Immune checkpoint inhibition in upper tract urothelial carcinoma.

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.

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.

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 platinum-pretreated 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 high-level 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.

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.

World journal of urology. 2020 Oct 31 [Epub ahead of print]

Gianluigi Califano, Idir Ouzaid, Paolo Verze, Jean-Francois Hermieu, Vincenzo Mirone, Evanguelos Xylinas

Department of Neurosciences, Reproductive Sciences and Odontostomatology, Urology Unit, Federico II University of Naples, Naples, Italy., Department of Urology, Bichat-Claude Bernard Hospital, Assistance-Publique Hôpitaux de Paris, Paris University, Paris, France., Department of Medicine and Surgery "Scuola Medica Salernitana", Urology Unit, University of Salerno, Salerno, Italy., Department of Urology, Bichat-Claude Bernard Hospital, Assistance-Publique Hôpitaux de Paris, Paris University, Paris, France. .