Complete Response to Pembrolizumab in a Patient with Castration-Resistant Prostate Cancer with Both BRCA Positivity and a High Frequency of Microsatellite Instability: A Case Report.

Introduction: There have been few reports of patients for whom a cancer gene panel test for solid tumors revealed the simultaneous presence of BRCA mutation and microsatellite instability (MSI)-high status. BRCA mutations have been reported in 13% of castration-resistant prostate cancer (CRPC) patients, and 3.1% of prostate cancer cases are MSI-high/mismatch repair deficient.

Case Presentation: A 71-year-old man with a history of urinary retention was referred to our department for clinically suspected prostate cancer and a high prostate-specific antigen (PSA) level (141 ng/mL). MRI revealed features of prostate cancer invading the bladder, seminal vesicles, and rectum. A histopathological examination of a transperineal needle biopsy specimen obtained from the prostate revealed adenocarcinoma. Bone scintigraphy revealed multiple metastases. The patient was treated with abiraterone acetate combined with androgen deprivation therapy followed by local radiation. Rectal wall thickening and lymph node metastasis were also observed, and docetaxel was administered. A cancer gene panel test was positive results for BRCA2 mutation with a MSI-high. After six courses of docetaxel, lymph node enlargement was observed and olaparib was initiated. Two months later, the metastatic lesions showed enlargement and the PSA level increased. Subsequently, pembrolizumab was administered. At 2 to the patient months after the initiation of pembrolizumab administration, PSA levels decreased to <0.025 ng/mL and the rectal lesions and lymph node metastases disappeared. The patient was continuing to receive pembrolizumab without any apparent adverse events or exacerbations, 9 months after initiation.

Conclusion: We herein report a case in which pembrolizumab treatment resulted in a complete response in a CRPC patient with both a BRCA2 mutation and an MSI-high status.