Stereotactic Radiation for Systemic Therapy-naïve Oligometastatic Kidney Cancer: Final Results of a Phase 2b Trial

Management of oligometastatic renal cell carcinoma (omRCC) remains undefined, especially in favorable- and intermediate-risk patients, in whom treatment de-escalation may reduce toxicity and preserve quality of life. This study aims to evaluate sequential stereotactic ablative radiotherapy (SAbR) as first-line therapy in systemic therapy-naïve patients with omRCC.

A prospective, single-arm, phase 2b trial enrolled systemic therapy-naïve renal cell carcinoma (RCC) patients with three or fewer extracranial metastases, all treated with SAbR to all sites. The primary endpoint was to measure the percentage of patients with time to systemic therapy (TTST) >1 yr. Modified progression-free survival (mPFS) was defined as the earliest time of developing one of the following predefined criteria for local therapy escalation: more than three new metastases, more than six total metastases, local failure at an SAbR-treated site, brain metastases, or lesions not amenable to SAbR. The secondary endpoints included mPFS, progression-free survival on subsequent therapy, overall survival (OS), cancer-specific survival (CSS), local control, toxicity, and health-related quality of life (HRQoL).

Twenty-three patients received SAbR to 69 lesions. The median follow-up was 45 mo. TTST >1 yr was achieved in 91% of patients; the median TTST was 55.6 mo. The median mPFS was 40 mo. Local control was 100%. The 3-yr OS and CSS rates were 68.7% and 87.0%, respectively. One patient developed grade 3 colitis possibly related to SAbR, progressing to grade 5 following immunotherapy. HRQoL remained stable. Single-arm design limits causal inference and generalizability.

Sequential SAbR achieved durable disease control and was not associated with significant changes in patient-reported quality of life, supporting a survivorship-centered, de-escalation strategy that avoids early systemic therapy in selected omRCC patients.