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

TL;DR

An immune checkpoint inhibitor helped a patient with advanced endometrial cancer regain mobility and return to work despite poor initial health.

Contribution

This case demonstrates the potential of immune checkpoint inhibitors in patients with poor performance status and MSI-high endometrial cancer.

Findings

The patient regained independent mobility and returned to work after ICI treatment.

ICI therapy led to lesion disappearance or calcification in a patient with MSI-high endometrial cancer.

Side effects were manageable with hormone replacement and temporary drug suspension.

Abstract

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.

The online version contains supplementary material available at 10.1007/s13691-025-00752-3.

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