Surgery Tops Surveillance for Small Differentiated Thyroid Cancer

Mitchel L. Zoler, PhD, for Medscape

March 07, 2022

Researchers published the study covered in this summary on Research Square as a preprint and it has not yet been peer reviewed.

    Key Takeaways

    • Patients with small, differentiated thyroid cancer (DTC) who underwent surgical resection of their tumor had significantly better overall survival (OS) when compared with patients who did not have surgery but instead underwent active surveillance.

    • The analyses, which relied on observational data, used propensity-score matching and, separately, multivariate adjustment to account for differences between patients who received these two different management strategies.

    • The survival benefit of surgery encompassed all histologic types of DTC and was consistent in patients with tumors less than 1 cm in size as well as those with tumors measuring 1-2 cm.

    Why This Matters

    • Recent decades have seen a rapid increase in the incidence of thyroid cancer in the United States and worldwide, most of which are DTCs.

    • The authors said their report is the largest real-world, observational study to compare survival outcomes of patients with small DTC between those who underwent surgical resection and those who did not have surgery.

    • Most prior studies that assessed an active surveillance approach for patients with DTC focused on patients with papillary thyroid cancer. In the current study, the authors evaluated the survival benefit of surgical resection in patients with any DTC histologic type.

    • The results highlight the importance of further studies that compare outcomes in patients with small DTC between those managed with active surveillance and those who undergo surgical resection. Additional data are needed from large-scale studies assessing disease-specific survival to evaluate benefits and risks of these alternative strategies.

    Study Design

    • The study included adults diagnosed with histologically proven, nonmetastatic, small (no larger than 2 cm) DTC in 2004-2016 in the US National Cancer Database.

    • The primary outcome was OS, defined as time in months from diagnosis to death for any reason.

    • Researchers used Kaplan-Meier survival curves to analyze OS. They used a log-rank test to evaluate survival differences between groups, and Cox regression analysis to conduct multivariable analyses to evaluate factors associated with improved OS. Multivariable analyses adjusted for facility type, age, gender, race, median household income, education level, insurance status, area, Charlson Comorbidity Index, histology type, tumor size, and surgery status.

    Key Results

    • The study included 98,501 patients with nonmetastatic small DTC who met the enrollment criteria, including having a known surgery status; 96,612 (98%) patients had surgery and 1889 (2%) did not have surgery.

    • The percentage of patients who did not have surgery increased during the 13-year period studied, which might reflect increased opting by patients for active surveillance.

    • In the unadjusted analysis, patients treated with surgery had significantly better OS, a mean of 171 months, compared with patients who did not have surgery, at a mean of 134 months.

    • Propensity-score matching identified 1889 matched pairs of patients from the surgery and no-surgery subgroups. In this analysis, OS among those who underwent surgery was a mean of 166 months, significantly better than the mean 134 months in the matched no-surgery patients.

    • The multivariable analysis showed that having surgery significantly reduced the relative risk of death from any cause by 78% compared with no surgery.

    • Several subgroup analyses showed that the significant OS advantage associated with surgery persisted regardless of tumor size (< 1 cm or 1-2 cm), histologic subtype, or patient's age (< 55 years old or ≥ 55 years old).


    • The database used for the study lacked details on whether patients who did not have surgical resection underwent active surveillance.

    • Aside from OS, the National Cancer Database does not have details about other cancer endpoints such as disease-free survival and cancer-specific survival. It is therefore possible that the higher mortality among surveillance patients was caused by nonthyroid cancer deaths rather than thyroid cancer deaths, particularly given the imbalance in baseline characteristics between the two subgroups, with older age and more comorbidities in the no-surgery patients. It is possible that factors such as age and comorbidity were part of the reason why some of those patients did not undergo surgery. To mitigate this limitation, the authors ran multivariable analyses that adjusted for age, comorbidity, and other nonthyroid cancer factors. They performed a propensity-score matching analysis and also ran multiple subgroup analyses.

    • The database did not supply details about all high-risk features, such as aggressive histological subtypes or history of prior neck irradiation.

    • The retrospective nature of the study the data collection methods of the National Cancer Database introduced various types of bias that might affect the accuracy of the analyses and interpretation of the results.


    • The study received no commercial funding.

    • One author, Omar Abdel-Rahman, has been an advisor to Bayer, Eisai, Ipsen, Lilly, and Roche. The other author had no disclosures.

    This is a summary of a preprint research study, "The Role of Surgery in Small Differentiated Thyroid Cancer," written by a researcher at the Cleveland Clinic and by a researcher at the University of Alberta on Research Square provided to you by Medscape. This study has not yet been peer reviewed. The full text of the study can be found on


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