Purpose: Early treatment intensification with neoadjuvant therapy may improve outcomes in patients with high-risk, localized prostate cancer treated with radical prostatectomy. Our objective was to compare pathologic, oncologic, and safety outcomes of neoadjuvant abiraterone acetate plus leuprolide acetate with or without cabazitaxel prior to radical prostatectomy in patients with localized, high-risk prostate cancer. Patients and Methods: This open-label, multicenter, phase II trial randomized men with clinically localized, D'Amico high-risk prostate cancer to neoadjuvant abiraterone acetate (1,000 mg/day) and leuprolide acetate (22.5 mg every 3 months) with or without cabazitaxel (25 mg/m2) prior to radical prostatectomy. The primary outcome was pathologic complete response (pCR) or minimal residual disease (MRD). Secondary outcomes included surgical margins, lymph node involvement, pathologic stage, 12-month biochemical relapse-free survival (BRFS) rates, and safety profile. Results: The per-protocol population consisted of 70 patients [cabazitaxel arm (Arm A): 37, no cabazitaxel arm (Arm B): 33]. Median patient age and prostate-specific antigen levels were 63.5 years [interquartile range (IQR), 58.0–68.0] and 21.9 ng/mL (IQR, 14.6–42.8), respectively. pCR/MRD occurred in 16 (43.2%) versus 15 patients (45.5%) in arms A and B, respectively (P = 0.85). pCR occurred in two (5.4%) versus three patients (9.1%) in arms A and B, respectively (P = 0.66). Patients with ≤ 25% total biopsy cores positive had increased odds of pCR/MRD (P = 0.04). Patients with pCR/MRD had superior 12-month BRFS rates (96.0% vs. 62.0%, P = 0.03). Grade 3+ adverse events occurred in 42.5% and 23.7% of patients in arms A and B, respectively (P = 0.078). Conclusions: Neoadjuvant cabazitaxel addition to abiraterone acetate/leuprolide acetate prior to radical prostatectomy did not improve pCR/MRD in clinically localized, high-risk prostate cancer.
Cribriform pattern and intraductal carcinoma prostate cancer were more commonly detected at multiparametric MRI–targeted biopsy compared with systematic biopsy.
Aims: Sporadic renal cell carcinomas with fibromyomatous stroma (RCC FMS) with coexistent haemangioblastoma (HB)‐like morphology have been previously reported. Such morphology has not, however, been documented in patients with tuberous sclerosis complex (TSC). We evaluated clinicopathologic, immunohistochemical and molecular findings of RCC FMS with HB‐like features in three TSC patients.Methods and results: All three patients were females with confirmed germline mutations in TSC1 in the absence of VHL or other alterations. One patient had bilateral nephrectomy with six separate tumours (three in each kidney), and two patients had one tumour each, resected by partial nephrectomy. Prominent fibromuscular stroma was present at the tumoral periphery and surrounding clear cell nests forming tubules and papillary formations (RCC FMS areas), admixed with solid, clear to eosinophilic and spindle cell areas (HB‐like areas). HB‐like areas were variably represented in individual tumours, but in some, HB‐like features were almost exclusive. HB‐like areas were negative for CK7 and showed inhibin‐α and S100 reactivity, in contrast to typical RCC FMS areas, which were CK7 positive, while negative for inhibin‐α and S100. GPNMB, which is consistently expressed in TSC/mTOR altered tumours, was positive in both components. On follow‐up (10 months–21 years), all patients had an indolent course.Conclusions: HB‐like morphology found in RCC FMS in TSC patients represents part of the morphologic spectrum of RCC FMS, which is a previously underreported and underrecognized feature. RCC FMS with HB‐like areas show uniform GPNMB reactivity and are associated with TSC/MTOR alterations, but not with VHL alterations.
Kidney transplantation is preferred for end-stage renal disease. The current gold standard for kidney preservation is static cold storage (SCS) at 4 °C. However, SCS contributes to renal graft damage through ischemia–reperfusion injury (IRI). We previously reported renal graft protection after SCS with a hydrogen sulfide donor, sodium thiosulfate (STS), at 4 °C. Therefore, this study aims to investigate whether SCS at 10 °C with STS and Hemopure (blood substitute), will provide similar protection. Using in vitro model of IRI, we subjected rat renal proximal tubular epithelial cells to hypoxia–reoxygenation for 24 h at 10 °C with or without STS and measured cell viability. In vivo, we preserved 36 donor kidneys of Lewis rats for 24 h in a preservation solution at 10 °C supplemented with STS, Hemopure, or both followed by transplantation. Tissue damage and recipient graft function parameters, including serum creatinine, blood urea nitrogen, urine osmolality, and glomerular filtration rate (GFR), were evaluated. STS-treated proximal tubular epithelial cells exhibited enhanced viability at 10 °C compared with untreated control cells (p < 0.05). Also, STS and Hemopure improved renal graft function compared with control grafts (p < 0.05) in the early time period after the transplant, but long-term function did not reach significance. Overall, renal graft preservation at 10 °C with STS and Hemopure supplementation has the potential to enhance graft function and reduce kidney damage, suggesting a novel approach to reducing IRI and post-transplant complications.