BACKGROUND
Thyroid cancer is common and usually has an excellent prognosis. This is largely because we have very effective treatments. Surgery to remove all (total thyroidectomy) or part (lobectomy) is the usual first treatment option. Many thyroid cancers are low risk, so lobectomy is often the best option. Total thyroidectomy is better option if a thyroid cancer has high risk features. One high risk feature is the size of the cancer. The ATA guidelines recommend total thyroidectomy rather than a lobectomy for thyroid cancers larger than 4 cm due to worse reported patient outcomes. However, there is limited research data available looking at the cancer size as a prognostic factor for thyroid cancer. The goal of this study is to evaluate: 1. whether a cancer size larger than 4 cm is associated with worse outcomes in the absence of other markers of aggressive disease, 2. whether the presence of other high-risk features affect the prognosis of large cancers, and 3. whether a cancer size of 4 cm is the best cut off for risk stratification in thyroid cancer.

THE FULL ARTICLE TITLE
Ginzberg SP, et al. Revisiting the relationship between tumor size and risk in well-differentiated thyroid cancer. Thyroid 2024;34(8):953-1063; doi: 10.1089/ thy.2023.0327. PMID: 38877803.

SUMMARY OF THE STUDY
The study included 193,133 patients from the National Cancer Database (NCDB), who were diagnosed with thyroid cancer between 2010 and 2015. A smaller group of 5,011 patients from the SEER database was used for comparison. Patient demographic, clinical and treatment data were used for analysis. The study compared the overall survival for patients with cancer sizes larger vs smaller than 4 cm, with and without the presence of other markers of aggressive disease. The average follow-up time was 87 months, with data available until 2020.

Most patients were white females (76% female, 76% white) with an average age of 50 years. The average cancer size was 1.3 cm, with 8% of patients having cancers larger than 4 cm. At least one marker of aggressive disease was present in 28% of patients with cancers 4 cm or smaller vs 61% with cancers larger than 4 cm. Total thyroidectomy was performed in 90% vs 88%, while radioactive iodine treatment was given to 67% vs 43% of patients with cancers smaller or larger than 4 cm, respectively. The overall 5-year survival was 96% in the entire group, with a decreased 5-year survival of 92% in patients with cancers larger than 4 cm as compared to 96% in patients with cancers 4 cm or smaller. Further analysis to adjust for differences between the two patient groups confirmed that a cancer size larger than 4 cm is associated with significantly worse overall survival compared to smaller cancers.

The presence of additional markers of aggressive disease worsened the prognosis. Patients with cancers larger than 4 cm had a greater risk of death if they had at least one additional risk factor. Patients with cancers larger than 4 cm and no additional risk factors had a similar survival with those with smaller cancers and additional risk factors. A higher number of high-risk features worsened survival, with a steeper increase of risk for cancers larger than 4 cm as compared to smaller cancers.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
Patients with thyroid cancers larger than 4 cm have worse survival as compared to smaller cancers, and the presence of other features of aggressive disease further reduces survival. There was an increased risk of death at the 2 cm and 5 cm cancer size cutoffs, but not at the 4 cm cutoff, which is used in current guidelines. These findings support a more individualized risk assessment approach in thyroid cancer patients for adequate treatment and follow-up. While a total thyroidectomy for a cancer larger than 4 cm with one or more associated high-risk features would be recommended, the cut off for lobectomy could be increased to 5 cm for cancers without other high-risk features.

— Alina Gavrila, MD, MMSC

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