Phase III randomized trial of stereotactic ablative radiotherapy (SAbR) for oligometastatic advanced renal carcinoma (EA8211-SOAR).

TPS615 Background: The optimal frontline management strategy for oligometastatic renal cell carcinoma (omRCC) is uncertain. Systemic therapy (ST) is the standard, but Stereotactic Ablative Radiation (SAbR) offers an alternative, and may potentially reduce ST-associated toxicity. However, concerns remain about occult micro-metastases progression with SAbR. Retrospective studies suggest focal therapies may improve outcomes in select patients, but prospective data is limited. This ECOG-ACRIN phase 3 randomized trial compares SAbR with ST in omRCC, assessing whether SAbR followed by delayed ST can offer non-inferior OS with lower toxicity compared to upfront ST. The co-primary endpoints are OS and grade ≥3 toxicity. Hypothesis: For omRCC patients with 2-5 measurable metastases, SAbR followed by delayed ST will result in non-inferior OS compared to immediate while reducing grade ≥3 toxicity. Methods: This phase 3 trial will enroll patients with oligometastatic RCC with 2-5 extracranial metastases amenable to SAbR and an ECOG performance status of 0-2, categorized as favorable or intermediate risk according to modified IMDC criteria. Patients must have their primary tumor treated by surgery or radiation before enrollment. Exclusions include brain metastases, sarcomatoid histology, prior systemic therapy for metastatic disease (adjuvant therapy is allowed), and poor-risk IMDC classification. Participants will be stratified by number of metastases, histology, IMDC risk, prior adjuvant therapy, and time since primary site treatment. Patients will be randomized to either upfront ST or SAbR with delayed ST. Statistical Design: The trial has 85% power to establish non-inferiority of SAbR with respect to OS, assuming a null hazard ratio of 1.24 and an alternative of 0.85. If non-inferior OS is shown, the study will test whether SAbR reduces grade ≥3 toxicity. Secondary endpoints include progression-free survival (PFS) and quality of life, measured by NFKSI-19 and EQ-5D-5L scales. Exploratory endpoints will assess cost-effectiveness and circulating tumor DNA (ctDNA) as a biomarker. The study opened in September 2023. Research sponsor: U.S. National Institutes of Health. Clinical trial information: NCT05863351 .