Long-term treatment outcomes from the International Multi-Institutional Stereotactic Body Radiation Therapy for High-Risk Localized Carcinoma of the Prostate (SHARP) Consortium.
Authors: Valle Luca Faustino , Romero Tahmineh , Jiang Tommy , Van Dams Ritchell , Fuller Donald B. , Loblaw Andrew , Kennedy Thomas , Collins Sean P. , Sharma Vaibhav , Suy Simeng , Murthy Vedang , Mallick Indranil , Nickols Nicholas George , Steinberg Michael L. , Kishan Amar Upadhyaya 
Published: January 2024

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Background: Stereotactic body radiation therapy (SBRT) leverages advanced image-guided radiotherapy techniques to deliver high doses of radiation over the course of 5 or fewer treatments. High-risk localized prostate cancer has been historically treated with more protracted conventional radiotherapeutic techniques, though use of SBRT is now supported in this setting by subgroup analyses of randomized trials as well as medium-term prospective data from phase II trials. However, most patients with high-risk prostate cancer continue to receive extended treatment courses in part due to trepidation surrounding the long-term outcomes of SBRT in high-risk disease. We sought to report long-term efficacy and toxicity outcomes from the SHARP consortium for men with high-risk prostate cancer treated with SBRT. Methods: Individual patient data from men prospectively treated on five clinical trials evaluating SBRT for high-risk prostate cancer across five institutions were pooled. Analysis was limited to patients with more than 24 months of follow-up. Adjusted 5-year overall survival (OS) was calculated for the entire cohort of high-risk patients. Kaplan-Meier analyses estimated 5-year biochemical recurrence-free survival (BCRFS) and 5-year distant metastasis-free survival (DMFS) stratified by receipt of androgen deprivation therapy (ADT). Multivariate analysis quantified the benefit of adding ADT to SBRT, adjusting for patient age, iPSA, Gleason Score, T category, ADT use, and nodal radiation. Crude rates of CTCAE grade 3 or greater GI or GU toxicity were calculated. Results: Data from 373 prospectively treated patients were pooled for analysis. Median follow-up time was 60.2 months. 282 (75.6%) patients received ADT for a median duration of 9 months. Adjusted 5-year overall survival was 87.9% (95% CI 84.2%-91.6%). Estimated 5-year BCRFS for men who received ADT was 81.4% (95% CI 76.2% - 86.5%) compared to 77.2% (95% CI 66.9% -87.6%) for men who did not (logrank p=0.04). Estimated 5-year DMFS was 92.4% (95% CI 89.1%-95.8%) for men who received ADT versus 93.6% (95% CI 87.5%-99.8%) for men who did not (logrank p=0.62). On MVA, adjusted HR for BCRFS with use of ADT compared to no ADT was 0.7 (p=0.017). Crude incidence rate of late grade 3 or greater genitourinary or gastrointestinal toxicity was 4.1%. Conclusions: The safety and efficacy profile of SBRT for high-risk prostate cancer remains favorable at long-term follow-up. ADT of medium duration improves BCRFS in men with high-risk prostate cancer but did not reduce the incidence of metastatic failure at a median of 60 months. SBRT and ADT should be routinely integrated into shared decision-making for men with high-risk prostate cancer pursuing definitive radiotherapeutic treatment.