Hirano Takayuki, Yonezawa Kousuke, Kawahara Takashi, Mizuno Nobuhiko, Hayashi Hiroyuki, Karibe Yuta, Asano Jun, Fusayasu Shusei, Makiyama Kazuhide, Uemura Hiroji, Ohta Junichi, Moriyama Masatoshi
Department of Urology, Yokohama Municipal Citizen's Hospital, Yokohama, Japan.
Department of Urology and Renal Transplantation, Yokohama City University Medical Center, Yokohama, Japan.
Case Rep Oncol. 2024 Aug 5;17(1):852-858. doi: 10.1159/000540419. eCollection 2024 Jan-Dec.
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.
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.
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.
关于实体瘤癌症基因检测显示同时存在BRCA突变和微卫星高度不稳定（MSI-H）状态的患者报告较少。据报道，13%的去势抵抗性前列腺癌（CRPC）患者存在BRCA突变，3.1%的前列腺癌病例为MSI-H/错配修复缺陷。
一名71岁有尿潴留病史的男性因临床怀疑前列腺癌和高前列腺特异性抗原（PSA）水平（141 ng/mL）转诊至我科。MRI显示前列腺癌侵犯膀胱、精囊和直肠的特征。对经会阴前列腺穿刺活检标本进行组织病理学检查，结果显示为腺癌。骨闪烁显像显示多处转移。该患者接受醋酸阿比特龙联合雄激素剥夺治疗，随后进行局部放疗。还观察到直肠壁增厚和淋巴结转移，并给予多西他赛治疗。癌症基因检测结果显示BRCA2突变且为MSI-H阳性。多西他赛六个疗程后，观察到淋巴结肿大，开始使用奥拉帕利。两个月后，转移病灶增大，PSA水平升高。随后给予帕博利珠单抗治疗。在开始使用帕博利珠单抗治疗2个月后，PSA水平降至<0.025 ng/mL，直肠病变和淋巴结转移消失。开始治疗9个月后，患者继续接受帕博利珠单抗治疗，未出现明显不良事件或病情加重。
我们在此报告一例帕博利珠单抗治疗使一名同时具有BRCA2突变和MSI-H状态的CRPC患者获得完全缓解的病例。
