Expanded Parameters in Active Surveillance for Low-risk Papillary Thyroid Carcinoma: A Nonrandomized Controlled Trial

Abstract

Importance: Unlike for prostate cancer, active surveillance for thyroid cancer has not achieved wide adoption. The parameters by which this approach is feasible are also not well defined, nor is the effect of patient anxiety.

Objective: To determine if expanded size/growth parameters for patients with low-risk thyroid cancer are viable, as well as to assess for cohort differences in anxiety.

Design, setting, and participants: This prospective nonrandomized controlled trial was conducted at a US academic medical center from 2014 to 2021, with mean [SD] 37.1 [23.3]-month follow-up. Of 257 patients with 20-mm or smaller Bethesda 5 to 6 thyroid nodules, 222 (86.3%) enrolled and selected treatment with either active surveillance or immediate surgery. Delayed surgery was recommended for size growth larger than 5 mm or more than 100% volume growth. Patients completed the 18-item Thyroid Cancer Modified Anxiety Scale over time.

Interventions: Active surveillance.

Main outcomes and measures: Cumulative incidence and rate of size/volume growth.

Results: Of the 222 patients enrolled, the median (IQR) age for the study population was 46.8 (36.6-58) years, and 76.1% were female. Overall, 112 patients (50.5%) underwent treatment with active surveillance. Median tumor size was 11.0 mm (IQR, 9-15), and larger tumors (10.1-20.0 mm) comprised 67 cases (59.8%). One hundred one (90.1%) continued to receive treatment with active surveillance, 46 (41.0%) had their tumors shrink, and 0 developed regional/distant metastases. Size growth of more than 5 mm was observed in 3.6% of cases, with cumulative incidence of 1.2% at 2 years and 10.8% at 5 years. Volumetric growth of more than 100% was observed in 7.1% of cases, with cumulative incidence of 2.2% at 2 years and 13.7% at 5 years. Of 110 patients who elected to undergo immediate surgery, 21 (19.1%) had equivocal-risk features discovered on final pathology. Disease severity for all such patients remained classified as stage I. Disease-specific and overall survival rates in both cohorts were 100%. On multivariable analysis, immediate surgery patients exhibited significantly higher baseline anxiety levels compared with active surveillance patients (estimated difference in anxiety scores between groups at baseline, 0.39; 95% CI, 0.22-0.55; P < .001). This difference endured over time, even after intervention (estimated difference at 4-year follow-up, 0.50; 95% CI, 0.21-0.79; P = .001).

Conclusions and relevance: The results of this nonrandomized controlled trial suggest that a more permissive active surveillance strategy encompassing most diagnosed thyroid cancers appears viable. Equivocal-risk pathologic features exist in a subset of cases that can be safely treated, but suggest the need for more granular risk stratification. Surgery and surveillance cohorts possess oppositional levels of worry, elevating the importance of shared decision-making when patients face treatment equivalence.

Trial registration: ClinicalTrials.gov Identifier: NCT02609685.

Figure 1.. CONSORT Diagram for Low-risk Papillary Thyroid Carcinoma (PTC) Active Surveillance Protocol

Unfavorable nodule features on ultrasonography (US) included extrathyroidal extension or close proximity to recurrent laryngeal nerve. Equivocal-risk pathologic features included metastatic lymph nodes, extrathyroidal extension, and aggressive histologic variants. LN indicates lymph node; MD, clinician.

Figure 2.. Growth Changes in Active Surveillance for Papillary Thyroid Carcinoma

A minimum of 6-month follow-up was required. A, Growth measured by largest size diameter. B, Growth measured by increase in volume.

Figure 3.. Disease Progression Incidence Over Time in Papillary Thyroid Carcinoma Followed by Active Surveillance

A, Diameter growth by 3 mm or 5 mm. Incidence rates between these 2 end points were not significantly different (8.0% vs 3.6%; P = .07). B, Volume growth by 50% or 100%. Incidence rates between these 2 end points were significantly different (17.0% vs 7.1%; P = .003).

Figure 4.. Comparison of Adjusted 18-Item Thyroid Cancer Modified Anxiety Scale Estimated Summary Scores for Active Surveillance and Immediate Surgery Cohorts

Immediate surgery patients exhibited significantly higher baseline anxiety levels compared with active surveillance patients. This difference endured over time, even after intervention. Shaded areas indicate 95% CIs.