Germline Radiosensitivity Biomarker for Radiation-Induced GU Toxicity Following Radiation Therapy in Localized Prostate Cancer (GARUDA): Two-Year Outcomes of a Phase II Clinical Trial
Journal of Clinical Oncology (2026)
Background: Stereotactic body radiation therapy (SBRT) is increasingly used for localized prostate cancer, yet treatment-related genitourinary (GU) toxicity remains a concern, with grade ≥2 GU toxicity after SBRT impacting nearly one-third of patients two years after treatment. PROSTOX, a biomarker based on germline genetic variants, may identify patients who are more likely to experience late grade ≥2 GU toxicity after SBRT. The GARUDA trial prospectively evaluated whether pre-treatment determination of PROSTOX status followed by shared decision-making on treatment choice would lead to lower rates of late grade ≥2 GU toxicity in a cohort of patients that would otherwise receive SBRT. Methods: GARUDA (NCT04624256) was a single-arm, prospective Phase II trial that enrolled patients with localized prostate cancer considering SBRT. Participants underwent PROSTOX testing prior to treatment and were offered SBRT (40 Gy in 5 fractions) or moderately hypofractionated radiotherapy (MHFRT, 60 Gy in 20 fractions). Co-primary endpoints were physician-scored acute and late GI and GU toxicity by CTCAE 4.03 and PROs assessed by the Expanded Prostate Cancer Index-26 (EPIC-26) and International Prostate Symptom Scores (IPSS). This is a secondary endpoint analysis of 2-year toxicity outcomes. Results: Between November 2020 and May 2022, 208 patients were enrolled. Median follow-up was 25 months (IQR: 24–30). Based on PROSTOX, 180 patients (86.5%) were classified as low-risk and 28 (13.5%) as high-risk for late grade ≥2 GU toxicity. Among low-risk patients, 98.6% elected SBRT and 1.4% chose MHFRT; among high-risk patients, 57.1% chose SBRT and 42.9% MHFRT. Of those treated with SBRT, 66% received MRI-guided SBRT. The 2-year cumulative incidence of late grade ≥2 GU toxicity for the whole cohort was 18%. Conclusions: Two-year data from the GARUDA trial support the clinical utility of a germline biomarker in predicting radiation-related GU toxicity. Despite high-dose SBRT being delivered in 93% of patients, the incidence of grade ≥2 GU toxicity at two years was lower than expected. These findings highlight the potential of integrating germline biomarkers into radiation planning for men with localized prostate cancer. Clinical trial information: NCT04624256.
Recommended citation: Juarez Casillas, J.E., Jamshidian, P., Casado, M.U., Flores, K., Marco, N., Steinberg, M.L., Lee, A., Xiang, M., Valle, L.F., Stube, A., Telesca, D., Weidhaas, J.B. and Kishan, A.U., 2026. Germline Radiosensitivity Biomarker for Radiation-Induced GU Toxicity Following Radiation Therapy in Localized Prostate Cancer (GARUDA): Two-Year Outcomes of a Phase II Clinical Trial. Journal of Clinical Oncology, 44(7_suppl), pp.359-359.