Predictors of Survival of Advanced Renal Cell Carcinoma: Long-Term Results From Southwest Oncology Group Trial S8949

Purpose: S8949 demonstrated improved overall survival for debulking nephrectomy in interferon treated patients with advanced renal cell carcinoma. We present an updated analysis of S8949, now, with a median followup of 9 years. We explored clinical predictors of overall survival. Materials and Methods: Univariate and multivariate Cox regression analysis was performed to evaluate the impact of clinical variables potentially influencing survival. Results: Of 246 patients 241 were eligible and randomized to interferon with or without nephrectomy. Patients randomized to nephrectomy continued to have improved overall survival (HR 0.74, 95% Cl 0.57-0.96, p = 0.022). Multivariate analysis showed that performance status I vs 0 (HR 1.95, p <0.0001), high alkaline phosphatase (HR 1.5, p = 0.002) and lung metastasis only (HR 0.73, p = 0.028) were overall survival predictors. There was no evidence of an interaction of performance status, measurable disease or lung metastases with nephrectomy (each p >0.30). In a patient subset that survived at least 90 days after randomization early progressive disease within 90 days was prognostic of overall survival in a multivariate model (HR 2.1, p <0.0001), as was performance status (HR 1.7, p = 0.0006). Conclusions: Nephrectomy prolonged long-term overall survival in this updated analysis, supporting its role as standard therapy in patients with advanced renal cell carcinoma. A nephrectomy benefit was seen across all prespecified patient subsets. Early progressive disease and performance status were strong predictors of overall survival. These results support efforts to identify biomarkers of renal cell carcinoma resistance to treatment and early progressive disease to facilitate rational patient selection for systemic therapy.