Medical Oncology Unit, 18630University Hospital of Parma, Parma, Italy.
Department of Medicine and Surgery, University of Parma, Parma, Italy.
Technol Cancer Res Treat. 2023 Jan-Dec;22:15330338231159753. doi: 10.1177/15330338231159753.
Urothelial carcinoma (UC) is the most frequent malignancy of the urinary tract, which consists of bladder cancer (BC) for 90%, while 5% to 10%, of urinary tract UC (UTUC). BC and UTUC are characterized by distinct phenotypical and genotypical features as well as specific gene- and protein- expression profiles, which result in a diverse natural history of the tumor. With respect to BC, UTUC tends to be diagnosed in a later stage and displays poorer clinical outcome. In the present review, we seek to highlight the individuality of UTUC from a biological, immunological, genetic-molecular, and clinical standpoint, also reporting the most recent evidence on UTUC treatment. In this regard, while the role of surgery in nonmetastatic UTUC is undebated, solid data on adjuvant or neoadjuvant chemotherapy are still an unmet need, not permitting a definite paradigm shift in the standard treatment. In advanced setting, evidence is mainly based on BC literature and retrospective studies and confirms platinum-based combination regimens as bedrock of first-line treatment. Recently, immunotherapy and target therapy are gaining a foothold in the treatment of metastatic disease, with pembrolizumab and atezolizumab showing encouraging results in combination with chemotherapy as a first-line strategy. Moreover, atezolizumab performed well as a maintenance treatment, while pembrolizumab as a single agent achieved promising outcomes in second-line setting. Regarding the target therapy, erdafitinib, a fibroblast growth factor receptor inhibitor, and enfortumab vedotin, an antibody-drug conjugate, proved to have a strong antitumor property, likely due to the distinctive immune-genetic background of UTUC. In this context, great efforts have been addressed to uncover the biological, immunological, and clinical grounds in UTUC patients in order to achieve a personalized treatment.
尿路上皮癌（UC）是最常见的泌尿道恶性肿瘤，其中膀胱癌（BC）占 90%，而 5%至 10%为尿路上皮癌（UTUC）。BC 和 UTUC 的特点是表型和基因型特征明显，以及特定的基因和蛋白质表达谱，这导致肿瘤的自然史多种多样。就 BC 而言，UTUC 往往在晚期被诊断出来，且临床预后较差。在本综述中，我们从生物学、免疫学、遗传分子学和临床角度出发，旨在突出 UTUC 的个体性，并报告 UTUC 治疗的最新证据。在这方面，虽然手术在非转移性 UTUC 中的作用是毋庸置疑的，但辅助或新辅助化疗的可靠数据仍然是未满足的需求，无法在标准治疗中实现明确的范式转变。在晚期，证据主要基于 BC 文献和回顾性研究，证实铂类联合方案是一线治疗的基石。最近，免疫疗法和靶向治疗在转移性疾病的治疗中崭露头角，pembrolizumab 和 atezolizumab 联合化疗作为一线策略显示出令人鼓舞的结果。此外，atezolizumab 作为维持治疗表现良好，而 pembrolizumab 作为单一药物在二线治疗中也取得了良好的效果。关于靶向治疗，成纤维细胞生长因子受体抑制剂 erdafitinib 和抗体药物偶联物 enfortumab vedotin 已被证明具有很强的抗肿瘤特性，这可能是由于 UTUC 独特的免疫遗传背景。在这种情况下，已经做出了巨大的努力来揭示 UTUC 患者的生物学、免疫学和临床基础，以实现个性化治疗。
