Definitive radiotherapy for extracranial oligoprogressive metastatic renal cell carcinoma as a strategy to defer systemic therapy escalation

Objective To study whether delivering definitive radiotherapy to sites of oligoprogression in metastatic renal cell carcinoma enabled deferral of systemic therapy changes without compromising disease control or survival. Materials/methods We identified patients with metastatic renal cell carcinoma who received radiotherapy to ≤3 sites of extracranial progressive disease in 2014-2019 at a large tertiary cancer center. Inclusion criteria were (1) controlled disease for ≥3 months before oligoprogression, (2) all oligoprogression sites treated with a biologically effective dose of ≥100 Gy, and (3) availability of follow-up imaging. Time-to-event endpoints were calculated from the start of radiotherapy. Results Seventy-two patients were identified (median follow-up time 22 months, 95% confidence interval [CI] 19-32 months), with oligoprogressive lesions in lung/mediastinum (n=35), spine (n=30), and non-spine bone (n=5). The most common systemic therapies before oligoprogression were none (n=33), tyrosine kinase inhibitor (n=23), and immunotherapy (n=13). At 1 year, the local control rate was 96% (95% CI 87%-99%); progression free survival, 52% (95% CI 40%-63%); and overall survival, 91% (95% CI 82%-96%). At oligoprogression, systemic therapy was escalated (n=16), maintained (n=49), or discontinued (n=7), with corresponding median progression free survival intervals of 19.7 months (95% CI 8.2-27.2 months), 10.1 months (95% CI 6.9-13.2 months), and 9.8 months (95% CI 2.4-28.9 months). Of the 49 patients maintained on the same systemic therapy at oligoprogression, 21 did not subsequently have systemic therapy escalation. Conclusion Patients with oligoprogressive metastatic renal cell carcinoma treated with radiotherapy had comparable progression free survival regardless of systemic therapy strategy, suggesting that radiotherapy may be a viable approach for delaying systemic therapy escalation. Randomized controlled trials comparing treatment of oligoprogression with radiotherapy vs. systemic therapy alone are needed.