Kizuki Yuza, Odysseas P Chatzipanagiotou, Andrea Ruzzenente, George A Poultsides, Kazunari Sasaki, Itaru Endo, Federico Aucejo, Irinel Popescu, Tom Hugh, Nazim Bhimani, Matthew J Weiss, Jin He, Timothy M Pawlik
A microscopically positive resection margin was associated with worse crude outcomes. The adjusted association was weaker and varied according to how missing data were handled. Although R0 resection should remain the operative goal, R1 margin status may be better interpreted as a context-dependent prognostic marker, associated with recurrence less often confined to the liver and a lower likelihood of repeat hepatectomy, rather than as a purely technical endpoint.
BACKGROUND: The prognostic significance of margin status after colorectal liver metastases (CRLM) resection remains debated in the era of effective systemic therapy. This study examined the prognostic meaning of microscopically positive (R1) margins, focusing on recurrence pattern and salvageability.
METHODS: Patients undergoing curative-intent resection for CRLM were identified from an international multi-institutional database (2000-2023). Institution-stratified Cox models estimated associations between margin status and survival endpoints, with sequential adjustment for clinical factors, primary lymph node status, tumor burden, and neoadjuvant chemotherapy.
RESULTS: Among 1060 patients, 228 (21.5%) had R1 margins. Whereas R1 status was associated with higher crude hazards of recurrence or death, the adjusted association was weaker (complete-case hazard ratio [HR], 1.17; 95% confidence interval [CI], 0.89-1.54; multiply imputed HR, 1.34; 95% CI, 1.03-1.74). Among the patients who experienced recurrence, isolated liver recurrence was less common after R1 resection than after R0 resection (31.1% vs 47.6%; p = 0.004), whereas liver plus extrahepatic recurrence was numerically more common (26.2% vs 18.6%; p = 0.114). Repeat hepatectomy was less frequent after R1 resection (16.4% vs 31.4%; p < 0.001), particularly among node-negative patients (10.5% vs 39.7%; p < 0.001). Among the node-negative patients who experienced recurrence, post-recurrence survival was shorter after R1 resection (27.4 vs 43.8 months; p = 0.029).
CONCLUSIONS: A microscopically positive resection margin was associated with worse crude outcomes. The adjusted association was weaker and varied according to how missing data were handled. Although R0 resection should remain the operative goal, R1 margin status may be better interpreted as a context-dependent prognostic marker, associated with recurrence less often confined to the liver and a lower likelihood of repeat hepatectomy, rather than as a purely technical endpoint.