Circulating Tumor Cells as a Tool of Minimal Residual Disease Can Predict Lung Cancer Recurrence: A longitudinal, Prospective Trial

Background: The role of circulating tumor cells (CTCs) for predicting the recurrence of cancer in lung cancer patients after surgery remains unclear. Methods: A negatively selected protocol of CTC identification was applied. For all the enrolled patients, CTC testing was performed before and after surgery on the operation day (day 0), postoperative day 1, and day 3. The daily decline and trend of CTCs were analyzed to correlate with cancer relapse. The mixed model repeated measures (MMRM) adjusted by cancer characteristics was applied for statistical significance. Results: Fifty patients with lung mass undergoing surgery were enrolled. Among 41 primary lung cancers, 26 (63.4%) were pathological stage Tis and I. A total of 200 CTC tests were performed. MMRM analysis indicated that surgery could contribute to a CTC decline after surgery in all patients with statistical significance (p = 0.0005). The daily decrease of CTCs was statistically different between patients with and without recurrence (p = 0.0068). An early rebound of CTC counts on postoperative days 1 and 3 was associated with recurrence months later. Conclusion: CTC testing can potentially serve as a tool for minimal residual disease detection in early-staged lung cancer after curative surgery.