Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2024 May 1;7(5):e2413157.
doi: 10.1001/jamanetworkopen.2024.13157.

Red Flag Signs and Symptoms for Patients With Early-Onset Colorectal Cancer: A Systematic Review and Meta-Analysis

Joshua Demb  1   2 , Jennifer M Kolb  3 , Jonathan Dounel  4 , Cassandra D L Fritz  5 , Shailesh M Advani  6 , Yin Cao  7   8   9 , Penny Coppernoll-Blach  10 , Andrea J Dwyer  11 , Jose Perea  12   13 , Karen M Heskett  10 , Andreana N Holowatyj  14 , Christopher H Lieu  15 , Siddharth Singh  1   16   2 , Manon C W Spaander  17 , Fanny E R Vuik  17 , Samir Gupta  1   2
Affiliations
Meta-Analysis

Red Flag Signs and Symptoms for Patients With Early-Onset Colorectal Cancer: A Systematic Review and Meta-Analysis

Joshua Demb et al. JAMA Netw Open. .

Abstract

Importance: Early-onset colorectal cancer (EOCRC), defined as a diagnosis at younger than age 50 years, is increasing, and so-called red flag signs and symptoms among these individuals are often missed, leading to diagnostic delays. Improved recognition of presenting signs and symptoms associated with EOCRC could facilitate more timely diagnosis and impact clinical outcomes.

Objective: To report the frequency of presenting red flag signs and symptoms among individuals with EOCRC, to examine their association with EOCRC risk, and to measure variation in time to diagnosis from sign or symptom presentation.

Data sources: PubMed/MEDLINE, Embase, CINAHL, and Web of Science were searched from database inception through May 2023.

Study selection: Studies that reported on sign and symptom presentation or time from sign and symptom presentation to diagnosis for patients younger than age 50 years diagnosed with nonhereditary CRC were included.

Data extraction and synthesis: Data extraction and quality assessment were performed independently in duplicate for all included studies using Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guidelines. Joanna Briggs Institute Critical Appraisal tools were used to measure risk of bias. Data on frequency of signs and symptoms were pooled using a random-effects model.

Main outcomes and measures: Outcomes of interest were pooled proportions of signs and symptoms in patients with EOCRC, estimates for association of signs and symptoms with EOCRC risk, and time from sign or symptom presentation to EOCRC diagnosis.

Results: Of the 12 859 unique articles initially retrieved, 81 studies with 24 908 126 patients younger than 50 years were included. The most common presenting signs and symptoms, reported by 78 included studies, were hematochezia (pooled prevalence, 45% [95% CI, 40%-50%]), abdominal pain (pooled prevalence, 40% [95% CI, 35%-45%]), and altered bowel habits (pooled prevalence, 27% [95% CI, 22%-33%]). Hematochezia (estimate range, 5.2-54.0), abdominal pain (estimate range, 1.3-6.0), and anemia (estimate range, 2.1-10.8) were associated with higher EOCRC likelihood. Time from signs and symptoms presentation to EOCRC diagnosis was a mean (range) of 6.4 (1.8-13.7) months (23 studies) and a median (range) of 4 (2.0-8.7) months (16 studies).

Conclusions and relevance: In this systematic review and meta-analysis of patients with EOCRC, nearly half of individuals presented with hematochezia and abdominal pain and one-quarter with altered bowel habits. Hematochezia was associated with at least 5-fold increased EOCRC risk. Delays in diagnosis of 4 to 6 months were common. These findings highlight the need to identify concerning EOCRC signs and symptoms and complete timely diagnostic workup, particularly for individuals without an alternative diagnosis or sign or symptom resolution.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Holowatyj reported receiving grants from National Institutes of Health, American Cancer Society, Pfizer, Dalton Family Foundation, and ACPMP Research Foundation and personal fees from MJH Life Sciences outside the submitted work. Dr Gupta reported receiving personal fees from Guardant Health, Universal Diagnostics, Geneoscopy, and InterVenn Biosciences and owning stock in CellMax Life outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Flowchart of Study Inclusion
Figure 2.
Figure 2.. Pooled Proportions of Presenting Signs and Symptoms for Early-Onset Colorectal Cancer
Figure 3.
Figure 3.. Association Between Symptoms and the Risk of Early-Onset Colorectal Cancer
Size of box indicates number of estimates.
Figure 4.
Figure 4.. Histogram of Study Frequencies of Time From Symptom Onset to Diagnosis, by Measurement Type
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Siegel RL, Torre LA, Soerjomataram I, et al. . Global patterns and trends in colorectal cancer incidence in young adults. Gut. 2019;68(12):2179-2185. doi:10.1136/gutjnl-2019-319511 - DOI - PubMed
    1. Saad El Din K, Loree JM, Sayre EC, et al. . Trends in the epidemiology of young-onset colorectal cancer: a worldwide systematic review. BMC Cancer. 2020;20(1):288. doi:10.1186/s12885-020-06766-9 - DOI - PMC - PubMed
    1. Brenner DR, Ruan Y, Shaw E, De P, Heitman SJ, Hilsden RJ. Increasing colorectal cancer incidence trends among younger adults in Canada. Prev Med. 2017;105:345-349. doi:10.1016/j.ypmed.2017.10.007 - DOI - PubMed
    1. Troeung L, Sodhi-Berry N, Martini A, et al. . Increasing incidence of colorectal cancer in adolescents and young adults aged 15-39 years in Western Australia 1982-2007: examination of colonoscopy history. Front Public Health. 2017;5:179. doi:10.3389/fpubh.2017.00179 - DOI - PMC - PubMed
    1. Wang W, Chen W, Lin J, Shen Q, Zhou X, Lin C. Incidence and characteristics of young-onset colorectal cancer in the United States: an analysis of SEER data collected from 1988 to 2013. Clin Res Hepatol Gastroenterol. 2019;43(2):208-215. doi:10.1016/j.clinre.2018.09.003 - DOI - PubMed

Publication types