Thyroid-stimulating hormone suppression in low-risk papillary thyroid cancer: a large-scale retrospective analysis of real-world data

Abstract

Background: Over 500,000 new cases are diagnosed with papillary thyroid cancer (PTC) globally per year, of whom the vast majority are in the low-risk stratification. Although thyroid-stimulating hormone (TSH) suppression is traditionally recommended for all postoperative PTCs in current guidelines, its necessity remains highly controversial in low-risk patients. Since relevant recommendations in current guidelines are still empirical, we aim to provide a direct, large-scale, real-world evidence.

Methods: This large-scale real-world retrospective study included 11,140 low-risk PTC patients from two Chinese large-volume centers (Fudan University Shanghai Cancer Center [FUSCC] and Cancer Hospital of Chinese Academy of Medical Sciences [CH-CAMS]) treated from January 1, 2000 to June 30, 2022. The mean TSH level was calculated based on postoperative serum TSH values during follow-up. The primary outcome was the association between postoperative TSH level and structural recurrence assessed by Kaplan-Meier, log-rank, multivariate Cox regression analyses and equivalence testing by Two One-Sided Tests (TOST) procedure. Propensity score matching (PSM) was used to adjust for confounders among groups.

Findings: A total of 11,140 patients with low-risk PTC were included with a median follow-up of 70 months. Based on the mean TSH level, we classified these patients into ≤0.5 (n = 1,504, 13.5%), (0.5-1] (n = 4,336, 38.9%), (1-2] (n = 4,285, 38.5%), (2-3] (n = 704, 6.3%) and >3 (n = 311, 2.8%) mU/L groups. After PSM adjusting for age, sex, T and N stage, 8991 patients were included in further analysis, for whom the log-rank analyses showed no significant differences between any two groups (all P > 0.05) in recurrence-free survival (RFS), locoregional recurrence-free survival (LRRFS) and distant metastasis-free survival (DMFS), and suppressed TSH was not associated with tumor recurrence in the multivariate Cox analysis (TSH > 2 group vs TSH ≤ 2 group: HR = 1.30, 95% CI = 0.85-2.01, P = 0.23). Furthermore, the TOST equivalence tests showed that tumor recurrence status of any two TSH groups were statistically comparable (all Bonferroni-corrected P values < 0.005). Subgroup multivariate analyses showed that TSH level did not impact tumor recurrence regardless of age, tumor size, lymph node metastasis, multifocality, surgical extent, biochemical evidence.

Interpretation: Our results suggested that postoperative TSH level was not associated with tumor recurrence in patients with low-risk PTC, for whom deliberate TSH suppression may be exempted to avoid potential secondary complications. Maintaining a TSH level within the normal range may be safe for these patients.

Funding: The study was supported by the National Natural Science Foundation of China (82072951 to Y.W.; 82373008 to X.S.), Shanghai Hospital Development Center (SHDC2020CR6003-001 to Y.W., SHDC2024CRI087 to Y.-J.W.), the Science and Technology Commission of Shanghai Municipality (22Y21900100/23DZ2305600 to Y.W.; 23ZR1412000 to X.S.), the Shanghai Anticancer Association Foundation (SACA-AX202213 to Yu Wang), Shanghai Municipal Health Commission and Shanghai Medicine and Health Development Foundation (WJWRC202302 to X.S.).

Keywords: Low-risk; Papillary thyroid cancer; Recurrence; TSH suppression; Thyrotropin.

Fig. 1

Selection process of the study cohort.

Fig. 2

Survival plots of (A) RFS, (B) LRRFS and (C) DMFS for the TSH ≤ 0.5, (0.5–1], (1–2], (2–3] and >3 groups in the overall post-PSM cohort (n = 8991). Abbreviations: RFS, recurrence-free survival; LRRFS, locoregional recurrence-free survival; DMFS, distant metastasis-free survival; TSH, thyroid-stimulating hormone.

Fig. 3

Forest plot summarizing the HRs and 95% CIs of subgroup analyses investigating the prognostic effect on RFS between the TSH ≤ 2 and >2 groups. Abbreviations: HR, hazard ratio; CI, confidence interval; RFS, recurrence-free survival; TSH, thyroid-stimulating hormone.

Fig. 4

Survival plots of RFS for the (A) TSH ≤ 2 and >2 groups, and (B) TSH ≤0.5 and >0.5 groups in Tg-positive low-risk PTC patients treated with total thyroidectomy of the post-PSM cohort (n = 1204). Abbreviations: RFS, recurrence-free survival; TSH, thyroid-stimulating hormone; Tg, thyroglobulin; PTC, papillary thyroid cancer; PSM, propensity score matching.