Association between rheumatoid arthritis, frailty status, mortality and anti-cancer therapy: a retrospective SEER-Medicare analysis in patients with non-metastatic renal cell carcinoma.

Background: Renal cell carcinoma (RCC) patients with rheumatoid arthritis (RA) represent a niche but understudied population that often suffers from comorbid frailty. Frailty and RA may adversely affect treatment and mortality outcomes in patients with cancer. We aim to evaluate the association between RA and mortality/treatment outcomes in patients with RCC, with attention to the impact of frailty on these associations. Methods: Retrospective cohort study examining patients aged 65 and older, with Medicare part A and B coverage and non-metastatic clear cell renal cell carcinoma (ccRCC) diagnosed between 2004-2017 via the Surveillance Epidemiology and End Results (SEER)-Medicare database. Patients stratified by RA, defined by having 2 or more ICD-9 and ICD-10 codes 30 to 365 days apart, and frailty status with a score of ≥0.25 using a validated claims-based frailty index (Kim et al. 2018). Receipt of immunotherapy and cancer-related surgery were assessed and compared. Cox proportional hazards regression models evaluated the association between RA, frailty and mortality (all-cause and cancer-specific). Competing risk analysis using fine-gray model used to assess interaction between RA and frailty with mortality. Results: The population included 31,989 patients, of which 802 patients had RA and 3,918 were frail. Approximately 60% of the population was male. Rates of cancer-related surgery were not significantly changed by RA status. No significant difference in immunotherapy administration based on RA status was observed [odds ratio (OR) 0.81, 95% confidence interval (CI): 0.59-1.12]. Frailty modified the relationship between RA and all-cause mortality (P=0.01). RA was associated with higher all-cause mortality risk in non-frail patients [hazard ratio (HR) 1.15, 95% CI: 1.03-1.29], but no difference in risk in frail patients (HR 0.94, 95% CI: 0.79-1.14). Frailty was associated with a higher risk of cancer-specific mortality (HR 1.37, 95% CI: 1.26-1.50), while RA was not (HR 1.08, 95% CI: 0.91-1.29). Conclusions: RA was an independent risk factor for all-cause mortality in non-frail patients with non-metastatic ccRCC, but not in frail patients. Frailty interacts with RA on the risk of all-cause mortality in this population. The presence of frailty, but not RA, was an independent risk factor for cancer-specific mortality. RA did not appear to significantly impact the receipt of immunotherapy and cancer-related surgery. The complex contributions of frailty and RA to mortality underscore the need for interdisciplinary collaboration between rheumatologists and oncologists in order to maximize treatment and mortality outcomes.