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.

A case of postoperative pancreatitis in patients with renal cell carcinoma with an inferior vena cava tumor thrombus treated by presurgical lenvatinib plus pembrolizumab.

Pancreatic injury is a rare, but noted complication of nephrectomy. We report a case involving a 56-year-old man who presented with cT3bN0M0 left locally advanced renal cell carcinoma with an inferior vena cava thrombus. Nephrectomy with thrombectomy was performed given the remarkable shrinkage of the primary tumor and thrombus following lenvatinib plus pembrolizumab administration. The patient developed postoperative pancreatitis associated with unrecognized minor pancreatic injury, which was treated conservatively. To our knowledge, this has been the first case that underwent nephrectomy for RCC with an IVC thrombus after presurgical lenvatinib plus pembrolizumab and received conservative treatment for postoperative pancreatitis.

A case of complete response to avelumab plus axitinib combination therapy for metastatic clear cell renal cell carcinoma in a kidney undergoing dialysis.

Introduction: Combination therapies of immune checkpoint and tyrosine kinase inhibitors for end-stage kidney disease and patients on hemodialysis need careful consideration as few case reports provide suitable management decisions. Case presentation: A 70-year-old man who had undergone hemodialysis for 6 years due to nephrosclerosis. Avelumab plus axitinib combination therapy was performed for repeated lung metastasis, and a complete response was achieved without major side effects. Conclusion: A complete response was achieved after Ave plus Axi combination therapy for clear cell renal cell carcinoma in a patient undergoing dialysis. This suggests that Ave plus Axi combination therapy may be safe and effective for dialysis patients.

A case of severe ureteral injury repaired by renal autotransplantation with an iliac vein patch using bovine pericardium.

Introduction: Renal autotransplantation is considered a surgical procedure for extensive ureteral defects. Herein, we report a case of severe ureteral injury repaired by laparoscopic nephrectomy and renal autotransplantation with an iliac vein patch using bovine pericardium. Case presentation: A 56-year-old woman who had previously undergone gynecological surgery complained of right-sided abdominal pain. She was then later diagnosed with a right middle ureteral injury with a 5-cm long defect. We performed retroperitoneal laparoscopic nephrectomy and renal autotransplantation. As the iliac vein was fragile, venous patching using bovine pericardium was performed. The patient's renal function was well preserved after surgery. Conclusion: Laparoscopic nephrectomy and renal autotransplantation is an effective method for repairing severe ureteral injury with the preservation of renal function. A venous patch using bovine pericardium might be considered as a replacement for a fragile vein.

Avelumab plus axitinib for translocation renal cell carcinoma: A case series and literature review.

Introduction: Patients with translocation renal cell carcinoma (tRCC) have a poor prognosis without standardized treatment. Case presentation: The first case was of a 72-year-old woman who underwent robot-assisted partial nephrectomy for a left renal tumor and was pathologically diagnosed with tRCC. Recurrence was observed in the left retroperitoneal soft tissue. After treatment with avelumab-axitinib, continued progression-free survival was confirmed at the 90-week follow-up. The second case was of a 41-year-old woman referred to our hospital and presented with translocation renal cell carcinoma metastasis to a para-aortic lymph node. After treatment with avelumab-axitinib, continued progression-free survival was confirmed at the 43-week follow-up. Conclusion: The outcomes of these cases indicate that avelumab-axitinib therapy has a long-term antitumor effect in some patients with tRCC.

Two cases of pelvic hematoma after prostatic urethral lift surgery.

Introduction: There are few reports of pelvic hematoma after prostatic urethral lift. Here, we report two cases of pelvic hematoma in Japan. Case presentation: The first case was a 71-year-old man with benign prostatic hyperplasia who underwent prostatic urethral lift. Although the procedure was uneventful, he experienced lower abdominal pain the day after the operation. CT revealed a hematoma in the right pelvis; however, it was manageable with conservative treatment. The second case was a 68-year-old man. The procedure was uneventful; however, 6 days after the operation, a subcutaneous hematoma appeared in the lower abdomen. CT revealed a hematoma in the left pelvis. We then performed pelvic hematoma removal surgery. Conclusions: Pelvic hematomas after PUL may requires attention, particularly in men with the narrow pelvises. Appropriate compression of the prostate and a high lithotomy position procedure could effectively avoid the occurrence of pelvic hematomas.

Successful treatment of eosinophilia associated with dialysis-related renal cancer with radical nephrectomy.

Introduction: Secondary eosinophilia due to solid tumors is a rare case. This is the first study to report secondary eosinophilia due to renal cancer in a patient on dialysis. Case presentation: A 70-year-old man, on long-term hemodialysis was incidentally detected with right renal cancer, and workup performed revealed eosinophilia. Allergic symptoms caused by hemodialysis were initially considered; however, treatment did not lead to any improvement in eosinophilia. Therefore, nephrectomy for renal cancer was performed. The resolution of symptoms and eosinophilia after surgery suggested renal cancer as the cause of eosinophilia. Conclusion: As demonstrated in this patient with dialysis-related renal cancer, eosinophilia associated with solid tumors may be addressed by treating the tumor.

Pathological complete response to neoadjuvant chemotherapy may improve antitumor immune response via reduction of regulatory T cells in muscle-invasive bladder cancer.

