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Improved Survival over Time After Resection of Colorectal Liver Metastases and Clinical Impact of Multigene Alteration Testing in Patients with Metastatic Colorectal Cancer

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Journal of Gastrointestinal Surgery Aims and scope

Abstract

Background

The past 20 years have seen advances in colorectal cancer management. We sought to determine whether survival in patients undergoing resection of colorectal liver metastases (CLM) has improved in association with three landmark advances: introduction of irinotecan- and/or oxaliplatin-containing regimens, molecular targeted therapy, and multigene alteration testing.

Methods

Patients undergoing CLM resection during 1998–2014 were identified and grouped by resection year. The influence of alterations in RAS, TP53, and SMAD4 was evaluated and validated in an external cohort including patients with unresectable metastatic colorectal cancer.

Results

Of 1961 patients, 1599 met the inclusion criteria. Irinotecan- and/or oxaliplatin-containing regimens and molecular targeted therapy were used for more than 50% of patients starting in 2001 and starting in 2006, respectively, so patients were grouped as undergoing resection during 1998–2000, 2001–2005, or 2006–2014. Liver resectability indications expanded over time. The 5-year overall survival (OS) rate was significantly better in 2006–2014, vs. 2001–2005 (56.5% vs. 44.1%, P < 0.001). RAS alteration was associated with worse 5-year OS than RAS wild-type (44.8% vs. 63.3%, P < 0.001). However, OS did not differ significantly between patients with RAS alteration and wild-type TP53 and SMAD4 and patients with RAS wild-type in our cohort (P = 0.899) or the external cohort (P = 0.932). Of 312 patients with genetic sequencing data, 178 (57.1%) had clinically actionable alterations.

Conclusion

OS after CLM resection has improved with advances in medical therapy and surgical technique. Multigene alteration testing is useful for prognostication and identification of potential therapeutic targets.

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Abbreviations

CLM:

Colorectal liver metastases

VEGF:

Vascular endothelial growth factor

EGFR:

Epidermal growth factor receptor

HR:

Hazard ratio

OS:

Overall survival

IQR:

Interquartile range

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Acknowledgements

The authors thank Mario De Bellis for reviewing the data used in the study, Ms. Ruth Haynes for administrative support in the preparation of this manuscript, and Ms. Stephanie Deming, an employee of the Research Medical Library at MD Anderson Cancer Center, for copyediting the manuscript.

Funding

This research was supported in part by the National Institutes of Health through MD Anderson Cancer Center Support Grant, CA016672.

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Authors and Affiliations

  1. Departments of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1484, Houston, TX, USA

    Yoshikuni Kawaguchi, Elena Panettieri, Hop S. Tran Cao, Ching-Wei D. Tzeng, Yun Shin Chun, Thomas A. Aloia & Jean-Nicolas Vauthey

  2. Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Scott Kopetz

  3. Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Hyunsoo Hwang & Xuemei Wang

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  1. Yoshikuni Kawaguchi
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Contributions

Substantial contributions to:

The conception or design of the work: YK and JNV.

The acquisition, analysis, or interpretation of data for the work: YK, SK, EP, HH, XW, HT, CWT, YSH, TA, and JNV.

Drafting the work or revising it critically for important intellectual content: All authors.

Final approval of the version to be published: All authors.

Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved: All authors.

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Correspondence to Jean-Nicolas Vauthey.

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Kawaguchi, Y., Kopetz, S., Panettieri, E. et al. Improved Survival over Time After Resection of Colorectal Liver Metastases and Clinical Impact of Multigene Alteration Testing in Patients with Metastatic Colorectal Cancer. J Gastrointest Surg 26, 583–593 (2022). https://doi.org/10.1007/s11605-021-05110-1

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