1253 - Impact of Early vs. Delayed All-Site Radiotherapy on Clinical Outcomes in High Gleason Score Metastatic Hormone-Sensitive Prostate Cancer: Results from a Long-Term Study

Purpose/Objective(s): The all-site radiotherapy for malignant prostate cancer may confer survival benefits. However, the optimal timing of radiotherapy (RT) in metastatic hormone-sensitive prostate cancer (mHSPC) patients receiving standard systemic therapy remains unclear. This study aimed to compare the efficacy and safety of early RT (within 6 months of systemic therapy initiation) versus delayed RT (>6 months) on castration-resistant prostate cancer-free survival (CRPCFS) for high Gleason Score mHSPC.

Materials/Methods: This study enrolled patients diagnosed with high Gleason Score (including a 5-score component) mHSPC from 2018 to 2025 who received standard systemic therapy followed by all-site RT (radiotherapy to all detectable lesions) at various time points. Patients were categorized into early RT (RT = 6 months) and delayed RT (RT > 6 months) groups based on actual RT timing at the landmark. Inverse probability of treatment weighting (IPTW) was applied to balance baseline characteristics. The primary endpoint was CRPCFS, analyzed using IPTW-weighted Cox proportional hazards models. Secondary endpoints included progression-free survival (PFS), overall survival (OS), prostate cancer-specific survival (PCSS), and PSA progression-free survival (PSAPFS). Sensitivity analyses included multivariable-adjusted IPTW Cox models, Fine-Gray competing risk models, and different landmark points.

Results: Of 196 mHSPC patients, 190 were included in the landmark analysis cohort after excluding 6 patients with pre-landmark events, with 65 patients (34.2%) in the early RT group and 125 patients (65.8%) in the delayed RT group. IPTW achieved excellent covariate balance. The median follow-up time was 33.1 months (IQR, 23.3-45.9). The 6-year outcomes demonstrated significant differences between the two groups. Early RT significantly improved CRPCFS compared to delayed RT (71.1% vs. 44.0%, median survival: Not reached vs. 38.6 m, P=0.002). Results were consistent in multivariable-adjusted models (P=0.002) and Fine-Gray competing risk analyses (P=0.008). Early RT also significantly improved PFS (median survival: 53.4m vs. 50.5m, P=0.036), OS (median survival not reached, P=0.041), PCSS (median survival not reached, P<0.001), and PSAPFS (median survival: 57.9m vs. 39.6m, P=0.002). Sensitivity analyses using different landmark points (3-24 months) and Fine-Gray competing risk models confirmed robustness. Subgroup analysis suggested consistent benefits across high and low tumor volume groups (P-interaction=0.191).

Conclusion: Early radiotherapy within 6 months of systemic therapy initiation significantly improves CRPCFS, PFS, OS, PCSS, and PSAPFS in high Gleason Score mHSPC patients compared to delayed radiotherapy, with a consistent treatment effect across tumor volume subgroups and tolerable adverse effects. These findings support early integration of all-site radiotherapy in the management of mHSPC.