Supplementary Material for: Exceptional response to pembrolizumab in a mismatch-repair deficient aggressive prostate cancer with somatic EPCAM, MSH2 and MSH6 co-deletion: a case report

Mismatch repair deficient (dMMR) prostate cancer (PCa) is a rare (1-5%) but highly actionable molecular subgroup of PCa, vulnerable to immune checkpoint inhibitors. Our case of sporadic dMMR PCa due to large monoallelic co-deletion of EPCAM, MSH2 and MSH6, features a clinically aggressive disease presentation and a major response to pembrolizumab. We report a 65-year-old patient with primary metastatic PCa, Gleason score 5+5=10, with penile and lymph node metastases at diagnosis. Patient showed rapid progression on first-line ADT and enzalutamide. Tumor next-generation sequencing (NGS) revealed microsatellite instability and a tumor mutational burden of 40.8 mutations/megabase. Immunohistochemistry showed co-loss of MSH2 and MSH6. Review of NGS row data confirmed large monoallelic deletion in chromosome 2p, including EPCAM, MSH2 and MSH6. No germline alterations in mismatch repair genes were detected. Patient showed excellent response to pembrolizumab, which is still ongoing. We conclude that early molecular tumor profiling is essential to enable personalized management of advanced prostate cancer, especially in patients with aggressive or atypical disease course.