Promising Study Indicates Some Can Skip Cancer Surgery
- A groundbreaking study shows that some patients with early-stage cancer may be able to avoid surgery and be treated with immunotherapy alone.
- This less-invasive treatment option showed promise for patients whose tumors have a specific characteristic known as mismatch repair-deficiency, or dMMR.
- After six months of treatment with immunotherapy drug dostarlimab (brand name: Jemperli), 82% of study participants had no remaining cancer.
- The treatment was particularly effective for patients with rectal cancer, and other types of gastrointestinal cancer like colon and gastric (stomach).
- Most patients who responded were able to skip surgery without compromising survival. This approach may preserve organs, reduce side effects, and improve quality of life.
- For patients, it’s important to talk to your doctor about whether your tumor is dMMR or MSI-high.
While surgery is often part of the treatment path for many cancers, many patients would prefer to avoid it and the side effects, long recovery periods, and life changes it can cause. Now, a groundbreaking study published in The New England Journal of Medicine is indicating that the immunotherapy approach could be just as successful as surgery for specific patients. The research was presented at the 2025 American Association for Cancer Research (AACR) meeting in April.
Read MoreWhat Is dMMR & Why Does It Matter?
Mismatch repair-deficiency, or dMMR, refers to a breakdown in the cell’s ability to correct mistakes during DNA replication. While this defect can lead to cancer, it also makes tumors especially vulnerable to immunotherapy, which uses the body’s own immune system to detect and destroy abnormal cells.- About 2-3% of all early-stage solid tumors (like colorectal, gastric, or endometrial cancers) have this dMMR characteristic
- These tumors are often labeled “MSI-high” (microsatellite instability-high), which also signals a potential response to immune checkpoint inhibitors like dostarlimab
About the Study: A Different Path to Cure
The phase 2 study (NCT04165772) was led by Dr. Andrea Cercek and Dr. Michael Foote at Memorial Sloan Kettering Cancer Center and included patients with early-stage dMMR cancers that were otherwise candidates for surgery.
- Total participants: 117
- Cancers studied: Rectal, colon, gastric, esophagogastric, hepatobiliary, urothelial, prostate, gynecologic, and more
- Treatment: Dostarlimab 500 mg IV every 3 weeks for 6 months (9 doses)
- Key assessments: Imaging, endoscopy (when feasible), and circulating tumor DNA (ctDNA)
After treatment, patients were evaluated for a clinical complete response (cCR) — meaning no visible signs of tumor remained on imaging or endoscopy. If that was the case, they could choose to skip surgery and be closely monitored instead.
The Results: Many Patients Avoided Surgery
Investigators found that most patients were able to avoid surgery.
Here’s a breakdown of the results:
- Rectal cancer patients: 100% had a complete clinical response
- Non-rectal solid tumor patients: 65% had a complete clinical response
- Overall (patients who completed treatment): 84 patients (82%) had no evidence of disease
- Surgery avoidance: 82 patients with cCR chose not to undergo surgery
Recurrence-free survival at 2 years was 96% for rectal cancer, 85% for non-rectal tumors, and 92% across both groups. No patients lost the opportunity for surgery due to progression.
This is, in short, a remarkable shift: a nonsurgical, organ-preserving path to remission for many patients.
The Future of Treatment
The results of the research far exceeded expectations. The team had previously published early findings showing that the first 14 patients with rectal cancer all experienced a complete response. With longer follow-up and broader inclusion, the numbers remained impressive.
“We believe this study provides a basis for treatment approaches and clinical trials in the neoadjuvant setting, where effective therapy can lead to responses, preserve organs, and drastically improve survivorship,” Dr. Luis A. Diaz Jr., head of Solid Tumor Oncology at MSKCC and senior author of the study, said in a press release.
Why Avoiding Surgery Matters
While surgery can be curative, it also comes with cost — both physical and emotional.
Possible issues include:
- Rectal surgery can result in infertility, sexual dysfunction, or the need for a permanent colostomy.
- Stomach, pancreatic, or bladder surgeries can alter digestion, nutrition, and quality of life.
- Younger patients, especially those with early-onset colorectal cancer, may fear missing work, losing insurance, or undergoing life-altering procedures in the prime of life.
Dr. Cercek, speaking at an AACR press conference, noted that these findings are particularly significant for young adults.
“Standard therapy is very morbid,” she explained. “Quality of life is incredibly important in survivorship, as people are living much, much longer.”
Who Might Benefit From This Approach?
This treatment strategy isn’t for everyone — but it may be an option for patients with early-stage, localized dMMR tumors.
To participate in the study, patients had to have stage 1-3 dMMR solid tumors (confirmed by immunohistochemistry), tumors that are technically resectable [could be removed with surgery], no distant metastases [cancer spread], and willingness to undergo frequent monitoring and follow-up.
People with the following cancer types responded well:
- Rectal
- Urothelial
- Hepatobiliary
- Colon
- Gastric
Esophagogastric junction tumors also had some response. In this trial, endometrial, prostate, and small bowel tumors did not show a complete response — but researchers are exploring ways to improve outcomes in these groups.
The study authors noted that differences in tumor microenvironments, immune cell infiltration, and microbiome composition may explain the variation. They are actively exploring these questions.
What About Side Effects?
Dostarlimab was generally well tolerated. Of the 124 patients treated, about 60% experienced only mild side effects, 35% had no side effects at all, and severe side effects such as hypothyroidism (when the thyroid doesn’t make enough thyroid hormone) or lung infection, were only seen in a few patients and were reversible.
Common reported side effects included:
- Fatigue (23%)
- Rash or dermatitis (21%)
- Itching (19%)
- Mild diarrhea
- Nausea
- Joint pain
These were typically short-lived and manageable.
A New Role for ctDNA: A “Liquid Biopsy” to Monitor Response
One of the most innovative aspects of the study was how researchers used circulating tumor DNA (ctDNA) to monitor response in real time. This test, which detects tumor-specific mutations in a blood sample, may help doctors track disease status without invasive biopsies — especially in tumors that can’t be easily reached with a scope.
- At baseline, 95% of patients had detectable ctDNA
- In those with a complete response, ctDNA cleared within a median of 1.4 months
- Among patients whose cancer came back, ctDNA remained elevated
What Comes Next?
These findings are game-changing — but they’re not the final word. The authors note that longer follow-up and additional randomized trials may be needed before this approach becomes standard across all cancer centers.
Still, for patients with early-stage dMMR tumors, this is real, immediate hope.
“These findings are very important because it’s likely these patients do not need surgery or radiation if treated first with immunotherapy for a sufficient amount of time,” said Dr. Cercek.
Questions To Ask Your Doctor
If you or a loved one has been diagnosed with a mismatch repair-deficient cancer, especially at an early stage, this study may open the door to a future without surgery.
Here’s what to ask your doctor:
- Is my tumor dMMR or MSI-high?
- Am I eligible for neoadjuvant (before surgery) immunotherapy?
- Can I be monitored for a complete clinical response with imaging or ctDNA?
- What are the risks of skipping surgery in my specific case?
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