Predicting Outcomes After Surgery for Colorectal Liver Metastases

Summary and Comment |
October 10, 2013

Predicting Outcomes After Surgery for Colorectal Liver Metastases

  1. Henry Mark Kuerer, MD, PhD, FACS

Presence of somatic RAS mutation is associated with poorer survival and recurrence of lung metastases.

  1. Henry Mark Kuerer, MD, PhD, FACS

Conventional scoring systems to predict prognosis after surgery for colorectal liver metastases (CLM) have provided inconsistent results in the era of modern systemic therapy. To test whether the presence of somatic mutations can help predict outcomes in this setting, investigators analyzed the effect of RAS mutation status on survival and recurrence in 193 CLM patients at a single center who underwent hepatectomy after modern first-line chemotherapy.

The researchers performed an extensive analysis of somatic gene mutations in liver resection specimens using Sequenom MassArray technology, which tests for 159 cancer mutations in 33 genes. RAS mutations (KRAS and NRAS) were identified in 34 patients (18%).

At a median follow-up of 33 months, the 3-year overall survival (OS) rate was lower in patients with mutant RAS versus wild-type RAS (52% vs. 81%; P=0.002), as was the 3-year recurrence-free survival rate (14% vs. 34%; P=0.001). In multivariate analysis, wild-type RAS was the most important predictor of OS (hazard ratio, 2.26; P=0.002). The 3-year recurrence rate for lung metastases was higher in RAS-mutant patients versus RAS wild-type patients (59% vs. 35%). RAS-mutant patients also had a higher risk of early lung recurrence. Liver recurrences did not appear to be influenced by RAS status.

Comment

RAS-mutation status is becoming increasingly important in modeling prognosis after resection of liver colorectal metastasis because of its association with aggressive tumor biology. The findings in the current study are useful for clinical practice because RAS status can be determined not only from biopsies of metastases, but also from primary resection specimens because of the high concordance (>90%) of RAS status between primary tumor and metastases. In this analysis, RAS mutation outperformed widely accepted postresection prognostic factors, such as the size and number of liver metastases and the presence of positive lymph nodes in the primary tumor. These results should not be used to deny surgery to patients with RAS mutations, but rather to encourage centers with surgical expertise to pursue resection in patients who are considered borderline resectable and have no RAS mutation. This is the first study in surgical patients to associate RAS mutations with lung metastases and to identify patients at high risk for lung metastases who may require closer evaluation and follow-up.

Editor Disclosures at Time of Publication

  • Disclosures for Henry Mark Kuerer, MD, PhD, FACS at time of publication Consultant / Advisory board Bayer Pharma AG Speaker's bureau AstraZeneca Grant / research support Susan G. Komen Foundation Leadership positions in professional societies Alliance for Clinical Trials in Oncology (Chair, Education Committee)

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Reader Comments (1)

Wang Hongbiao Master

very good

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