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KRAS Mutation Status Predicts Site-Specific Recurrence and Survival After Resection of Colorectal Liver Metastases Irrespective of Location of the Primary Lesion

  • Colorectal Cancer
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

The KRAS mutation status is reportedly correlated with poor survival outcome in patients with colorectal liver metastases (CLM); however, its true prognostic impact and the reason for the poor prognosis remain unclear.

Methods

Data on 163 patients with a known KRAS mutation status who underwent curative resection for CLM were retrospectively reviewed. The long-term survival and site-specific incidence of recurrence were then compared between patients with a KRAS mutation (mtKRAS) and those without a mutation (wtKRAS).

Results

The mtKRAS group had a poorer 3-year disease-specific survival (DSS) rate (59.8 vs. 83.6 %, p = 0.016), 3-year recurrence-free survival (RFS) rate (0 vs. 20.2 %, p = 0.069), and median time to surgical failure (TSF) [18.8 vs. 39.7 months, p = 0.001] than the wtKRAS group. The cumulative incidences of liver recurrence and lung recurrence at 3 years were also higher in the mtKRAS group (76.2 vs. 54.7 %, p = 0.060; and 71.9 vs. 37.3 %, p < 0.001, respectively). A multivariate analysis confirmed that an mtKRAS status had a significant effect on the DSS rate (hazard ratio [HR] 2.9, p = 0.006), RFS (HR 2.0, p = 0.004), TSF (HR 2.4, p < 0.001), liver recurrence (HR 1.7, p < 0.001), and lung recurrence (HR 2.6, p < 0.001). Lung-related unresectable recurrences were more frequent (41 vs. 18 %, p = 0.048) and were associated with an earlier TSF (9.6 vs. 14.0 months, p = 0.14) in the mtKRAS group, regardless of the location of the primary lesions.

Conclusions

mtKRAS is associated with poor survival outcome after CLM resection because of a relatively high incidence of lung recurrence and a relatively short TSF.

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Acknowledgment

This study was supported by a study grant from Okinaka Memorial Institute for Medical Disease (No. 2015-15) and JSPS KAKENHI Grant No. 26861063.

Conflict of interest

Junichi Shindoh, Yujiro Nishioka, Ryuji Yoshioka, Toshitaka Sugawara, Yoshihiro Sakamoto, Kiyoshi Hasegawa, Masaji Hashimoto, and Norihiro Kokudo have no conflicts of interest to declare that are directly relevant to the content of this study.

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Authors and Affiliations

  1. Hepatobiliary-Pancreatic, Surgery Division, Department of Digestive Surgery, Toranomon Hospital, Tokyo, Japan

    Junichi Shindoh MD, PhD, Yujiro Nishioka MD, Toshitaka Sugawara MD & Masaji Hashimoto MD, PhD

  2. Okinaka Memorial Institute for Medical Disease, Tokyo, Japan

    Junichi Shindoh MD, PhD

  3. Hepatobiliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

    Yujiro Nishioka MD, Ryuji Yoshioka MD, Yoshihiro Sakamoto MD, PhD, Kiyoshi Hasegawa MD, PhD & Norihiro Kokudo MD, PhD

Authors
  1. Junichi Shindoh MD, PhD
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  2. Yujiro Nishioka MD
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  3. Ryuji Yoshioka MD
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  4. Toshitaka Sugawara MD
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  5. Yoshihiro Sakamoto MD, PhD
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  6. Kiyoshi Hasegawa MD, PhD
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  7. Masaji Hashimoto MD, PhD
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  8. Norihiro Kokudo MD, PhD
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Corresponding authors

Correspondence to Junichi Shindoh MD, PhD or Norihiro Kokudo MD, PhD.

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Shindoh, J., Nishioka, Y., Yoshioka, R. et al. KRAS Mutation Status Predicts Site-Specific Recurrence and Survival After Resection of Colorectal Liver Metastases Irrespective of Location of the Primary Lesion. Ann Surg Oncol 23, 1890–1896 (2016). https://doi.org/10.1245/s10434-016-5087-5

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  • DOI: https://doi.org/10.1245/s10434-016-5087-5

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