• Yun Shin Chun, Guillaume Passot, Yujiro Nishioka, Riham Katkhuda, Elsa M Arvide, Nazim Benzerdjeb, Jonathan Lopez, Scott E Kopetz, Dipen M Maru, and Jean-Nicolas Vauthey.
• From the Departments of Surgical Oncology (Chun, Nishioka, Arvide, Vauthey), University of Texas MD Anderson Cancer Center, Houston, TX.
• J. Am. Coll. Surg. 2022 Jul 1; 235 (1): 8168-16.

BackgroundMicrometastases, defined as microscopic cancer cells spatially separated from the macroscopically evident metastasis, are identified in 24% to 56% of resected colorectal liver metastases (CLMs). Somatic gene mutations have emerged as independent prognostic factors in CLM. This study aimed to determine the prognostic impact and risk factors for the presence of micrometastases, including somatic gene mutations.Study DesignProspective evaluation for micrometastases was performed at 2 centers in the US and France from 2015 to 2019. CLM specimens were cut radially from the tumor margin to surrounding grossly normal liver for a distance of 2 cm. Depending on CLM size, 3 to 8 specimens per patient were submitted for microscopic analysis. Somatic gene mutations were detected by next-generation sequencing.ResultsAmong 140 patients undergoing CLM resection in the US (n = 84) and France (n = 56), 36 (26%) patients were found to have micrometastases. Five-year overall and recurrence-free survival rates with micrometastases were 39% and 0%, respectively, compared with 61% and 20% without micrometastases (both p < 0.05). In multivariable analyses, the presence of micrometastases was an independent risk factor for worse overall survival (hazard ratio 2.88, 95% CI 1.46 to 5.70, p = 0.002) and recurrence-free survival (hazard ratio 1.56, 95% CI 1.01 to 2.41, p = 0.046). In binary logistic regression analysis, RAS/TP53 co-mutation was found to significantly increase the risk of micrometastases (odds ratio 2.77, 95% CI 1.15 to 6.71, p = 0.024).ConclusionsMicrometastases are associated with significantly worse survival after CLM resection. RAS/TP53 co-mutation correlated with increased risk of micrometastases. Further studies are needed to determine strategies to eradicate micrometastases.Copyright © 2022 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.

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