Predictive factors for central neck compartment lymphnodes metastases' in sporadic medullary thyroid cancer patients

Introduction: Total thyroidectomy (TT) plus central neck compartment (CC) lymphnode dissection is still the recommended initial gold standard treatment for medullary thyroid cancer (MTC), even in the absence of a pre-surgical positive neck US evidence of lymphnode metastases. Considering the risk of surgical complications of this prophylactic surgery and the low rate of histologic finding of CC lymphnode metastases, a more tailored lymphnode’ surgery should be proposed. Aim of this study was to analyze the presence of possible predictive risk factors for the presence of CC lymphnode metastases in patients with sporadic MTC Patients and methods: Data from 280 sporadic MTC patients, followed at our Institution from 2000 and 2018, were retrospectively analyzed. All underwent TT and prophylactic CC lymphnode dissection, while lateral dissection was performed only according to the pre-surgical US findings. Univariate analysis with chi-square test and multiple logistic regression analysis were applied to identify the clinico-pathological features associated with CC lymphnode metastases Results: 170/280 (60.7%) patients were female and 110/280 (39.37) were male. The mean age at MTC diagnosis was 54.72±13.82 years. At the end of follow-up, 209/280 (74.6%) patients were cured, while 60/280 (21.4%) showed a biochemical/structural persistence of disease. CC lymphnode metastases were histologically found in 82/280 patients (29.3%). At the univariate analysis, the absence of tumor capsule (P < 0.001), the presence of intrathyroidal (P < 0.001)/extrathyroidal extension (P < 0.001), multifocality (P < 0.001), neoplastic embolization (P = 0.001), higher pre-surgical serum calcitonin levels (P = 0.016) and bigger tumor diameter (P < 0.001) were associated with the presence of CC lymphnode metastases. At the multivariate analysis, only the absence of tumor capsule (OR 4.13 [95% CI 1.78-9.59] P = 0.001), the presence of extrathyroidal extension (OR 5.06 [95% CI 1.99-12.8] P = 0.0006), multifocality (OR 4.17 [95% CI 1.67-10.41] P = 0.002) and tumor diameter (OR 1.95 [95% CI 1.46-2.6] P < 0.0001) were confirmed as independent predictive risk factors. We separately analyzed the subgroup of 131 microMTC. At the univariate analysis the absence of tumor capsule (P < 0.001), the presence of intrathyroidal (P < 0.001)/extrathyroidal extension (P = 0.02) and multifocality (P = 0.002) were associated with CC lymphnode metastases. At the multivariate analysis, multifocality was the only independent risk factor associated with a 5-time greater risk (OR 5.63 [95%CI 1.95-16.4] P = 0.001]. Conclusions: According to our data, the histological prevalence of CC lymphnode metastases in sporadic MTC patients is below 30%. The absence of tumor capsule, the presence extrathyroidal invasion, tumor multifocality and tumor diameter were found as the independent predictive risk factors for CC metastases, while in microMTC only multifocality was associated with higher risk of CC metastases