Clinical Significance of a Circulating Tumor Cell-Based Classifier in Stage IB Lung Adenocarcinoma: A Multicenter, Cohort Study.

OBJECTIVE: To investigate the effectiveness of a circulating tumor cell (CTC)-based classifier in stratifying stage IB lung adenocarcinoma (LUAD).

SUMMARY BACKGROUND DATA: Stage IB LUADs have an approximately 70% 5-year survival rate. The clinical application of adjuvant chemotherapy (ACT) is controversial due to inconsistent results in a series of trials and few useful guide biomarkers. Thus, there is a pressing need for robust biomarkers to stratify stage IB patients to define which group would most likely benefit from ACT.

METHODS: 212 stage IB LUAD patients were enrolled and were divided into three independent cohorts. The aptamer-modified NanoVelcro system was used to enrich the CTCs.

RESULTS: A cutoff of < 4 or ≥ 4 CTCs as the optimal prognostic threshold for stage IB LUAD was generated to stratify the patients in a 70-patient cohort into low-risk and high-risk groups. Patients with ≥ 4 CTCs in the training cohort had shorter progression-free survival (PFS, P < 0.0001) and overall survival (OS, P < 0.0001) than patients with < 4 CTCs. CTC number remained the strongest predictor of PFS and OS even in a multivariate analysis including other clinicopathological parameters. Furthermore, a nomogram based on the CTC count was developed to predict the 3-year and 5-year survival in the training cohort and performed well in the other two validation cohorts (C-index: 0.862, 0.853 and 0.877).

CONCLUSION: The presence of ≥ 4 CTCs can define a high-risk subgroup, providing a new strategy to make optimal clinical decisions for stage IB LUAD.