Treatment Response Predicts Medullary Thyroid Cancer Outcome

Miriam E Tucker

February 19, 2015

Monitoring the response to initial therapy provides useful prognostic information in medullary thyroid cancer (MTC), just as it does in differentiated thyroid cancer, a new analysis shows.

The findings were published in the February issue of Thyroid by Susan C Lindsey, MD, of Universidade Federal de São Paulo, Brazil, and colleagues.

Dynamic stratification of risk by response to initial tumor therapy is increasingly being adopted in oncology in general and in thyroid cancer specifically.

In this new study, Dr Lindsey and colleagues developed a medullary thyroid-cancer–specific nomenclature based on the possible calcitonin and carcinoembryonic antigen (CEA) responses and found that the approach provided clinically useful information beyond that obtained from the static Tumor, Node, Metastasis/American Joint Cancer Committee (TNM/AJCC) staging system.

"Multiple papers show that in classic papillary and follicular thyroid cancer, this response to therapy approach works really well….As patients come back over time, they change. Depending on what happens, we can either increase or decrease their risk [assessment]," coauthor R Michael Tuttle, MD, from Memorial Sloan Kettering Cancer Center, New York, told Medscape Medical News.

This is the first time the approach is being applied to medullary thyroid cancer. "We want people treating thyroid cancer with the same general framework; that's why we went ahead and applied this to medullary," he explained.

Dynamic Approach

The authors reviewed charts for 287 MTC patients seen at Memorial Sloan-Kettering Cancer Center between July 1973 and July 2013 and stratified them by the TNM/AJCC system as MTC stages I to IVc.

They then stratified 279 patients for whom adequate data existed by response to therapy as assessed every 6 to 12 months. They divided them into three MTC-specific categories based on the best response within a year of initial therapy, using data from previous work by Dr Tuttle and colleagues (Oral Oncol.2013;49:695-701):

  • Excellent — Undetectable calcitonin, CEA within the reference range, and no structural evidence of disease by imaging.

  • Biochemical incomplete — Detectable calcitonin or abnormal CEA in the absence of structural evidence of disease.

  • Structural incomplete — Persistent/recurrent structural disease regardless of calcitonin and CEA.

In the first postoperative year, 27% had an excellent response to initial therapy, 35% had biochemical evidence of persistent disease without a structural correlate, and 38% had structural persistent disease. At a median of 5 years' follow-up, 26% had died of thyroid cancer while 21% were alive without evidence of disease.

The AJCC staging system predicted disease-specific mortality (ranging from 2% of the 65 patients with stage I to 40% of the 164 with stage IV) and the likelihood of having no evidence of disease at follow-up (from 71% for stage I to 3% for stage IV).

The AJCC stage also correlated with response to therapy. Specifically, 80% of the stage I group achieved an excellent response vs just 2% with a structural incomplete response. Among patients with stage IV disease, 6% achieved an excellent response and 61% had a structural incomplete response.

However, Kaplan-Meier survival curves show that the best-response-to-therapy measure more accurately predicted overall survival than the AJCC staging system (P < .0001). The 5-, 10-, and 20-year survival rates among patients in the excellent-response group were 100%, 95%, and 87.1%, respectively. By contrast, the rates were 51%, 36.4%, and 8.1%, respectively, among patients in the structural-incomplete-response group.

The best-response-to-therapy stratification system was also better able to distinguish between patients who would have no evidence of disease from those who would have recurrence or persistent disease than was the AJCC system (portion of variance, 54.3% vs 23.9%).

How Different Are Medullary Thyroid Tumors?

Medullary thyroid cancer, which accounts for only 3% to 4% of all thyroid cancers, has traditionally been thought of differently from papillary and follicular thyroid cancers, Dr Tuttle told Medscape Medical News.

"Medullary has the reputation for being a much more aggressive tumor than papillary and follicular. That's what you're taught in oncology in medical school. With this response-to-therapy [system] you can quickly find out within the first year or so who's really going to have aggressive disease and who isn't. It turns out most of the medullary thyroid cancers are not really all that aggressive. I think this sort of paradigm will give doctors more realistic goal setting and expectations for patients, rather than just assuming all these medullaries are bad."

Dr Tuttle is a consultant to Veracyte, AstraZeneca, Bayer/Onyx, Eisai, Genzyme, Sanofi, and Novo Nordisk. The coauthors have reported they have no relevant financial relationships.

Thyroid. 2015;25:242-249. Abstract

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