Cancer Treatment Without Surgery Is Possible: Organ Preservation With Immunotherapy in dMMR Tumors

Surgery, a cornerstone of cancer treatment, is still considered the most effective curative option for early-stage solid (organ-based) tumors. However, surgery is not always without consequences: Organ loss, substantial impairment of quality of life, and loss of functions such as fertility are serious concerns, particularly in the rectum, bladder, and esophagus. At this point, immune checkpoint inhibitors , which enable the immune system to target the tumor, challenge conventional oncology.

Published on April 27, 2025, in NEJM , a notable study shows that tumors characterized by defective DNA repair, or mismatch repair deficiency (dMMR), can be completely eliminated with an immune-activating medicine alone, potentially allowing surgery to be omitted entirely. This applies not only to rectal cancer but also to early-stage dMMR tumors in other parts of the body.

Who Might Be Suitable for Cancer Treatment Without Surgery?

• Study Design: Phase 2, multicenter prospective clinical trial

• Medicine: Dostarlimab (an anti-PD-1 agent), every 3 weeks for a total of 6 months

• Participants:

  • Cohort 1: 49 patients with early-stage (stage I–III) dMMR rectal cancer

  • Cohort 2: 54 patients with early-stage dMMR solid tumors, including gastric, colon, bladder, and gynecological tumors

• Primary objective: Nonoperative monitoring of patients achieving a clinical complete response and the durability of that response over 12 months

Patient Enrollment, Treatment, and Response Assessment

The illustration below shows how patients were distributed after study enrollment, treatment, and clinical response assessment.

Results: Can Treatment Without Surgery Become a Reality?

• Cohort 1 (Rectal Cancer):

  • 49/49 patients achieved a clinical complete response (100%)

  • 37 patients maintained a complete response for 12 months

  • Chose nonoperative monitoring: 100%

• Cohort 2 (Other dMMR Tumors):

  • 35/54 patients achieved a clinical complete response (65%)

  • 33 patients chose nonoperative monitoring

  • 2 patients nevertheless underwent surgery; neither had residual tumor

• Overall:

  • 84 of 103 patients (82%) achieved a clinical complete response

  • 82 patients (80%) did not require surgery

  • No patient lost the opportunity for curative surgery because of tumor progression

The chart aboveshows the post-treatment complete clinical responses of patients with dMMR (mismatch repair deficiency), individually by tumor type . Each bar represents one patient.

• Clinical complete response rates were high in rectal, urothelial, HPB (hepatobiliary, cholangiocarcinoma), and colon tumors.

• Rates were lower in gastric and GEJ (gastroesophageal junction) tumors.

• In dMMR tumors arising in the esophagus, small intestine, endometrium, or prostate, a clinical complete response was not achieved.

• Pathological assessment of patients who underwent surgery demonstrated either residual disease or a pathological complete response.

The Most Striking Finding: 92% Recurrence-Free Survival at 2 Years

• Across all participants, 2-year recurrence-free survival was 92%

  • Rectal cancer group: 96%

  • Other tumors: 85%

• Only 5 patients had disease recurrence, most of which was confined to lymph nodes

• Dostarlimab was restarted in 4 patients with recurrence, and the tumor completely regressed in 3

Adverse-Effect Profile: Safe and Tolerable

• In 60% of patients, only mild adverse effects (grade 1–2) occurred

  • Most common: Fatigue (23%), skin rash (21%), itching (19%)

  • Only 1 patient developed grade 4 neutropenic fever

Molecular Monitoring: Tracking Response in Real Time With ctDNA

• At the start of treatment, ctDNA positivity: 95%

• ctDNA cleared completely in every patient who achieved a clinical complete response

• ctDNA levels remained elevated in patients with recurrence or no response

• Kappa agreement coefficient: 0.76 — ctDNA and biopsy results showed strong agreement

What Does This Mean for Clinical Practice?

• This study opens the door to a major change, particularly for cancers in which surgery causes organ loss, such as rectal, bladder, and esophageal cancer.

• Surgery may be omitted entirely in early-stage solid tumors with the dMMR phenotype.

• Biomarkers such as ctDNA may provide a valuable complement to conventional imaging and endoscopic assessment.

• 3 patients with rectal cancer who gave birth during the study preserved their fertility by avoiding surgery—a particularly striking social outcome.

Conclusion: Organ Preservation Is More Than a Dream

For patients with early-stage dMMR cancers, treatment without surgery is no longer science fiction. Larger studies, perhaps randomized and specific to individual tumor types, are needed before this approach can become standard practice. Nevertheless, the available data seriously challenge assumptions about the necessity of surgery. The high efficacy of PD-1 blockade and sensitive ctDNA measurement could make a "minimally invasive revolution" possible in oncology.