Ca19.9 Positivity Indicative of Mortality from Medullary Thyroid Cancer

In advanced medullary thyroid cancer (MTC), mortality may be predicted by serum carbohydrate antigen 19.9 (Ca19.9) positivity in patients as well as by doubling times (DTs) less than 6 months and less than 1 year. Results of a retrospective study suggest that these 2 new prognostic factors should be considered when initiating treatment for patients with MTC.

The idea that Ca19.9 could be predictive of mortality in MTC stems from early research which showed that serum creatinine and increased carcinoembryonic antigen levels were not important markers in MTC, but that Ca19.9, which is secreted in MTC, was significantly associated with progressive disease.

Investigators led by Loredana Lorusso, MD, retrospectively evaluated 107 consecutive patients who were largely female (43%) who were hospitalized for evaluation of their advanced structural persistent/recurrent MTC from 2011 to 2017. For the purposes of the analysis, only patients with local disease and/or metastatic lymph node and/or distant metastases, and who showed more than 1 measurement of Ca19.9 were included. At the time of diagnosis, patients had a median age of 45.5 years (range, 13-79 years).

To assess Ca19.9 routinely, patients were evaluated every 6 to 12 months. For 23 of the study subjects, Ca19.9 measurements were performed retrospectively using stored blood samples. The median number of Ca19.9 measurements taken was 5 (range, 2-10).

Assessment of patients’ disease characteristics showed that 30 patients had progressive disease (PD). Of the total population, 91 patients underwent total thyroidectomy, central compartment lymphadenectomy, and lateral cervical lymph node dissection. In addition, 5 patients had a total thyroidectomy and central lymph node dissection and 11 patients underwent total thyroidectomy alone. Lymph node metastases were observed in 26.2% of patients at the time of selection, as well as both lymph node and distant metastases in 62.6% of patients, and only distant metastases in 11.2%.

The full study population was tested for germline RET mutation, and 15.8% of patients tested positive.

According to the protocol of the retrospective study, a comparison of mortality between patients with MTC who were negative for Ca19.9 and those who were positive would be considered statistically significant if the P-value was less than 0.05. To evaluate this finding, Kaplan-Meier survival curves for mortality were calculated then assessed using a log-rank test.

“We demonstrate the utility of serum Ca19.9 to identify a subgroup of a MTC with a greater probability of dying of their disease,” wrote Lorusso et al, in the published study.

Prior to evaluation, 99 patients out of 107 had Ca19.9-negative MTC and 8 out of 107 had Ca19.9-positive disease. At the end of the follow-up period, 76.6% of the population remained negative, but all patients who were initially positive remained so and 17 more patients who were originally negative had become positive. At the end of the analysis, the Ca19.9 positivity rate had climbed from 7.5% to 23.4%.

The 6-month Ca19.9 DT was 5.6% and the 1-year Ca19.9 DT was 8.4%.

Association between categorical variables was evaluated in the study using the Chi-squared test. First, Ca19.9 DTs were not shown to be associated with the development of distant metastases during follow-up (P = .27). Ca19.9 DT at 6 months and 1 year, on the other hand, were found to correlate with the presence of bone metastases at the end of follow-up. The P value was less than .0001 at 6 months and .0002 at 12 months. In addition, no association was found between Ca19.9 DTs and the presence of liver or lung metastases.

Regarding Ca19.9 positivity and the occurrence of mortality of PD, 31 patients in the study died of MTC. Notably, 60% of the patients who succumbed to their disease were positive for Ca19.9, while 19% were negative for Ca19.9 (P < .0001). In terms of PD, 28.8% showed PD at the end of follow-up while 71.2% displayed stable disease. The difference in PD for the Ca19.9-positive population versus the Ca19.9-negative group was not statistically significant (P = .11).

“Our findings suggest these patients should probably be immediately treated with systemic agents like cabozantinib or vandetanib or other systemic therapies if available,” wrote Lorusso et al.

_Reference:

_{Lorusso L, Romei C, Piaggi P, et al. 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. Thyroid. Published online January 7, 2021. doi:10.1089/thy.2020.0060}