Abstract Background This study investigates the impact of margin status after colorectal liver metastasis (CLM) resection on outcomes of patients after neoadjuvant treatment versus those who underwent upfront resection. Methods An international collaborative database of CLM patients who underwent surgical resection was used. Proportional hazard regression models were created for single and multivariable models to assess the relationship between independent measures and median overall survival (mOS). Results R1 was associated with worse OS in the neoadjuvant group (mOS: 51.8 m for R0 vs. 26.0 m for R1; HR: 2.18). In the patients who underwent upfront surgery, R1 was not associated with OS. (mOS: 46.7 m for R0 vs. 42.6 m for R1). When patients with R1 in each group were stratified by adjuvant treatment, there was no significant difference in the neoadjuvant group, while in the upfront surgery group with R1, adjuvant treatment was associated with significant improvement in OS (mOS: 42.6 m for adjuvant vs. 25.0 m for no adjuvant treatment; HR: 0.21). Conclusion R1 is associated with worse outcomes in the patients who receive neoadjuvant treatment with no significant improvement with the addition of adjuvant therapy, likely representing an aggressive tumor biology. R1 did not impact OS in patients with upfront surgery who received postoperative chemotherapy.

Prognostic implications of margin status in association with systemic treatment in a cohort study of patients with resection of colorectal liver metastases