Worse Survival in Co-Altered RAS-TP53 Patients With Resected Colorectal Liver Metastases.

Area of Science:

• Oncology
• Genomics
• Surgical Oncology

Background:

• Next-generation sequencing (NGS) offers insights into mutations in colorectal liver metastases (CRLMs) affecting survival.
• Current research often focuses on single gene mutations, overlooking combined genetic alterations.
• This study investigates the prognostic impact of co-occurring KRAS/NRAS and TP53 mutations in CRLMs.

Purpose of the Study:

• To evaluate the clinical significance of RAS-TP53 co-alterations (RTC) in patients with CRLM.
• To determine the association between RTC and oncologic outcomes following surgical resection.
• To explore the utility of comprehensive genomic profiling in managing CRLM.

Main Methods:

• Retrospective analysis of 155 patients with CRLM who underwent surgical management and NGS.
• Stratification of patients into groups based on the presence or absence of RTC.
• Assessment of associations between RTC and clinical outcomes, including survival and recurrence patterns.

Main Results:

• Patients with RTC (27%) more frequently had right-side primary tumors, synchronous CRLM, and were initially unresectable.
• RTC was independently associated with worse recurrence-free and overall survival (HR, 2.076; P = 0.035).
• RTC patients experienced earlier extrahepatic recurrences (median, 9 vs. 14 months; P = 0.014).

Conclusions:

• RTC is linked to more aggressive tumor biology in CRLM, presenting with synchronous disease and poorer survival.
• Genomic data, including co-alterations, provide crucial prognostic information for CRLM management.
• Integrating comprehensive genomic sequencing can enhance decision-making for CRLM patients.