Natural History and Tumor Volume Kinetics of Papillary Thyroid Cancers During Active Surveillance

Abstract

Importance: Active surveillance of low-risk papillary thyroid cancer (PTC) is now an accepted alternative to immediate surgery, but experience with this approach outside of Japan is limited. The kinetics (probability, rate, and magnitude) of PTC tumor growth under active surveillance have not been well defined.

Objective: To describe the kinetics of PTC tumor growth during active surveillance.

Design, setting, and participants: Cohort study of 291 patients undergoing active surveillance for low-risk PTC (intrathyroidal tumors ≤1.5 cm) with serial tumor measurements via ultrasonography at a tertiary referral center in the United States.

Intervention: Active surveillance.

Main outcomes and measures: The cumulative incidence, rate, and magnitude of the change in tumor diameter or volume, as well as associations with patient and tumor characteristics.

Results: Of the 291 patients, 219 (75.3%) were women; mean (SD) age was 52 (15) years. During a median (range) active surveillance of 25 (6-166) months, growth in tumor diameter of 3 mm or more was observed in 11 of 291 (3.8%) patients, with a cumulative incidence of 2.5% (2 years) and 12.1% (5 years). No regional or distant metastases developed during active surveillance. In all cases, 3-dimensional measurements of tumor volume allowed for earlier identification of growth (median, 8.2 months; range, 3-46 months before increase in tumor diameter). In multivariable analysis, both younger age at diagnosis (hazard ratio per year, 0.92; 95% CI, 0.87-0.98; P = .006) and risk category at presentation (hazard ratio for inappropriate, 55.17; 95% CI, 9.4-323.19; P < .001) were independently associated with the likelihood of tumor growth. Of the tumors experiencing volume growth, kinetics demonstrated a classic exponential growth pattern, with a median doubling time of 2.2 years (range, 0.5-4.8 years; median r2 = 0.75; range, 0.42-0.99).

Conclusions and relevance: The rates of tumor growth during active surveillance in a US cohort with PTCs measuring 1.5 cm or less were low. Serial measurement of tumor volumes may facilitate early identification of tumors that will continue to grow and thereby inform the timing of surveillance imaging and therapeutic interventions.

Figure 1.. Cumulative Incidence of Increase in Tumor Diameter and Volume Among Papillary Thyroid Cancers During Active Surveillance

A, Time to increase in tumor diameter of 3 mm or more. B, Increase in tumor volume of more than 50%.

Figure 2.. Percentage Change in Tumor Volume During Active Surveillance for Each Patient

Of 284 patients undergoing active surveillance with complete 3-D measurements, tumor size decreased >50% in 19 patients (6.7%), was stable in 229 (80.2%), and increased >50% in 36 (12.7%). In 7 patients (2.4%), tumor volume could not be calculated because of the lack of reproducible 3-D measurements. Tumor diameter increased ≥3 mm in 11 (3.8%).

Figure 3.. Tumor Measurements in Representative Patients

A, Measurements during active surveillance for all 36 patients demonstrating a greater than 50% increase. Markers on the lines (eg, triangles, bars) indicate individual patient measures. B, Pattern of exponential growth in 1 patient (r² = 0.72; tumor volume doubling time [DT], 4 years; diameter, from 10 to 13 mm; volume, from 0.3 to 0.5 mL). C, Pattern of exponential growth in another patient (r² = 0.90; DT, 2.7 years; diameter, from 6 to 9 mm; volume, from 0.05 to 0.1 mL). D, Measurements in a patient with stable disease (r² = 0.98; diameter, from 15 to 13 mm; volume, from 1.0 to 0.9 mL).