Male gender as a poor prognostic factor in medullary thyroid carcinoma: behavior or biological difference?

Background: Due to the low incidence and heterogeneous behavior of medullary thyroid carcinoma (MTC), its prognostic factors are still not well stablished. While several large studies have investigated the impact of gender in differentiated thyroid cancer (DTC), its role in MTC outcomes remains controversial. We aim to identify MTC prognostic features, specially focusing on the role of gender.

Methods: The present study is a retrospective analysis of 76 patients diagnosed with MTC between 1984 and 2018 at a Portuguese Comprehensive Cancer Center.

Results: Patients presented a median age at diagnosis of 49 years and multiple endocrine neoplasia type 2 (MEN2) was identified in 27.6% of them, with those individuals being significantly younger (P<0.001). Most cases were diagnosed as stage IV disease (46.9%), except for the subgroup detected through presymptomatic genetic screening (55.6% at stage I). The 5- and 10-year survival rates were 87.6% and 75.6%, respectively. Univariate analysis identified male gender (P=0.010), age ≥45 years (P=0.007), presence of distant metastasis at diagnosis (P<0.01), capsule invasion (P=0.004), extrathyroidal invasion (P=0.003) and absence of biochemical cure after surgery (P=0.042) as having a negative impact on prognosis. On multivariate analysis, male gender (P=0.046) remained an independent predictor of mortality, as well as an older age (P<0.001) and the presence of distant metastases (P=0.012).

Conclusions: Male gender independently predicted worse survival in MTC patients even after adjusting for age and disease stage. The few older studies on the topic pointed to a behavioral explanation regarding medical care seeking patterns by men, but our study and newer genetic and basic-science oriented publications raise the possibility of a true biological difference between genders in the tumorigenesis of MTC that should me further investigated.