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Prognostic Implication of KRAS Status after Hepatectomy for Colorectal Liver Metastases Varies According to Primary Colorectal Tumor Location

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

ABSTRACT

Background

Right-sided and left-sided colorectal cancer (CRC) is known to differ in their molecular carcinogenic pathways. We sought to investigate the variable prognostic implication of KRAS mutation after hepatectomy for colorectal liver metastases (CRLM) according to the site of primary CRC.

Methods

A total of 426 patients who underwent a curative-intent hepatic resection and whose KRAS status was available were identified. Clinicopathologic characteristics and long-term outcomes were stratified by KRAS status (wild type vs. mutant type) and primary tumor location (right-sided vs. left-sided). Cecum, right and transverse colon were defined as right-sided, whereas left colon and rectum were defined as left-sided.

Results

Among patients with a right-sided CRC, 5-year recurrence-free survival (RFS) and overall survival (OS) were not correlated with KRAS status (wild type: 30.8 and 47.2 % vs. mutant type: 38.5 and 49.1 %, respectively) (both P > 0.05). Specifically, mutant-type KRAS was not associated with either RFS or OS on multivariable analysis (hazard ratio [HR] 1.51, 95 % confidence interval [CI] 0.73–3.14, P = 0.23 and HR 1.03, 95 % CI 0.51–2.08, P = 0.95, respectively). In contrast, among patients who underwent resection of CRLM from a left-sided primary CRC, 5-year RFS and OS were worse among patients with mutant-type KRAS (wild type: 23.7 and 57.2 % vs. mutant type: 19.6 and 38.2 %, respectively) (both P < 0.05). On multivariable analysis, mutant-type KRAS remained independently associated with worse RFS and OS among patients with a left-sided primary CRC (HR 1.57, 95 % CI 1.01–2.44, P = 0.04 and HR 1.81, 95 % CI 1.11–2.96, P = 0.02, respectively).

Conclusions

KRAS status has a variable prognostic impact after hepatic resection for CRLM depending on the site of the primary CRC. Future studies examining the impact of KRAS status on prognosis after hepatectomy should take into account the primary CRC tumor site.

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Author notes

    Authors and Affiliations

    1. Department of Surgery, The Johns Hopkins Hospital, Baltimore, MD, USA

      Kazunari Sasaki MD, Georgios A. Margonis MD, PhD, Ana Wilson DO, Yuhree Kim MD, MPH, Stefan Buettner B.Sc, Nikolaos Andreatos MD, Faiz Gani MD, Neda Amini MD, Gaya Spolverato MD & Timothy M. Pawlik MD, MPH, PhD, FACS

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    1. Kazunari Sasaki MD
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    2. Georgios A. Margonis MD, PhD
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    Correspondence to Timothy M. Pawlik MD, MPH, PhD, FACS.

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    Kazunari Sasaki and Georgios A. Margonis have contributed equally to this article, and both should be considered first author.

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    10434_2016_5361_MOESM1_ESM.tif

    Kaplan-Meier estimates of overall survival patients with left-sided primary and wild-type KRAS vs. others (Log-rank: P = 0.03). Supplementary material 1 (TIFF 972 kb)

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    Sasaki, K., Margonis, G.A., Wilson, A. et al. Prognostic Implication of KRAS Status after Hepatectomy for Colorectal Liver Metastases Varies According to Primary Colorectal Tumor Location. Ann Surg Oncol 23, 3736–3743 (2016). https://doi.org/10.1245/s10434-016-5361-6

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