Clinicopathological characteristics and biomarker alterations in early-onset vs. late-onset colorectal cancer: a systematic review and meta-analysis.

BACKGROUND

The clinicopathological and molecular characteristics of early-onset colorectal cancer (EOCRC) are unclear. In this study, we compared the clinicopathological features, biomarkers, and prognoses between EOCRC and late-onset colorectal cancer (LOCRC).

METHODS

A search was conducted on PubMed, Web of Science, Embase, and Cochrane Library from inception to May 2024. The key outcomes were clinicopathological features, prevalence of molecular biomarker alterations, and 5-year overall survival (OS), with pooled odds ratios (ORs) and hazard ratios (HRs), along with their corresponding 95% confidence intervals (CIs), calculated for each outcome.

RESULTS

Forty studies were included in the final analysis. EOCRC exhibited distal colon and rectum localization (OR: 0.59; 95% CI: 0.55-0.62; P < 0.001), was poorly differentiated (OR: 0.56; 95% CI: 0.52-0.60; P = 0.01), tended to be more mucinous or signet-ring cell carcinoma (OR: 0.56; 95% CI: 0.52-0.60; P < 0.001), and was associated with advanced stages (OR: 1.49; 95% CI: 1.30-1.71; P < 0.001), lymph node metastasis (LNM) (OR: 0.56; 95% CI: 0.53-0.60; P < 0.001), and distant metastasis (OR: 1.29; 95% CI: 1.04-1.60; P = 0.02). EOCRC exhibited higher TP53 mutation rates (OR: 1.33; 95% CI: 1.13-1.58; P < 0.001), MSI-H status (OR: 1.45; 95% CI: 1.10-1.92; P = 0.01), but lower PIK3CA mutation rates (OR: 0.93; 95% CI: 0.88-0.99; P = 0.03). EOCRC and LOCRC had similar 5-year OS rates (HR: 1.01; 95% CI: 0.79-1.30; P = 0.92). Although no significant difference was observed in the APC, BRAF, KRAS, NRAS, SM4D4, and MMR, subgroup analyses revealed that BRAF ( P = 0.01), KRAS mutations ( P < 0.001), and DNA hypermethylation ( P = 0.01) were less prevalent among westerners.

CONCLUSION

EOCRC often presents with more aggressive and metastatic features due to its frequent diagnosis at advanced stages. TP53 mutations and the MSI-H status are prevalent in EOCRC. EOCRC's prognosis is often comparable to LOCRC. Radical and tailored treatment strategies should be developed to improve the survival outcomes in advanced and metastatic EOCRC.