Background: The role of cytoreductive local radiotherapy (RT) in metastatic prostate cancer (mPCa) has recently been established. This study aimed to evaluate the biochemical outcome of local RT in mPCa.

Methods: This randomised controlled phase III study was conducted at the Clinical Oncology Department, Suez Canal University Hospital. Eligible participants were de-novo or metachronous mPCa patients with Eastern Cooperative Oncology Group performance status of 0–2. Participants were randomised to receive either cytoreductive prostate-directed RT in addition to standard care or standard care alone. The conventional radiation schedule of 70 Gy/35 fractions or the hypofractionated schedule of 55 Gy/20 fractions were delivered. The primary endpoint was biochemical progression-free survival (BPFS), and the secondary endpoint was overall survival (OS). Survival and post-hoc analyses were performed using Cox regression and the Kaplan-Meier method with the log-rank test.

Results: Between 23 November 2020 and 21 2022, 70 patients were enrolled in this study. Of them, 34 patients were assigned to the prostate RT group, and 29 patients were assigned to the control group. At a median follow-up of 12 months, the median BPFS has not been reached for the prostate RT group compared to 4.067 months for the control group (HR: 0.147, p < 0.001). Subgroup analysis showed that the median BPFS was statistically significantly correlated with low-volume (95% CI, 0.004 to 0.262, p = 0·001) and hormonal-sensitive metastatic disease (95% CI, 0.010 to 0.192, p < 0·001). The median OS was 16.33 months for the prostate-RT group compared to 11.33 months for the control group (HR: 0.313, p = 0.003).

Conclusion: Prostate-directed RT improved BPFS and OS in mPCa patients, particularly in those with low volume and hormonal-sensitive disease.

Trial Registration: This trial is registered on (27/4/2023), retrospectively registered with pactr.samrc.ac.za, PACTR202305854600529, URL: https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=25510