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.
Xiang et al. (Thu,) studied this question.