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.
World J Urol. 2021 May;39(5):1357-1367. doi: 10.1007/s00345-020-03502-7. Epub 2020 Oct 31.
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.
免疫疗法正在改变我们对膀胱癌（UC）的思考和治疗方式。在局部晚期和转移性不可切除疾病患者中，PD-1/PD-L1 通路抑制显示出强大的疗效，且具有可接受的毒性特征，这解决了一个存在了几十年的未满足的医疗需求。
我们使用 Pubmed 数据库，对截至 2020 年 6 月发表的英文文献进行了综述。评估了使用 ICIs 进行 UC 免疫治疗的最高可用证据。纳入了主要的 I 期、II 期和 III 期临床试验（n = 12）。从描述 UTUC 亚群的研究中提取患者数据。
两种针对 PD-1 的单克隆抗体（pembrolizumab 和 nivolumab）和三种针对其配体 PD-L1 的单克隆抗体（atezolizumab、avelumab 和 durvalumab）已分别于 2016 年至 2019 年获得美国食品药品监督管理局（FDA）和欧洲药品管理局（EMA）批准，用于铂类预处理患者的二线治疗。Atezolizumab 和 Pembrolizumab 目前甚至被批准用于 PD-L1 阳性肿瘤的顺铂不耐受患者的一线治疗。局部高危疾病的新辅助方案仍在不断发展，迄今为止，可用的首批数据仅限于肌层浸润性膀胱癌。由于疾病的罕见性，上尿路尿路上皮癌（UTUC：肾盂和输尿管）患者的管理缺乏具体的高级别证据，这使得情况变得复杂。目前尚无针对仅接受免疫治疗的 UTUC 患者的研究。旨在治疗 UC 患者的最大临床试验，无论原发性肿瘤位于上尿路还是下尿路，都仅纳入了少数 UTUC 患者，为我们目前的知识提供了数据基础。然而，需要有针对性的科学努力来提高我们的护理水平。
本综述总结了目前关于 PD-1/PD-L1 通路抑制在伴有 UTUC 患者中的应用的主要可用证据。
