BACKGROUND
Papillary thyroid cancer is the most common type of thyroid cancer. Overall prognosis of papillary thyroid cancer is excellent, as we currently have very effective treatments. There are several subtypes of papillary thyroid cancer. One such subtype is tall-cell subtype, defined as a cancer containing more than 30% tall cells, which have a height at least three times their width. Tall-cell papillary thyroid cancer displays a more aggressive behavior compared to the classical papillary thyroid cancer. Because of this, tall-cell papillary thyroid cancer is included in the American Thyroid Association (ATA) intermediate-risk for cancer recurrence category. According to the 2015 ATA Guidelines, radioactive iodine therapy should be considered after total thyroidectomy in these patients. However, 90% of patients with tall-cell papillary thyroid cancer have a BRAF gene mutation, which is known to decrease the cancer responsiveness to radioactive iodine therapy.

The goal of this study is to evaluate the impact of the radioactive iodine therapy on cancer-specific survival (CSS) in patients with tall-cell papillary thyroid cancer, using the Surveillance, Epidemiology, and End Results (SEER) database.

THE FULL ARTICLE TITLE
Dai P et al. Effect of radioactive iodine therapy on cancerspecific survival of papillary thyroid cancer tall cell variant. J Clin Endocrinol Metab 2024;109(3):e1260-e1266; doi: 10.1210/clinem/dgad580. PMID: 37804527.

SUMMARY OF THE STUDY
This study included 1281 adult patients from the SEER database who underwent total thyroidectomy for patients with tall-cell papillary thyroid cancer between 2004 and 2019. Patients who were less than 18 years of age, had less than one month of follow-up data, received externalbeam radiation, or had missing data were excluded from analysis. Information collected for each patient included age at diagnosis, gender, race, cancer size and stage, degree of spread outside the thyroid, number of lymph nodes involved, radioactive iodine therapy, follow-up outcomes, survival time, and cause of death.

For the statistical analysis, patients were grouped based on age at diagnosis (younger than 55 years of age or 55 and older), cancer size (smaller than 20 mm, 20–40 mm, or larger than 40 mm), and year of diagnosis (2004–2008, 2009–2014, or 2015–2019). The patients who received radioactive iodine therapy were compared to those who did not receive radioactive iodine therapy treatment. The main study outcome was the cancer-specific survival (CSS), which was calculated as the time from diagnosis to death from thyroid cancer or the last follow-up visit.

Among the 1281 patients with tall-cell papillary thyroid cancer included in the study, 866 (68%) received radioactive iodine therapy and 415 (32%) did not. Patients who received radioactive iodine therapy had a higher proportion of males, larger cancer size, more advanced stage, more frequent spread outside the thyroid, and higher proportion of positive lymph nodes as compared to those who did not receive radioactive iodine therapy. The study group was followed for an average of 60 months (range 27-102 months). A total of 58 patients (4.5%) died from thyroid cancer during this time. The 5-year and 10-year CSS for the entire group was 96.1% and 92.4%, respectively. Unfavorable prognostic factors were age of 55 or older, presence of distant metastasis and more than 5 positive neck lymph nodes.

There was no difference in cancer-specific survival between the radioactive iodine therapy and non- radioactive iodine therapy treatment groups. Subgroup analysis showed no effect of the radioactive iodine therapy treatment on cancer- specific survival even in patients with more aggressive features, including age of 55 or older, cancer size larger than 40 mm, advanced cancer stage, distant metastasis and more than 5 positive neck lymph nodes.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
This study shows that survival of patients with the rare tall-cell papillary thyroid cancer is worse than with classical papillary thyroid cancer. Still, the 5 and 10-year survivals continue to be well higher than 90%. This study suggests that radioactive iodine therapy does not improve survival in tall-cell papillary thyroid cancer regardless of age, gender, race, and cancer stage, including size, spread outside of the thyroid and number of positive lymph nodes. Additional larger and longer studies are needed for a definitive answer regarding the usefulness of radioactive iodine therapy in tall-cell papillary thyroid cancer to help tailor the treatment for these patients.

— Alina Gavrila, MD, MMSC

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