Predictors of Safety and Efficacy of 2-Stage Hepatectomy for Bilateral Colorectal Liver Metastases

Abstract

Background: In patients with bilateral colorectal liver metastases (CLM) not resectable in 1 operation, 2-stage hepatectomy is the standard surgical approach. The objective of this study was to determine factors associated with safety and efficacy of 2-stage hepatectomy.

Study design: The study included all 109 patients for whom 2-stage hepatectomy for CLM was planned during 2003 to 2014. The RAS mutation status and other clinicopathologic factors were evaluated for association with major complications and survival using multivariate analysis.

Results: Two-stage hepatectomy was completed in 89 of 109 patients (82%). Reasons for dropout after the first stage were disease progression (n = 12), insufficient liver growth (n = 5), and complications after first stage or portal vein embolization (n = 3). More than 6 cycles of preoperative chemotherapy were associated with failure to proceed to the second stage (p = 0.009). Rates of major complications (26% vs 6%; p < 0.001) and 90-day mortality (7% vs 0%; p = 0.006) were higher after the second stage. The cumulative rate of major complications was 15% (n = 29). Factors independently associated with major complications were rectal primary tumor, metachronous CLM, and more than 1 lesion resected at first stage. At median follow-up of 29.5 months, 3-year (68% vs 6%; p < 0.001) and 5-year overall survival rates (49% vs 0%; p < 0.001) were better after 2-stage hepatectomy completion than noncompletion. Factors independently associated with poor overall survival were rectal primary tumor (p = 0.044), more than 5 CLMs (p = 0.043), need for chemotherapy after first stage (p = 0.046), and RAS mutation (p < 0.001).

Conclusions: The RAS mutation independently predicts the oncologic efficacy of 2-stage hepatectomy and may help guide patient selection for this aggressive surgical strategy.

Figure 1

Overall survival from the date of first-stage resection in patients with bilateral colorectal liver metastases in whom 2-stage hepatectomy was and was not completed.

Figure 2

Overall survival on intent-to-treat from the date of first-stage resection in patients with bilateral colorectal liver metastases for whom 2-stage resection was planned, by RAS status.

Figure 3

(A) Overall survival and (B) progression-free survival in patients with bilateral colorectal liver metastases who underwent second-stage resection, by RAS status.

Figure 3

(A) Overall survival and (B) progression-free survival in patients with bilateral colorectal liver metastases who underwent second-stage resection, by RAS status.