Early-onset colorectal cancer: from biology to clinical care and survivorship

Early-onset colorectal cancer (EOCRC), conventionally defined as colorectal cancer (CRC) diagnosed before age 50, is increasing across multiple regions despite stable or declining incidence in older adults. This review synthesises current evidence on its epidemiology, aetiology, biology, diagnosis, treatment and survivorship. EOCRC differs from average-onset CRC in its epidemiological trajectory, anatomical and clinicopathological distribution, and the prevalence of selected molecular alterations, although no single molecular or environmental mechanism defines the disease. Life-course metabolic and dietary exposures, accelerated biological ageing and selected microbial mutational processes are under investigation as potential contributors to the birth-cohort effect. Most cases are sporadic, but germline pathogenic variants are sufficiently frequent to support multigene germline testing alongside universal mismatch-repair assessment. Somatic molecular profiling may additionally identify clinically actionable subgroups, including mismatch-repair-deficient and rare polymerase-proofreading-deficient tumours. EOCRC is more often distal or rectal, frequently presents symptomatically and at an advanced stage, and is commonly preceded by diagnostic delay. Lowering average-risk screening thresholds may improve detection in adults aged 45–49, but cannot address disease arising earlier and may increase colonoscopy demand; therefore, risk-stratified screening, improved symptom recognition and timely investigation remain essential. Treatment principles should generally follow those used in average-onset disease and be guided by tumour biology rather than age alone. Younger patients nevertheless receive more intensive treatment, often without proportionate survival benefit, and face substantial long-term consequences affecting fertility, sexual function, bowel function, psychological health, employment and finances. Emerging biomarker-defined strategies, including immunotherapy for mismatch-repair-deficient tumours and organ-preservation approaches in rectal cancer, may be particularly valuable. Progress will require integrated, age-attuned pathways spanning prevention, diagnosis, molecular assessment, treatment and survivorship, alongside prospective research linking life-course exposures to tumour biology and clinically meaningful outcomes, ensuring access across diverse populations and health systems.