Contemporary best practice in the management of urothelial carcinomas of the renal pelvis and ureter

Abstract

Upper tract urothelial carcinoma (UTUC) accounts for 5% of urothelial carcinomas (UCs), the estimated annual incidence being 1–2 cases per 100,000 inhabitants. Similarly to bladder UC, divergent differentiations and histologic variants confer an adverse risk factor in comparison with pure UTUC. Molecular and genomic characterization studies on UTUC have shown changes occurring at differing frequencies from bladder cancer, with unique molecular and clinical subtypes, potentially with different responses to treatment. Systemic chemotherapy is the standard approach for patients with inoperable locally advanced or metastatic UCs. Although initial response rates are high, the median survival with combination chemotherapy is about 15 months. In first-line chemotherapy several cisplatin-based regimens have been proposed. For patients with advanced UC who progress to first-line treatment, the only product licensed in Europe is vinflunine, a third-generation, semisynthetic, vinca alkaloid. Better response rates (15–60%), with higher toxicity rates and no overall survival (OS) benefit, are generally achieved in multidrug combinations, which often include taxanes and gemcitabine. The US FDA has recently approved five agents targeting the programmed death-1 and programmed death ligand-1 pathway as a second-line therapy in patients with locally advanced or metastatic UC with disease progression during or following platinum-containing chemotherapy. Potential therapeutic targets are present in 69% of tumours analyzed. Specific molecular alterations include those involved in the RTK/Ras/PI(3)K, cell-cycle regulation and chromatin-remodeling pathways, many of them have either targeted therapies approved or under investigation. Angiogenic agents, anti-epidermal growth factor receptor therapy, phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) pathway inhibitors and immunotherapeutic drugs are being successfully investigated.

CSF-1 Overexpression Predicts Poor Prognosis in Upper Tract Urothelial Carcinomas

“…UTUC is a rare cancer with vastly different characteristics between eastern and western countries; e.g., the male-to-female ratio is 1 : 1.2 in Taiwanese UTUC patients [3] but the ratio of patients in western countries is reversed [4]. In western countries, the incidence of urothelial carcinomas presenting as UCB is 90-95% [5], while UTUC is rare, accounting for only 5-10% of all urothelial carcinomas [6–8]. However, the incidence of UTUC in Taiwan is markedly higher at 30% of all urothelial carcinomas [9].…”

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“…Previous research suggests that the slower blood flow and reduced shear stress in veins might create an environment conducive to interactions between ECs and immune cells (52), possibly explaining the immunomodulatory role of vein ECs in the TME. The discovery of these alterations in vein ECs in this study not only deepens our understanding of UTUC but also suggests that antiangiogenic treatments may be effective in the managements of this disease (86). Similarly, we discovered that various subtypes of fibroblasts in the UTUC TME exhibited distinctive features.…”

Investigating cellular similarities and differences between upper tract urothelial carcinoma and bladder urothelial carcinoma using single-cell sequencing

“…Previous research suggests that the slower blood flow and reduced shear stress in veins might create an environment conducive to interactions between ECs and immune cells ( 52 ), possibly explaining the immunomodulatory role of vein ECs in the TME. The discovery of these alterations in vein ECs in this study not only deepens our understanding of UTUC but also suggests that antiangiogenic treatments may be effective in the managements of this disease ( 86 ). Similarly, we discovered that various subtypes of fibroblasts in the UTUC TME exhibited distinctive features.…”