Pembrolizumab for high TMB castration-resistant prostate cancer: A precision medicine case report

Abstract This case report describes the clinical management of a 68-year-old man with concurrent invasive melanoma and metastatic castration-resistant prostate cancer (mCRPC). Initially diagnosed with BRAF V600E-mutated melanoma, he received Dabrafenib and Trametinib. Later, prostate cancer was diagnosed with bilateral pulmonary metastases. Despite initial treatment with Triptorelin, Docetaxel, and Abiraterone, disease progression occurred. A liquid biopsy revealed an extremely high Tumor Mutational Burden (TMB) and mutations including POLE, BRCA2, ATM, and TP53. Due to the high TMB, off-label Pembrolizumab was initiated. Radiological evaluations at 3 and 6 months showed a marked response, with disappearance of target lung metastases and durable remission maintained through February 2025. Only grade 1 asthenia was reported, without significant treatment interruptions. This case illustrates the value of precision medicine and the role of liquid biopsy in guiding immunotherapy decisions for complex oncological cases. It supports the relevance of molecular profiling in selecting effective treatments beyond standard indications.