Immunotherapy & Chemo: 50% Lower Recurrence in Colon Cancer

Colon cancer is the third most prevalent form of cancer in the U.S., and its incidence is increasing among younger adults, particularly those younger than 50. While colon cancer screening has helped prevent and detect it before spreading, major advancements in treating colon cancer have been limited.

Now, new research led by Mayo Clinic Comprehensive Cancer Center found that adding immunotherapy to chemotherapy after surgery for patients with stage 3 (node-positive) colon cancer—and with a specific genetic makeup called deficient DNA mismatch repair (dMMR)—was associated with a 50% reduction in cancer recurrence and mortality compared to chemotherapy alone.

Approximately 15% of people diagnosed with colon cancer exhibit dMMR, and, to date, these tumors have shown reduced sensitivity to chemotherapy. The results of the multicenter study were presented during a plenary session at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.

“The findings from our study represent a major advance in the adjuvant treatment of dMMR stage 3 colon cancer and will now change clinical practice,” says Frank Sinicrope, M.D., a Mayo Clinic oncologist who led the study published in the New England Journal of Medicine. “It’s very rewarding to be able to offer our patients a new treatment regimen that can reduce the risk of recurrence and improve their chances of survival.”

Until now, the standard treatment after surgery for any stage 3 colon cancer has been chemotherapy. However, the researchers note that approximately 30% of patients with stage 3 tumors experience cancer recurrence despite this treatment.

The clinical trial enrolled 712 patients with dMMR stage 3 colon cancer that had been surgically removed and who had cancer cells in their lymph nodes. The immunotherapy given in this study was an immune checkpoint inhibitorknown as atezolizumab, which reactivates a person’s anti-tumor immunity to enable the killing of cancer cells, which are responsible for cancer recurrence and spread. The patients—who lived in the U.S. and Germany—were randomized to receive chemotherapy for six months along with immunotherapy, with the immunotherapy continued alone for another six months versus the other study arm being chemotherapy alone.

Dr. Sinicrope and others previously studied patients with the type of colon cancer evaluated in the clinical trial, in which tumor cells cannot properly repair errors that occur when DNA is copied, due to dMMR. They noted that these patients’ tumors showed a striking increase in inflammatory cells, including immune cells that are targets of immune checkpoint inhibitors. These findings provided the rationale for using immune checkpoint inhibitors as a strategy to enable immune cells to be more effective in attacking and killing cancer cells.

Based on the data from the clinical trial, the combination of atezolizumab and chemotherapy represents a new standard treatment for stage 3 deficient mismatch repair colon cancer. The guidelines developed by the National Comprehensive Cancer Networka nonprofit organization consisting of 33 leading cancer centers, including Mayo Clinic, have been updated to include this treatment recommendation. The guidelines also include patients with high-risk stage 2 colon cancer where the tumor invades or adheres to adjacent structures but does not involve lymph nodes.

The study included patients with Lynch syndromethe most common form of hereditary colon cancer, as these patients have tumors that show dMMR and are typically diagnosed at a younger age.

“We’re changing the paradigm in colon cancer treatment. By using immunotherapy at earlier stages of disease, we are achieving meaningful benefits for our patients,” says Dr. Sinicrope.