Neutrophil-to-lymphocyte ratio as prognostic indicator in gastrointestinal cancers: a systematic review and meta-analysis

Abstract

An accurate, time efficient, and inexpensive prognostic indicator is needed to reduce cost and assist with clinical decision making for cancer management. The neutrophil-to-lymphocyte ratio (NLR), which is derived from common serum testing, has been explored in a variety of cancers. We sought to determine its prognostic value in gastrointestinal cancers and performed a meta-analysis of published studies using the Meta-analysis Of Observational Studies in Epidemiology guidelines. Included were randomized control trials and observational studies that analyzed humans with gastrointestinal cancers that included NLR and hazard ratios (HR) with overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and/or cancer-specific survival (CSS).We analyzed 144 studies comprising 45,905 patients, two-thirds of which were published after 2014. The mean, median, and mode cutoffs for NLR reporting OS from multivariate models were 3.4, 3.0, 5.0 (±IQR 2.5-5.0), respectively. Overall, NLR greater than the cutoff was associated with a HR for OS of 1.63 (95% CI, 1.53-1.73; P < 0.001). This association was observed in all subgroups based on tumor site, stage, and geographic region. HR for elevated NLR for DFS, PFS, and CSS were 1.70 (95% CI, 1.52-1.91, P < 0.001), 1.64 (95% CI, 1.36-1.97, P < 0.001), and 1.83 (95% CI, 1.50-2.23, P < 0.001), respectively.Available evidence suggests that NLR greater than the cutoff reduces OS, independent of geographic location, gastrointestinal cancer type, or stage of cancer. Furthermore, DFS, PFS, and CSS also have worse outcomes with elevated NLR.

High neutrophil‐to‐lymphocyte ratio (NLR) is associated with treatment failure and death in patients who have melanoma treated with PD‐1 inhibitor monotherapy

“…Our findings may help explain the biologic relationship between the NLR and prognosis in patients with cancer. The prognostic significance of an elevated NLR is observed with remarkable consistency across many cancer types and stages of disease . What remains unclear is whether NLR elevation represents a reaction to immunosuppressive factors from the tumor or, alternatively, reflects an intrinsic host variable (ie, dysfunctional immune response) that leads to a more aggressive clinical course.…”

“…The neutrophil‐to‐lymphocyte ratio (NLR) is biomarker of systemic inflammation that can be readily obtained from a peripheral complete blood count. The NLR has consistently been found to be prognostic of survival in patients with cancer, other diseases, and the general population . In patients without cancer, the NLR increases with age; the median value plateaus between 3 and 4 from the third to sixth decades, then it continues to rise in the elderly .…”

“…In contrast, patients with metastatic cancer often have substantially higher values. An NLR cutoff ≥5 is most commonly used to define abnormal elevation in the metastatic setting …”

“…The NLR has consistently been found to be prognostic of survival in patients with cancer, other diseases, and the general population. [1][2][3][4][5] In patients without cancer, the NLR increases with age; the median value plateaus between 3 and 4 from the third to sixth decades, then it continues to rise in the elderly. 6 In contrast, patients with metastatic cancer often have substantially higher values.…”

“…An NLR cutoff ≥5 is most commonly used to define abnormal elevation in the metastatic setting. 1,2 Patients with cancer and an NLR above the defined cutoff have consistently been found to have worse outcomes than patients with a lower NLR across cancer types. 1 In melanoma, elevated NLR is associated with a poorer prognosis in both localized and metastatic disease.…”