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Precision surgery for colorectal liver metastases: Current knowledge and future perspectives.

Georgios Antonios Margonis1,2, Jean-Nicolas Vauthey3

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Biomarkers like BRAF and KRAS mutations are improving patient selection for colorectal liver metastases surgery. However, combining these with clinical factors is needed for better oncological outcomes.

Keywords:
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Area of Science:

  • Surgical Oncology
  • Genetics
  • Hepatobiliary Surgery

Background:

  • Patient selection for colorectal liver metastases (CRLM) surgery is crucial for optimal outcomes.
  • Previous reliance on clinical risk scores for patient selection has proven insufficient.
  • Biomarkers are increasingly integrated into strategies for selecting patients for CRLM surgery.

Purpose of the Study:

  • To review current and emerging strategies for patient selection in CRLM surgery, focusing on the role of biomarkers.
  • To evaluate the utility of specific genetic mutations (BRAF, KRAS, TP53, SMAD4) in guiding surgical decisions.
  • To assess the refined criteria for selecting patients for specialized procedures like two-stage hepatectomy (TSH), Associating Liver Partition and Portal vein Ligation for staged hepatectomy (ALPPS), and liver transplant (LT).

Main Methods:

  • Review of literature on patient selection for CRLM surgery, emphasizing biomarker integration.
  • Analysis of specific genetic mutations (BRAF V600E, KRAS G12V, RAS, TP53, SMAD4) and their prognostic significance.
  • Examination of criteria for selecting patients for single-stage hepatectomy and complex staged procedures (TSH, ALPPS, LT).

Main Results:

  • BRAF V600E, KRAS G12V, and triple mutations (RAS, TP53, SMAD4) are promising biomarkers but not definitive contraindications alone.
  • Combining biomarkers with clinicopathologic factors may improve patient selection, requiring external validation.
  • BRAF mutations and right-sided tumor laterality are proposed contraindications for LT.
  • Right-sided laterality, especially with RAS mutations, is associated with poor outcomes in ALPPS.
  • RAS mutations may indicate poor survival in TSH and could guide TSH selection.
  • Right-sided tumors with RAS mutations may contraindicate LT and ALPPS.

Conclusions:

  • Biomarker-driven patient selection is refining CRLM surgical strategies.
  • Specific mutations and tumor locations influence the choice and contraindications for different surgical approaches (hepatectomy, TSH, ALPPS, LT).
  • Further research is needed for robust validation and integration of biomarkers into clinical decision-making for CRLM management.