Authors: Hebaallah Elsandoby1, Praveen Baskar1, Oliver Benfield1, Nitesh Dulal1, Mariam Saleh1,2, Zainab Nisar1, Raafat A.Malek1,2

Affiliations: North West Cancer Centre, Derry/Londonderry, Northern Ireland

Background/ Introduction: Colorectal cancer (CRC) is a biologically heterogeneous disease, with molecular alterations guiding prognosis and treatment decisions. Since January 2022, next-generation sequencing (NGS) has been implemented as a routine diagnostic tool for CRC patients at our centre. This study evaluates the genomic landscape of CRC and its correlation with survival outcomes.

Material & Methods: A retrospective analysis was conducted of CRC patients referred to the North West Cancer Centre between January 2020 and December 2025 for chemotherapy and/or radiotherapy. Patients with complete molecular profiling were included. Data collected included demographics, tumour site and stage, microsatellite instability (MSI) status, and KRAS, NRAS, and BRAF mutation status. Overall survival was analysed by molecular subtype.

Results: A total of 370 CRC patients were identified, of whom 340 (92%) had complete molecular profiling. MSI-high (MSI-H) tumours accounted for 11% of cases, most being sporadic and associated with BRAF mutations. Microsatellite-stable (MSS) tumours with KRAS or NRAS mutations were present in 51% of patients, while 6% were MSS with BRAF mutations. The remaining 32% were MSS tumours wild type for KRAS, NRAS, and BRAF. Three-year overall survival was 74% for MSI-H tumours, 64% for wild-type MSS tumours, 58% for KRAS/NRAS-mutant MSS tumours, and 35% for BRAF-mutant MSS tumours.

Conclusion: These data confirm prognosis of MSI-H CRC compared with molecular subtypes, likely reflecting earlier-stage presentation, with fewer than 20% presenting with metastatic disease, and access to first-line immunotherapy. Despite therapeutic advances and targeted agents in later treatment lines, BRAF-mutant MSS CRC continues to demonstrate the poorest survival outcomes.