Progression of Low-Risk Papillary Thyroid Microcarcinoma During Active Surveillance: Interim Analysis of a Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma in Korea

Abstract

Background: Active surveillance (AS) is an alternative to thyroidectomy for the management of low-risk papillary thyroid microcarcinoma (PTMC). However, prospective AS data collected from diverse populations are needed. Methods: This multicenter prospective cohort study enrolled patients from three referral hospitals in Korea. The participants were self-assigned into two groups, AS or immediate surgery. All patients underwent neck ultrasound every 6-12 months to monitor for disease progression. Progression under AS was evaluated by a criterion of tumor size increment by 3 mm in one dimension (3 mm), 2 mm in two dimensions (2 × 2 mm), new extrathyroidal extension (ETE), or new lymph node metastasis (LNM), and a composite outcome was defined using all four criteria. Results: A total of 1177 eligible patients with PTMC (919 female, 78.1%) with a median age of 48 years (range 19-87) were enrolled; 755 (64.1%) patients chose AS and 422 (35.9%) underwent surgery. Among 755 patients under AS, 706 (female 537, 76.1%) underwent at least two ultrasound examinations and were analyzed. Over a follow-up period of 41.4 months (standard deviation, 16.0), 163 AS patients (23.1%) underwent surgery. Progression defined by the composite outcome was observed in 9.6% (68/706) of patients, and the 2- and 5-year progression estimates were 5.3% and 14.2%, respectively. The observed progression rates were 5.8% (41/706) and 5.4% (38/706) as defined by tumor size enlargement by 3 mm and 2 × 2 mm, respectively, and 1.3% (9/706) and 0.4% (3/706) for new LNM and ETE, respectively. No distant metastases developed during AS. In multivariate logistic regression analysis examining variables associated with progression under AS, age at diagnosis <30 years (odds ratio [OR], 2.86; 95% confidence interval [CI], 1.10 - 7.45), male sex (OR, 2.48; 95% CI, 1.47 - 4.20), and tumor size ≥6 mm (OR, 1.89; 95% CI, 1.09 - 3.27) were independently significant. Conclusions: The progression of low-risk PTMC during AS in the Korean population was low, but slightly higher than previously reported in other populations. Risk factors for disease progression under AS include younger age, male sex, and larger tumor size. Clinical trial registration: Clinicaltrials.gov NCT02938702.

Keywords: active surveillance; immediate surgery; microcarcinoma; papillary; thyroid cancer; thyroidectomy; watchful waiting.

FIG. 1.

Study population and flowchart. A total of 1177 patients of newly diagnosed low-risk PTMC were enrolled and assigned to two groups of AS and iOP. After excluding those who were not followed up after the decision or evaluated less than twice with ultrasound until December 2021, 706 patients in the AS group were analyzed. AS, active surveillance; iOP, immediate surgery; PTMC, papillary thyroid microcarcinoma.

FIG. 2.

Progression in AS group. (A) Progression rates and a mean time to progress by each criterion. The composite outcome was defined by any progression of tumor growth of 3 mm in one dimension, 2 mm in two dimensions, new ETE, or new LNM. (B) The time to progress that each patient showed a disease progression (*one case who developed tumor growth more than 3 mm and new LNM simultaneously). (C) Follow-up duration of each AS patient until progression, surgery, or last follow-up. ETE, extrathyroidal extension; LNM, lymph node metastasis.

FIG. 3.

Survival analysis for progression defined by the composite outcome according to age (A), sex (B), and tumor size (C) groups of PTMC during AS. Cox proportional HRs were adjusted with age at diagnosis, sex, tumor size, or enrolled hospital. A composite outcome was defined by any progression of tumor growth of 3 mm in one dimension, 2 mm in two dimensions, new ETE, or new LNM. CI, confidence interval; HR, hazard ratio.