Improving IMDC Prognostic Prediction Through Evaluation of Initial Site of Metastasis in Patients With Metastatic Renal Cell Carcinoma

Background Several models are adopted in clinical practice to estimate prognosis of patients with metastatic renal cell carcinoma (mRCC); however, none of these models have evaluated patients treated by immune-checkpoint inhibitors. The aim of this study was to investigate if the site of initial metastasis could be a parameter able to stratified prognosis among patients with mRCC among different risk groups defined by the International Metastatic Renal Cell Database Consortium (IMDC) model. The site of initial metastasis was defined as the primary tissue or organ in which metastasis was diagnosed in the course of the medical history of the disease. Patients and Methods A total of 134 patients treated between January 2010 and December 2018 in our institution were retrospectively evaluated. The primary outcome was overall survival (OS) defined as the time from initiation of first-line therapy to death from any cause. Of note, 26 (19.4%) patients received immune-checkpoint inhibitors. Univariable analysis was performed through the log-rank test to estimate the effect of number of metastatic sites and site of initial metastasis on OS. Subsequently, a Cox regression proportional hazards model was employed in multivariable analysis. Results Of the 12 variables analyzed, 4 were statistically associated to worse OS in univariable analysis (number of metastases and liver, bone, or central nervous system metastases). Multivariate analysis confirmed that bone (hazard ratio [HR], 1.92; 95% confidence interval [CI], 1.17-3.13), liver (HR, 2.65; 95% CI, 1.59-4.42), and central nervous system (HR, 3.3; 95% CI, 1.62-6.74) initial metastases were independent parameters related to worse OS. The presence of 1 or more of the selected sites recognized specific populations of patients associated to worse prognosis in both good (P = .003) and intermediate (P = .047) risk groups. Conclusion The site of initial metastasis defines specific populations of patients associated with worse prognosis in the good and intermediate IMDC groups.