The Effect of Pathologic Response to Preoperative Therapy on Margin Status and Outcomes After Resection of Colorectal Liver Metastases

The prognostic value of the closest margin and margin of the largest tumor may depend on pathologic response to preoperative chemotherapy in colorectal liver metastases (CRLM). This study investigated the effect of margin status on overall survival (OS) stratified by pathologic response to preoperative chemotherapy. Patients with resected CRLM who received preoperative therapy were included. Responders were stratified by ≥ 75% pathologic response. R0 resection was defined as ≥ 1 mm margin. OS was calculated from the time of resection to last follow-up or death. Between 1992 and 2016, 873 patients were identified (448 with multiple tumors). R1 resection occurred in 98 (11%) patients, and 227 (26%) were responders. With a median follow-up of 80 months, median OS between responders and nonresponders (92 [77, 156] versus 58 [52, 64], p < 0.001) and R1 and R0 resections (48 [35, 58] versus 68 [63, 78] months, p = 0.001) differed significantly. There was no difference in OS between R1 and R0 in the responder cohort (111 [78, 156] versus 72 [45, 180] months, p = 0.242), but there was a difference in the nonresponder cohort (40 [30, 49] versus 62 [54, 68] months, p < 0.001), where R1 remained an independent predictor of survival (HR 1.59 [1.16, 2.16], p = 0.004). In the multiple tumor cohort ( n = 448), there was no difference in OS between R0 and R1 in the largest tumor (63 [55, 68] versus 46 [31, 58] months, p = 0.109). Margin status remains an important prognostic factor in CRLM. However, its prognostic significance is abrogated by response to preoperative chemotherapy. The largest tumor margin was not associated with survival, regardless of response.