Comparative Analysis of the Growth Pattern of Thyroid Cancer in Young Patients Screened by Ultrasonography in Japan After a Nuclear Accident: The Fukushima Health Management Survey

Abstract

Importance: Thyroid cancer generally grows at a very slow rate in adults, and overdiagnosis is a global issue. However, the detection of early-stage thyroid cancer by screening is not well described in young patients. To prevent overdiagnosis, it is essential to understand the natural course of thyroid cancer growth detection by ultrasonography screening in young patients.

Objective: To evaluate the natural progression of thyroid cancer in young patients.

Design, setting, and participants: An observational study evaluated changes in the diameter of malignant or suspected malignant thyroid tumors on 2 occasions. Changes in malignant thyroid tumor diameter were estimated during the observation period between the screening and confirmatory examinations in the first-round thyroid ultrasonography examination of the Fukushima Health Management Survey in patients younger than 21 years after a nuclear accident at a power plant in Fukushima, Japan. In total, 116 patients cytologically diagnosed with or suspected to have thyroid cancer were classified into 3 groups based on a greater than 10% reduction, a change of -10% to +10% in diameter, and a greater than 10% increase in tumor diameter. The association between tumor growth rate and tumor diameter was analyzed. The study was conducted from March 1, 2016, to August 6, 2017.

Main outcomes and measures: Tumor volume changes, the coefficient of growth of thyroid cancer in young patients, and the association between the observation period or tumor diameter and them.

Results: Of 116 patients, 77 were female; the mean age was 16.9 years (median, 17.5 years). The mean observation period was 0.488 (range, 0.077-1.632) years. No significant differences in age, sex, tumor diameter, observation period, or serum levels of thyrotropin and thyroglobulin were observed among the groups. Whereas tumor volume changes were not linearly correlated with the observation period (Pearson R = 0.121; 95% CI, -0.062 to 0.297), the coefficient of growth was significantly and negatively correlated with the tumor diameter in the screening examination (Spearman ρ = -0.183; 95% CI, -0.354 to -0.001), suggesting growth arrest after the initial proliferation phase.

Conclusions and relevance: Ultrasonography screening could reveal asymptomatic thyroid cancer that is falling into a growth arrest pattern in many young patients. Considering the long life expectancy, prevention of overdiagnosis necessitates careful long-term monitoring without immediate diagnosis for suspected noninvasive thyroid cancer.

Figure 1.. Two Hypothesized Patterns of Thyroid Cancer Progression

A, Linear semilogarithmic progression (exponential cell growth) pattern. B, Linear semilogarithmic progression and virtual growth arrest (relatively rapid growth in the initial phase with subsequent growth arrest) pattern.

Figure 2.. Correlation Between Observation Period and Tumor Growth

A, Percentage change in tumor diameter. B, Logarithmic index of volume change by length of observation period. Y₁ indicates tumor diameter in the screening examination (millimeters); Y₂, tumor diameter in the confirmatory examination (millimeters). There were no significant correlations between the observation period and either the percentage change of the tumor diameter (Pearson R = 0.098; 95% CI, –0.085 to 0.276) or the logarithmic index of volume change (Pearson R = 0.121; 95% CI, –0.062 to 0.297). The logarithmic index of volume change well reflects the percent change in tumor diameter. The tumor growth rate is not exponential.

Figure 3.. Correlation Between Age and Tumor Growth

A, Percentage change in maximum tumor diameter at the screening examination. B, Logarithmic index of volume change. Y₁ indicates tumor diameter in the screening examination (millimeters); Y₂, tumor diameter in the confirmatory examination (millimeters). There were no significant correlations (Spearman ρ = –0.065; 95% CI, –0.245 to 0.118).

Figure 4.. Coefficient of Growth by Tumor Diameter and Growth Curve of Tumor Volume

A, Correlation between tumor diameter and coefficient of growth. There was a significant negative correlation between the coefficient of growth and the tumor diameter (Spearman ρ = −0.183; 95% CI, –0.354 to –0.001). The data were divided into 2 groups according to tumor size (small and large). The threshold tumor diameter Y_T in the screening examination was estimated as 12.4 mm. The coefficient of growth was almost zero (0.010 year⁻¹) in the large tumor group (n = 47). B, Growth curve of tumor volume in a linear semilogarithmic progression period and a growth arrest period. The 95% CIs were estimated by Monte Carlo simulation. The mean number of years during which the tumor grew from a diameter of 5 mm until reaching the growth arrest point was calculated as approximately 8.0 (range, 5.1–17.6) years. Solid lines and broken lines represent mean and 95% CI, respectively.