Prognostic Model for Survival in Patients with Metastatic Renal Cell Carcinoma: Results from the International Kidney Cancer Working Group
Year of Publication
Manola, J; Royston, P; Elson, P; Bacik McCormack, J; Mazumdar, M; Negrier, S; Escudier, B; Eisen, T; Dutcher, J; Atkins, M; Heng, DYC; Choueiri, TK; Motzer, R; Bukowski, R
Clin Cancer Res
Antibodies; Benzenesulfonates/therapeutic use; Female; Indoles/therapeutic use; Kidney Neoplasms/diagnosis; Monoclonal; Protein Kinase Inhibitors/therapeutic; Pyridines/therapeutic; Pyrroles/therapeutic; Renal Cell/diagnosis Carcinoma; Renal Cell/therapy
PURPOSE: To develop a single validated model for survival in metastatic renal cell carcinoma (mRCC) using a comprehensive international database. EXPERIMENTAL DESIGN: A comprehensive database of 3,748 patients including previously reported clinical prognostic factors was established by pooling patient-level data from clinical trials. Following quality control and standardization, descriptive statistics were generated. Univariate analyses were conducted using proportional hazards models. Multivariable analysis using a log-logistic model stratified by center and multivariable fractional polynomials was conducted to identify independent predictors of survival. Missing data were handled using multiple imputation methods. Three risk groups were formed using the 25th and 75th percentiles of the resulting prognostic index. The model was validated using an independent data set of 645 patients treated with tyrosine kinase inhibitor (TKI) therapy. RESULTS: Median survival in the favorable, intermediate and poor risk groups was 26.9 months, 11.5 months, and 4.2 months, respectively. Factors contributing to the prognostic index included treatment, performance status, number of metastatic sites, time from diagnosis to treatment, and pretreatment hemoglobin, white blood count, lactate dehydrogenase, alkaline phosphatase, and serum calcium. The model showed good concordance when tested among patients treated with TKI therapy (C statistic = 0.741, 95% CI: 0.714-0.768). CONCLUSIONS: Nine clinical factors can be used to model survival in mRCC and form distinct prognostic groups. The model shows utility among patients treated in the TKI era.