Treatment Options for Stage II pMMR Colon Cancer
For stage II pMMR colon cancer, fluoropyrimidine monotherapy is recommended for average-risk patients, while combination chemotherapy regimens are recommended for high-risk patients. 1
Risk Stratification
The first step in determining treatment is to assess the risk level of the stage II pMMR colon cancer:
Low-risk Stage II pMMR
- T3N0M0 without high-risk features
Average-risk Stage II pMMR
- T3N0M0 without high-risk features
High-risk Stage II pMMR
- T3N0M0 with high-risk features, or
- T4N0M0
High-risk features include:
- Lymph node sampling <12
- Poorly differentiated histology (high grade)
- Vascular invasion
- Lymphatic invasion
- Perineural invasion
- Tumor presentation with obstruction
- Tumor site perforation
- Positive or uncertain margins
- Inadequate margin distance
- pT4 stage
- High preoperative CEA levels 1
Treatment Algorithm
1. Surgical Management
- Wide surgical resection with anastomosis is the primary treatment 1
- Resection should include at least 5 cm of colon on either side of the tumor 1
- Complete regional lymph node dissection with at least 12 lymph nodes examined 1
- Laparoscopic approach is a valid alternative to open surgery with similar oncological outcomes 2
2. Adjuvant Chemotherapy Based on Risk
Low-risk Stage II pMMR:
- Observation is recommended (no adjuvant chemotherapy) 1
Average-risk Stage II pMMR:
- Fluoropyrimidine monotherapy (Category 1A) 1
- Options include:
- Capecitabine 1250 mg/m² PO twice daily (q day 22)
- 5-FU with leucovorin (LV5-FU2, de Gramont regimen)
- Options include:
High-risk Stage II pMMR:
- Combination chemotherapy regimen (Category 1A) 1
- Options include:
- XELOX: Capecitabine 1000 mg/m² PO twice daily days 1-15, oxaliplatin 130 mg/m² day 1 (q day 22)
- mFOLFOX6: 5-FU 400 mg/m² IV bolus and LV 400 mg/m² IV followed by 5-FU 2400 mg/m² IV 46h-infusion, oxaliplatin 85 mg/m² day 1
- FOLFOX4: 5-FU 400 mg/m² IV bolus and LV 200 mg/m² IV followed by 5-FU 600 mg/m² IV 22h-infusion days 1+2, oxaliplatin 85 mg/m² day 1
- Options include:
Special Considerations
MMR/MSI Status Implications
- pMMR (proficient mismatch repair) status indicates potential benefit from adjuvant chemotherapy, unlike dMMR tumors 1
- pMMR tumors have a higher risk of recurrence compared to dMMR tumors 1
- The addition of oxaliplatin to fluoropyrimidine therapy in high-risk stage II pMMR patients remains controversial:
Duration of Treatment
- Standard duration is 6 months for adjuvant chemotherapy 1
- For high-risk stage II patients receiving CAPEOX (XELOX), 3 months may be considered based on IDEA study results 1
Timing of Adjuvant Therapy
- Should be initiated as soon as possible after postoperative recovery
- Generally starts around 3 weeks post-surgery
- Should not be started later than 2 months postoperatively 1
Important Caveats
- Age considerations: Limited evidence shows benefit of adding oxaliplatin to 5-FU/LV in patients aged 70 or older 1
- Toxicity management: In case of clinically relevant neurotoxicity with oxaliplatin, it should be discontinued while continuing the fluoropyrimidine component 1
- Infusional vs. bolus 5-FU: Infusional 5-FU is preferred over bolus due to better tolerability, especially in elderly patients 1
- Oral vs. IV fluoropyrimidines: Oral fluoropyrimidines (capecitabine) should be preferred when applicable as they don't require central venous access 1
- FLOX regimen: Generally not recommended due to associated toxicity and lack of survival benefit 1
By following this algorithm and considering these factors, clinicians can make evidence-based decisions for the management of stage II pMMR colon cancer patients, optimizing outcomes while minimizing unnecessary treatment toxicity.