Abstract
e14529 Background: Accurate, simple and inexpensive biomarkers will enable better use of cancer treatments. The neutrophil to lymphocyte ratio (NLR) is prognostic in advanced colorectal cancer (CRC). BRAF and mismatch repair (MMR) status also have prognostic utility and can be identified using immunohistochemical (IHC) analyses of surgical samples. We investigated the prognostic significance of the preoperative NLR in combination with BRAF and MMR status on CRC survival in patients with stages I-IV CRC. Methods: 899 consecutive patients admitted to Northern Sydney Local Health District from 2006-2009 for resection of CRC were evaluated. BRAF and MMR status were determined via IHC methods. Blood counts were retrospectively analysed. Prognostic value of the 3-marker combination was assessed, dividing the cohort into 4 groups according to high and low risk factors from individual marker states: Group 1 all high risk (high NLR, BRAF mutant, microsatellite stable); Group 2, 1 low and 2 high; Group 3, 2 low and 1 high; Group 4 all low risk factors. Kaplan-Meier and Cox regression was used to analyse prognostic utility. Results: The cohort comprised 50% males; median age 72 yrs; stage I 17%, II 36%, III 43%, IV 3%; ≥5 year outcome data. Increased NLR was independently associated with shorter overall survival (OS) after adjustment for other prognostic variables (HR 0.414, 95% CI 0.310-0.554, p<0.001). The combination of NLR, BRAF and MMR status demonstrated prognostic utility for OS by univariate (p<0.001) and multivariate analyses (p<0.001). Group 3 had significantly better outcome than Group 1 (HR 0.231, 95% CI 0.121-0.443, p<0.001) with Group 2 (HR 0.543, CI 0.290-1.016, p=0.056) and Group 4 (HR 0.386, CI 0.106-1.415, p=0.151) trending towards better outcomes than Group 1. Conclusions: A significant association between preoperative NLR was demonstrated with OS for patients with stage I-IV CRC, indicating shorter OS for patients with systemic inflammation prior to surgery. The combination of NLR with BRAF and MMR status demonstrated superior prognostic ability to known factors such as stage, forming a powerful prognostic tool for all stages of CRC from the preoperative setting.
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