Prevalence of germline BRCA1/2 pathogenic variants in Japanese patients treated with castration-resistant prostate cancer and efficacy of CRPC treatment in real-world clinical practice.

OBJECTIVE: The companion diagnosis for olaparib, a poly (ADP-ribose) polymerase inhibitor for prostate cancer, aims to detect BRCA1/2 gene variants. In clinical practice, the frequency of germline BRCA1/2 variants in patients receiving castration-resistant prostate cancer treatment is unknown. We aimed to evaluate the prevalence of germline BRCA1/2 variants and their relationship to prognosis and treatment efficacy in castration-resistant prostate cancer. METHODS: Between June 2021 and 2023, 92 patients receiving castration-resistant prostate cancer treatment were examined for germline BRCA1/2 variants using BRACAnalysis CDx®. Furthermore, the associations between BRCA1/2 pathogenic variants and clinical outcomes were assessed. RESULTS: Of the 92 patients referred for genetic testing, 6 (6.5%) carried germline pathogenic variants in BRCA1/2. The BRCA2 variant was the most frequent (n = 5), followed by BRCA1 variant (n = 1). Among the five variants in BRCA2, the p.Asp427Thrfs*3 variant was identified for the first time in prostate cancer. Overall survival from castration-resistant prostate cancer for patients with BRCA1/2 variants was significantly shorter than for patients without BRCA1/2 variants (P = 0.043). Progression-free survival of androgen receptor signaling inhibitors for patients with BRCA1/2 variants was significantly shorter than for those without (P = 0.003). Progression-free survival of taxane chemotherapy was significantly shorter in patients with BRCA1/2 variants than in those without (P = 0.0149). CONCLUSIONS: In clinical practice, 6.5% of patients treated with castration-resistant prostate cancer carried germline BRCA1/2 pathogenic variants. Japanese castration-resistant prostate cancer patients with germline BRCA1/2 mutants have a poor prognosis and may be less responsive to treatment with androgen receptor signaling inhibitors and taxane-based chemotherapy for castration-resistant prostate cancer.

Metastatic bladder cancer forming a sigmoidorectal fistula after enfortumab vedotin therapy: a case report.

We report the case of a 68-year-old man who developed a sigmoidorectal fistula after marked response to enfortumab vedotin for advanced bladder cancer. The patient had undergone radical cystectomy with ileal conduit after neoadjuvant chemotherapy. Six months after surgery, local recurrence in the pelvic cavity and multiple lung metastases were found, and the patient was administered pembrolizumab as second-line therapy. Due to worsening local recurrence and suspected invasion of the sigmoid colon and rectum, enfortumab vedotin was initiated as third-line therapy and comprehensive genomic profiling was simultaneously performed. Enfortumab vedotin was remarkably effective, the lung metastases disappeared, and the local recurrent lesion shrank in volume although a sigmoidorectal fistula was found to form through the tumor cavity. Immunohistochemical analysis of the tumor specimens exhibited increased nectin-4 expression. This rare case of metastatic bladder cancer with sigmoidorectal fistula associated with effective enfortumab vedotin therapy suggests that nectin-4 expression and comprehensive genomic profiling might be useful in predicting treatment response to enfortumab vedotin.

[A Case of Metastatic Renal Cell Carcinoma with Arthritis and Colitis Due to Immune-Related Adverse Events During Ipilimumab-Nivolumab Combination Therapy].

A 73-year-old man with renal cell carcinoma underwent a left-sided open radical nephrectomy at our center. The pathological diagnosis was Fuhrman Grade 2, stage pT3a, clear cell renal cell carcinoma. A follow-up computed tomography (CT) scan revealed lung metastases 9 months after the surgery. The patient was started on ipilimumab with nivolumab combination therapy; however, after two cycles of administration, he developed arthralgia and swelling of the knee. Furthermore, he developed diarrhea almost simultaneously, resulting in the interruption of the ipilimumab plus nivolumab treatment. We diagnosed arthritis and colitis with immune-related adverse events (irAE) and initiated steroid therapy with rehabilitation. His condition improved dramatically, and nivolumab treatment could be resumed after 3 months of treatment interruption.

