Stereotactic Ablative Radiation Therapy for Oligoprogressive Metastatic RCC: Predictors of Prolonged Benefit from Ongoing Systemic Therapy.

Abstract

Stereotactic Ablative Radiation Therapy (SABR) is increasingly employed to treat limited sites of oligoprogression in metastatic renal cell carcinoma during systemic therapy (ST). The patient subgroups most likely to benefit remain undefined. We retrospectively analyzed 96 patients with oligoprogression in metastatic renal cell carcinoma who received SABR to 153 lesions between 2010 and 2023, representing one of the largest and longest-followed cohorts reported to date. We applied the novel endpoint of modified progression-free survival (mPFS), defined as time from SABR to ST switch or death, and evaluated systemic therapy escalation as a competing risk event. Secondary endpoints included overall survival, local control, and toxicity. At a median follow-up of 59 months (IQR, 44-70), median mPFS was 9.2 months, with a 1-year estimate of 38% (95% CI, 29-49). Compared with patients with a single lesion, those with 2-3 (hazard ratio [HR], 2.10; 95% CI, 1.29-3.43; P = .003) and 4-5 lesions (HR, 2.84; 95% CI, 1.00-8.13; P = .05) had significantly higher hazard of ST switch or death. Patients receiving immunotherapy showed a nonsignificant evidence toward improved mPFS (HR, 0.66; 95% CI, 0.41-1.05; P = .08). More than one prior line of ST before SABR was associated with worse overall survival (HR, 1.29; 95% CI, 1.02-1.65; P = .04). Local control was 93%, with only one grade 3 toxicity. In patients with OP-RCC treated with SABR, those with a single progressing lesion had the best outcomes. This approach provided high local control with minimal toxicity while deferring systenic therapy escalation, supporting its role as a resource-sparing, patient-centered strategy. Patients treated concurrently with immunotherapy demonstrated a nonsignificant evidence toward improved outcome, highlighting the need for prospective studies to determine whether SABR affects the benefit from immunotherapy in selective patients.