Outcomes Of Radiotherapy Plus Immunotherapy In Metastatic Renal Cell Carcinoma: Results From The Canadian Kidney Cancer Information System (Ckcis)

With the integration of immunotherapy (IT) in the management of metastatic renal cell carcinoma (mRCC), there has been interest in potential synergy with radiotherapy (RT) based on intriguing preclinical data. However, with prospective trials ongoing, real world evidence is thus far limited. The purpose of this study was to evaluate outcomes in mRCC patients receiving both RT and IT compared to IT alone. Data was collected from CKCis from January 2011 to September 2019 across 16 academic centers. Patients who were diagnosed with mRCC, received IT as first-line or second-line therapy, and had ≥3 months of follow-up were included. RT was further refined into ablative doses with radical intent (RRT) or palliative intent (PRT). Kaplan-Meier estimates were reported for overall survival (OS) and time to treatment failure (TTF). Log-rank tests were used to compare the KM curves and Cox proportional hazard models were used adjust for age and International Metastatic RCC Database Consortium (IMDC) risk categories. In total, 525 patients were included in the study: 199 who received both RT and IT and 326 who received IT alone. Median follow-up was 13.6 months. There were no significant differences in IMDC risk categories between the two cohorts; however, patients receiving RT had more brain (21.6% vs. 5.5%) and bone (59.8% vs. 23.3%) metastases. Overall, 245 patients received first-line combination IT and 280 received second-line monotherapy. In the RT cohort, 54 patients underwent RRT and 145 received PRT. Patients receiving RT had worse TTF (adjusted hazard ratio (aHR): 1.33, p = 0.014; 95% CI: 1.06-1.67) and numerically worse OS compared to patients with IT alone (2-year OS: 47.6% vs. 65.9%), although this difference was not significant (aHR: 1.41, p = 0.051). For first-line patients, there was no significant difference in OS between those who had RT versus IT alone (aHR: 1.22, p = 0.563) but RT patients had worse TTF (aHR: 1.42, p = 0.038; 95% CI: 1.02-1.98). Within the first-line IT cohort, there was no differences in OS between patients receiving RRT (aHR: 0.50, p = 0.352) or PRT (aHR: 1.60, p = 0.198), compared to IT alone. In this exploratory analysis, patients with mRCC receiving RT appear to have more bone and brain metastasis, which are known poor prognostic metastatic sites. The addition of RT to IT resulted in similar OS and TTF compared to IT alone in mRCC. Limitations include population heterogeneity and potential for selection bias. Case-matched investigations in subgroups of interest, with a focus on RT and IT timing and sequencing, are part of ongoing evaluation. Prospective clinical trials evaluating potential benefits of RT in an IT era remain an important need.