The prognosis for patients who achieve a pathologic complete response in bladder cancer is excellent, but the association between their prognosis and the tumor microenvironment is unclear. We investigated the tumor immune microenvironment of those with pathological complete response after platinum-based neoadjuvant chemotherapy for cT2-4aN0M0 bladder cancer using multiplex fluorescence immunohistochemistry. Our retrospective study included 12 patients with pathological complete response who underwent radical cystectomy following neoadjuvant chemotherapy for cT2-4aN0M0 muscle-invasive bladder cancer. We assessed the density of several immune cell types in pretreatment and posttreatment tissues via multiplex fluorescence immunohistochemical analysis. The median age was 67 years; 10 patients were male. Nine (75%) and 3 (25%) patients were cT2 and cT3, respectively. The 5-year progression-free and overall survivals were 90% and 100%, respectively. The densities of regulatory T cells (Treg; CD3+CD4+FoxP3+ cell) were significantly decreased and almost disappeared in the tumor microenvironment of posttreatment tissue compared with pretreatment tissue. Other immune cells, such as effector T cells or M2 macrophages, were not significantly changed between posttreatment and pretreatment tissues. In pathological complete response, Tregs in the tumor immune microenvironment were significantly decreased after platinum-based chemotherapy for muscle-invasive bladder cancer. The temporary arresting of immune response in the tumor microenvironment may reflect a favorable prognosis due to the decrease of Tregs with tumor shrinkage and improve the host tumor immune response.

Changes in Renal Function After Nephroureterectomy for Upper Tract Urothelial Cancer in Elderly Patients.

Introduction Decreased renal function after radical nephroureterectomy is one of the most important complications because it contributes to the decision to initiate adjuvant chemotherapy. This study aimed to investigate clinical factors associated with changes in renal function after radical nephroureterectomy in elderly patients. Methodology A total of 145 patients who underwent radical nephroureterectomy for upper tract urothelial carcinoma were evaluated. The renal function was calculated preoperatively, postoperatively, and one month postoperatively, and the long-term change in renal function was investigated once a year. The association between clinical factors and changes in renal function following radical nephroureterectomy in univariate and multivariate analyses was stratified by age ≥75 years and <75 years. Results The median age of the patients was 71 years, with 94 patients (65%) aged <75 years and 51 patients (35%) aged ≥75 years. The median estimated glomerular filtration rates (eGFRs) were 57.1 (21.8-100) preoperatively, 36.1 (9.1-100) postoperatively, and 42.4 (19.5-100) in one month after radical nephroureterectomy. The median eGFRs in elderly patients were 50.8 (21.8-85.4) preoperatively. In the elderly group, only 8% had an eGFR of ≥50 as cisplatin-eligible at one month postoperatively. The long-term renal function in the elderly may decline further than during the stable postoperative periods. In the multivariate analysis, hydronephrosis (HN) was a significant predictor of decreased renal function in patients aged ≥75 years between the pre- and postoperative periods. Conclusions Elderly patients with HN who have upper tract urothelial carcinoma have a lower risk of decreased renal function after radical nephroureterectomy. This result may be useful in determining adjuvant therapy.

Detection of anterior prostate cancer using a magnetic resonance imaging-transrectal ultrasound fusion biopsy in cases with initial biopsy and history of systematic biopsies.

Background: Prostate cancer in the anterior region may be missed on a transrectal systematic biopsy (SBx). Therefore, this study aimed to evaluate the performance of magnetic resonance imaging-transrectal ultrasound (MRI-TRUS) fusion targeted biopsy (TBx) in detecting anterior region cancer in patients with a history of SBxs. Methods: Prostate biopsies were performed in 224 patients after multiparametric MRI, among whom 119 patients with prostate imaging reporting and data system (PI-RADS version 2) scores of 3 to 5 underwent MRI-TRUS fusion TBxs. Afterward, cancer detection rates (CDRs) and TBx-positive core regions were compared by categorizing patients into those with or without a history of SBxs. Results: Total CDR was 68.8% (44/64 cases) in the initial biopsy group (Initial-Bx group) and 47.3% (26/55 cases) in the previous-negative-systematic biopsy group (Pre-Neg-SBx group) (P = 0.018). Interestingly, both TBx- and SBx-core positive cases were more common in the Initial-Bx group than in the Pre-Neg-SBx group (Initial-Bx group: 75% [33/44 cases] vs. Pre-Neg-SBx group: 42.3% [11/26 cases], P = 0.006). However, only TBx-core positive cases were more common in the Pre-Neg-SBx group than in the Initial-Bx group (Initial-Bx group: 11.4% [5/44 cases] vs. Pre-Neg-SBx group: 30.8% [8/26 cases], P = 0.043). In addition, the proportion of anterior lesions detected by TBx cores was higher in the Pre-Neg-SBx group than in the Initial-Bx group (Initial-Bx group: 26.3% [10/38 cases] vs. Pre-Neg-SBx group: 52.6% [10/19 cases], P = 0.049). Conclusion: Using MRI-TRUS fusion TBx in the evaluation of previously negative SBx cases improved the detection rate of anterior lesions, which might have been missed in previous SBxs. Especially in patients with a history of SBxs mpMRI should be performed to screen for anterior lesions.