Purpose <p>Early-onset colorectal cancer (EOCRC), defined as colorectal cancer diagnosed before the age of 50&#xa0;years, is increasing worldwide and represents a growing clinical and public health challenge. Whether EOCRC constitutes a biologically distinct entity remains uncertain, and current diagnostic and therapeutic strategies are largely extrapolated from late-onset disease.</p> Methods <p>This narrative review summarizes recent evidence on EOCRC biology, diagnosis, and management, focusing on molecular and genomic features, tumor microenvironment, exposome-related factors, diagnostic pathways, treatment paradigms, and emerging strategies for early detection. We critically examine the gap between biological insights and real-world clinical practice and outline priorities for future research.</p> Results <p>EOCRC displays a heterogeneous molecular landscape that substantially overlaps with late-onset colorectal cancer. Although advances in multiomics profiling, liquid biopsy, and microbiome research have improved biological understanding, these findings have not yet translated into EOCRC-specific diagnostic or therapeutic approaches. Diagnosis remains delayed due to age-based screening paradigms and symptom misattribution, resulting in advanced-stage presentation. Younger patients frequently receive intensified treatment despite limited age-specific evidence and insufficient attention to long-term toxicity, fertility, and survivorship.</p> Conclusion <p>EOCRC underdiagnosis is likely multifactorial. While limitations in biological knowledge and diagnostic tools may play a role, the discrepancy between current paradigms and the age-specific risk profiles of younger patients likely represents an important contributing factor. Progress will require biology-informed, risk-adapted screening strategies and EOCRC-focused clinical research.</p>

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Early-onset colorectal cancer: a comprehensive review reframing hypotheses and defining research priorities

  • Greta Catani,
  • Juan Manuel O’Connor,
  • Antonino Spinelli,
  • José Perea

摘要

Purpose

Early-onset colorectal cancer (EOCRC), defined as colorectal cancer diagnosed before the age of 50 years, is increasing worldwide and represents a growing clinical and public health challenge. Whether EOCRC constitutes a biologically distinct entity remains uncertain, and current diagnostic and therapeutic strategies are largely extrapolated from late-onset disease.

Methods

This narrative review summarizes recent evidence on EOCRC biology, diagnosis, and management, focusing on molecular and genomic features, tumor microenvironment, exposome-related factors, diagnostic pathways, treatment paradigms, and emerging strategies for early detection. We critically examine the gap between biological insights and real-world clinical practice and outline priorities for future research.

Results

EOCRC displays a heterogeneous molecular landscape that substantially overlaps with late-onset colorectal cancer. Although advances in multiomics profiling, liquid biopsy, and microbiome research have improved biological understanding, these findings have not yet translated into EOCRC-specific diagnostic or therapeutic approaches. Diagnosis remains delayed due to age-based screening paradigms and symptom misattribution, resulting in advanced-stage presentation. Younger patients frequently receive intensified treatment despite limited age-specific evidence and insufficient attention to long-term toxicity, fertility, and survivorship.

Conclusion

EOCRC underdiagnosis is likely multifactorial. While limitations in biological knowledge and diagnostic tools may play a role, the discrepancy between current paradigms and the age-specific risk profiles of younger patients likely represents an important contributing factor. Progress will require biology-informed, risk-adapted screening strategies and EOCRC-focused clinical research.