An overview of epidemiological pattern of upper tract urothelial carcinoma (UTUC), including outcome of UTUC over past decades as well as factors responsible for observed epidemiological changes was performed. Gender and racial disparities influencing incidence of UTUC were reviewed. The incidence of multifocal urothelial carcinoma and relation of UTUC to urothelial carcinoma of bladder were examined.

Renal cell carcinoma (RCC) is the sixth most common cancer in the US. However, no significant changes in management have occurred since the tyrosine kinase era until the recent breakthrough with checkpoint inhibitors. Therefore, the need for more therapeutic options is paramount. Our objective was to determine whether PARP inhibition represents a novel therapeutic option for RCC. We used publicly available COSMIC, GDC Data Portal, and cBioPortal databases to explore mutations in DNA repair genes in RCC tissues from the TCGA cohort. We treated a human normal renal epithelial cell line RPTEC/TERT1 and two human renal cancer cell lines ACHN and CAKI-2 with PARPi niraparib, olaparib, rucaparib, veliparib, and talazoparib. Cell survival, cell proliferation, clonogenic ability, and apoptosis were assessed. RCC xenografts in SCID mice were treated with PARPi to evaluate their efficacy in vivo. Data mining revealed that ~27-32% of RCC tissues contain mutations in homologous recombination genes. Niraparib and talazoparib were the most effective at reducing cell survival, proliferation, and clonogenic ability in vitro. Niraparib, talazoparib, and rucaparib were the most effective in reducing RCC xenograft growth in vivo. Agents such as PARPi that exploit mutations in DNA damage repair genes may be effective therapeutic options for RCC.

Objective: To assess the differential response to neoadjuvant chemotherapy (NAC) in patients with urothelial carcinoma of the bladder (UCB) compared to upper tract urothelial carcioma (UTUC) treated with radical surgery. Patients and Methods: Data from 1299 patients with UCB and 276 with UTUC were obtained from multicentric collaborations. The association of disease location (UCB vs UTUC) with pathological complete response (pCR, defined as a post‐treatment pathological stage ypT0N0) and pathological objective response (pOR, defined as ypT0‐Ta‐Tis‐T1N0) after NAC was evaluated using logistic regression analyses. The association with overall (OS) and cancer‐specific survival (CSS) was evaluated using Cox regression analyses. Results: A pCR was found in 250 (19.2%) patients with UCB and in 23 (8.3%) with UTUC ( P  < 0.01). A pOR was found in 523 (40.3%) patients with UCB and in 133 (48.2%) with UTUC ( P = 0.02). On multivariable logistic regression analysis, patients with UTUC were less likely to have a pCR (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.27–0.70; P < 0.01) and more likely to have a pOR (OR 1.57, 95% CI 1.89–2.08; P < 0.01). On univariable Cox regression analyses, UTUC was associated with better OS (hazard ratio [HR] 0.80, 95% CI 0.64–0.99, P = 0.04) and CSS (HR 0.63, 95% CI 0.49–0.83; P < 0.01). On multivariable Cox regression analyses, UTUC remained associated with CSS (HR 0.61, 95% CI 0.45–0.82; P < 0.01), but not with OS. Conclusions: Our present findings suggest that the benefit of NAC in UTUC is similar to that found in UCB. These data can be used as a benchmark to contextualise survival outcomes and plan future trial design with NAC in urothelial cancer.