What is the recommended management of colon adenocarcinoma in an adolescent, including staging, surgery, systemic therapy, fertility preservation, and follow‑up?

Treatment of Colon Adenocarcinoma in Adolescents

Adolescents with colon adenocarcinoma should be managed by a multidisciplinary team at specialized centers with expertise in both adolescent/young adult (AYA) oncology and colorectal cancer, with treatment following standard adult colon cancer protocols while incorporating AYA-specific considerations including fertility preservation, genetic testing, and psychosocial support. 1

Immediate Pre-Treatment Evaluation

Mandatory Assessments Before Initiating Therapy

• Comprehensive genetic testing must be performed immediately after diagnosis using multiplex gene panels, regardless of family history, as germline mutations are common in young-onset colon cancer and will inform surgical decisions 2
• Fertility preservation counseling is required before any cancer-directed therapy (surgery, chemotherapy, or radiation) for all adolescents of reproductive age 1, 2
• Pregnancy testing must be completed in female adolescents before starting treatment 1
• Psychosocial assessment addressing developmental issues specific to adolescents including education, peer relationships, and family dynamics 1

Staging Workup

• Complete colonoscopy with biopsy confirmation 1
• CBC, comprehensive metabolic panel, and baseline CEA 1
• Contrast-enhanced CT chest/abdomen/pelvis 1
• Molecular testing: MSI/MMR status, RAS mutations (KRAS/NRAS), and BRAF V600E 3, 2

Surgical Management

Timing of Genetic Results

Genetic testing results should be obtained pre-operatively whenever possible, as they directly impact surgical decision-making (e.g., extended resection for Lynch syndrome) 2

Surgical Approach by Stage

• Stage I-III resectable disease: Colectomy with en bloc removal of regional lymph nodes, examining minimum 12 lymph nodes 1, 4
• Obstructing lesions: One-stage colectomy preferred; stenting or diversion as alternatives 1
• Stage IV with resectable metastases: Synchronous or staged resection after neoadjuvant chemotherapy (2-3 months FOLFOX, FOLFIRI, or CapeOX ± bevacizumab or cetuximab if RAS wild-type) 1

Adjuvant Chemotherapy Decision Algorithm

Stage I

• No adjuvant therapy required after complete surgical resection 4

Stage II

• High-risk features (T4, perforation, obstruction, <12 lymph nodes examined, poorly differentiated histology, lymphovascular invasion): Consider adjuvant chemotherapy 4
• MSI-high tumors: Observation preferred; chemotherapy may be detrimental 2
• Standard-risk: Observation acceptable 4

Stage III

• All patients require adjuvant chemotherapy: FOLFOX or CapeOX for 3-6 months 4
• Adolescents tolerate full-dose combination regimens better than older adults; avoid dose reductions 3

Stage IV

• MSI-high/dMMR: First-line pembrolizumab or nivolumab monotherapy (superior to chemotherapy) 3
• MSI-stable: FOLFOX, FOLFIRI, or CapeOX ± bevacizumab; add cetuximab if RAS wild-type 1, 3

Fertility Preservation Specifics

Female Adolescents

• Oocyte or embryo cryopreservation before chemotherapy initiation 1, 5
• Ovarian tissue cryopreservation for prepubertal patients or when chemotherapy cannot be delayed 1
• GnRH agonists during chemotherapy (category 2B evidence for protection) 1
• Risk stratification: Alkylating agents and pelvic radiation pose highest gonadotoxicity risk 1

Male Adolescents

• Sperm banking before any chemotherapy 5, 6
• Testicular tissue cryopreservation for prepubertal patients (experimental) 5

Clinical Trial Enrollment

Enrollment in clinical trials is especially critical for adolescents, as only 10% of 15-19 year-olds and 1-2% of 20-39 year-olds currently participate, contributing to poor outcome improvements in this age group 1

Location of Care Considerations

• Pediatric cancer centers enroll 35% of adolescents in trials versus 12% at adult centers 1
• Specialized AYA centers should be considered when feasible, though only 43% of AYA patients currently receive care at such centers 1
• For colon adenocarcinoma specifically, adult protocols are appropriate, but the center must have AYA-specific supportive services 1

Surveillance After Curative Treatment

Years 1-2

• CEA every 3 months 1
• CT chest/abdomen/pelvis every 3-6 months 1
• Colonoscopy at 1 year (or 3-6 months if obstructing lesion prevented preoperative colonoscopy) 1

Years 3-5

• CEA every 6 months 1
• CT chest/abdomen/pelvis every 6-12 months 1
• Colonoscopy: If advanced adenoma found, repeat in 1 year; if no advanced adenoma, repeat in 3 years, then every 5 years 1

Hereditary Syndrome Surveillance

• Lynch syndrome patients require syndrome-specific screening for extracolonic cancers (endometrial, gastric, urinary tract, ovarian) starting in early adulthood 1, 2
• FAP patients (if applicable) require upper endoscopy starting age 20-25 years and annual thyroid examination 1

Critical Pitfalls to Avoid

• Never delay fertility preservation discussions until after treatment initiation; 27% of young adults lack documentation of these discussions 6
• Never assume family history is negative; obtain detailed three-generation pedigree as up to 20% of colon cancers have familial clustering 1
• Never treat MSI-high stage IV disease with chemotherapy alone; immunotherapy is superior 3
• Never perform inadequate lymph node harvest; minimum 12 nodes required for accurate staging 1, 4
• Avoid dose reductions in adolescents who tolerate full-intensity regimens better than older adults 3