Endocrine Abstracts

Background: Distant metastases at diagnosis is the worst prognostic factor for disease specific survival (DSS) in sporadic medullary thyroid carcinoma (MTC). Also, lymph node metastases are negative prognostic factors both for DSS and recurrence free survival (RFS). The question whether central (N1a) and latero-cervical compartment lymph nodes metastasis (N1b), separately evaluated, can have a different impact on DSS and RFS remains to be clarified.

Patients and methods: We evaluated 674 sporadic MTC patients (2000-2020), all of them followed at the Unit of Endocrinology of the Pisa University Hospital. We excluded all patients with distant metastases at diagnosis (60/674 – 8.9%). From the remaining (n =614) we excluded those in whom central and/or latero-cervical compartment lymph nodes dissection was not performed (Nx) (57/614 – 9.3%) and patients lost to follow-up (11/614 – 1.8%). Then, according to histology, we defined 3 groups: 1) N0 (310/546 – 56.8%) without lymph nodes metastases, 2) N1a (105/546 – 19.2%) with metastatic lymph nodes of the central compartment alone, 3) N1b (131/546 – 24%) with metastatic lymph nodes of the latero-cervical ± central compartment.

Results: In a median time of 110 months (IQR 60-164.25) we observed 37 (6.8%) cancer related death (CRD): 5/310 (1.6%) in N0 and 32/131 (24.4%) in N1b group; no CRD were observed in N1a. Indeed, Kaplan Meier (KM) analysis showed a DSS of 100% at 5 and 10 years in N0 and N1a, while 83% and 78% in N1b group (P < 0.01). After excluding patients with structural disease at first post-operative evaluation (67/546 – 12.3%) we observed 69/479 (14.4%) structural recurrences in a median follow-up time of 75 (IQR 32.75-130) months. Of these, 14/308 (4.5%) in N0, 17/99 (17.2%) in N1a and 38/72 (52.8%) in N1b group. KM showed a RFS of 99% and 97% in N0, 87% and 82% in N1a and 58% and 48% in N1b group, at 5 and 10 years respectively (P < 0.01). When directly comparing N0 and N1a (P < 0.01) and N1a and N1b (P < 0.01) a RFS was significantly different.

Conclusions: In our series of sporadic MTC patients without known distant metastases at diagnosis, regardless of other potential risk factors, the presence of N1b at diagnosis was confirmed as a negative prognostic factor both for DSS and RFS. Conversely, the presence of N1a alone, regardless of number and dimension of the metastatic lymph nodes, has no impact on DSS and is comparable to N0 patients. However, in N1a patients the occurrence of recurrence over time cannot be overlooked, since they showed a risk significantly higher than N0, but lower than N1b, of having a structural recurrence over time.