Study Overview
Objective. To determine whether the use of imaging tests following primary treatment of differentiated thyroid cancer is associated with an increase in treatment for recurrence and improved survival.
Design. Population-based retrospective cohort study.
Setting and participants . Participants were patients from the Surveillance, Epidemiology, and End Results (SEER) Medicare-linked cancer registry who were diagnosed with differentiated thyroid cancer between 1 January 1998 and 31 December 2011. The study cohort included 28,220 patients. Patient follow up continued to 2013.
Main outcome measures . The primary outcome measures were treatment of differentiated thyroid cancer and deaths due to differentiated thyroid cancer. Number of diagnoses, imaging tests (neck ultrasounds, radioiodine scans, and PET scans), treatments for recurrence (repeat neck surgery, further radioactive iodine treatment, and radiotherapy), and disease-specific deaths were obtained for each year between 1998 and 2011. Propensity score analyses were performed to assess the relation between imaging and treatment for recurrence (logistic model) and death (Cox proportional hazards model).
Main results . Between 1998 and 2011, there was a significant increase in incident thyroid cancer (rate ratio 1.05; 95% confidence interval [CI] 1.05 to 1.06), imaging (rate ratio 1.13; 95% CI 1.12 to 1.13), and treatment for recurrence (rate ratio 1.01, 95% CI 1.01 to 1.02), but the overall death rate from thyroid cancer did not change. 56.7% of patients underwent surveillance ultrasound, 23.9% radioiodine scan, and 14.9% PET scan. After controlling for patient and tumor characteristics, patients who under-went ultrasound were more likely to have additional surgery (odds ratio [OR] 2.3, 95% CI 2.05 to 2.58) and additional radioactive iodine treatment (OR 1.45, 95% CI 1.26 to 1.69) but not radiotherapy (OR 1.08; 95% CI 0.97 to 1.20). Patients who underwent radioiodine scans and PET scans were more likely to have surgery (OR 3.39, 95% CI 3.06 to 3.76 and OR 2.31, 95% CI 2.09 to 2.55), radioactive iodine treatment (OR 17.83, 95% CI 14.49 to 22.16 and OR 2.13, 95% CI 1.89 to 2.40), and radiotherapy (OR 1.89, 95% CI 1.71 to 2.10 and OR 4.98, 95% CI 4.52 to 5.49). Thyroid cancer was the cause of death in 4.1% of the cohort. Disease-specific survival was increased in patients who had radioiodine scans (hazard ratio [HR] 0.70, 95% CI 0.60 to 0.82) but not in those who underwent ultrasound (HR 1.14, 95% CI 0.98 to 1.27) or PET scans (HR 0.91, 95% CI 0.77 to 1.07).
Conclusion. Increased use of imaging after primary treatment of thyroid cancer is associated with increased treatment for recurrence but not with improved disease-specific survival, except for radioiodine scans in presumed iodine-avid disease.
Commentary
Thyroid cancer is the most rapidly increasing cancer in the United States. An estimated 64,000 new cases will be diagnosed in 2016, which represents a tripling in thyroid cancer incidenceover the past 30 years [1]. During this time, mortality from thyroid cancer has remained stable. Most of the increase incidence is attributable to enhanced detection and diagnosis of low-risk disease (ie, papillary tumors) [2]. Although long-term survival following treatment of low-risk thyroid cancer is excellent, with 10-year survival ranging from 96% to 100% [3], concern about risk for recurrence appears to be driving an increased use of imaging in post-treatment surveillance. It is not clear, however, if the benefits of more imaging outweigh its associated costs, which include increased patient anxiety and financial costs, radiation exposure, and the potential for harm from additional treatment.
This retrospective observational study by Banerjee et al evaluated how frequently imaging is used after patients undergo primary treatment of thyroid cancer and whether post-treatment surveillance imaging affects disease-specific survival. The authors used SEERS-Medicare data from 28,220 patients diagnosed with differentiated thyroid cancer. They found a high rate of imaging after primary treatment of thyroid cancer, and all 3 imaging modalities—ultrasound, radioiodine scans, and PET scan—were associated with a higher likelihood that patients would undergo treatment for recurrence. However, only use of radioiodine scans was associated with improved survival. Radioiodine scans are recommended only for persons who have had iodine-avid disease and have evidence of recurrence on biochemical testing. This form of testing may be associated with improved survival because radioactive iodine itself frequently is effective treatment for iodine-avid disease, and iodine-avid disease is usually well differentiated and has a good prognosis. The findings of this study suggest that more imaging following primary treatment is detecting more recurrences but without having a beneficial impact on patient survival.
This study has several limitations. The study’s retrospective, observational design allows it to demonstrate only associations between imaging and treatment for recurrence or survival without providing insight into causes. The SEER-Medicare database lacks data on patient-specific variables, such as iodine avidity, patient preference, and indications for imaging, which could provide alternative explanations for the observed associations. The median age of patients in this study was 65 years, which could limit the applicability of the findings to other populations.
Applications for Clinical Practice
The approach to surveillance following treatment of differentiated thyroid cancer continues to evolve, but evidence to guide the use of imaging in recurrence monitoring is lacking. This study provides an evidence base for strategies that reduce unnecessary testing and that base surveillance plans on individual patient risk. Future studies should explore the cost-effectiveness of imaging tests and the role of physicians and patients in determining when imaging is done. Randomized controlled trials that compare outcomes when small recurrences are followed rather than treated are also needed.