C-Reactive Protein and Lymphocyte-to-Monocyte Ratio Predict Recurrence in Stage III Melanoma Patients with Microscopic Sentinel Lymph Node Metastasis

Simple Summary Indicators of a potential recurrence of melanoma in patients after the detection of lymph node metastasis are needed in order to not treat patients unnecessarily with a systemic therapy. Blood parameters such as the number of white blood cells and ratios of different white blood cell subtypes are collected in the clinical routine and could be useful indicators of a possible disease relapse. The aim of our present study was to identify blood parameters which predict the recurrence of melanoma in melanoma patients with microscopic sentinel lymph node metastasis. We identified the lymphocyte-to-monocyte ratio (LMR) and C-reactive protein (CRP) to be the strongest predictors for melanoma recurrence. Although adjuvant therapies with immune checkpoint inhibitors (ICI) and BRAF/MEK inhibitors improve recurrence-free survival (RFS) in stage III melanoma patients significantly, prognostic factors are needed to identify patients with a high risk of disease recurrence. Therefore, the aim of our study was to investigate the prognostic potential of routinely collected blood parameters for stage III melanoma patients with microscopic sentinel lymph node (SLN) metastasis. Altogether, we retrospectively analyzed 138 stage III melanoma patients who were diagnosed with microscopic SLN metastasis at the skin cancer center of the University Hospital Cologne between 2011 and 2020 and who did not receive prior adjuvant therapy with ICI or BRAF/MEK-inhibitors. Univariate and multivariate Cox regression analyses, Kaplan-Meier survival analyses and receiver operating characteristic (ROC) curves were performed to assess the impact of preoperatively collected blood parameters and blood ratios on recurrence-free survival (RFS; primary endpoint) and overall survival (OS). A high neutrophil-to-lymphocyte ratio (NLR), low lymphocyte-to-monocyte ratio (LMR) and high C-reactive protein (CRP) value were significantly associated with shorter RFS in multivariate analysis. For LMR (cut-off 3.5) and for CRP (cut-off 3.0) this effect remained after dichotomization. CRP showed a stronger association with RFS than NLR or LMR, with the highest association being detected for the combination of low LMR and high CRP. Additionally, derived NLR >= 2.0 was significantly associated with shorter OS in multivariate analysis. In summary, our data suggest that CRP in combination with LMR should be considered as a marker for melanoma recurrence in stage III melanoma patients with microscopic SLN metastasis.