Monocyte-to-Lymphocyte Ratio as New Prognostic Factor in Patients with Medullary Thyroid Carcinoma

Objectives: Medullary thyroid carcinoma (MTC) is a rare but biologically aggressive neuroendocrine tumor for which reliable preoperative prognostic biomarkers are still lacking. This study aimed to evaluate the association between preoperative blood immunological markers and disease recurrence in patients with MTC undergoing curative surgery. Methods: We conducted a retrospective cohort study at a single tertiary academic center including 52 consecutive patients who underwent curative surgery for MTC between January 1999 and December 2023. The study size was determined by including all eligible consecutive patients meeting predefined inclusion/exclusion criteria within the study period. Preoperative inflammatory indices (MLR, NLR, PLR, SII, SIRI) were calculated from standardized complete blood count tests performed within 30 days before surgery. Disease-free survival (DFS) was calculated using the Kaplan-Meier method. Cox proportional hazards regression analysis with a backward stepwise selection based on the Akaike Information Criterion was used to identify independent predictors of recurrence, adjusting for potential confounders. Results: The mean age was 55.0 years (range 31-75), and 73% of patients were female. The ROC-derived cut-off for preCT was 181 pg/mL. Locally advanced disease (T3-T4) was observed in 12% of cases, and cervical node metastases in 27%. With a mean follow-up of 75.48 months, the 3- and 5-year DFS rates were 91% and 86%, respectively. On multivariable Cox regression, a high monocyte-to-lymphocyte ratio (MLR ≥0.37), positive surgical margins, and pathological nodal involvement remained independently associated with worse DFS after confounder adjustment (HR 9.73, 10.78, and 17.71, respectively). Conclusions: Elevated MLR, histological node metastases, and positive surgical margins independently predict recurrence in MTC after curative treatment. Preoperative MLR may represent a simple, inexpensive, and reproducible biomarker to improve preoperative risk stratification and personalize surgical and follow-up strategies: patients with MLR ≥0.37 may benefit from more aggressive management and/or closer follow-up.