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

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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. 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. 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. 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. 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.).