Abstract Purpose: Preoperative risk stratification for papillary thyroid cancer (PTC) is a significant clinical challenge, as current systems primarily rely on postoperative pathology, limiting their utility for initial treatment planning. This study aimed to evaluate the effectiveness of using circulating tumor cells (CTCs) as a non-invasive liquid biopsy tool to stratify patient risk preoperatively. Experimental Design: We conducted a prospective study evaluating preoperative CTC levels in 210 patients diagnosed with PTC. A dual-threshold model was developed to analyze the diagnostic performance of CTC counts. The study particularly focused on the Papillary Thyroid Microcarcinoma (PTMC) subgroup (n=100) to address clinical uncertainty regarding active surveillance versus definitive therapy. Patients were monitored over a median follow-up period of 44 months to assess progression-free survival (PFS) and long-term prognostic outcomes. Results: The dual-threshold model demonstrated excellent diagnostic performance. A cutoff of ≥ 2 CTCs effectively identified high-risk patients with 93.2% specificity and 88.2% positive predictive value (PPV). In the PTMC cohort, a CTC count 2 reliably identified low-risk patients suitable for active surveillance (NPV=94.0%), while a count ≥ 2 pinpointed those with high-risk features warranting surgery (Specificity=96.4%, PPV=80.0%). Prognostic analysis revealed that CTC-negative patients had improved PFS. This was most significant in the PTMC subgroup, where the CTC-negative cohort remained recurrence-free and showed significantly longer PFS compared to CTC-positive cases (HR=0.035, 95% CI: 0.002-0.726; P=0.030). Conclusions: Preoperative CTC detection enables precise risk stratification for PTC patients. This liquid biopsy approach allows clinicians to personalize therapy—confidently selecting conservative management for low-risk individuals and recommending aggressive treatment for high-risk patients—thereby optimizing clinical decision-making and long-term outcomes.
Jiang et al. (Fri,) studied this question.