What is the recommended adjuvant chemotherapy regimen for a patient with well-differentiated sigmoid adenocarcinoma staged as pT4aN0M0 (pathological T4a, node-negative, metastasis-negative)?

Adjuvant Chemotherapy for Well-Differentiated Sigmoid Adenocarcinoma pT4aN0M0

For well-differentiated sigmoid adenocarcinoma staged pT4aN0M0, adjuvant chemotherapy with FOLFOX (oxaliplatin plus infusional 5-FU/leucovorin) or CAPOX (capecitabine plus oxaliplatin) is strongly recommended, as T4 stage represents a high-risk feature for recurrence in node-negative colon cancer. 1, 2

Rationale for Treatment

• T4 disease is explicitly identified as a high-risk factor in stage II colon cancer that warrants consideration of adjuvant chemotherapy, even in the absence of nodal involvement 1
• The ESMO guidelines specifically list T4 tumors among high-risk features including poorly differentiated histology, vascular invasion, lymphatic vessel invasion, obstruction, perforation, and inadequate lymph node examination (≤12 nodes) 1
• Well-differentiated histology does not negate the high-risk designation conferred by T4a staging, as tumor depth of invasion through the serosa carries significant recurrence risk 1

Recommended Regimens

First-Line Option: FOLFOX

• Oxaliplatin 85 mg/m² IV over 2 hours on day 1, plus leucovorin 200 mg/m² IV over 2 hours on days 1-2, plus 5-FU 400 mg/m² IV bolus followed by 600 mg/m² as 22-hour infusion on days 1-2, repeated every 2 weeks for 12 cycles (6 months total) 2
• The MOSAIC trial demonstrated that FOLFOX4 significantly improved 3-year disease-free survival compared to 5-FU/LV alone in stage II and III colon cancer, with a hazard ratio of 0.80 (95% CI 0.68-0.93, p=0.003) 2
• The combination of 5-FU/LV plus oxaliplatin significantly improves disease-free survival at 3 years compared with 5-FU/LV alone 1

Alternative Option: CAPOX

• Capecitabine 1000 mg/m² orally twice daily on days 1-14, plus oxaliplatin 130 mg/m² IV on day 1, repeated every 3 weeks for 8 cycles 1, 3
• Capecitabine has been shown to be at least as effective and less toxic than bolus 5-FU/LV 1
• This oral regimen may be preferred in elderly patients or those seeking to minimize infusion center visits 3

Treatment Duration and Monitoring

• Complete all 12 cycles of FOLFOX (6 months) or 8 cycles of CAPOX (6 months) to achieve optimal disease-free survival benefit 2
• The median relative dose intensity in the MOSAIC trial was 80.5% for oxaliplatin and 84.4% for 5-FU, with a median of 11 cycles completed 2
• Monitor complete blood count, renal function, liver function tests, and assess for peripheral neuropathy at each cycle 2, 3

Key Considerations

• Adequate lymph node examination (≥15 nodes) is essential for accurate staging; if fewer than 12 nodes were examined, this further strengthens the indication for adjuvant therapy 1
• The presence of other high-risk features (vascular invasion, lymphatic invasion, obstruction, or perforation at presentation) would provide additional rationale for treatment, though T4a staging alone is sufficient 1
• Oxaliplatin-based regimens are superior to fluoropyrimidine monotherapy for high-risk stage II disease, making single-agent capecitabine inadequate for T4a tumors 1, 2

Common Pitfalls to Avoid

• Do not withhold adjuvant chemotherapy based solely on well-differentiated histology when T4 staging is present, as depth of invasion supersedes grade as a risk factor 1
• Do not confuse stage II (node-negative) with low-risk disease; T4aN0M0 is stage IIB with approximately 72% 5-year survival, significantly worse than T3N0M0 (stage IIA, >80% survival) 1
• Ensure adequate staging with examination of at least 12-15 lymph nodes before confirming N0 status 1
• Carboplatin should not be substituted for oxaliplatin in the adjuvant colon cancer setting, as the evidence base specifically supports oxaliplatin-containing regimens 2