Stage-specific characterization of "early-onset colorectal cancer": Localized and synchronous metastatic disease

Int J Cancer. 2025 Jun 15;156(12):2340-2351. doi: 10.1002/ijc.35336. Epub 2025 Jan 30.

Abstract

Early-onset colorectal cancer (EOCRC) is an alarming entity worldwide. Yet, stage-specific characteristics and prognosis in localized and synchronous metastatic EOCRC are not well-defined. Two cohorts of CRC patients (localized and synchronous metastatic) were evaluated, defining EOCRC as the diagnosis <50 years old. Five hundred sixty-eight patients were included (n = 432 localized, 14.4% [n = 62] EOCRC and n = 136 synchronous metastatic, 20.6% [n = 28] EOCRC). 93.5% of localized and 96.5% of synchronous metastatic EOCRC patients were symptomatic at diagnosis. Among localized patients, female gender (58.1% vs. 40%, p = .008), perineural invasion (41.9% vs. 24.9%, p = .005), folinic acid, 5-fluorouracil, and oxaliplatin chemotherapy (45.2% vs. 25.2%, p = .003), and perioperative chemotherapy cycles (9.21 [± 3.10] vs. 7.98 [± 2.92], p = .006) were higher in EOCRC compared with ≥50-year. Median recurrence-free survival (RFS) and overall survival were not reached in either group (p = .234 and p = .831). Only RAS mutant status was associated with RFS (Hazard ratio: 7.09 [95% confidence interval (CI): 1.87-26.76], p < .001) in EOCRC. Among synchronous metastatic patients, urgent surgery (32.1% vs. 11.1%, p = .014) and local treatments (39.3% vs. 20.4%, p = .037) were more frequent in EOCRC. Median progression-free survival and overall survival in the EOCRC and ≥50 years were 8.07 months (95% CI: 5.03-12.97) vs. 10.03 months (95% CI, 8.40-13.10) (p = .450) and 18.57 months (95% CI, 13.33-43.03) vs. 19.83 months (95% CI, 16.07-27.30) (p = .833), respectively. Synchronous metastatic EOCRC more frequently underwent urgent surgery (32.1% vs. 8%, p = .008) and had RAS mutation (43.5% vs. 16.7%, p = .032) than localized EOCRC. This study suggests that localized and synchronous metastatic EOCRC patients may have different characteristics than average onset, without survival differences. Implementation of stage-specific characteristics into daily practice is necessary for decision-making processes in these young patients.

Keywords: RAS; colorectal cancer; early onset; localized; synchronous metastatic.

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Colorectal Neoplasms* / drug therapy
  • Colorectal Neoplasms* / mortality
  • Colorectal Neoplasms* / pathology
  • Colorectal Neoplasms* / therapy
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Neoplasms, Multiple Primary* / pathology
  • Prognosis

Substances

  • Fluorouracil