Immune checkpoint inhibitor restores daily function in patient with microsatellite instability (MSI)-high advanced endometrial cancer and poor performance status.

The immune checkpoint system suppresses T-cell activity. Unlike cytotoxic anticancer drugs that directly kill cells, immune checkpoint inhibitors (ICIs) are generally safer by stimulating tumor immunity. However, most clinical trials require patients to have a better performance status (PS), leaving limited evidence for those with poorer PS. In practice, patients may be classified with poor PS due to tumor-induced pain and motor dysfunction, even if major organs remain functional. Real-world data on non-small cell lung cancer has shown no safety difference between patients with PS 3/4 and those with lower PS. Approximately 20-30% of endometrial cancer cases show microsatellite instability-high (MSI-high), the highest among common malignancies. A 46-year-old patient with advanced, recurrent endometrial cancer resistant to standard chemotherapy, and PS of 4 from severe pelvic pain, was diagnosed with MSI-high. Pembrolizumab was initiated and continued for 19 courses, after which lesions had disappeared or calcified, leading to drug discontinuation. Now, 4 and a half years post-treatment, she has regained independent mobility and returned to work, and her PS has improved to approximately 1. Side effects included Grade 2 or lower thyroiditis, hypothyroidism, and hypoadrenalism, manageable with hormone replacement therapy and temporary pembrolizumab suspension. This case underscores the need to test for MSI-high/mismatch repair deficiency in endometrial cancer and to consider ICI therapy in patients with poor PS but no major organ dysfunction. In such cases, ICI can rapidly improve overall condition, a phenomenon known as a Lazarus-type response, as seen in other cancers such as non-small cell lung cancer. Supplementary Information: The online version contains supplementary material available at 10.1007/s13691-025-00752-3.