ArticleESMO open2026
Distinct molecular and clinical aggressiveness in very early-onset metastatic colorectal cancer: survival and genomic divergence between patients aged 30-39 versus 40-49 years.
Article in ESMO open, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundEarly-onset colorectal cancer (EOCRC) is increasing worldwide and exhibits clinical heterogeneity. Patients younger than 40 years may constitute a biologically distinct subgroup within EOCRC. We investigated whether 'very early-onset' metastatic colorectal cancer (VEOCRC, ages 30-39) exhibits specific clinical and genomic features compared with EOCRC in patients aged 40-49 and whether these differences lead to variations in survival from the time of metastatic diagnosis. MATERIALS AND
methodsWe analysed the data of metastatic EOCRC patients in a multi-institutional database, divided into two predefined age groups: 30-39 years and 40-49 years. Overall survival (OS) from metastatic diagnosis was estimated using Kaplan-Meier methods, and hazard ratios (HRs) were calculated with Cox regression. Comprehensive genomic profiling was carried out using the Foundation Medicine next-generation sequencing platform (FoundationOne®). Key molecular alterations were compared using odds ratios (ORs). Baseline clinicopathologic characteristics were assessed using χ
resultsA total of 264 patients were included (aged 30-39: n = 65; aged 40-49: n = 199). Median OS was shorter in patients aged 30-39 years than in those aged 40-49 years (30.0 versus 38.0 months; log-rank P = 0.0269; HR 0.67). A distinct genomic profile appeared in patients with VEOCRC, characterised by higher KRAS mutation rates (55.4% versus 42.0%; OR 1.71; one-sided P = 0.041) and fewer APC alterations (69.2% versus 82.0%; one-sided P = 0.024). NRAS, BRAF, PTEN, and POLE alterations were directionally consistent with a more aggressive biology, although event counts were limited. Clinically, overall Eastern Cooperative Oncology Group performance status (ECOG PS) distribution was similar (χ
conclusionsPatients aged 30-39 years constitute a biologically distinct subgroup within EOCRC, with shorter survival, KRAS mutation enrichment, fewer APC alterations, and increased peritoneal involvement. These findings support the emerging idea of an 'ultra-young', genomically driven CRC subtype, with implications for disease biology, risk assessment, and treatment development.
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