Prognostic Value of Hematological Inflammatory Indices (PLR, NLR, SII) in Medium and High‐Risk Papillary Thyroid Carcinoma: A Multicenter Cohort Study

ABSTRACT Background Patients with medium and high‐risk papillary thyroid carcinoma (PTC) demonstrate significantly poorer clinical outcomes compared to their low‐risk counterparts. However, current prognostic stratification for this patient population remains suboptimal due to the absence of reliable biomarkers. This investigation aims to evaluate the clinical utility and prognostic potential of three hematological inflammatory indices: the platelet‐lymphocyte ratio (PLR), neutrophil‐lymphocyte ratio (NLR), and systemic immune‐inflammation index (SII) in medium and high‐risk PTC cases. Methods This study analyzed 1070 PTC patients from the “DTCC study” (2014–2016), a multicenter prospective cohort investigating the initial management of differentiated thyroid cancer (DTC) in China. Preoperative hematological parameters (including PLR, NLR, and SII) and baseline clinical characteristics were evaluated to assess their prognostic significance. Results In medium and high‐risk PTC patients, PLR ≤ 115.6 predicted increased recurrence risk (OR = 4.579, 95% CI: 1.863–11.255, p = 0.001) and worse disease‐free survival (DFS; p = 0.001). Multivariate Cox regression confirmed PLR ≤ 115.6 as an independent prognostic factor for reduced DFS (HR = 3.080, 95% CI: 1.115–8.507, p = 0.030). Notably, this association persisted in intermediate‐risk patients. Among high‐risk PTC patients, however, SII ≤ 360.9 (rather than PLR) demonstrated stronger predictive value for recurrence (OR = 15.154, 95% CI: 1.873–122.640, p = 0.011). Consistently, multivariate analysis identified SII ≤ 360.9 as an independent risk factor for shorter DFS (HR = 14.399, 95% CI: 1.823–113.730, p = 0.011). Conclusion Our findings demonstrate that PLR and SII emerged as risk stratification‐specific prognostic biomarkers: PLR independently predicted prognosis in intermediate‐risk cases, while SII showed superior predictive value for prognosis in high‐risk patients. The differential utility of these indices—PLR for intermediate‐risk stratification patients and SII for high‐risk stratification patients—highlights their complementary roles in clinical decision‐making. As routinely available, cost‐effective inflammatory markers, PLR and SII may enhance risk‐adapted surveillance strategies, though further validation is warranted to standardize cutoff values and integrate them into existing clinical management systems. Trial Registration The trial was registered at ClinicalTrials. gov under the identifier NCT02638077.