What treatment is recommended for a patient with stage II colon cancer and vascular invasion, but no lymph node involvement, after surgical resection?

Treatment for Stage II Colon Cancer with Vascular Invasion

Adjuvant chemotherapy may be offered to patients with stage II colon cancer and lymphovascular invasion (vascular invasion), as this represents a high-risk feature that increases recurrence risk, though the survival benefit is modest and should be discussed thoroughly with the patient. 1

Risk Stratification

Lymphovascular invasion (LVI) is explicitly recognized as a high-risk feature in stage II colon cancer that warrants consideration of adjuvant chemotherapy. 1

• Stage IIA (T3) tumors with LVI are classified as high-risk, distinguishing them from low-risk stage II patients who should not receive routine chemotherapy. 1

• The presence of multiple high-risk factors increases recurrence risk substantially—5-year disease-free survival drops to 74.8% with two or more risk factors compared to 87.3% with only one risk factor. 1

• Other high-risk features to assess include: fewer than 12 lymph nodes examined, poorly or undifferentiated tumor grade, perineural invasion, intestinal obstruction, tumor perforation, and grade BD3 tumor budding (≥10 buds). 1

Treatment Recommendation Algorithm

Step 1: Confirm adequate staging

• Verify that at least 12 lymph nodes were examined in the surgical specimen. 1
• If fewer than 12 nodes were sampled, this adds an additional high-risk feature. 1

Step 2: Assess microsatellite instability (MSI) status

• Test for mismatch repair deficiency (dMMR) or high microsatellite instability (MSI-H). 1, 2, 3
• If dMMR/MSI-H is present, fluoropyrimidine-only chemotherapy should NOT be routinely offered, as harms outweigh benefits in this molecular subtype. 1, 2, 3
• For dMMR/MSI-H tumors with T4 stage or multiple other high-risk features (excluding poor differentiation alone), oxaliplatin-containing chemotherapy may be considered. 1

Step 3: Count total number of high-risk features

• Lymphovascular invasion alone may justify chemotherapy discussion, but the presence of additional risk factors strengthens the indication. 1
• The absolute benefit of chemotherapy in stage II disease is small (approximately 1-2% improvement in 5-year survival for low-risk patients, potentially higher for high-risk subgroups). 1

Recommended Chemotherapy Regimen

For microsatellite stable (MSS) or proficient MMR (pMMR) tumors:

• Fluoropyrimidine monotherapy for 6 months is the standard approach. 2, 3, 4
• Options include capecitabine 1250 mg/m² orally twice daily on days 1-14 every 21 days, or infusional 5-FU/leucovorin (de Gramont regimen). 1, 5
• Capecitabine is at least as effective as bolus 5-FU/LV with less myelosuppression but more hand-foot syndrome, and avoids central venous catheter complications. 4

Regarding oxaliplatin addition:

• The addition of oxaliplatin to fluoropyrimidine therapy is NOT routinely recommended for stage II disease, even with high-risk features including LVI. 1, 4
• Oxaliplatin may be considered only through shared decision-making in patients with multiple high-risk factors or younger age, but does not provide proven overall survival benefit and increases toxicity (particularly peripheral neuropathy). 1, 4
• The MOSAIC trial showed only a non-significant trend for improved disease-free survival in high-risk stage II patients with oxaliplatin, without overall survival benefit. 1

Important Caveats and Pitfalls

Common pitfall: Overtreatment of stage II disease

• The absolute survival benefit of chemotherapy in stage II colon cancer is small, and harms may outweigh benefits in unselected populations. 1, 4
• Research data specifically examining vascular invasion as an isolated risk factor showed no clear survival benefit from adjuvant chemotherapy when it was the only high-risk feature present. 6

Timing considerations:

• Chemotherapy should be initiated within 6-8 weeks of surgery, ideally as soon as the patient has recovered from surgical complications. 1, 4

Age considerations:

• Age alone should NOT alter treatment recommendations—elderly patients tolerate capecitabine well, and younger low-risk patients should not receive chemotherapy based solely on age. 1, 4

Patient counseling points:

• The decision requires thorough discussion of the modest absolute benefit versus chemotherapy-related toxicity. 1, 4
• For patients with LVI as the sole high-risk feature, observation may be reasonable after informed discussion. 6
• The presence of two or more high-risk features (including LVI) strengthens the case for chemotherapy. 1