Presence of Intratumoral Neutrophils Is an Independent Prognostic Factor in Localized Renal Cell Carcinoma

PURPOSE: We have previously demonstrated a significant negative impact of intratumoral neutrophils in metastatic renal cell carcinoma. This study assessed intratumoral neutrophils in localized clear cell renal cell carcinoma (RCC). PATIENTS AND METHODS: The study comprised 121 consecutive patients who had a nephrectomy for localized RCC. Biomarkers (intratumoral CD8+, CD57+ immune cells, CD66b+ neutrophils, and carbonic anhydrase IX CA IX) were assessed by immunohistochemistry, and the relationship with clinical and histopathologic features and patient outcome was evaluated. RESULTS: The intratumoral neutrophils ranged from zero to 289 cells/mm(2) tumor tissue. The presence of intratumoral neutrophils was statistically significantly associated with increasing tumor size, low hemoglobin, high creatinine, and CA IX < or = 85%. In multivariate analysis, the presence of intratumoral neutrophils (hazard ratio HR, 3.0; 95% CI, 1.7 to 5.4; P < .0001), pT stage T3b/T4 (HR, 2.1; 95% CI, 1.2 to 3.6; P = .007), and low hemoglobin (HR, 1.8; 95% CI, 1.0 to 3.1; P = .03) were independent prognostic factors significantly associated with short recurrence-free survival. The presence of intratumoral neutrophils was also an independent prognostic factor for cancer-specific survival (HR, 3.5; 95% CI, 1.9 to 6.4; P < .0001) and overall survival (HR, 3.1; 95% CI, 1.9 to 5.0; P < .0001). Applying the prognostic value of intratumoral neutrophils to the Leibovich low-/intermediate-risk group (n = 78) showed a 5-year recurrence-free survival of 53% (95% CI, 34.6% to 71.8%; presence of intratumoral neutrophils) versus 87% (95% CI, 77.8% to 96.8%; absence of intratumoral neutrophils). The estimated concordance index was 0.74 using the Leibovich risk score and 0.80 when intratumoral neutrophils were added. CONCLUSION: The presence of intratumoral neutrophils is a new, strong, independent prognostic factor for short recurrence-free, cancer-specific, and overall survival in localized clear cell RCC.