Immunotherapy could replace surgery, enabling patients to retain their organs and enhance their quality of life

New results from a clinical trial led by Memorial Sloan Kettering Cancer Center (MSK), gastrointestinal oncologists Andrea Cercek, MD, and Luis Diaz Jr., MD, demonstrate how immunotherapy alone can allow people with mismatch repair-deficient (MMRd) cancers to avoid surgery and preserve their quality of life.

The results, presented at the American Association of Cancer Research Annual Meeting (AACR 2025) and published simultaneously in the New England Journal of Medicine, found that 80% of patients did not require surgery, radiation, or chemotherapy after six months of treatment with immunotherapy alone.

"This study shows that immunotherapy can replace surgery, radiation, and chemotherapy for mismatch repair-deficient solid tumors, which could help patients preserve their organs and avoid the harsh side effects of chemo and radiation," said Dr. Cercek, gastrointestinal oncologist and co-director of the Center for Young Onset Colorectal and Gastrointestinal Cancer at MSK.

"Preserving a patient's quality of life while also successfully achieving positive results in eliminating their cancer is the best possible outcome. They can return to their daily routines and maintain their independence."

This phase 2 trial is an extension of a groundbreaking study in which all rectal cancer patients treated with the immunotherapy dostarlimab experienced a complete clinical response, meaning their tumors disappeared. The U.S. Food and Drug Administration (FDA) gave dostarlimab "Breakthrough Therapy Designation" for the treatment of this type of rectal cancer in December 2024.

The updated trial included 103 patients with stage 1–3 cancer; 49 with rectal cancer; and 54 with non-rectal cancers, including gastroesophageal, hepatobiliary, colon, genitourinary, and gynecologic. For six months, they were treated with Jemperli (dostarlimab), a PD-1 inhibitor made by GSK. Checkpoint inhibitors work by helping the immune system recognize and attack cancer cells.

The results of this trial showed that 80% of patients with several types of cancer were successfully treated with only immunotherapy. The standard of care for many cancers that have this specific MMRd genetic mutation has been surgery, radiation, and chemotherapy.

Still, the patients who responded positively did not require surgery to remove an organ and did not experience chemotherapy or radiation, which improved their quality of life. This trial is the first time that immunotherapy has been shown to replace surgery for a variety of solid tumors.

"The majority of patients in the trial saw their tumors completely disappear," said Dr. Diaz, gastrointestinal oncologist and Head of the Division of Solid Tumor Oncology at MSK. "These results could change how we treat some cancers. Current treatments like surgery, radiation, and chemotherapy can seriously affect quality of life. For example, treating rectal cancer this way can lead to infertility and problems with bowel, bladder, and sexual function, as well as other daily challenges."

Maureen Sideris, who was diagnosed with gastroesophageal junction cancer in 2022 and was able to avoid surgery, said, "I was afraid that if I got surgery on my esophagus, I wouldn't be able to talk for a while, which would be awful. To have immunotherapy alone was just amazing."

The study also found that ctDNA testing, using Haystack MRD, a tumor-informed approach from Quest Diagnostics, was a "reliable liquid biopsy" that identified complete response at 1.4 months. Results suggest that in the future, ctDNA will play an important role in treatment response assessment as novel therapies expand into the neoadjuvant setting, particularly when tumors are located in areas where direct visualization or biopsy is not practical.

For Drs. Cercek and Diaz, the goal is now to expand this approach to even more types of cancer.

This article was originally published on MedicalXpress Breaking News-and-Events.