The Effect of Thyrotropin Suppression on Survival Outcomes in Patients with Differentiated Thyroid Cancer: A Systematic Review and Meta-analysis.

BACKGROUND:Long-term management of intermediate- and high-risk differentiated thyroid cancer (DTC) involves thyrotropin (TSH) suppression with thyroid hormone to prevent potential stimulation of TSH receptors on DTC cells, leading to tumor growth. However, the current guidelines recommending TSH suppression are based on low-to-moderate quality evidence. METHODS:We performed a systematic review and meta-analysis of studies evaluating the role of TSH suppression in intermediate- and high-risk DTC patients (≥18 years) treated as per regional guideline-based therapy with a follow-up duration of 5 years (PROSPERO #252396). TSH suppression was defined as 'below normal reference range' or, when known, <0.5 mIU/L. Primary outcome measures included A. composite of progression-free survival (PFS), disease-free survival (DFS), and relapse-free survival (RLFS), and B. composite of disease-specific survival (DSS), and overall survival (OS). Secondary outcome included a composite of cardiac or skeletal adverse events. All outcomes and comparisons were represented as TSH suppression versus TSH non-suppression. Randomized controlled trials, cohort studies, and case-control studies were included for analysis. Pooled hazard ratio (HR) and 95% confidence interval (CI) were calculated using random-effects model. RESULTS:Abstract screening was performed on 6,369 studies. After the exclusion of irrelevant studies and full-text screening, 9 studies were selected for the final meta-analysis. Based on 7 studies (3,591 patients), the composite outcome of PFS, DFS, and RLFS was not significantly different between TSH suppression and non-suppression groups (HR: 0.75; 95% CI: 0.48 - 1.17; I2=76%). Similarly, a DSS and OS composite outcome assessment based on 4 studies (3,616 patients) did not favor TSH suppression (HR: 0.69; 95% CI: 0.31 - 1.52; I2 = 88%). Even after excluding studies of lower quality, the primary outcomes were not significantly different between the TSH suppression and non-suppression cohorts. The secondary outcome, obtained from 2 studies (1,294 patients), was significantly higher in the TSH-suppressed groups (HR: 1.82; 95% CI: 1.30 - 2.55; I2 = 0%). Significant study heterogeneity was noted for primary outcomes. CONCLUSION:TSH suppression in intermediate- and high-risk DTC may not improve survival outcomes but may increase the risk of secondary complications. However, the limited evidence and study heterogeneity warrant cautious interpretation of our findings.