Table 4.

Statements Pertaining to Endoscopic Detection and Treatment (E), Therapy (T), and Supportive Care (C) of Early-Onset Colorectal Cancer

Question and statement	Level of evidence, grade of recommendation, agreement level, and clarity
Endoscopic detection, diagnosis, and treatment of early-onset colorectal cancer (E)
E.1: Should additional endoscopic technologies be routinely used to improve the diagnostic capabilities for eoCRC?    We suggest high-quality, high-definition white-light endoscopy as the standard modality for colonoscopy. There is currently insufficient evidence for the routine use of adjuncts such as dye or virtual chromoendoscopy, add-on devices, and artificial intelligence systems.	LE 5; GR D Agreement: 96.4% (A+ 42.9%|A 53.6% |D 3.6%)
E.2: Are standard quality metrics for colonoscopy appropriate?    Standard quality metrics for diagnostic and surveillance colonoscopy in eoCRC have not been established for adenoma detection rate. However, other established standard key performance indicators should be applied.	LE 2A; GR B Agreement: 93.1% (A+ 27.6 %|A 65.5%|A− 3.4% |D− 3.4%)
E.3: What diagnostic workup is necessary before surgery for eoCRC?    Complete evaluation of the colon should be performed before surgical treatment, with colonoscopy preferred to computed tomography-colonography. If complete colonoscopy is not technically feasible, a complete colonoscopy should be done within 3–6 months postoperatively.	LE 2A; GR B Agreement: 96.7% (A+ 23.3%|A 73.3%|D− 3.3%)
E.4: Should T1 CRC receive endoscopic therapy in rectal or colonic eoCRC?    There is insufficient evidence to recommend T1 CRC be managed differently in eoCRC.	LE 2B; GR B Agreement: 97.1% (A+ 35.3%|A 61.8%IA− 2.9%)
E.5: What endoscopic follow-up is recommended after treatment?    A. Patients with non-syndromic eoCRC should receive standard surveillance after the CRC curative resection (at 1 and 3 years) and should continue colonoscopies at a minimum of every 5 years.    B. Patients diagnosed with hereditary CRC syndromes should receive variant- and phenotype-specific surveillance intervals.	LE2B; GRC Agreement: 89.7% (A+ 31.0%|A 58.6%|A− 10.3%) LE 2A; GR B Agreement: 96.8% (A+ 16.1%|A 80.6% |D 3.2%)
Treatment of early-onset colorectal cancer (T)
T.1: Should the surgical approach differ for eoCRC?    A. Standard segmental resections should be offered to eoCRC. Extended surgery to reduce metachronous cancer risk should only be considered for individuals with a demonstrated risk-enhancing predisposition.    B. In the presence of a demonstrated risk-enhancing predisposition, an extended colorectal resection should be recommended by incorporating the variant-specific guidance, patient characteristics, and patient preference.    C. For individuals with eoCRC with high risk of gynecologic cancers (due to specific syndromic likely pathogenic/pathogenic variants), combined surgery with colorectal resection and prophylactic hysterectomy with or without bilateral oophorectomy may be considered (if childbearing has been completed).	LE 2B; GR C Agreement: 96.8% (A+ 22.6%|A 74.2%| D 3.2%) LE 2A; GR B Agreement: 87.0% (A+ 21.7%|A 65.2%|A− 8.7%|D 4.3%) LE 2B; GR C Agreement: 93.8% (A+ 18.8%|A 75.0%|A− 6.3%) Clarity: 92.6%
T.2: Which information should patients receive about the risk of infertility related to treatment of eoCRC?    Clinicians should provide eoCRC patients with referral to a reproductive medicine specialist before treatment and/or infertility information to discuss:    (1) The impact of cancer diagnosis and treatments on reproductive function and on potential risks for infertility.    (2) Fertility preservation options, ovarian transposition, and issues related to cryo- preservation storage after fertility preservation.    (3) Pregnancy-related and menopause-related issues after gonadotoxic treatment or underlying condition and other childbearing and parenting options.	LE 2B; GR B Agreement: 81.6% (A+ 13.2%|A 68.4%|A− 13.2%|D− 2.6%|D 2.6%)
T.3: Which criteria make patients candidates for fertility preservation?    The following criteria should be considered: the estimated risk of gonadotoxicity, the characteristics of the proposed treatment, the patient’s characteristics, and the disease stage and severity.	LE 3A; GR C Agreement: 85.7% (A+ 17.1%|A 68.6%|A− 8.6%|D+ 2.9%)
Supportive care of early-onset colorectal cancer (C)
C.1: Are there peculiarities in the management of cancer-related symptoms in eoCRC (ie, pain, fatigue, nausea, vomiting, constipation, diarrhea, cachexia)?    A. For symptom management, patients with eoCRC should be managed as recommended in the ASCO and ESMO guidelines for the general population with CRC.    B. Patients with eoCRC may be more prone to chemotherapy-induced nausea and vomiting (CINV) compared with patients with later-onset CRC, particularly female patients with low body mass index. Therefore, enhanced prophylaxis may be considered.    C. Patients with eoCRC can benefit from early personalized physical activity and nutritional support programs. Such programs could favor the maintenance and recovery of muscle mass.    D. Patients with eoCRC benefit from discussions about sexual health and dysfunction resulting from cancer or its treatment. Psychosocial and/or psychosexual counseling should be offered to improve sexual response, body image, intimacy and relationship issues, and overall sexual functioning and satisfaction.	LE 1B; GR A Agreement: 96.2% (A+ 30.8%|A 65.4%|D 3.8%) LE 3B; GR C Agreement: 100% (A+ 34.6%|A 65.4%) LE 3B; GR B Agreement: 88.0% (A+ 24.0%|A 64.0%|A− 12.0%) LE 4; GR D Agreement: 91.3% (A+ 34.8%|A 56.5%|A− 8.7%)
C.2: How should supportive care programs be organized for eoCRC patients?    For eoCRC patients, a multidisciplinary team including psychosocial support and fertility preservation experts should be made available because of the specific psychosocial and informational needs (symptom management, fears, and behavior modifications).	LE 4; GR C Agreement: 91.3% (A+ 26.1%|A 65.2%|A− 8.7%)