Phase II Trial Investigating Definitive Radiation Therapy in Lieu of Systemic Therapy for Oligometastatic Renal Cell Carcinoma

Background: The role of definitive radiation therapy (RT) in metastatic renal cell carcinoma (RCC) is controversial. We prospectively tested the feasibility, efficacy, and safety of definitive RT to defer systemic therapy for patients with oligometastatic RCC. Methods: This single-arm phase 2 study (NCT03575611) enrolled patients with histologically confirmed RCC, ≤5 metastatic lesions, and ≤1 prior systemic therapy. Patients were treated with definitive RT to all lesions and maintained off systemic therapy. Additional rounds of RT were allowed to treat new sites of progression. The co-primary endpoints were progression-free survival (PFS) and feasibility. Criteria for initiating systemic therapy were progression in >3 lesions, toxicity, local progression, or patient/provider preference. Findings: Thirty patients were enrolled in July 2018–September 2020 (median follow-up time 17.5 months). All patients had clear cell histology and had undergone nephrectomy before enrollment. Nine patients (30%) had received one prior systemic therapy. All patients completed initial RT and 13 (43%) received a second round. Median PFS was 22·7 months (1-year PFS rate 64%). All patients were alive at last follow-up, and one local failure was observed. The 1-year systemic therapy–free survival was 82%, with 7 patients (23%) initiating systemic therapy at a median 8.1 months from enrollment. Adverse events were grade ≥2 in six patients and ≥3 in three patients. At first follow-up, no viable tumor cells were detected in 5 of 14 biopsy samples obtained after RT (36%). For patients in whom viable tumor was present, the Ki-67 labeling index was significantly reduced (P =0·0068).  Interpretation: Sequential definitive RT is a feasible and effective strategy for patients with oligometastatic RCC seeking to defer systemic therapy. Clinical Trial Registration: This study is registered with ClinicalTrials.gov as NCT03575611. Funding: Grant support from the Anna Fuller Foundation, the Cancer Prevention and Research Institute of Texas (CPRIT), and the National Cancer Center, National Institutes of Health (P30 CA016672, PI P. Pisters). Declaration of Interest: PM has received honoraria for service on scientific advisory boards for Mirati Therapeutics, Bristol- Myers Squibb, and Exelixis; consulting for Axiom Healthcare Strategies; non-branded educational programs supported by Exelixis and Pfizer; and research funding for clinical trials from Takeda, Bristol- Myers Squibb, Mirati Therapeutics, Gateway for Cancer Research, and UT MD Anderson Cancer Center. INCOMPLETE Ethical Approval: This protocol underwent full approval by the Institutional Review Board at MD Anderson. All patients provided written informed consent to participate.