The impact of neutrophil-lymphocyte ratio on risk reclassification of patients with advanced renal cell cancer to guide risk-directed therapy

Background: An elevated neutrophil-lymphocyte ratio (NLR) is associated with poor prognosis in advanced renal cell carcinoma (RCC). We examined whether the addition of NLR improves the risk reclassification of advanced RCC using current prognostic tools from the Memorial Sloan Kettering Cancer Center (MSKCC) and International Metastatic Renal Cell Carcinoma Database Consortium (IMDC). Methods: Using randomised data from the COMPARZ trial of first-line pazopanib vs. sunitinib in advanced RCC, we constructed multivariable models containing MSKCC and IMDC predictor variables with and without NLR. We evaluated model discrimination using the concordance index (C-index). We computed net reclassification improvement to quantify patient reclassification into low/intermediate/poor risk groups with the addition of NLR. Results: Of 1102 patients, NLR ≥ 5 (16%) was associated with shorter survival adjusting for MSKCC variables (adjusted HR 1.89, p < .001). Adding NLR to MSKCC variables increased the C-index by 0.01. Among patients who died before 24 months (N = 415), adding NLR reclassified 8% and 2% to a higher and lower risk category, respectively. Among those alive at 24 months (N = 636), adding NLR reclassified 4% and 1% to a higher and lower risk category, respectively. This finding translates to a net benefit of eight additional patients who die within 24 months correctly identified as poor risk per 1000 patients tested. We obtained similar results when evaluating NLR with IMDC variables. Conclusions: NLR does not substantially improve risk reclassification over pre-existing prognostic tools. MSKCC and IMDC classifications remain the standard for guiding risk-directed therapy and trial stratification of patients with advanced RCC.