Abstract
Urothelial carcinoma (UC) is a common malignancy of the lower and upper urinary tract. Recurrent UC has poor prognosis due to delayed diagnosis and a lack of clinical management guidance, especially for upper urinary tract UC. Patients with germline or somatic BRCA1/2 mutations are a special population in UC. No evidence is available so far on the effectiveness of poly ADP-ribose polymerase inhibitor (PARPi) in this population. Here, we report a 60-year-old female patient diagnosed with left ureter high-grade UC. Recurrent lesions were found 20 months after radical surgery. Computed tomography (CT) examination showed a slightly high-density soft tissue mass (3.2 × 3.1 cm) on the left posterior wall of the abdomen (waist), soft tissue mass adjacent to the left inner wall of the pelvis (3.2 × 4.2 cm), and multiple enlarged lymph nodes to the left of abdominal aorta. A next-generation sequencing (NGS)-based 605-gene panel detected a novel BRCA2 pathogenic germline mutation c.1670T>A (p.L557*), and a series of somatic insertion and deletion (INDEL) mutations of BRCA1, RB1, and JAK2, and single nucleotide variation (SNV) mutations of TP53, KMT2D, MET, ROS1, and IL7R. The above lesions were reduced significantly or disappeared (partial response, PR) after a 3-month Olaparib treatment, and the patient's general condition remained well. In conclusion, this study proved for the first time that PARPi was effective for UC treatment in patients carrying germline BRCA2 pathogenic mutations, providing new treatment options for such patients. In addition, the circulating tumor DNA (ctDNA) test can be used for drug selection and response monitoring in UC treatment.