Dai Koguchi, Hideyasu Tsumura, Ken-Ichi Tabata, Takefumi Satoh, Yutaka Shiono, Shuhei Hirano, Masaomi Ikeda, Yasufumi Yamada, Kazuki Matsushita, Rena Tanaka, Daisuke Ishii, Hiromichi Ishiyama, Kazumasa Matsumoto
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.
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.