Immune checkpoint inhibition in upper tract urothelial carcinoma
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TOPIC PAPER
Immune checkpoint inhibition in upper tract urothelial carcinoma Gianluigi Califano1,2 · Idir Ouzaid2 · Paolo Verze3 · Jean‑Francois Hermieu2 · Vincenzo Mirone1 · Evanguelos Xylinas2 Received: 20 July 2020 / Accepted: 14 October 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Introduction Immunotherapy is changing the way we think about and treat urothelial carcinoma (UC). The PD-1/PD-L1 pathway inhibition has shown robust efficacy, associated with an acceptable toxicity profile, in patients with locally advanced and metastatic unresectable disease, addressing a high decades-old unmet medical need. Material and methods Using the Pubmed database, we conducted a literature review for English written published articles up to June 2020. The highest available evidence for the immunotherapy treatment of UC with ICIs were evaluated. The leading phase one, two and three clinical trials were considered for inclusion (n = 12). Patient’s data were extracted from studies depicting the UTUC subpopulation. Results Two monoclonal antibodies targeting PD-1 (pembrolizumab and nivolumab) and three to its ligand PD-L1 (atezolizumab, avelumab, and durvalumab) have obtained US FDA and EMA approval for the second-line treatment of platinumpretreated patients, between 2016 and 2019. Atezolizumab and Pembrolizumab are even currently approved in the first-line setting for cisplatin ineligible patients, with PD-L1- positive tumor. The neoadjuvant scenario in localized high-risk disease is still evolving, with the first data available to date limited to the muscle-invasive bladder carcinoma. The management of patients with upper tract urothelial carcinoma (UTUC: renal pelvis and ureters) is complicated by the lack of specific highlevel evidence, due to the rarity of the disease. No published studies addressing immunotherapy in UTUC patients only are available. The largest clinical trials aimed at UC patients, regardless of the upper or lower location of the primary tumor, have enrolled a minority of patients with UTUC, providing the data on which our current knowledge is based. However, targeted scientific efforts are needed to improve our level of care. Conclusions This review summarizes the main currently available evidence on the use of the PD-1/PD-L1 pathway inhibition with reference to patients presenting with UTUC. Keywords Immunotherapy · Upper tract urothelial carcinoma · Urothelial carcinoma · Immune checkpoint inhibitors · PD1 · PD-L1 inhibition
Introduction
* Evanguelos Xylinas [email protected] 1
Department of Neurosciences, Reproductive Sciences and Odontostomatology, Urology Unit, Federico II University of Naples, Naples, Italy
2
Department of Urology, Bichat‑Claude Bernard Hospital, Assistance‑Publique Hôpitaux de Paris, Paris University, Paris, France
3
Department of Medicine and Surgery “Scuola Medica Salernitana”, Urology Unit, University of Salerno, Salerno, Italy
Urothelial carcinoma (UC) is the most common malignant histologic variant arising fro
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