Clinical, pathological, and molecular characteristics of advanced colorectal cancer in younger vs older patients: Results from a Latin American cancer center.

Abstract

226 Background: Colorectal cancer (CRC) is the third most common malignancy worldwide, with over 1.9 million new cases annually. Although incidence in older adults is declining, early-onset CRC (<50 years) now accounts for 10–15% of cases, with rising trends in Western and Latin American populations. Evidence on clinical and molecular features of advanced CRC in younger patients from this region remains scarce. We aimed to compare clinicopathologic characteristics, treatment patterns, and prognostic factors by age group. Methods: We retrospectively analyzed 107 patients with stage IV CRC who underwent tumor sequencing at the Instituto Nacional de Cancerología (Mexico) from 2010–2022. Patients were stratified as <50 years (n=29) and ≥50 years (n=78). Clinical features, mutational profiles, and systemic treatments were compared. Progression-free survival (PFS) was estimated using Kaplan-Meier and Cox regression. Results: Median age was 60 years (range 22–82); 27.1% were <50. Younger patients more frequently presented with obstruction (51.7% vs 24.4%, p=0.02), peritoneal metastases (41.4% vs 20.5%, p=0.02), and transverse colon primaries (10.3% vs 1.3%, p=0.02). Family history of cancer was comparable (44.8% vs 43.6%). KRAS mutations were frequent in both groups (58.6% vs 53.8%), while TP53 mutations were less common in younger patients (48.3% vs 73.1%, p=0.01). BRAF mutations occurred more often in younger patients (6.9% vs 1.3%). Median PFS did not differ by age (<50: 5.4 months; ≥50: 5.8 months, p=0.97). Cox regression identified BRAF mutation as an adverse factor in younger patients (HR 2.1, p=0.02). Among older patients, irresectable tumors predicted worse PFS (HR 1.73, p=0.02), whereas right-sided location showed significant trend toward improved outcomes (HR 0.66, p=0.01). Conclusions: Younger patients with advanced CRC exhibited distinct features, including higher rates of obstruction, peritoneal disease, and BRAF mutations, while older patients more often carried TP53 alterations. BRAF mutation and irresectability were adverse prognostic factors, whereas right-sided tumors appeared protective in older patients. These findings highlight the heterogeneous biology of CRC across age groups and underscore the importance of regional molecular profiling to guide treatment strategies.