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Background <p>The global incidence of early-onset colorectal cancer (EOCRC) is increasing. The prognostic impact of EOCRC remains controversial, as it is largely confounded by hereditary syndromes and mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) tumors. We aimed to evaluate the clinicopathological features and stage-adjusted outcomes of sporadic, proficient MMR/microsatellite stable (pMMR/MSS) EOCRC.</p> Methods <p>We retrospectively reviewed 1,600 consecutive patients who underwent primary tumor resection for Stage 0–IV CRC. After excluding patients with known hereditary cancer syndromes or inflammatory bowel disease (IBD)-related CRC, as well as those with dMMR/MSI-H tumors or unknown MMR/MSI status, 1,218 patients with sporadic pMMR/MSS CRC were analyzed. Patients were stratified into EOCRC (&lt; 50 years, <i>n</i> = 86) and late-onset CRC (LOCRC, ≥ 50 years, <i>n</i> = 1,132) cohorts. Cancer-specific survival (CSS) and time to recurrence (TTR) were evaluated.</p> Results <p>Patients with EOCRC were more often diagnosed at an advanced stage than those with LOCRC (<i>P</i> &lt; 0.001). Unadjusted CSS was worse in the EOCRC group (<i>P</i> = 0.042); however, multivariable analysis showed that EOCRC was not an independent predictor of worse CSS (adjusted hazard ratio [HR] 0.84, 95% confidence interval [CI] 0.49–1.37, <i>P</i> = 0.512). Among 987 patients with curatively resected Stage I–III disease, the EOCRC group received significantly more intensive perioperative treatments (<i>P</i> &lt; 0.001). Unadjusted TTR did not significantly differ between the age groups (<i>P</i> = 0.510), and multivariable analysis showed a non-significant tendency toward a lower recurrence risk in patients with EOCRC (adjusted HR 0.52, 95% CI 0.23–1.03, <i>P</i> = 0.084).</p> Conclusions <p>After exclusion of hereditary syndromes, IBD-related CRC, and dMMR/MSI-H tumors, pMMR/MSS EOCRC more often presented with advanced disease, but its stage-adjusted cancer-specific survival and recurrence outcomes did not significantly differ from those of LOCRC.</p>

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Clinicopathological characteristics and stage-adjusted outcomes of sporadic pMMR/MSS early-onset colorectal cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月21日

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  • Tomoyuki Momma,
  • Hirokazu Okayama,
  • Makoto Hasegawa,
  • Takahiro Kawamata,
  • Chiaki Takiguchi,
  • Satoshi Fukai,
  • Takahiro Sato,
  • Misato Ito,
  • Daisuke Ujiie,
  • Shun Chida,
  • Motonobu Saito,
  • Koji Kono

摘要

Background

The global incidence of early-onset colorectal cancer (EOCRC) is increasing. The prognostic impact of EOCRC remains controversial, as it is largely confounded by hereditary syndromes and mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) tumors. We aimed to evaluate the clinicopathological features and stage-adjusted outcomes of sporadic, proficient MMR/microsatellite stable (pMMR/MSS) EOCRC.

Methods

We retrospectively reviewed 1,600 consecutive patients who underwent primary tumor resection for Stage 0–IV CRC. After excluding patients with known hereditary cancer syndromes or inflammatory bowel disease (IBD)-related CRC, as well as those with dMMR/MSI-H tumors or unknown MMR/MSI status, 1,218 patients with sporadic pMMR/MSS CRC were analyzed. Patients were stratified into EOCRC (< 50 years, n = 86) and late-onset CRC (LOCRC, ≥ 50 years, n = 1,132) cohorts. Cancer-specific survival (CSS) and time to recurrence (TTR) were evaluated.

Results

Patients with EOCRC were more often diagnosed at an advanced stage than those with LOCRC (P < 0.001). Unadjusted CSS was worse in the EOCRC group (P = 0.042); however, multivariable analysis showed that EOCRC was not an independent predictor of worse CSS (adjusted hazard ratio [HR] 0.84, 95% confidence interval [CI] 0.49–1.37, P = 0.512). Among 987 patients with curatively resected Stage I–III disease, the EOCRC group received significantly more intensive perioperative treatments (P < 0.001). Unadjusted TTR did not significantly differ between the age groups (P = 0.510), and multivariable analysis showed a non-significant tendency toward a lower recurrence risk in patients with EOCRC (adjusted HR 0.52, 95% CI 0.23–1.03, P = 0.084).

Conclusions

After exclusion of hereditary syndromes, IBD-related CRC, and dMMR/MSI-H tumors, pMMR/MSS EOCRC more often presented with advanced disease, but its stage-adjusted cancer-specific survival and recurrence outcomes did not significantly differ from those of LOCRC.