Red-flag signs and symptoms for earlier diagnosis of early-onset colorectal cancer

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 (Ptrend < .001), respectively, with stronger associations for younger ages (Pinteraction < .001) and rectal cancer (Pheterogenity = .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.

Figure 1.

Number of red-flag signs and symptoms and risk of early-onset colorectal cancer according to 3-month time intervals prior to the index date. The total number of signs and symptoms were derived from the 4 red-flag signs and symptoms identified to be associated with an increased risk of early-onset colorectal cancer (abdominal pain, rectal bleeding, diarrhea, and iron deficiency anemia) between 3 months and 2 years prior to the index date. The multivariable models were adjusted for the same set of variables as in Table 2, model c. CI = confidence interval; OR = odds ratio.

Figure 2.

Diagnostic intervals of early-onset colorectal cancer with the first red-flag sign and symptom between 3 months and 2 years before diagnosis. ^aA total of 983 cases have had 1 or more of the 4 red-flag signs and symptoms associated with increased risk of early-onset colorectal cancer (abdominal pain, rectal bleeding, diarrhea, and iron deficiency anemia) between 3 months and 2 years prior to diagnosis. ^bFor cases with 1 sign or symptom between 3 months and 2 years prior to diagnosis, the diagnostic interval accrued from the date of first sign or symptom claim to date of diagnosis. For patients who had 2 or more red-flag signs and symptoms between 3 months and 2 years prior to diagnosis, the diagnostic interval accrued from the time point when all the red-flag signs and symptoms have been presented to the date of diagnosis. IQR = interquartile range (P25 to P75).