Colorectal cancer is a leading cause of cancer-related deaths worldwide, with metastatic disease responsible for the majority of fatalities [1][2]. While colorectal cancer has traditionally been seen as a disease affecting mostly adults aged 65 years and older, recent data shows a concerning rise in cases among younger individuals [2][3]. This shift has prompted a reassessment of current screening and prevention strategies to better address changing risk patterns.

Global cancer surveillance data continues to highlight colorectal cancer as a significant public health challenge, with millions of new cases and deaths reported annually [1]. Focusing specifically on metastatic colorectal cancer (mCRC) is critical, as it represents the most advanced stage of disease and is frequently associated with poor prognosis, substantial morbidity, and limited therapeutic options [2]. Understanding how mCRC affects different age groups can guide efforts to improve early detection and tailor interventions more effectively.

Most epidemiologic studies rely on cancer registries, which provide valuable information about incidence and survival but may not capture detailed hospitalization data or reflect healthcare utilization patterns [4]. In contrast, inpatient hospitalization data offer a unique perspective by revealing trends in severe disease requiring hospital care, associated comorbidities, and resource use. This approach can help identify populations with the greatest clinical burden and inform strategies to optimize management and outcomes.

Recent changes in colorectal cancer screening guidelines reflect growing recognition of shifting disease patterns across age groups. In the United States, the U.S. Preventive Services Task Force currently recommends routine colorectal cancer screening for average-risk adults beginning at age 45 years and continuing through age 75 years, with individualized decision-making for adults aged 76 - 85 years based on overall health and prior screening history [5][6]. Recommended screening modalities include colonoscopy, fecal immunochemical testing (FIT), and stool DNA-based tests, among others. Despite these recommendations, screening uptake remains variable across age groups, potentially contributing to delayed diagnosis and advanced-stage disease at presentation [7].

In this study, we used a large, nationally representative inpatient database to evaluate age-specific trends in metastatic colorectal cancer from 2016 to 2019. By examining these patterns, we aim to identify populations that may benefit from more targeted screening and early detection efforts.

This study demonstrates a sustained and increasing burden of metastatic colorectal cancer among adults aged 66 - 75 years. This increase may reflect both true epidemiologic change and cohort aging, as the Baby Boomer generation transitions into the 66 - 75 age bracket. In addition, nearly one-third of metastatic cases occurred in patients aged ≤ 45 years or ≥76 years, underscoring a substantial burden of advanced disease among age groups that fall outside routine colorectal cancer screening recommendations, which in the United States generally target adults aged 45 - 75 years.

Figure 1. Temporal trends in age-specific metastatic colorectal cancer hospitalizations from 2016 to 2019.

Multiple factors may hypothetically contribute to delayed diagnosis across these populations, although such mechanisms cannot be directly assessed using administrative inpatient data. In older adults, potential contributors include procedural risk, comorbidity burden, and reduced adherence to colonoscopy-based screening, which may limit timely detection. Conversely, younger individuals may experience diagnostic delays related to lower clinical suspicion and reduced awareness of colorectal cancer risk. Emerging noninvasive screening modalities, including circulating tumor DNA assays and liquid biopsy technologies, have shown promise in detecting colorectal cancer and may offer age-tailored strategies that improve screening uptake and early diagnosis [8]-[10].

Several limitations should be considered. This analysis was retrospective and relied on administrative data, precluding assessment of tumor biology, treatment patterns, screening history, or survival outcomes. Because the National Inpatient Sample captures inpatient encounters only, these findings reflect the burden of hospitalizations rather than the total population-level burden of metastatic colorectal cancer. A substantial proportion of metastatic colorectal cancer management occurs in outpatient settings, which are not represented in this dataset and may lead to underestimation or differential characterization of disease burden across age groups. Despite these limitations, the use of a large, nationally representative inpatient dataset provides valuable insight into age-specific hospitalization trends for advanced colorectal cancer.

Metastatic colorectal cancer affects a broad age spectrum, with a substantial and persistent burden among adults aged 56 - 65 years and a rising burden among those aged 66 - 75 years, alongside a notable proportion of hospitalizations occurring at younger and older age extremes. These findings highlight potential gaps in current screening strategies and underscore the importance of age-aware approaches to early detection and healthcare planning.

The authors would like to acknowledge the Healthcare Cost and Utilization Project (HCUP) and the Agency for Healthcare Research and Quality (AHRQ) for providing access to the National Inpatient Sample (NIS), which made this study possible. The interpretations and conclusions expressed in this manuscript are those of the authors and do not necessarily represent the views of HCUP or AHRQ.