Circulating Tumor Cells from Surgical Manipulation Predict Recurrence and Poor Prognosis in Non-Small Cell Lung Cancer

<b>Background/Objectives:</b> In our previous multicenter prospective controlled study (UMIN000018602), we investigated the impact of surgical manipulation on circulating tumor cells (CTCs) in patients with non-small cell lung cancer (NSCLC). CTCs were detected after surgery in four patients (4/29, 13.8%), although CTCs were not present before surgery. These four patients had tumor cells leaked into their bloodstream by surgeons' manipulation. We aimed to clarify long-term outcomes according to the presence of CTCs. <b>Methods:</b> Patients with cT1b-2N0M0 NSCLC scheduled for lobectomy were enrolled, based on the selection criteria of a consolidation-to-ground-glass opacity ratio (over 50%). Peripheral blood samples (≥3 mL) were collected before surgery (for pre-CTCs), during surgery, and immediately after pulmonary vein dissection (for post-CTCs). CTCs were isolated from these samples using ScreenCell^®'s size-selective method. <b>Results:</b> From July 2015 to January 2016, 29 patients were enrolled, yielding paired pre- and post-CTC samples for all patients. Thirteen patients were pre-CTC positive, and post-CTCs were detected in 17 patients. Survival analysis revealed a statistically significant difference in recurrence-free survival between patients with and without post-CTCs (<i>p</i> = 0.043), while pre-CTCs status had no significant impact on recurrence (<i>p</i> = 0.226). Patients with post-CTCs had a significantly higher recurrence rate than those without (<i>p</i> = 0.043). Half of patients with post-CTCs but without pre-CTCs had recurrence within 5 years after surgery. <b>Conclusions:</b> Post-CTCs emerged as a significant predictor of recurrence following lobectomy; however, it could be possible for thoracic surgeons to prevent recurrence by improving surgical techniques for NSCLC patients with post-CTCs but without pre-CTCs.