Prognostic Impact of the Addition of Prostate-Directed Radiotherapy With or Without Metastasis-Directed Radiotherapy Under Upfront Doublet Therapy for High-Volume Metastatic Hormone-Sensitive Prostate Cancer
In brief
Prostate radiotherapy halves risk of castration resistance in high-volume metastatic hormone-sensitive prostate cancer
In a retrospective series of 239 men receiving upfront doublet therapy, adding prostate-directed radiotherapy (32 patients) extended castration-resistance-free survival by roughly 50% compared with standard care (hazard ratio 0.47). The benefit appeared stronger when metastasis-directed radiotherapy was also used, but the analysis is exploratory and needs prospective confirmation.
- Journal
- The Prostate (Q1)
- Published
- 23 August 2026
- Study design
- Prospective / inception cohort
- Evidence level
- Level 2, Moderate (CEBM 2b)
- Authors
- Dai Koguchi, Hideyasu Tsumura, Ken-Ichi Tabata, Takefumi Satoh, Yutaka Shiono, Shuhei Hirano, et al.
- PMID
- 42633691
- DOI
- 10.1002/pros.70238
Why clinicians should know about it
- Picked for Urology (paper of the day, 24 August 2026): Retrospective cohort of prostate‑directed RT
Abstract
BACKGROUND: Radiotherapy is established as a standard treatment for low-volume metastatic hormone-sensitive prostate cancer (mHSPC), but its prognostic impact for high-volume mHSPC under upfront therapy is unclear. This study investigates the effect of adding prostate-directed radiotherapy (PDRT) with or without metastasis-directed radiotherapy (MDRT) to upfront doublet therapy for high-volume mHSPC. METHODS: We retrospectively assessed 239 patients who received upfront doublet therapy for synchronous high-volume mHSPC between 2018 and 2025. Patients were divided into a PDRT (with or without MDRT; n = 32) and a non-PDRT group (n = 207). The primary endpoint was castration resistance-free survival (CRFS). RESULTS: The median time from treatment initiation for mHSPC to PDRT initiation was 7.0 months. We excluded 31 patients from the non-PDRT group who progressed to castration-resistant prostate cancer within 7.0 months. Our 7-month landmark analysis found significantly prolonged CRFS in the PDRT group compared with the non-PDRT group in a propensity score-matched cohort (hazard ratio [HR] 0.47, 95% CI: 0.23-0.97, p = 0.045). An interaction analysis demonstrated that the effect of MDRT differed according to PDRT status (HR 0.37, 95% CI: 0.22-0.57, p = 0.008). The prolonged survival in the PDRT group remained significant in a time-dependent multivariable Cox analysis (HR 0.47, 95% CI: 0.22-0.88, p = 0.021). CONCLUSIONS: We found significantly prolonged CRFS in the PDRT group compared with the non-PDRT group among patients receiving upfront doublet therapy for high-volume mHSPC. Interaction analysis also suggested that the effect of MDRT may differ according to PDRT status; however, these findings should be regarded as hypothesis-generating. Further large prospective studies are needed to validate these findings in patients with high-volume mHSPC.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.