What are the treatment options for colon cancer?

Management of Colon Cancer

Surgery is the cornerstone of colon cancer treatment, with the addition of adjuvant chemotherapy for stage III disease and selective use in high-risk stage II disease, while metastatic disease requires a multidisciplinary approach combining surgical resection of metastases when feasible with systemic chemotherapy, targeted therapy, or immunotherapy based on molecular profiling. 1

Preoperative Preparation

• Standard bowel preparation includes washout with hypertonic solution combined with low-residue diet 1, 2
• Intravenous broad-spectrum antibiotic prophylaxis should be administered 1, 2
• Mark planned stoma sites preoperatively if applicable 1, 2

Surgical Approach by Stage

Stage I Disease

• Surgical resection alone is curative with 5-year survival exceeding 60% 3
• No adjuvant therapy indicated for stage I disease 2
• Perform excision of primary tumor with safe margins and excision of vessels and associated mesocolon containing lymphatic channels and nodes 1, 2

Stage II Disease

• Surgery remains the primary treatment 3
• Adjuvant chemotherapy is selective, reserved only for high-risk features including T4 tumors, poorly differentiated histology, vascular/lymphatic/perineural invasion, obstruction, perforation, or <12 lymph nodes examined 2, 3
• Outside of clinical trials, use prognostic factors to guide adjuvant therapy decisions 4

Stage III Disease

• 6-month course of adjuvant chemotherapy with 5-fluorouracil (5-FU) plus folinic acid (leucovorin) is standard 2, 4
• FOLFOX (5-FU, leucovorin, and oxaliplatin) improves 3-year disease-free survival compared to 5-FU/leucovorin alone 5

Surgical Technique

• Use median laparotomy incision 1, 2
• Perform intraoperative examination of liver, pelvis, and ovaries (in women), with sampling or frozen section of suspicious masses 1, 2
• Ensure adequate lymph node harvest using complete mesocolic excision (CME) technique with high vessel ligation to achieve adequate nodal staging 2
• For tumors invading neighboring organs, perform en bloc resection rather than attempting to separate adherent structures 1, 2
• In post-menopausal women, perform prophylactic bilateral oophorectomy 1, 2
• For Lynch syndrome, perform subtotal colectomy 1, 2

Management of Metastatic Disease

Resectable Metastases (Liver or Lung)

For low-risk patients (Clinical Risk Score 0-2):

• Colon resection + simultaneous or staged resection of metastatic lesions + postoperative adjuvant chemotherapy 1, 2

For high-risk patients (Clinical Risk Score 3-5):

• Neoadjuvant chemotherapy + colon resection + simultaneous or staged resection + radiofrequency ablation (RFA) and other local treatments + postoperative adjuvant chemotherapy 1, 2

Technical requirements for resectable liver metastases:

• Sufficient residual liver volume (>30% normal liver in situ) 1, 2
• R0 resection margins with 1 cm healthy liver margin around each metastasis 1, 2

Clinical Risk Score parameters include:

• Positive lymph nodes in primary tumor 3
• Synchronous metastases or metachronous within 12 months 3

• 1 liver metastasis 3

• CEA >200 ng/mL 3
• Maximum metastasis diameter >5 cm 3

Initially Unresectable Metastases

For asymptomatic primary lesion:

• Palliative drug therapy ± colostomy 1
• Concurrent chemoradiotherapy for select T4b sigmoid colon cancers 1

For symptomatic primary lesion with potentially resectable metastases:

• Surgery for symptom relief + conversion therapy with drugs 1
• Interventional embolization/endoscopic treatment + conversion therapy with drugs 1

For symptomatic primary lesion with unresectable metastases:

• Surgery for symptom relief + palliative drug therapy 1
• Interventional embolization/endoscopic treatment + palliative drug therapy 1

Systemic Therapy Regimens

Chemotherapy Options for Unresectable Disease

First-line therapy:

• Fluoropyrimidine monotherapy 1
• Combination chemotherapy with oxaliplatin or irinotecan 1
• Triple-drug combination chemotherapy based on patient-specific factors 1

For conversion therapy (potentially resectable):

• High response rate chemotherapy regimen or combination of chemotherapy and targeted therapy 1
• Re-evaluate every 2 months for potential conversion to resectability 1, 2

Targeted Therapy

Bevacizumab (anti-VEGF):

• FDA-approved in combination with intravenous fluorouracil-based chemotherapy for first- or second-line treatment of metastatic colorectal cancer 6
• Dosing: 5 mg/kg IV every 2 weeks in combination with bolus-IFL 6
• Dosing: 10 mg/kg IV every 2 weeks in combination with FOLFOX4 6
• Last treatment should be at least 6 weeks before surgery; resume 6-8 weeks postoperatively if continuing 1, 2
• Withhold for at least 28 days prior to elective surgery 6

Cetuximab (anti-EGFR):

• Chemotherapy combined with cetuximab improves prognosis 1
• Combination of two targeted drugs is not recommended 1

Immunotherapy

For MSI-H/dMMR tumors:

• PD-1 immune checkpoint inhibitors should be prioritized for conversion therapy or palliative treatment regardless of stage 1, 3
• Based on KEYNOTE-177 study results 1

Special Considerations

T4b Colon Cancer with Obstruction

• Endoscopic stent implantation or bypass surgery to relieve obstruction 1

Locally Invasive Sigmoid Colon Cancer (T4b)

• Local radiotherapy can improve remission rate and increase probability of conversion resection 1

Elderly Patients

• Age alone should not preclude aggressive curative treatment in fit elderly patients 1, 3
• Preoperative comprehensive geriatric assessment recommended for patients >65 years requiring surgery 1
• Comorbidity, functional dependency, and older age are associated with early postoperative mortality 1

Monitoring and Follow-up

Post-treatment surveillance includes:

• Clinical examination 1, 3
• Endoscopy/colonoscopy 1, 3
• CEA monitoring 3
• Liver ultrasonography every 3 months for 2 years, then every 6 months for 5 years 1
• Annual chest X-ray 1

Evaluation of chemotherapy efficacy:

• Assess after 2-3 months of treatment 1
• Discontinue chemotherapy in the face of progressive disease 1
• Second-line chemotherapy using a different protocol is an option after progression 1

Common Pitfalls to Avoid

• Avoid inadequate bowel preparation, which compromises anastomotic integrity 2
• Avoid incomplete resection of invaded organs by always performing en bloc resection 2
• Consider neoadjuvant chemotherapy to improve resectability for borderline resectable metastatic disease 2
• Do not use bevacizumab for adjuvant treatment of colon cancer—it is not indicated 6
• Ensure adequate wound healing before resuming bevacizumab postoperatively (6-8 weeks) 1