Basal neutrophil-to-lymphocyte ratio is associated with overall survival in melanoma

Abstract

Several studies have reported that a high neutrophil-to-lymphocyte ratio (NLR) is associated with poor clinical outcomes in several cancers, but this ratio has not been thoroughly studied in melanoma except in stage IV. This is the first study on NLR in melanoma stages I-III. This was a retrospective study of 742 melanoma patients. The NLR was classified into NLR<2 and a NLR≥2 on the basis of a receiver operating characteristic curve. Associations of NLR with clinicopathological characteristics and survival were examined. The median patient age was 57 years (range: 15-91; Q1=46, Q3=70), and the median Breslow's thickness was 3.0 mm (range: 0.5-60; Q1=1.0, Q3=7). Clinical stage at presentation was as follows: (i) stage I in 27%; (ii) stage II in 33.2%; (iii) stage III in 36.5%; and (iv) stage IV in 3.3%. NLR≥2 was associated with lymph node metastasis (36.6 vs. 18.1%) and recurrence (28.2 vs. 22.1%). The 5-year overall survival (OS) was 63% for the NLR<2 group and 53% for the NLR≥2 group. Stage-by-stage analysis showed that the 5-year OS in the NLR≥2 group for stages I, II, III, and IV were 91, 60, 28, and 0%, respectively, whereas for the NLR<2 group the 5-year OS were 98, 68, 31, and 0%, respectively. Significant differences between NLR<2 and ≥2 occurred only in stage II (P=0.014). Univariate analysis showed that factors associated with decreased OS clinical stage were Breslow's thickness, ulceration, male sex, and NLR≥2. In the multivariate analysis, all of these factors were predictors of decreased survival. The NLR appears to be an accurate prognostic marker for decreased OS in patients with melanoma, especially in clinical stage II. NLR≥2 correlated with lymph node metastasis and recurrence.

The neutrophil–lymphocyte ratio and locoregional melanoma: a multicentre cohort study

“…There are three published works concerning the NLR and lymph node metastases of melanoma [34,37,38], all of which agree with our findings that a raised NLR is associated with occult metastatic disease. Gandini et al [34] compared absolute blood counts between SLN biopsy positive and negative individuals using rank-based methods and found no evidence of a difference; but when modelled against disease progression using Cox regression (from Stage I/II to III, i.e.…”

“…This agrees with our data whereby the crude blood counts were not different between groups and highlights the power of ratios which magnify smaller differences to appreciable levels. Lino-Silva and colleagues [38] showed that a NLR > 2 was associated with nodal metastasis; however, their study concerned acral lentiginous melanoma in the Mexican population which is a biologically distinct tumour and population, respectively. This reduces the generalisability to the majority of affected individuals who are Caucasian with nodular or superficial spreading melanoma [51].…”

“…Overall, our findings agree with the literature and suggest that a raised baseline NLR is associated with occult metastatic melanoma. Previous works investigated NLR incidentally or as a secondary outcome of interest [34,37,38] whereas this study adds an important dimension to the literature because the biomarker was of primary interest, analysed in a comprehensive fashion and adjusted for potential confounding variables. None-the-less, we feel that further prospective research is needed to mitigate biases of selection and information before the NLR is utilised in the management of patients with locoregional melanoma.…”

“…Blood counts (and ratios) were skewed but lognormal, so are summarised by the geometric mean and compared using t-based methods. The threshold for NLR (2.3) was informed by previous work [34,[37][38][39] and selected based on the optimum Harrell C-statistic and assessment of restricted cubic splines. The association between NLR and the odds ratio (OR) for SLN metastasis was estimated using multilevel (mixed-effects) logistic regression, with random-effects carrying by the hospital, i.e.…”

“…This inflammatory response is manifested in the peripheral blood neutrophil-lymphocyte ratio (NLR) [26][27][28][29], which has become an established biomarker of systemic inflammation and various outcomes in numerous cancers [30][31][32]. Further, the NLR has a strong association with survival in melanoma [33][34][35][36][37][38][39]. Currently, there is a gap in the literature concerning the relationship between NLR and outcomes in locoregional melanoma, the most prevalent form of the disease, which formed the rationale for this study.…”