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Association of RAS Mutation Location and Oncologic Outcomes After Resection of Colorectal Liver Metastases

  • Hepatobiliary Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

RAS mutations are prognostic for patients with metastatic colorectal cancer (mCRC). We investigated clinical, pathologic, and survival differences based on RAS exon for patients with colorectal liver metastases (CRLM).

Methods

This retrospective, single-center study included patients with R0/R1 resection of CRLM from 1992 to 2016. Patients with unresected extrahepatic disease or liver-first resection were excluded. Overall survival (OS) and recurrence-free survival were assessed and stratified by mutation status and location. Fisher’s exact test, Wilcoxon rank-sum test, and log-rank test were used, where appropriate.

Results

A total of 938 mCRC patients were identified with median age of 57 (range 19–91). Of the 445 patients with KRAS mutations, 407 (91%) had a mutation in exon 2, 14 (3%) exon 3, and 24 (5%) exon 4. Median OS was 71.4 months (95% confidence interval [CI] 66.1–76.5). Patients with KRAS mutations had worse OS compared with KRAS wild-type patients (median 55.5 vs. 91.3 months, p < 0.001). While there was no significant difference in OS based on the exon mutated (p = 0.12), 5-year OS was higher for patients with exon 4 mutations [68.8% (95% CI 0.45–0.84)] compared with those with mutations in exon 2 [45.7% (95% CI 0.40–0.51)] or exon 3 [39.1% (95% CI: 0.11–0.68)]. Patients with NRAS mutant tumors also had worse OS compared with NRAS wild-type patients (median 50.9 vs. 73.3 months, p = 0.03).

Conclusions

NRAS and KRAS exon 3/4 mutations are present in a minority of mCRC patients. Patients with exon 4 mutant tumors may have a more favorable prognosis, although the difference in oncologic outcomes based on mutated exon appears to be smaller than previously reported.

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Acknowledgments

We gratefully acknowledge the members of the Molecular Diagnostics Service in the Department of Pathology.

Funding

This work was funded in part by the Marie-Josée and Henry R. Kravis Center for Molecular Oncology and the National Cancer Institute Cancer Center Core Grant No. P30-CA008748.

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Authors and Affiliations

  1. Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Lily V. Saadat MD, Thomas Boerner MD, T. Peter Kingham MD, William R. Jarnagin MD, Alice C. Wei MD, Kevin C. Soares MD & Michael I. D’Angelica MD

  2. Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Debra A. Goldman MS & Mithat Gonen PhD

  3. Department of Surgery, University of Michigan, Ann Arbor, MI, USA

    Timothy L. Frankel MD

  4. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Efsevia Vakiani MD, PhD

  5. Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    David B. Solit MD

  6. Marie-Josee and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    David B. Solit MD

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  1. Lily V. Saadat MD
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Correspondence to Lily V. Saadat MD.

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DISCLOSURES

David Solit: served as a consultant/received honoraria from Pfizer, Loxo Oncology, Lilly Oncology, Q.E.D. Therapeutics, Vivideon Therapeutics, and Illumina.

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Saadat, L.V., Boerner, T., Goldman, D.A. et al. Association of RAS Mutation Location and Oncologic Outcomes After Resection of Colorectal Liver Metastases. Ann Surg Oncol 28, 817–825 (2021). https://doi.org/10.1245/s10434-020-08862-3

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