Abstract
Upper tract urothelial carcinoma (UTUC) is a rare and challenging-to-treat malignancy. In most patients it is a sporadic tumor entity, less commonly it falls on the spectrum of Lynch syndrome, an autosomal dominant familial tumor syndrome. Localized UTUC with high-risk features as well as the metastatic disease scenario might require systemic therapy. Platinum-based combination chemotherapy is currently the recommended management option. However, the introduction of immune checkpoint inhibitors into the therapeutic armamentarium has led to a paradigm shift in treatment standards. Immunotherapy has been shown to be safe and effective in treating at least metastatic UTUC, although UTUC-specific high-level evidence is still lacking. Recent technological advances and noteworthy research efforts have greatly improved the general understanding of the biological landscape of UTUC. According to the main findings, UTUC represent a particular subtype of urothelial carcinoma frequently associated with activated FGFR3 signaling, a luminal–papillary phenotype and a T-cell-depleted microenvironment. This improved knowledge promises precision oncology approaches that match treatment decision strategies and genomic profile to ultimately result in better clinical outcomes. The aim of this review was to summarize the main currently available evidence on immune checkpoint inhibition and clinical genomics in UTUC.
Highlights
Upper tract urothelial carcinoma (UTUC) is a rare and challenging-to-treat malignancy.It defines urothelial carcinomas (UCs) with primary pyelocaliceal and ureteral tumor location
This review summarizes the main currently available evidence on immune checkpoint (IC) inhibition and clinical genomics in UTUC
10 mg/kg/2 wks IV: intravenous; n/a: not available; ORR: objective response rate; PD-1: Programmed Death-1; PD-L1: Programmed Death-Ligand 1; randomized controlled trials (RCT): randomized controlled trial; UTUC: upper tract urothelial carcinoma. * The percentage is relative to the overall urothelial carcinoma patients enrolled in the study trial. } The percentage is only referred to patients with UTUC. † Defined as radiological and endoscopic complete response. # UTUC
Summary
Upper tract urothelial carcinoma (UTUC) is a rare and challenging-to-treat malignancy. It defines urothelial carcinomas (UCs) with primary pyelocaliceal and ureteral tumor location. Non-metastatic UTUC with high-risk features is already considered an early systemic disease [3]. Radical nephroureterectomy (RNU) still represents the mainstay of treatment for patients with high-risk localized UTUC. Major advances in the understanding of UTUC biology have been provided by recent genomic and gene expression studies [8]. This improved knowledge promises precision oncology approaches that match treatment decision strategies and genomic profile to result in better clinical outcomes. This review summarizes the main currently available evidence on IC inhibition and clinical genomics in UTUC
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