Background High rates of recurrence after resection severely worsen hepatocellular carcinoma (HCC) prognosis. This study aims to explore whether circulating tumor cell (CTC) is helpful in determine the appropriate liver resection margins for HCC patients. Methods HCC patients who underwent liver resection were enrolled into training ( n =117) or validation ( n =192) cohorts, then classified as CTC-positive (CTC≥1) or CTC-negative (CTC=0). A standardized pathologic sampling method was used in the training cohort to quantify microvascular invasion (mVI) and the farthest mVI from the tumor (FMT). Findings CTC number positively correlated with mVI counts ( r =0.655, P 1?cm independently protected against early recurrence (training cohort, P =0.004; validation cohort, P =0.001) with lower early recurrence rates (training cohort, 20.0% vs. 65.1%, P =0.005; validation cohort, 36.4% vs. 65.1%, P =0.003) compared to surgical margins of ≤1?cm. No differences in postoperative liver function were observed between patients with margins 1?cm vs . ≤1?cm. Surgical margin size minimally impacted early postoperative HCC recurrence in CTC-negative patients when using 0.5?cm or 1?cm as the threshold. Interpretations Preoperative CTC status predicts mVI severity in HCC patients and is a potential factor for determining optimal surgical margin size to ensure disease eradication and conserve liver function. A surgical margin of 1?cm should be achieved for patients with positive CTC. Funding A full list of funding bodies that contributed to this study can be found in the Acknowledgement section.
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