Drastic Response to Olaparib in a Patient With Metastatic Castration‐Resistant Prostate Cancer Harboring BRCA2 Alterations and Near‐Threshold Tumor Mutational Burden

Introduction: BRCA2 alterations and high tumor mutational burden (TMB-H) are responsible for prostate cancer; however, their co-occurrence is uncommon, and evidence for PARP inhibition in the castration-sensitive setting remains limited. We describe a case of metastatic castration-resistant prostate cancer (CRPC) harboring both biomarkers, showing a marked response to olaparib. Case Presentation: A 74-year-old man presented with urinary retention. Initial prostate-specific antigen (PSA) level was 11 ng/mL. Follow-up MRI revealed bilateral PI-RADS 5 lesions with seminal-vesicle invasion. Biopsy confirmed adenocarcinoma (Gleason score 5 + 5 = 10). Staging revealed osseous and 30-mm right internal iliac nodal metastasis. Genomic profiling identified a pathogenic BRCA2 mutation and near-threshold TMB. Chemohormonal therapy was discontinued early owing to severe infection, and olaparib was initiated. Over 3 months, MRI showed further regression of the primary lesion and nodal disease, and PSA and SCC decreased. Conclusion: In metastatic CRPC harboring a BRCA2 mutation and near-threshold TMB, olaparib produced clear radiological and serological responses.