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Prognostic Impact of the Addition of Prostate-Directed Radiotherapy With or Without Metastasis-Directed Radiotherapy
Dai Koguchi1, Hideyasu Tsumura1, Ken-Ichi Tabata2
1Department of Urology, Kitasato University School of Medicine, Sagamihara, Japan.
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.
