Neutrophil-to-Lymphocyte Ratio in Colorectal Liver Metastases: Simply Prognostic or Clinically Relevant?

Abstract

In recent years, there has been considerable interest in using inflammatory biomarkers to improve prognostication for patients with cancer. Typically available on standard serum laboratory tests, these investigations have led to an alphabet soup of potential markers: neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), systemic inflammation response index (SIRI), systemic immune inflammation index (SII), prognostic nutritional index (PNI), modified systemic inflammation score (mSIS), fibrinogen and neutrophil-to-lymphocyte ratio score (FNLR), albumin-to-fibrinogen ratio (AFR), platelet–lymphocyte ratio (PLR), fibrinogen-to-pre-albumin ratio (FPR), and more. Of these, NLR has become one of the most commonly studied due to its simplicity and cost-effectiveness that results from the inclusion of a complete blood count with differentiation in most patients’ cancer workup. Previous studies have linked elevated NLR to worse long-term survival outcomes among patients with metastatic colorectal cancer (mCRC), but its clinical value in the management of patients with resectable colorectal liver metastases (CRLM) remains unproven. In that context, Verter et al. performed a retrospective single-institutional analysis of all patients who underwent resection of CRLM between 2005 and 2017 to evaluate the association between preoperative NLR and overall (OS), disease-specific (DSS), and recurrence-free survival (RFS). After stratifying patients based on normal (NLR B 3, n = 231) or high (NLR[3, n = 53) NLR, they found that the groups were relatively well matched on most clinicopathologic characteristics except for a higher rate of simultaneous primary resections in the high-NLR group despite similar rates of synchronous disease. On univariate analysis, elevated NLR was associated with decreased OS (HR 1.6, 95% CI 1.1–2.3, p = 0.01), decreased DSS (HR 1.6, 95% CI 1.1–2.4, p = 0.02), and decreased RFS (HR 1.6, 95% CI 1.0–1.9, p = 0.049), and the associations with OS (HR 1.6, 95% CI 1.1–2.3, p = 0.02) and DSS (HR 1.6, 95% CI 1.0–1.9, p = 0.03) were maintained on multivariable analysis as well. Furthermore, using a competing risk analysis, elevated NLR was associated with increased risk of extrahepatic recurrence but not intrahepatic recurrence. Limitations to the study by Verter et al. should be acknowledged. First, the study is retrospective, from a single institution, and has a relatively small sample size. Second, some pertinent clinical factors known to influence survival were not included, namely embryonic origin (i.e., rightversus left-sided cancer) and tumor mutation status. Third, the influence of neoadjuvant therapy (administered to 76% of patients in the study) on NLR values is unknown. The exact timing of the preoperative blood draw could have varied from 30 days prior (perhaps even during final cycle of chemotherapy) to the day of surgery, with unknown but potentially significant impact on the NLR value. Finally, these findings are not novel; the role of the NLR as a prognostic factor in patients undergoing resection for CRLM has been examined previously; For example, Halazun et al. demonstrated that NLR [ 5 was independently associated with decreased OS following resection of CRLM, while Giakoustidis et al. reported an increased risk of extrahepatic recurrence and decreased OS among patients with CRLM undergoing neoadjuvant therapy and resection and McCluney et al. found that NLR predicted postoperative complications. Society of Surgical Oncology 2021