Stage migration and increasing proportion of favorable-prognosis metastatic renal cell carcinoma patients: implications for clinical trial design and interpretation

Abstract

Background: The Memorial Sloan-Kettering Cancer Center risk model classifies patients with metastatic renal cell carcinoma (RCC) by 5 pretreatment features as favorable, intermediate, and poor risk. The number of Memorial Sloan-Kettering Cancer Center patients in each risk group was examined by year of treatment to analyze stage migration.

Methods: The distribution of risk groups was examined retrospectively in 789 Memorial Sloan-Kettering Cancer Center patients with metastatic RCC treated in a first-line therapy clinical trial from 1975 to 2007. Date of treatment onset was divided into 6 cohorts between 1975 and 2007 (1975-1980, 1981-1985, 1986-1990, 1991-1995, 1996-2001, and 2001-2007).

Results: The median age of the first-line metastatic RCC clinical trial patients was 59 years (range, 20-82 years). Most patients received cytokine therapy (55%), 37% received chemotherapy/other, and 8% received vascular endothelial growth factor-targeted therapies. Overall survival increased with each consecutive cohort year group (P < .001). Median survival was 0.43 years (95% confidence interval [CI], 0.27-0.68) in the 1973-1980 cohort and 1.5 years in the 2001-2007 cohort (95% CI, 1.15-2.11). Memorial Sloan-Kettering Cancer Center risk-group distribution shifted between 1975 and 2007 (P < .0001). The poor-risk group proportion became smaller (from 44% in 1975-1980 to 13% in 2001-2007), whereas the favorable-risk group increased (from 0% in 1975-1980 to 49% in 2001-2007). The intermediate-risk group remained stable at 50%. After adjusting for type of therapy, the shifts continue to be significant (P < .0001).

Conclusions: The risk-group distribution for metastatic RCC patients in clinical trials shifted from 1975 to 2007. These shifts have direct implications for data analysis, interpretation of metastatic RCC trends, and drug development.