Ca19.9 positivity and doubling time are prognostic factors of mortality in patients with advanced medullary thyroid cancer with no evidence of structural disease progression according to RECIST

Background: Serum Ca19.9 positivity is a prognostic factor for mortality in patients with advanced medullary thyroid cancer (aMTC), independently from calcitonin (Ct) doubling time (DT). However, it is unknown whether aMTC patients who become positive for Ca19.9 also have progressive disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) and whether Ca19.9 DT has a role in the management of aMTC patients. The aims of this study was to evaluate whether in aMTC, when serum Ca19.9 become positive, PD develops and to determine the role of Ca19.9 DT in predicting mortality and PD. Patients and methods: Serum Ca19.9 was periodically measured in 107 aMTC patients, and the DTs were calculated. Restaging of the disease was radiologically performed in 104/107 and PD was evaluated according to RECIST. Results: At the end of follow-up, 25 of 107 patients were Ca19.9 positive and PD was identified in 30 of 104 patients. No significant association was found between Ca19.9 positivity and PD while there was a significant association between Ca19.9 positivity and mortality (p<0.0001). Ca19.9 DTs <6 months and <1year were not associated with PD but were associated with mortality (p<0.0001 and p<0.0001, respectively). In particular, 3 patients who had a Ca19.9 DT <6 months with no evidence of PD according to RECIST died of their disease after 6, 5 and 3 months, respectively. Conclusions: Serum Ca19.9 positivity and DTs <6 months and < 1 year are prognostic factors for mortality but not for PD. Serum Ca19.9 positivity and DTs <6 months and < 1 year should be considered in the decision-making process of whether to initiate systemic therapy even if there is no evidence of PD according to RECIST.