Clinical and genetic drivers of oligo-metastatic disease in colon cancer

Abstract

Background: Oligo-metastatic disease (OMD) in colon cancer patients exhibits distinct clinical behavior compared to poly-metastatic disease (PMD), with a more responsive and indolent course. This study aims to identify clinical and biological factors uniquely associated with oligo-metastatic behavior. Methods: Metastatic colon cancer patients from an academic center underwent genetic characterization. OMD was defined as ≤3 lesions per organ, each with a total diameter 70 vs. <70 years), gender (male vs. female), tumor side (right vs. left), metastatic involvement (more than one site vs. one site), response to first-line therapy (disease control vs. no disease control), and RAS/BRAF variants (wild-type vs. mutated) identified OMD vs. PMD as the strongest independent predictor of survival (HR: 0.14; 95 % CI: 0.06-0.33; P<0.0001). OMD patients exhibited distinct molecular characteristics, including lower frequencies of BRAF p.V600E (P=0.0315) and KRAS mutations (P=0.0456), as well as a higher frequency of high tumor mutational burden (P=0.0127). Additionally, by integrating data from public datasets and our case study, we hypothesize that some gene alterations (i.e.: BRAF, SMAD4, RAF1, and mTOR) may prevent OMD occurrence. Conclusion: OMD, characterized by male predominance, single-site involvement, and distinct molecular features in colon cancer, suggests the need for tailored management strategies.

Keywords

• Oligo-metastatic disease
• Next generations sequencing
• Prognosis
• BRAF
• KRAS
• Tumor mutational burden