Longitudinal evaluation of circulating tumor cells in operable locally advanced esophageal squamous cell carcinoma

Objective: The detection of circulating tumor cells (CTCs) at a single time point offers restricted insights into prognostic assessment. This study aims to longitudinally investigate alterations in CTCs status throughout the neoadjuvant chemotherapy, surgical, and postoperative chemotherapy phases within a homogeneous cohort. Further more, an assessment of the interrelation between patients' treatment response, survival prognosis, and CTCs status was conducted. Materials and methods: Thirty-one patients diagnosed with operable locally advanced esophageal squamous cell carcinoma were randomly allocated to either the surgical or neoadjuvant group. CTCs detection was systematically conducted at various time points throughout the treatment on individual patients. Associations between the presence of CTCs/CTM and therapeutic efficacy, as well as clinical outcomes, were subject to rigorous analysis. Results: We performed a total of 136 CTCs detections at the time points of pre-neoadjuvant chemotherapy, preoperative, postoperative day 2, post-operative 1 week, post-operative 3 months. The CTCs were detected in 6/12(50％), 14/31(45.16％), 22/31(70.97％), 16/31(51.6％) and 5/31(16.1％) of patients before neoadjuvant treatment, prior to surgery, on postoperative day 2, one week after surgery, and three months post-surgery, respectively. The CTC count exhibited an increase before and after surgery, whereas a decrease was observed before and after neoadjuvant chemotherapy. Among patients initially identified with CTCs+, those in the neoadjuvant group experienced extended progression-free survival (PFS) (p=0.05) and overall survival (OS) (p=0.04) compared to those in the surgical group. On postoperative day 2, 17 patients had CTCs＜4, while 14 patients had CTCs≥4. Individuals with CTCs＜4 demonstrated significantly prolonged PFS (p＜0.01, HR=6.26, 95% CI 1.96-19.96) and OS (p＜0.01, HR=6.63, 95% CI 2.08-21.13) compared to those with CTCs≥4. CTM was detected in 45.16% of patients at any given time. Survival analysis indicated that CTM- patients exhibited longer PFS (p=0.029, HR=2.92, 95% CI 1.05-8.07) and OS (p=0.03, HR=2.92, 95% CI 1.06-8.09) than CTM+ patients. Conclusions: Single-time detection offers limited information for prognostic evaluation, a dynamic fluctuation in the quantity of CTCs/CTM throughout the course of treatment, exhibiting a robust predictive impact on patient prognosis.