Implications of RAS Mutations on Oncological Outcomes of Surgical Resection and Thermal Ablation Techniques in the Treatment of Colorectal Liver Metastases.

Linda Rached,Rami Rhaiem,Olivier Bouché,Ahmad Tashkandi,Reza Kianmanesh

doi:10.3390/cancers14030816

Abstract

Simple SummaryModern management of colorectal liver metastases (CRLM) requires a thorough knowledge of tumor biology and oncogenes mutations. RAS mutations are of paramount interest for the indication of targeted therapies and is increasingly considered as a negative prognostic factor for patients undergoing surgical resection or ablation for CRLM. Several studies discussed the results of specific technical considerations according to RAS mutational status on the oncological outcomes after surgical resection/ablation for CRLM. We reviewed the available data on the real impact of RAS mutations on the prognosis with special regard to the need of a tailored surgical (ablation) approach according to tumoral biology.Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related death. More than 50% of patients with CRC will develop liver metastases (CRLM) during their disease. In the era of precision surgery for CRLM, several advances have been made in the multimodal management of this disease. Surgical treatment, combined with a modern chemotherapy regimen and targeted therapies, is the only potential curative treatment. Unfortunately, 70% of patients treated for CRLM experience recurrence. RAS mutations are associated with worse overall and recurrence-free survival. Other mutations such as BRAF, associated RAS /TP53 and APC/PIK3CA mutations are important genetic markers to evaluate tumor biology. Somatic mutations are of paramount interest for tailoring preoperative treatment, defining a surgical resection strategy and the indication for ablation techniques. Herein, the most relevant studies dealing with RAS mutations and the management of CRLM were reviewed. Controversies about the implication of this mutation in surgical and ablative treatments were also discussed.

Highlights

Management of colorectal liver metastases (CRLM) has evolved considerably during recent decades
The same conclusions were recently reported by Zhang et al [51] in a consecutive cohort of 251 patients treated for CRLM with more micrometastases, thicker margins and a higher rate of R1 resection in the KRAS mutated group [51]
rat sarcoma viral oncogenes (RAS) mutations seem to present a negative impact on the oncological outcome of patients treated for CRLM

Summary

Introduction

Management of colorectal liver metastases (CRLM) has evolved considerably during recent decades. Recent advances of surgical techniques, including portal vein embolization and total venous deprivation to prepare 2-stage hepatectomy, associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) and ablative treatments, allowed a wider indication of surgery [4]. This explains the high survival rates after surgery in selected patients for CRLM up to 40–65% at 5-year [2,5], and 25% at 10-year [5], while such long survival rates are uncommon after chemotherapy alone. In particular RAS mutations, is obviously among the strongest prognostic factors of CRLM It is of paramount interest in the choice of the appropriate chemoand targeted therapy regimens. We will report and discuss data reporting the role of RAS mutations in tailoring the surgical and/or ablation approach

RAS Mutations and Prognosis after CRLM Treatment

Implication of RAS Mutations in the Surgical Resection of CRLM

Implication of RAS Mutations in Ablative Treatment of CRLM

Results

Conclusions