Characteristics of early-onset vs late-onset colorectal cancer: a review

REACCT Collaborative

Research output: Contribution to journalReview articlepeer-review


Importance: The incidence of early-onset colorectal cancer (younger than 50 years) is rising globally, the reasons for which are unclear. It appears to represent a unique disease process with different clinical, pathological, and molecular characteristics compared with late-onset colorectal cancer. Data on oncological outcomes are limited, and sensitivity to conventional neoadjuvant and adjuvant therapy regimens appear to be unknown. The purpose of this review is to summarize the available literature on early-onset colorectal cancer.

Observations: Within the next decade, it is estimated that 1 in 10 colon cancers and 1 in 4 rectal cancers will be diagnosed in adults younger than 50 years. Potential risk factors include a Westernized diet, obesity, antibiotic usage, and alterations in the gut microbiome. Although genetic predisposition plays a role, most cases are sporadic. The full spectrum of germline and somatic sequence variations implicated remains unknown. Younger patients typically present with descending colonic or rectal cancer, advanced disease stage, and unfavorable histopathological features. Despite being more likely to receive neoadjuvant and adjuvant therapy, patients with early-onset disease demonstrate comparable oncological outcomes with their older counterparts.

Conclusions and Relevance: The clinicopathological features, underlying molecular profiles, and drivers of early-onset colorectal cancer differ from those of late-onset disease. Standardized, age-specific preventive, screening, diagnostic, and therapeutic strategies are required to optimize outcomes.

Original languageEnglish
Pages (from-to)865-874
Number of pages10
JournalJAMA Surgery
Issue number9
Early online date30 Jun 2021
Publication statusPublished - Sept 2021

Bibliographical note

Funding Information:
reported grants from Medical Research Council South Africa as part of a Medical Research Council CURE grant and personal fees from Wits Consortium Salary as a past head of colorectal surgery during the conduct of the study; also, as a researcher in the developing world, Dr Bebington is constantly seeking opportunities to collaborate with institutions such as the Sloan Kettering, which has not unduly affected the honesty of data provided for the research nor the contribution he has made to intellectual content but could be construed as such. Dr Bruns reported personal fees from Medtronic as an advisory board member and Promedicis for Excellence in Oncology and grants from Intuitive for the ESOMAP trial and SIRTex for the ESSURE registry outside the submitted work. Dr Daniels reported personal fees from Origin Sciences, where he is a chief medical officer, appointed in August 2020; personal fees from Medtronic/Covidien and BD/Bard for teaching and advising; and nonfinancial support from Colostomy UK as honorary president of a charity focused on support for people with stomas, outside the submitted work. Dr Dunlop reported grants from University of Edinburgh during the conduct of the study. Dr Fleming reported author royalties from UptoDate outside the submitted work. Dr Frasson reported personal fees from J&J Consultory outside the submitted work. Dr Figueiredo reported personal fees for consulting and lectures from Johnson & Johnson outside the submitted work. Dr Frizelle reported serving as the editor of another Journal. Dr Hampel reported advisory board membership with Invitae Scientific, Genome Medical Scientific, and Promega Scientific outside the submitted work. Dr Karimuddin reported speaker’s fees from Servier outside the submitted work. Dr Lynch reported proctoring fees from Device Technologies and honoraria from Stryker outside the submitted work. Dr Mayol reported personal fees from Novartis, Boehringer Ingelheim, Astellas, Rovi, SOBI, Shionogi, Alcon, Roche, and Johnson & Johnson outside the submitted work. Dr São Julião reported personal fees from Johnson and Johnson, Roche, and Merck Sharp & Dohme outside the submitted work. Dr Pfeffer reported a research grant from Intuitive Surgical outside the submitted work. Dr Ris reported personal fees from Arthrex, Distal Motion, and Stryker and grants from Quantgene outside the submitted work. Dr Saraste reported grants from Bengt Ihre Foundation and Mag-Tarmfonden during the conduct of the study. Dr Seppälä reported being the CEO and co-owner from Healthfund Finland Ltd and interview honoraria from Boehringer Ingelheim Finland outside the submitted work. Dr Smart reported personal fees (speaker’s fees for hernia surgery) from Medtronic and WL Gore outside the submitted work. Dr Spinelli reported personal fees from Ethicon, Takeda, Janssen, Sofar, and Oasis outside the submitted work. Dr Tanis reported grants from LifeCell and Allergan outside the submitted work. Dr Vailati reported personal fees from Medtronic and Johnson & Johnson outside the submitted work. Dr Wexner reported consulting fees from Intuitive Surgical, Stryker, Medtronic, Tigenix, Axonics, Baxter, LiCor, and AISChannel; stock options from Regentys, LifeBond, Pragma, and Renew Medical; royalties from Medtronic, Intuitive Surgical, Karl Storz Endoscopy America, and Unique Surgical Innovations; and inactive consulting relationships with CRH Medical and Intuitive Surgical. Dr de Wilt reported grants from Dutch Cancer Society, ZonMW (The Netherlands Organisation for Health Research and Development), Bergh in het Zadel Foundation, and Medtronic to his institution outside the submitted work. No other disclosures were reported.

Publisher Copyright:
© 2021 American Medical Association. All rights reserved.

ASJC Scopus subject areas

  • Surgery


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