Abstract and Introduction
Abstract
Background: Prompt detection of colorectal cancer (CRC) among individuals younger than age 50 years (early-onset CRC) is a clinical priority because of its alarming rise.
Methods: We conducted a matched case-control study of 5075 incident early-onset CRC among US commercial insurance beneficiaries (113 million adults aged 18–64 years) with 2 or more years of continuous enrollment (2006–2015) to identify red-flag signs and symptoms between 3 months to 2 years before the index date among 17 prespecified signs and symptoms. We assessed diagnostic intervals according to the presence of these signs and symptoms before and within 3 months of diagnosis.
Results: Between 3 months and 2 years before the index date, 4 red-flag signs and symptoms (abdominal pain, rectal bleeding, diarrhea, and iron deficiency anemia) were associated with an increased risk of early-onset CRC, with odds ratios (ORs) ranging from 1.34 to 5.13. Having 1, 2, or at least 3 of these signs and symptoms were associated with a 1.94-fold (95% confidence interval [CI] = 1.76 to 2.14), 3.59-fold (95% CI = 2.89 to 4.44), and 6.52-fold (95% CI = 3.78 to 11.23) risk (P trend < .001), respectively, with stronger associations for younger ages (P interaction < .001) and rectal cancer (P heterogenity = .012). The number of different signs and symptoms was predictive of early-onset CRC beginning 18 months before diagnosis. Approximately 19.3% of patients had their first sign or symptom occur between 3 months and 2 years before diagnosis (median diagnostic interval = 8.7 months), and approximately 49.3% had the first sign or symptom within 3 months of diagnosis (median diagnostic interval = 0.53 month).
Conclusions: Early recognition of red-flag signs and symptoms (abdominal pain, rectal bleeding, diarrhea, and iron-deficiency anemia) may improve early detection and timely diagnosis of early-onset CRC.
Introduction
Early-onset colorectal cancer (CRC)—CRC diagnosed before age 50 years—is increasing in the United States and globally.[1] In the United States, a 2% annual increase was documented between 2011 and 2016,[2,3] which is expected to more than double by 2030.[4] To address this trend, the American Cancer Society[5] and the US Preventive Services Task Force[6] lowered the recommended screening initiation age for average-risk individuals to 45 years. However, younger patients are more likely to be uninsured with lower adherence to screening, even if they have a family history of CRC.[7,8] Moreover, half of the early-onset CRC patients are younger than age 45 years and thus will not be detected via screening.[9] Therefore, most early-onset CRC patients will continue to be diagnosed after developing symptoms.[10,11] To date, early-onset CRC patients, compared with older patients, are more likely to experience diagnostic delays,[12–14] indicating a lack of awareness of red-flag signs and symptoms. Younger patients with CRC are more often diagnosed at advanced stages (27% distant disease vs 20% distant disease in older patients).[15–17] This has clinically significant implications as the 5-year survival decreases from 90% for early stage disease to only 14% for unresectable metastatic disease.[18] Earlier detection of early-onset CRC could be critical to reducing the higher mortality associated with advanced disease.[19] Additionally, earlier detection of early-onset CRC could reduce the need for aggressive treatment and improve survivor quality of life.[18] Thus, identifying red-flag signs and symptoms to facilitate earlier detection is an unmet priority.[20,21]
Signs and symptoms of early-onset CRC have been under investigation.[22] Prior work has highlighted rectal bleeding, iron deficiency anemia, and rectal or abdominal pain.[10,11,15,23–31] Yet, the majority of these studies have aggregated symptoms until the time of diagnosis, limiting information on early sign and symptom recognition to improve earlier detection. Although a study including average to late-onset CRC has demonstrated an increased risk of CRC with abdominal pain, rectal bleeding, and iron deficiency anemia as early as 6 months prior to diagnosis,[32] similar studies are thus far lacking for early-onset CRC.
To address these critical knowledge gaps, we conducted a population-based case-control study, leveraging longitudinal claims data to identify red-flag signs and symptoms associated with early-onset CRC, with a primary focus on those that occurred between 3 months and 2 years before the index (diagnosis) date. We also reported the diagnostic delays associated with the identified red-flag signs and symptoms.
J Natl Cancer Inst. 2023;115(8):909-916. © 2023 Oxford University Press
