Neoadjuvant Chemotherapy vs Upfront Surgery in Locally Advanced Colon Cancer

Key Takeaways

• The preoperative approach was not associated with better 3-year disease-free survival than upfront surgery.
• The neoadjuvant strategy was feasible and safe, was associated with tumor downstaging, and left fewer patients meeting criteria for adjuvant chemotherapy.
• Postoperative complications, adverse events, and quality of life were similar between groups, while exploratory mismatch repair analyses suggested different disease-free survival estimates by mismatch repair status.

In locally advanced colon cancer, 3-year disease-free survival was 87% with upfront surgery and 83% with preoperative capecitabine and oxaliplatin, without a significant difference. The randomized phase III NeoCol trial compared these open-label strategies in patients with computed tomography-staged locally advanced colon cancer without distant metastases. It assessed whether chemotherapy before resection improved outcomes over initial surgery. The primary comparison showed no disease-free survival benefit with the preoperative approach.

The multicenter study enrolled patients at 9 hospitals in Denmark, Norway, and Sweden from October 14, 2013, to November 27, 2020. Eligible participants had computed tomography-staged locally advanced colon cancer, Eastern Cooperative Oncology Group performance status 0 to 2, and no distant metastases. Of 250 enrolled patients, 248 were included in the analyses; median age was 66 years, and 111 were women and 137 were men. Patients were assigned to upfront surgery with adjuvant chemotherapy if indicated or to 3 cycles of neoadjuvant capecitabine and oxaliplatin before surgery, with postoperative chemotherapy if indicated. The primary endpoint was 3-year disease-free survival in this nonmetastatic, locally advanced population.

The investigators did not find a disease-free survival advantage with preoperative chemotherapy, with the primary comparison yielding P = .36. Fewer patients in the neoadjuvant group met adjuvant chemotherapy criteria after surgery, at 59% versus 73% after upfront surgery, a difference that reached statistical significance (P = .02). Tumor downstaging was also observed with neoadjuvant treatment. Together, these findings showed changes in pathologic or postoperative treatment-related features without improvement in the primary endpoint.

Postoperative complications were similar between groups, and adverse event profiles were comparable. Quality of life also appeared similar across the two treatment approaches during follow-up. In exploratory analyses, disease-free survival estimates appeared higher after upfront surgery among patients with mismatch repair-deficient tumors. That biomarker signal remained exploratory rather than confirmatory, leaving the question unresolved.

Neoadjuvant capecitabine and oxaliplatin was feasible and safe within the trial, even though it did not improve disease-free survival. The results combined a negative primary endpoint with downstaging and less frequent eligibility for postoperative chemotherapy. Follow-up for the disease-free survival endpoint extended to 3 years, and data were analyzed from January 2024 to October 2024.