Early findings from the GARUDA trial: The impact of a genetic signature of late radiation toxicity on prostate cancer treatment decision-making

As definitive treatments for localized prostate cancer are highly effective, post-treatment quality of life has become a key consideration in patient-physician shared decision-making.¹ 

A significant side effect of definitive radiotherapy is late grade ≥ 2 genitourinary (GU) toxicity—typically presenting three to six months after treatment as urinary frequency, urgency, or incontinence—which affects approximately 15% of patients.^2,3 These rates appear comparable between conventional fractionation and stereotactic body radiotherapy (SBRT).^4,5

PROSTOX is a diagnostic test that identifies prostate cancer patients at risk for late GU toxicity from SBRT before treatment begins.⁶ It analyzes a patient’s germline DNA for microRNA-associated single nucleotide polymorphisms (mirSNPs). Its purpose is to help guide safer, more personalized treatment choices.

In the GARUDA phase II prospective study, researchers at UCLA’s Department of Radiation Oncology evaluated whether PROSTOX results would influence joint treatment decisions in patients with prostate cancer and their physicians. Patients evaluated for SBRT were tested for PROSTOX, and results were shared. Patients who chose either SBRT or moderately/conventionally fractionated radiation therapy (MHFRT/CFRT) after receiving a low-risk or high-risk PROSTOX score were enrolled in the study.

Key findings:

• Treatment choices were impacted based on PROSTOX results.
• Observed toxicity aligned with genetic risk prediction.
• No significant differences in risk classification by age, race, or ethnicity.

The GARUDA study demonstrates that PROSTOX results influence treatment selection, with patients and physicians adjusting decisions based on predicted toxicity. These results support the utility of using genetic toxicity risk assessment in guiding more personalized approaches to prostate cancer radiation therapy.

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References

1. Hoffman KE, et al. Patient-reported outcomes through 5 years for active surveillance, surgery, brachytherapy, or external beam radiation with or without androgen deprivation therapy for localized prostate cancer. JAMA 2020 Jan;323:149.
2. Michalski JM, et al. Effect of standard vs dose-escalated radiation therapy for patients with intermediate-risk prostate cancer: The NRG Oncology RTOG 0126 Randomized Clinical Trial. JAMA Oncol 2018 Jun;4:e180039.
3. Meier RM, et al. Multicenter trial of stereotactic body radiation therapy for low- and intermediate-risk prostate cancer: survival and toxicity endpoints. Int J Radiat Oncol Biol Phys 2018 Oct;102:296-303.
4. Fransson P, et al. Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer: 5-year outcomes of the HYPO-RT-PC randomised, non-inferiority, phase 3 trial. Lancet 2019 Feb;394:385-95.
5. Kishan AU, et al. Long-term outcomes of stereotactic body radiotherapy for low-risk and intermediate-risk prostate cancer. JAMA Netw Open 2019 Feb;2:e188006.
6. Kishan AU, et al. Germline variants disrupting microRNAs predict long-term genitourinary toxicity after prostate cancer radiation. Radiother Oncol 2022 Feb;167:226-232.