Significant benefit with neoadjuvant chemotherapy in patients with resectable colon cancer

March 2023 Cancer trials Robin van Amersfoort
Colon cancer. Colon disease concept

The use of neoadjuvant chemotherapy in the treatment of resectable colon cancer is controversial. An international randomised controlled trial performed by the American Society of Clinical Oncology aimed to evaluate the efficacy of neoadjuvant chemotherapy in improving survival outcomes for these patients. The results, published in the Journal of Clinical Oncology, showed a significant improvement in disease-free survival with the use of neoadjuvant chemotherapy over surgery alone in patients with operable colon cancer.

Despite the use of surgery as the standard treatment for operable colon cancer, the risk of relapse remains high.1 Preoperative or neoadjuvant chemotherapy (NAC) has substantially improved outcomes in other gastrointestinal cancers.2 However, there is a lack of consensus on the benefit of preoperative chemotherapy in the context of colon cancer. Therefore, this randomised controlled trial aimed to provide evidence of the benefit of using NAC in operable colon cancer patients.3

Methods

Eligible patients had histologically confirmed, operable colon cancer, radiologically staged T3-4, N0-2, M0. Patients were randomised in a 2:1 ratio to NAC (n=699) plus surgery or surgery alone (n=354). The first group received 6 weeks of oxaliplatin-fluoropyrimidine preoperatively and 18 weeks postoperatively. The latter received the same chemotherapy for 24 weeks postoperatively (control group). The primary endpoint was overall survival, and secondary endpoints included disease-free survival, toxicity, and response rate.

Results

In total, 98.1% and 99.2% of patients from the NAC and control groups underwent surgery, respectively. In the NAC group, tumour (T) and lymph node involvement (N) were downstaged compared to the control group (p<0.001), and results indicated histologic tumour regression compared to the control group (p<0.001). Furthermore, the resection was more often histologically complete in the NAC group than in the control group (94% vs. 89%, p<0.001). In the NAC group, patients had fewer residual or recurrent disease within 2 years (16.9% vs. 21.5, p=0.037). Tumour regression was strongly correlated with freedom from recurrence.

Conclusion

Administering oxaliplatin-fluoropyrimidine chemotherapy for six weeks before surgery for operable colon cancer is safe and does not raise perioperative morbidity. Additionally, this strategy causes significant histopathologic downstaging, reduces the number of incomplete resections, and improves the 2-year disease control. After preoperative chemotherapy, the histologic regression has a strong correlation with lower postoperative recurrence risk and could be used as a guide for postoperative therapy. Consequently, six weeks of NAC should be considered as a treatment option for locally advanced colon cancer treatment.

References       

  1. Grothey A, Sobrero AF, Shields AF, et al. Duration of adjuvant chemotherapy for stage III colon cancer. New England Journal of Medicine. 2018; 378: 1177-1188.
  2. Cunningham D, Allum WH, Stenning SP, et al. For the MAGIC trial participants: Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. New England Journal of Medicine. 2006; 355: 11-20.
  3. Morton D, Seymour M, Magill L, et al. Preoperative Chemotherapy for Operable Colon Cancer: Mature Results of an International Randomized Controlled Trial. Journal of Clinical Oncology. 2023; 41; 1541-1552.