Radiotherapy for metastatic ductal adenocarcinoma of the prostate with TP53, FOXA1, and BRCA2 mutations: A case report

To report the multidisciplinary management and favorable outcome of a patient with metastatic Prostate ductal adenocarcinoma (PRAD) who harbors co-mutations in TP53, FOXA1, and BRCA2. A 70-year-old man presented with dysuria and a high prostate specific antigen (PSA) level (74.58 ​ng/ml). Imaging revealed a large prostatic tumor with seminal vesicle invasion, lymph node involvement, and extensive bone metastases. Biopsy confirmed Gleason score 9 (4 ​+ ​5) adenocarcinoma with ductal and intraductal components. Genetic testing identified pathogenic mutations in TP53, FOXA1, and BRCA2. Initial treatment with androgen deprivation therapy (ADT) plus abiraterone and radical prostatectomy achieved biochemical response. However, he later developed symptomatic iliac bone metastasis with a sharply rising carcinoembryonic antigen (CEA) level despite undetectable PSA, prompting a biopsy that confirmed metastatic PRAD. The patient received stereotactic body radiation therapy (SBRT) to the metastatic iliac and vertebral lesions, delivering a radical biological effective dose (BED 10 ​= ​117.6 ​Gy). This was followed by chemotherapy and subsequent maintenance therapy with the Poly (ADP-ribose) Polymerase (PARP) inhibitor olaparib combined with goserelin. The patient achieved sustained biochemical and radiographic remission with no disease progression at the 5-year follow-up. This case highlights the aggressive nature of PRAD. The combination of high-dose SBRT and PARP inhibitor therapy, tailored to the patient's molecular profile, resulted in prolonged disease control. It underscores the importance of genetic testing and multidisciplinary precision therapy in managing advanced prostate cancer with rare histologic subtypes.