Treatment of Stage IA Endometrial Cancer with Positive Peritoneal Washings and MMR Deficiency

Primary Treatment Strategy

Immunotherapy is strongly recommended as the initial approach for dMMR/MSI-H tumors across cancer types, with PD-1 inhibitors demonstrating superior outcomes compared to conventional chemotherapy, according to the American College of Obstetricians and Gynecologists 1
Pembrolizumab, dostarlimab, or nivolumab are all appropriate first-line options for dMMR/MSI-H endometrial cancer, as recommended by the National Comprehensive Cancer Network 1
Dostarlimab achieved 100% clinical complete response rates in locally advanced rectal cancer with dMMR status, with zero progression or recurrence at 2024 data analysis, demonstrating the remarkable efficacy of immunotherapy in MMR-deficient tumors, as reported by the American Society of Clinical Oncology 1

dMMR tumors show significantly reduced response to traditional chemotherapy, with response rates of only 5% versus 44% in MMR-proficient tumors, according to the European Society for Medical Oncology 2, 3, 4, 5
Preclinical studies demonstrate that dMMR colorectal cancer cell lines are at least 18-fold more resistant to 5-fluorouracil than pMMR cell lines, as reported by the American Association for Cancer Research 6
The chemotoxicity induced by 5-FU treatment is partially mediated by the MMR pathway itself; when this pathway is deficient, the mechanism of chemotherapy action is compromised, according to the National Cancer Institute 6

If rapid tumor downstaging is urgently needed, chemotherapy with or without monoclonal antibodies may be preferable over immunotherapy in selected cases, as 29.4% of patients on pembrolizumab had primary progressive disease versus 12.3% on chemotherapy, as reported by the European Society for Medical Oncology 2, 3
For patients who fail immunotherapy, combination chemotherapy regimens may be considered as second-line treatment, according to the National Comprehensive Cancer Network 2, 3, 4, 5

No grade 3 or higher adverse events were reported with dostarlimab monotherapy in dMMR tumors, indicating excellent tolerability, as reported by the American Society of Clinical Oncology 1
Regular surveillance imaging and clinical assessment should be performed every 3-6 months during the first 2 years, according to the National Comprehensive Cancer Network 1
Immune-related adverse events should be monitored and managed according to standard immunotherapy protocols, as recommended by the Society for Immunotherapy of Cancer 1