early docetaxel was given to 367 (18%) patients.
• Before randomization, 1082 (52%) participants were nominated the daily radiotherapy schedule and 979 (48%) the weekly schedule.
• A low metastatic burden was noted in 819 (40%) men, a high metastatic burden in 1,120 (54%) men, and the metastatic burden was unknown for 122 (6%).
• Radiotherapy led to enhanced failure-free survival (HR 0.76, 95% CI 0.68–0.84; p < 0.0001) but not overall survival (0.92, 0.80–1.06; p = 0.266).
• Patients tolerated radiotherapy, with 48 (5%) adverse events (Radiation Therapy Oncology Group grade 3–4) reported during radiotherapy and 37 (4%) after radiotherapy.
• Treatment groups were similar in terms of proportion reporting at least one severe adverse event (Common Terminology Criteria for Adverse Events grade 3 or worse) in the safety population (398 [38%] with control and 380 [39%] with radiotherapy).