Prognostic Factors in Medullary Thyroid Cancer: A Real-World Study in a Referral Center

Background: Several factors have been reported to influence the prognosis of medullary thyroid cancer (MTC). This study aimed to identify prognostic variables associated with progression-free survival (PFS) and overall survival (OS) in a cohort of patients treated at our institution. Patients and Methods: We performed a retrospective analysis of 107 consecutive patients with histologically confirmed MTC who were followed for at least 12 months. Demographic, clinical, and pathological data were retrieved from medical records. The association between baseline variables and survival outcomes was evaluated using univariate Cox proportional hazards regression models. The study was approved by the local ethics committee. Results: The median age at diagnosis was 56 years (range, 10-80 years), and 63% of the patients were female. Germline REarranged during Transfection (RET) mutations were identified in 10% of cases. The median follow-up duration was 100 months (range, 12-464 months). At diagnosis, disease stages were distributed as follows: stage I, 52%; stage II, 12%; stage III, 17%; and stage IV, 19%. Female patients showed significantly longer PFS compared with males (Hazard Ratio (HR) = 0.41, 95% Confidence Interval (CI) (0.21-0.82); p = 0.012). Factors associated with PFS by Cox regression models were post-operative serum calcitonin (CT) values after 1 and 3 months of surgery (HR = 0.08, 95% CI (0.03-0.20); p < 0.001; HR = 0.03, 95% CI (0.01-0.11); p < 0.001, respectively), Tumor, Node, and Metastasis (TNM) stage III-IV (HR = 16.86, 95% CI (5.87-48.44); p < 0.001), presence of lymph nodes metastasis at diagnosis (HR = 9.6, 95% CI (3.59-25.63); p < 0.001), multifocal disease (HR = 2.37, 95% CI (1.07-5.28); p = 0.034) and capsular invasion (HR = 10.72, 95% CI (4.45-25.87); p < 0.001). Factors associated with OS by Cox regression models were age at diagnosis (HR = 1.07, 95% CI (1.01-1.12); p = 0.019) and TNM Classification of Malignant Tumours stage III-IV (HR = 6.69, 95% CI (1.42-31.62); p = 0.016). Although lymph node metastasis and capsular invasion were not significantly associated with overall survival (p = 0.178 and p = 0.094, respectively), both variables showed a trend toward an association with OS. Conclusions: The study confirmed that post-operative serum CT values, male sex, lymph nodes metastasis at diagnosis, TNM stage III and IV and capsular invasion were all associated with a lower PFS. Factors associated with OS were age at diagnosis, presence of lymph nodes metastasis, TNM stage III-IV and capsular invasion.