Metastasis-directed stereotactic ablative radiotherapy (SABR/SBRT) prolongs systemic therapy efficacy and improves cancer control in oligoprogressive castration-resistant prostate cancer

Abstract

Background: Systemic therapies for castration-resistant prostate cancer (CRPC) provide limited survival benefit, creating interest in metastasis-directed therapy (MDT) for oligometastatic or oligoprogressive prostate cancer to improve clinical outcomes. Objective: To report outcomes after MDT with stereotactic ablative radiotherapy (SABR; stereotactic body radiotherapy, SBRT) for oligoprogressive CRPC. Design, Setting, and Participants: Patients with oligoprogressive CRPC were retrospectively evaluated, and outcomes after MDT were analyzed. Outcomes were also compared with those in patients with oligoprogressive CRPC managed with a change in systemic therapy alone. Intervention: SABR delivered to oligoprogressive metastatic lesions. Outcome Measurements and Statistical Analysis: Endpoints were time to prostate-specific antigen (PSA) failure, time to next intervention (TTNI), distant metastasis-free survival (DMFS), and overall survival. Survival was estimated using the Kaplan-Meier method, with univariable analysis and multivariable analysis (MVA). Results and Limitations: Overall, 68 patients were included. After MDT, median time to PSA recurrence, TTNI, and DMFS were 9.7, 15.6, and 10.8 months, respectively. Across 112 treated lesions, the cumulative incidences of local failure at 12 and 24 months were 2.1% and 13.8%, respectively. On univariable analysis, factors associated with risk of local recurrence were age (hazard ratio [HR] 1.07, p = 0.03) and Gleason grade group (HR 2.20, p = 0.07). Compared with change in systemic therapy alone (n = 52), MDT (n = 31) was associated with longer median time to PSA failure (9.7 vs 4.2 months, p = 0.066), TTNI (14.9 vs 8.8 months, p = 0.025), and DMFS (12.7 vs 8.9 months, p = 0.045), and remained associated with improved outcomes on MVA. Conclusions: In this retrospective cohort of patients with oligoprogressive CRPC, MDT using SABR was associated with favorable outcomes and improved cancer control compared with change in systemic treatment alone. Prospective trials are needed to confirm these findings. Patient Summary: We retrospectively analyzed patients with oligoprogressive castration-resistant prostate cancer treated with radiation therapy to progressing lesions. The results suggest that SABR to these lesions can produce sustained periods of disease-free survival and may add benefit to systemic therapy at progression. These findings require prospective verification to define optimal integration of radiotherapy into metastatic castration-resistant prostate cancer care.