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<p>Contemporary colorectal cancer (CRC) epidemiology reveals evolving risk factors have reconfigured CRC as a societally-modulated, quasi-age-dependent disease. Nevertheless, temporal drivers of incidence/incidence-based mortality (IBM) patterns and longitudinal trends in clinicopathological profiles, therapeutic modalities, and 5-year survival (5-YS) remain incompletely defined, necessitating methodologically rigorous studies. The Surveillance, Epidemiology, and End Results Program data (1975–2019) were analyzed using the National Cancer Institute’s (NCI’s) Age-Period-Cohort Analysis Tool to examine temporal drivers of US CRC epidemiology. Longitudinal trends in clinicopathological profiles, therapeutic modalities, and 5-YS were further assessed via NCI’s Joinpoint Regression Program. The relative risk (RR) of incidence increased exponentially in sequentially younger birth cohort, with the annual percentage change (APC) peaking at 6.11% in 20 − 24 years, while the RR of IBM declined in successively older birth cohorts and showed no improvement in younger birth cohorts. Early-onset CRC with regional- or distant-predominant disease (notably hepatic) showed a marked shift from adjuvant to neoadjuvant therapy, including a notable increase in preoperative radiotherapy for regional rectal cancer from 19.7% (2000) to 53.8% (2019), and preoperative systemic therapy for distant colon cancer from 5.5% (2007) to 17.6% (2019). Correspondingly, stage-specific 5-YS was also superior in early-onset CRC (e.g., regional rectal cancer: 82.5% vs. 67.8%; distant colon cancer: 22.9% vs. 14.7%), with greater annual improvement (e.g., APC for regional rectal cancer: 1.60% vs. 1.46%; APC for distant colon cancer: 3.59% vs. 2.55%). However, over 50% of distant metastatic patients, especially those with late-onset disease, still received no effective treatment. While overall CRC burden decreased in the US, extreme early-onset CRC surged with poor prognosis. Despite higher regional/metastatic burden, early-onset CRC showed better survival owing to aggressive treatment and adherence. Urgent actions are needed to address the rising risk in youth and therapeutic gaps in metastatic disease.</p>

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Temporal trends of clinicopathological features, therapeutic modalities, and survival outcomes in pseudo-age-related colorectal cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月14日

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  • Renshen Xiang,
  • Hanwen Hu,
  • Bo Li,
  • Dongzhi Hu,
  • Shiwen Mei,
  • Junfeng Wang,
  • Jiefu Wang

摘要

Contemporary colorectal cancer (CRC) epidemiology reveals evolving risk factors have reconfigured CRC as a societally-modulated, quasi-age-dependent disease. Nevertheless, temporal drivers of incidence/incidence-based mortality (IBM) patterns and longitudinal trends in clinicopathological profiles, therapeutic modalities, and 5-year survival (5-YS) remain incompletely defined, necessitating methodologically rigorous studies. The Surveillance, Epidemiology, and End Results Program data (1975–2019) were analyzed using the National Cancer Institute’s (NCI’s) Age-Period-Cohort Analysis Tool to examine temporal drivers of US CRC epidemiology. Longitudinal trends in clinicopathological profiles, therapeutic modalities, and 5-YS were further assessed via NCI’s Joinpoint Regression Program. The relative risk (RR) of incidence increased exponentially in sequentially younger birth cohort, with the annual percentage change (APC) peaking at 6.11% in 20 − 24 years, while the RR of IBM declined in successively older birth cohorts and showed no improvement in younger birth cohorts. Early-onset CRC with regional- or distant-predominant disease (notably hepatic) showed a marked shift from adjuvant to neoadjuvant therapy, including a notable increase in preoperative radiotherapy for regional rectal cancer from 19.7% (2000) to 53.8% (2019), and preoperative systemic therapy for distant colon cancer from 5.5% (2007) to 17.6% (2019). Correspondingly, stage-specific 5-YS was also superior in early-onset CRC (e.g., regional rectal cancer: 82.5% vs. 67.8%; distant colon cancer: 22.9% vs. 14.7%), with greater annual improvement (e.g., APC for regional rectal cancer: 1.60% vs. 1.46%; APC for distant colon cancer: 3.59% vs. 2.55%). However, over 50% of distant metastatic patients, especially those with late-onset disease, still received no effective treatment. While overall CRC burden decreased in the US, extreme early-onset CRC surged with poor prognosis. Despite higher regional/metastatic burden, early-onset CRC showed better survival owing to aggressive treatment and adherence. Urgent actions are needed to address the rising risk in youth and therapeutic gaps in metastatic disease.