Prognostic Significance of Surgical Margin Size After Neoadjuvant Chemotherapy for Colorectal Liver Metastases: Implications for Post-Resection Chemotherapy

Abstract

Background: Optimal margin size for patients undergoing resection of colorectal liver metastases (CRLM) remains unclear, particularly in the setting of perioperative chemotherapy. We evaluated the prognostic significance of margin status and size in patients who received neoadjuvant chemotherapy with modern agents prior to resection of CRLM. Methods: Clinicopathologic factors were collected for all patients who underwent curative liver resections for CRLM between 4/2004- 1/2016 and received neoadjuvant chemotherapy with Irinotecan and/or Oxaliplatin and 5-FU (FOLFOX, FOLFIRI). Margin sizes were categorized as <1, ≥1-<5, ≥5-<10, or ≥10 mm, and evaluated for association with overall (OS) and disease-free survival (DFS) by Cox multiple regression analysis. Margin status was classified as positive (<1 mm) or negative (≥ 1mm) and similarly evaluated. Results: Many of the 227 patients had synchronous (80%) or bilobar (43%) lesions. Median age was 58 years and 48% were female. The majority of patients had colon cancers (75%), while 25% had rectal cancers. Margin sizes were as follows: 13% <1mm, 27% ≥1-<5mm, 23% ≥5-<10mm, and 36% ≥10mm. Adjuvant chemotherapy post liver resection was administered to 63% of patients. Five-year OS and DFS were 54% (95% CI: 46-62%) and 22% (95% CI: 16-28%), respectively. Positive margins significantly reduced OS (HR= 4.27, p=0.0012) if patients did not receive adjuvant chemotherapy, but not if patients did receive adjuvant chemotherapy (HR= 1.20, p=0.70). Negative margin sizes of ≥1-<5, ≥5-<10, and ≥10 mm were not independent predictors of OS (p>0.05 for all). Conclusion: Patients undergoing liver resection for colorectal liver metastases should undergo post liver resection chemotherapy if negative margins (>1mm) cannot be achieved. In the era of modern chemotherapy, size of the negative resection margin did not impact OS. These findings highlight the importance of obtaining negative margins, but a wide margin is not necessary for long term survival.