Active Surveillance for Locoregional Recurrent Differentiated Thyroid Cancer: A Systematic Review and Meta-Analysis

Abstract

Background:

Active surveillance (AS) has been proposed as a management option for recurrence of thyroid cancer. However, the current evidence for AS remains limited because of retrospective study designs, small sample sizes, and follow-up loss. We therefore performed a systematic review and meta-analysis to provide a more reliable estimate of disease progression during AS for recurrent thyroid cancers.

Methods:

This systematic review is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. We searched MEDLINE, EMBASE, and COCHRANE databases through July 2025. Eligible studies included patients with recurrent thyroid cancer (thyroid bed nodules or lymph node metastases) managed with AS after complete resection of the primary tumor. Pooled progression rates were calculated using a random-effects model, with subgroup, sensitivity, and meta-regression analyses also being performed. Progression rates were also adjusted using modeling for follow-up loss.

Results:

Ten retrospective studies (n = 841) were included. All included lesions were locoregional metastases from differentiated thyroid cancer (DTC). The pooled mean follow-up duration was 51.6 months (95% confidence interval [CI], 36.0–67.2). Across 10 studies, the overall pooled progression rate was 23% [95% CI, 12–34%] and was higher in biopsy-confirmed cases (32%; 95% CI, 15–55%). Progression was higher in studies with <40 months of mean follow-up than in studies with ≥40 months of mean follow-up (36% vs. 17%, p < 0.05). Log-transformed baseline serum thyroglobulin levels were significantly higher in the progression group compared with the stable group (1.02 vs. −0.07, p < 0.05). Subgroup analyses revealed higher progression rates in studies with <75% Stage I patients (30% vs. 11%, p < 0.05) and with ≥5% Stage IV patients (28% vs. 14%, p < 0.05). Adjustment for follow-up loss increased the estimated pooled progression rate up to 35–70%.

Conclusions:

Reported progression rates of AS for locoregional recurrent DTC may be underestimated due to heterogeneity and follow-up loss. Consequently, AS should be considered with caution. Higher progression rates were observed in patients with elevated baseline serum thyroglobulin levels and advanced tumor stage, suggesting that these factors may help identify patients who require closer monitoring or earlier intervention.