Oncologic Impact of Margin-to-Size Ratio for Intrahepatic Cholangiocarcinoma

INTRODUCTION: The optimal surgical margin width for intrahepatic cholangiocarcinoma (ICC) remains uncertain. We hypothesized that the oncologic benefit of a wide margin may be modulated by tumor-related factors. METHODS: Patients who underwent curative-intent liver resection for solitary ICC were identified from a large international multi-institutional database. A novel metric, the margin-to-size ratio (MSR), was defined as the ratio of surgical margin width (mm) to tumor size (mm), integrating both parameters into a single variable. Multivariable Cox regression models were used to evaluate the association between MSR and recurrence-free survival (RFS). RESULTS: Among 1,172 patients, the median tumor size was 57.0 mm, median margin width was 4.0 mm (IQR, 1.0-10.0), and median MSR was 0.07 (IQR, 0.02-0.20). On multivariable analysis, a higher MSR was independently associated with improved RFS (HR 0.59; 95% CI, 0.36-0.96; p = 0.033), whereas neither absolute margin width nor R1 resection status was associated with RFS. Using maximally selected rank statistics, an MSR threshold of 0.142 was identified. Patients with a high MSR (≥ 0.142) had superior 3-year RFS compared with individuals with a low MSR (< 0.142) (55.7% [95% CI, 46.0-67.6] vs. 45.2% [95% CI, 38.0-53.8]; p = 0.016). CONCLUSIONS: MSR was independently associated with RFS following ICC resection, whereas conventional margin metrics, including absolute margin width and R1 resection status, were not associated with RFS. MSR may provide a clinically interpretable framework to contextualize margin adequacy relative to tumor size and inform individualized decision-making.