Efficacy of combination therapy with pembrolizumab and axitinib for metastatic renal collecting duct cell carcinoma: A report on two cases.

Introduction: Immunotherapy-based combinations have become the standard first-line therapy for metastatic renal cell carcinoma. However, combined immunotherapy for renal collecting duct carcinoma had been reported, but its therapeutic efficacy had been unclear. Case presentation: The first case was a 62-year-old man treated with pembrolizumab and axitinib for renal collecting duct carcinoma with multiple bone metastases. After 7 months, the primary and metastatic lesions shrunk and were evaluated as a partial response. The second case was a 71-year-old man treated with pembrolizumab and axitinib for renal collecting duct carcinoma with lymph node and lung metastases. After 9 months, the primary and metastatic lesions shrunk and were evaluated as a partial response. In both cases, the tumor cell expression of programmed death ligand-1 was negative, and CD4+ and CD8+ cells were observed in the tumor. Conclusion: Combined immunotherapy with pembrolizumab and axitinib may be effective for metastatic renal collecting duct carcinoma.

Hyperprogressive disease after avelumab maintenance therapy in a patient with advanced ureter cancer: A case report.

In the early stages of immunocheckpoint inhibitor administration, we should be aware of rapid cancer progression, known as hyperprogressive disease, in real-world clinical practice. We report a case of a 73-year-old man who presented with right abdominal pain and was diagnosed with advanced right ureteral cancer involving the duodenum. He received four cycles of chemotherapy with gemcitabine plus cisplatin, followed by maintenance with avermab. After two cycles of avermab within a month, his primary cancer dramatically progressed and he died. This is the first report of a case in which unresectable ureteral cancer caused hyperprogressive disease after avelumab maintenance therapy.

Advance renal pelvic cancer caused obstructive jaundice: A case report.

We report a case of advanced renal pelvic cancer in a 69-year-old woman who presented with fatigue, appetite loss, and yellow sclera. Contrast-enhanced computed tomography revealed a large lesion mass extending from the right renal pelvis to the duodenum and surrounding enlarged lymph nodes. Gastroduodenal endoscopy revealed a mass in the ampulla of Vater, and an endoscopic biopsy was performed. Histological and immunohistochemical examination of the biopsy specimen confirmed a diagnosis of urothelial carcinoma. To the best of our knowledge, this is the first report of advanced renal pelvic cancer causing obstructive jaundice.

Selective electrothermolysis of the sebaceous glands: treatment of facial seborrhea.

BACKGROUND: There are few publications on facial seborrhea treatment. A focused therapy is needed. OBJECTIVE: Our aim was to evaluate the efficacy of electrothermolysis of the sebaceous glands. METHODS: In the preliminary studies, histologic changes in the cheek skin by electrothermolysis were examined by light microscopy. In the clinical studies, 15 adult women subjects with facial seborrhea were treated four times by the same procedure. A 1.50-mm-long needle with a 0.45-mm base insulation was inserted into pores in the forehead and cheeks, and a high-frequency electrical current was applied for 0.25 to 0.50 seconds with an output of 40 W. Each treatment took 60 to 90 minutes. The subjects returned for 6-months follow-up after their fourth treatment. RESULTS: Histology 1 and 6 months later showed fewer sebaceous glands and the development of fibrosis. All 12 subjects who completed the 6-month follow-up gave a subjective assessment of continuous reduction of facial seborrhea. On a scale of 0.0 to 3.0, the mean improvement score was 1.67+/-0.75. The mean reduction rate of skin surface lipids was 31.5% by sebumeter (p< .01). CONCLUSIONS: Even though this is a pilot, uncontrolled clinical assessment study, electrothermolysis of sebaceous glands may be an effective and safe approach for facial seborrhea treatment.