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Limited Prognostic Value of KRAS in Patients Undergoing Hepatectomy for Colorectal Liver Metastases

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

Abstract

Background

RAS mutation status is considered a powerful prognostic factor in patients undergoing hepatectomy for colorectal liver metastases (CLM). However, whether its prognostic power is robust regardless of administration of preoperative chemotherapy or tumor burden remains unclear.

Methods

Consecutive patients who underwent initial hepatectomy for CLM from April 2010 through March 2017 in two hospitals were included. The prognostic value of KRAS was compared based on whether patients received preoperative chemotherapy and their tumor burden score (TBS).

Results

We included 409 patients (median follow-up 38 months). In the preoperative chemotherapy group, patients with mutant KRAS (mt-KRAS) CLM had poorer overall survival (OS) than those with wild KRAS (wt-KRAS; 5-year OS: 37.7% vs 53.8%, p = 0.024), although their OS was not different from patients undergoing upfront surgery. Similarly, patients with mt-KRAS had poorer OS than those with wt-KRAS in TBS of 3–9 (5-year OS: 33.1% vs 63.2%, p = 0.001), although their OS was not different from patients with TBS < 3 or ≥ 9. In multivariate analysis, mt-KRAS was an independent prognostic factor of OS among patients receiving preoperative chemotherapy (hazard ratio [HR] 1.61, 95% confidence interval [CI]: 1.034–2.491; p = 0.035) and patients with TBS of 3–9 (HR 1.836, 95% CI 1.176–2.866; p = 0.008). However, it was not a prognostic factor in patients who underwent upfront surgery or with TBS > 3 or ≥ 9.

Conclusions

In patients undergoing hepatectomy for CLM, the prognostic value of KRAS depends on their history of preoperative chemotherapy or tumor burden.

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Authors and Affiliations

  1. Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan

    Yoshinori Takeda MD, PhD, Yoshihiro Mise MD, PhD, Ryuji Yoshioka MD, PhD & Akio Saiura MD, PhD

  2. Department of Hepatobiliary and Pancreatic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Ariake, Tokyo, Japan

    Yoshinori Takeda MD, PhD, Yoshihiro Mise MD, PhD, Yu Takahashi MD, PhD, Hiromichi Ito MD, FACS, Yosuke Inoue MD, PhD, Yoshihiro Ono MD, PhD & Akio Saiura MD, PhD

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  1. Yoshinori Takeda MD, PhD
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  2. Yoshihiro Mise MD, PhD
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  4. Hiromichi Ito MD, FACS
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  5. Yosuke Inoue MD, PhD
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Correspondence to Akio Saiura MD, PhD.

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Supplementary Information

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10434_2021_11015_MOESM1_ESM.tiff

Supplemental Fig. 1 Kaplan–Meier estimates of recurrence-free survival stratified by KRAS mutation status in patients with tumor burden score (TBS) <3 (a), in those with TBS 3–9 (b), and in those with TBS >9 (c). RFS, recurrence-free survival. (TIFF 28566 kb)

Supplementary file2 (DOCX 40 kb)

10434_2021_11015_MOESM3_ESM.tiff

Supplemental Fig. 2 Kaplan–Meier estimates of extrahepatic recurrence-free survival stratified by KRAS mutation status in patients with tumor burden score (TBS) <3 (a), in those with TBS 3–9 (b), and in those with TBS >9 (c). EHRFS, extrahepatic recurrence-free survival. (TIFF 28566 kb)

10434_2021_11015_MOESM4_ESM.tiff

Supplemental Fig. 3 Kaplan–Meier estimates of overall survival stratified by tumor burden score in patients with KRAS wild-type (a) and in patients with KRAS mutant-type (b). OS, overall survival. (TIFF 28566 kb)

10434_2021_11015_MOESM5_ESM.tiff

Supplemental Fig. 4 Kaplan–Meier estimates of overall survival of patients with tumor burden score of 3–9 stratified by KRAS mutation status in patients receiving preoperative chemotherapy (a) and patients undergoing upfront surgery (b). OS, overall survival. (TIFF 28566 kb)

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Takeda, Y., Mise, Y., Takahashi, Y. et al. Limited Prognostic Value of KRAS in Patients Undergoing Hepatectomy for Colorectal Liver Metastases. Ann Surg Oncol 29, 2383–2391 (2022). https://doi.org/10.1245/s10434-021-11015-9

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  • DOI: https://doi.org/10.1245/s10434-021-11015-9

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