Elevated Blood Neutrophil-to-Lymphocyte Ratio: A Readily Available Biomarker Associated with Death due to Disease in High Risk Nonmetastatic Melanoma

Abstract

Background Elevated peripheral blood neutrophil-to-lymphocyte ratio (NLR) is associated with poor oncologic outcomes in patients with stage IV melanoma and other solid tumors, but its impact has not been characterized for patients with high-risk, non-metastatic melanoma. Methods Retrospective review of a melanoma database identified patients with high-risk melanoma who underwent operation with curative intent at a single institution. NLR was calculated from blood samples obtained within two-weeks prior to operation. Multiple primary melanomas and concurrent hematologic or other metastatic malignancies were excluded. Cumulative incidence of death due to disease was estimated, and Gray’s test was used to examine the effect of NLR on melanoma disease specific death (DOD). Multivariable competing risks regression models assessed associated factors. Results Data on 1,431 patients with high-risk non-metastatic melanoma were analyzed. Median follow-up for survivors was 4 years. High NLR (≥3 or as continuous variable) was associated with older age, male sex, thicker primaries, higher mitotic index and more advanced nodal status. On multivariate analysis, high NLR (≥ 3 or as a continuous variable), older age, male sex, ulcerated primary, lymphovascular invasion and positive nodal status were all independently associated with worse DOD. Conclusions NLR is a readily available blood test that was independently associated with DOD in patients with high risk non-metastatic melanoma. It is unclear whether high NLR is a passive indicator of poor prognosis, or a potential therapeutic target. Further studies to evaluate the prognostic role of NLR to potentially identify those more likely to benefit from adjuvant immunotherapy may prove informative.

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

“…We show that a baseline NLR ≥5 is independently prognostic for both TTF and OS in patients with stage IV metastatic melanoma undergoing initial PD‐1 inhibition. These findings are consistent with the prognostic significance of the NLR, particularly in melanoma . Despite the large clinical magnitude of the difference in survival and its independent significance, an elevated baseline NLR does not preclude long‐term survival (30% of patients with an elevated baseline NLR survived for >3 years) (Fig.…”

“…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 prognostic significance of an elevated NLR is observed with remarkable consistency across many cancer types and stages of disease. 1,2,7,13,14,24 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. We find that the NLR shows a trend toward an association with a primary tumor factor (primary melanoma site), a significant association with a potential host factor (ECOG performance status), and a factor likely associated with the interaction of the 2 (the number of involved metastatic sites).…”

“…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 . In melanoma, elevated NLR is associated with a poorer prognosis in both localized and metastatic disease . In other cancers, the NLR has been hypothesized to be a marker of disease burden, yet it appears to be independently prognostic after adjustment for disease stage, sites of metastatic disease, and established tumor markers .…”

“…1 In melanoma, elevated NLR is associated with a poorer prognosis in both localized and metastatic disease. [7][8][9][10] In other cancers, the NLR has been hypothesized to be a marker of disease burden, yet it appears to be independently prognostic after adjustment for disease stage, sites of metastatic disease, and established tumor markers. [11][12][13] Alternatively, an elevated NLR may reflect an innately dysfunctional host immune response, a byproduct of tumor-related immune suppression, or some combination of both.…”