Shifting Paradigms in Thyroid Cancer Follow-Up

Data are now emerging that confirm that many of the same risk factors that predict mortality also predict recurrence, Dr. Cooper said. Tumor size of more than 3 centimeters predicts lymph node recurrence rate, and the number of lateral nodes predicts recurrence rates in lateral nodes. Furthermore, the degree of extrathyroidal extension of the tumor, along with aggressive tumor histology, all indicate how aggressive the tumor is and can predict not only mortality but also recurrence.

European Standard Should be Used for Serum Tg Tests

But what about the use of serum Tg? There are a number of issues related to the use of serum Tg; to address some of these, the new ATA guidelines recommend using the European Tg standard. However, even when assays are standardized against this standard, there is still a lot of variability in thyroglobulin measurements among the various kits that are available at different institutions, he said.

Another hurdle is that anti-Tg antibodies occur in a larger percentage of thyroid cancer patients than in the general population. False negatives in immunometric assays and false positives in radioimmuno assays also continue to exist as problems. These are all areas that require further research to solve them, Dr. Cooper said. There can also be undetectable Tg, including stimulated Tg, in low-volume disease, in poorly differentiated tumors, and in people with previous radioiodine therapy for metastatic disease of the lymph nodes.

False positive Tg is important to note, and occurs in about 2% of patients. If a patient has a Tg of 10, or 20, or 30, and it cannot be found on imaging, the patient may end up being treated unnecessarily with radioactive iodine (RAI).

Another relevant issue in follow-up is that a rising Tg indicates that there is probably tumor progression, which may become clinically apparent at some point in the future, Dr. Cooper said. The new guidelines recommend that Tg be measured every six to 12 months by immunometric assay standardized against the European standard CRM 457, and it should be measured in the same laboratory using the same assay.

Additionally, periodic Tg measurement should be considered during follow-up with patients who have undergone less than a total thyroidectomy, and in patients who have not received RAI. This recommendation is new. We still think thyroglobulin can be useful in such patients, but we really don’t know what the cutoff should be in someone who hasn’t had a total thyroidectomy or RAI, Dr. Cooper said.