Resection margin and survival in 2368 patients undergoing hepatic resection for metastatic colorectal cancer: surgical technique or biologic surrogate?

Abstract

Objectives: The impact of margin width on overall survival (OS) in the context of other prognostic factors after resection for colorectal liver metastases is unclear. We evaluated the relationship between resection margin and OS utilizing high-resolution histologic distance measurements.

Methods: A single-institution prospectively maintained database was queried for all patients who underwent an initial complete resection of colorectal liver metastases between 1992 and 2012. R1 resection was defined as tumor cells at the resection margin (0 mm). R0 resection was further divided into 3 groups: 0.1 to 0.9 mm, 1 to 9 mm, and 10 mm or greater.

Results: A total of 4915 liver resections were performed at Memorial Sloan Kettering Cancer Center between 1992 and 2012, from which 2368 patients were included in the current study. Half of the patients presented with synchronous disease, 43% had solitary metastasis, and the median tumor size was 3.4 cm. With a median follow-up for survivors of 55 months, the median OS of the R1, 0.1 to 0.9 mm, 1 to 9 mm, and 10 mm or more groups was 32, 40, 53, and 56 months, respectively (P < 0.001). Compared with R1 resection, all margin widths, including submillimeter margins correlated with prolonged OS (P < 0.05). The association between the margin width and OS remained significant when adjusted for all other clinicopathologic prognostic factors.

Conclusions: Resection margin width is independently associated with OS. Wide margins should be attempted whenever possible. However, resection should not be precluded if narrow margins are anticipated, as submillimeter margin clearance is associated with improved survival. The prolonged OS observed with submillimeter margins is likely a microscopic surrogate for the biologic behavior of a tumor rather than the result of surgical technique.

Figure 1. Interaction between the resection margin width and overall survival

A smoothed-fit curve of the median overall survival for each patient depending on the resection margin width as a continuous variable. A continuous interaction between the margin width and OS is demonstrated with an initial sharp increase in median OS in the narrow margin zone, until an inflection point around 3–4-mm margin width, which is followed by a more gradual increase. This descriptive graph does not adjust for any confounder nor does it account for censoring over the follow-up time. Thus, no comparative analysis was performed.

Figure 2

Overall survival curves stratified according to four categories of resection margin width. ^X, P = NS; ^*, P < 0.05.