Neoadjuvant Pembrolizumab Enables Successful Downstaging and Resection of Borderline Resectable MSI-H/dMMR Pancreatic...

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a poor prognosis. While immunotherapy has shown limited efficacy in most PDAC cases due to an immunosuppressive tumour microenvironment, tumours with microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) status exhibit increased responsiveness to immune checkpoint inhibitors.

We report the case of a 45-year-old woman with Lynch syndrome who was diagnosed with MSI-H/dMMR PDAC during routine surveillance. Given the borderline resectable nature of her tumour and previous chemotherapy-related neurotoxicity, she was treated with neoadjuvant pembrolizumab instead of conventional chemotherapy. Following four cycles of pembrolizumab, imaging revealed a marked metabolic response, allowing for successful R0 pancreatoduodenectomy. Postoperative histology confirmed a significant reduction in tumour size, and immunohistochemical analysis demonstrated increased CD8 + T cell infiltration, supporting an enhanced anti-tumour immune response. The patient continues adjuvant pembrolizumab therapy without complications.

This case highlights the potential role of neoadjuvant pembrolizumab in MSI-H/dMMR PDAC, demonstrating successful tumour downstaging and facilitating surgical resection. Our findings support further investigation into the integration of immunotherapy as a neoadjuvant strategy for select PDAC patients.