Clinical Practice Guidelines
Delphi Initiative for Early-Onset Colorectal Cancer (DIRECt) International Management Guidelines

https://doi.org/10.1016/j.cgh.2022.12.006Get rights and content
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Background & Aims

Patients with early-onset colorectal cancer (eoCRC) are managed according to guidelines that are not age-specific. A multidisciplinary international group (DIRECt), composed of 69 experts, was convened to develop the first evidence-based consensus recommendations for eoCRC.

Methods

After reviewing the published literature, a Delphi methodology was used to draft and respond to clinically relevant questions. Each statement underwent 3 rounds of voting and reached a consensus level of agreement of ≥80%.

Results

The DIRECt group produced 31 statements in 7 areas of interest: diagnosis, risk factors, genetics, pathology-oncology, endoscopy, therapy, and supportive care. There was strong consensus that all individuals younger than 50 should undergo CRC risk stratification and prompt symptom assessment. All newly diagnosed eoCRC patients should receive germline genetic testing, ideally before surgery. On the basis of current evidence, endoscopic, surgical, and oncologic treatment of eoCRC should not differ from later-onset CRC, except for individuals with pathogenic or likely pathogenic germline variants. The evidence on chemotherapy is not sufficient to recommend changes to established therapeutic protocols. Fertility preservation and sexual health are important to address in eoCRC survivors. The DIRECt group highlighted areas with knowledge gaps that should be prioritized in future research efforts, including age at first screening for the general population, use of fecal immunochemical tests, chemotherapy, endoscopic therapy, and post-treatment surveillance for eoCRC patients.

Conclusions

The DIRECt group produced the first consensus recommendations on eoCRC. All statements should be considered together with the accompanying comments and literature reviews. We highlighted areas where research should be prioritized. These guidelines represent a useful tool for clinicians caring for patients with eoCRC.

Keywords

Recommendation
Clinical
Young
50 Years
Colorectal Cancer

Abbreviations used in this paper

ADR
adenoma detection rate
CI
confidence interval
CINV
chemotherapy-induced nausea and vomiting
CRC
colorectal cancer
DIRECt
Delphi Initiative Recommendations on EoCRC
eoCRC
early-onset colorectal cancer
ESGE
European Society of Gastrointestinal Endoscopy
ESMO
European Society of Medical Oncology
FIT
fecal immunochemical testing
GI
gastrointestinal
IHC
immunohistochemistry
LE
level of evidence
loCRC
late-onset colorectal cancer
LPV
likely pathogenic variants
LS
Lynch syndrome
MMR
mismatch repair
MMR-d
mismatch repair deficiency
MMR-p
mismatch repair proficiency
MSI
microsatellite instability
MSI-H
microsatellite instability high
NCCN
National Comprehensive Cancer Network
NGS
next-generation sequencing
OR
odds ratio
PICO
population, intervention, comparison, and outcome
PRS
polygenic risk scores
PV
pathogenic variants
RR
relative risk
SNP
single nucleotide polymorphism
USMSTF
U.S. Multi-Society Task Force
USPSTF
U.S. Preventive Service Task Force

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Conflicts of interest Refer to the online form to see conflicts of interest.

This article has an accompanying continuing medical education activity, also eligible for MOC credit, on page e7. Upon completion of this module, successful learners will be able to evaluate high-risk symptoms of early-onset colorectal cancer, explain the utility of tumor testing and germline testing in this setting, integrate the oncological management with the fertility management, and cite the surveillance protocol after cure from colorectal cancer <50 years.

Authors share co-first authorship.

Chairs of the Working Panels.