Colon to Rectum
J Clin Oncol. 2023;41(8):1541−52
Preoperative chemotherapy for operable colon cancer: Mature results of an international randomized controlled trial
Purpose: Neoadjuvant chemotherapy (NAC) has potential advantages over standard postoperative chemotherapy for locally advanced colon cancer but requires formal evaluation.
Methods: Patients with radiologically staged T3−4, N0−2, M0 colon cancer were randomly allocated (2:1) to 6 weeks oxaliplatin-fluoropyrimidine preoperatively plus 18 postoperatively (NAC group) or 24 weeks postoperatively (control group). Patients with RAS wild-type tumors could also be randomly assigned 1:1 to receive panitumumab or not during NAC. The primary end point was residual disease or recurrence within 2 years. Secondary outcomes included surgical morbidity, histopathologic stage, regression grade, completeness of resection, and cause-specific mortali-ty. Log-rank analyses were by intention-to-treat.
Results: Of 699 patients allocated to NAC, 674 (96%) started and 606 (87%) completed NAC. In total, 686 of 699 NAC patients (98.1%) and 351 of 354 control patients (99.2%) underwent surgery. 30 patients (4.3%) allocated to NAC developed obstructive symptoms requiring expedited surgery, but there were fewer serious postoperative complications with NAC than with control. NAC produced marked T and N downstaging and histologic tumor regression (all p < 0.001). Resection was more often histopathologically complete: 94% (648/686) versus 89% (311/351), p < 0.001. Fewer NAC than control patients had residual or recurrent disease within 2 years (16.9% [118/699] vs. 21.5% [76/354]; rate ratio = 0.72, 95% confidence interval: 0.54−0.98; p = 0.037). Tumor regression correlated strongly with freedom from recurrence. Panitumumab did not enhance the benefit from NAC. Little benefit from NAC was seen in mismatch repair-deficient tumors.
Conclusion: Six weeks of preoperative oxaliplatin-fluoropyrimidine chemotherapy for operable colon cancer can be delivered safely, without increasing perioperative morbidity. This chemotherapy regimen, when given preoperatively, produces marked histopathologic downstaging, fewer incomplete resections, and better 2-year disease control. Histologic regression after neoadjuvant chemotherapy (NAC) is a strong predictor of lower postoperative recurrence risk and so has potential use as a guide for postoperative therapy. Six weeks of NAC should be considered as a treatment option for locally advanced colon cancer.
DOI: 10.1200/jco.22.00046