BACKGROUND
Thyroid cancer is the fastest rising cancer in recent years. Most patients with thyroid cancer are at low risk of cancer recurrence after the initial surgery to remove the cancer. However, there are some features found on pathology after surgery that increases the risk of the thyroid cancer returning. One such feature is minimal extrathyroidal extension (ETE) which means that a small amount of thyroid cancer is found extending outside of the thyroid gland after examining the cancer under the microscope. This finding was removed from the current thyroid cancer staging guidelines because it is not associated with increased likelihood of death. However, it is still important and may be associated with an increased risk of the thyroid cancer coming back (recurrence).

Most patients at low risk of thyroid cancer recurrence are usually just treated with surgery then thyroid hormone. Patients with an increased risk of the thyroid cancer returning based on the results of the initial surgery usually are treated additionally with radioactive iodine therapy. This study was done to look at the impact of minimal ETE in predicting initial treatment response in papillary thyroid cancer, with and without treatment with radioactive iodine therapy.

THE FULL ARTICLE TITLE
Forleo R et al. 2021 Minimal extrathyroidal extension in predicting 1-year outcomes: A longitudinal multicenter study of low-to-intermediate-risk papillary thyroid carcinoma (ITCO#4). Thyroid. Epub 2021 Sept 19. PMID: 34541894.

SUMMARY OF THE STUDY
This study looked at the Italian Thyroid Cancer Observatory (ITCO), a web-based database started in 2013, which includes 9000 patients with thyroid cancer from 49 thyroid cancer centers.

Of these, 2237 subjects met all the criteria to be included in this study. Initial treatment was classified as thyroid lobectomy (partial thyroid removal) or total thyroidectomy (total thyroid removal) and if radioactive iodine therapy was given following total thyroidectomy. Risk of recurrence was classified based on the 2015 American Thyroid Association guidelines for thyroid nodules and thyroid cancer, and response to initial treatment was classified based on diagnostic scans and blood thyroglobulin and thyroglobulin antibody levels at the 1-year follow-up visit.

Of the 2237 subjects included in the analysis, 1,153 (51.5%) patients received radioactive iodine therapy and minimal ETE was documented in 470 patients (21%). According to the American Thyroid Association risk classification system, 1632 (73%) were classified as low risk of recurrence and 605 (27%) as intermediate risk of recurrence. At the 1-year follow-up, there was no difference in initial therapy response rates between patients with and without minimal ETE. Other factors, including cancer size, aggressive thyroid cancer types and age at diagnosis were also looked at. Only the combination of minimal ETE with a cancer size of >2 cm showed a difference in treatment response.

Among the 470 patients with minimal ETE, 370 had received radioactive iodine therapy. Subjects who received radioactive iodine therapy were more likely to have an excellent response initially but there was no difference in the response once the investigators corrected for the other variables.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
Minimal ETE is not an independent prognostic marker in predicting the initial response to therapy in patients with papillary thyroid cancer who do not have spread of the cancer to the lymph nodes. However, the combination of minimal ETE and cancer size >2 cm can predict worse outcomes. Knowing this information is important for patients with thyroid cancer to understand the management decisions that are being made to treat their cancer, as these decisions are dependent on factors associated with their prognosis.

— Maria Brito, MD

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