Aurilio Gaetano, Cimadamore Alessia, Lopez-Beltran Antonio, Scarpelli Marina, Massari Francesco, Verri Elena, Cheng Liang, Santoni Matteo, Montironi Rodolfo
Medical Oncology Division of Urogenital and Head and Neck Tumours, IEO, European Institute of Oncology IRCCS, Milan, Italy.
Section of Pathological Anatomy, United Hospitals, School of Medicine, Polytechnic University of the Marche Region, Ancona, Italy.
Transl Androl Urol. 2021 Mar;10(3):1521-1529. doi: 10.21037/tau-20-1436.
Over the last few years efficacy of immunotherapy using immune checkpoint inhibitors (ICI) has been investigated in patients with bladder cancer (BC) at all stages. The present article aims to assess new therapeutic options with emerging agents in BC patients, shedding light on ICI-based treatments encompassing all disease stages, from non-muscle invasive (NMIBC) to muscle-invasive (MIBC) BC, concluding with metastatic MIBC. In bacillus Calmette-Guerin (BCG) unresponsive patients with carcinoma in situ, pembrolizumab has been recently approved. In the neoadjuvant setting, results from two clinical trials seem to identify pathological and genomic features of highly responsive tumors. Squamous cells and lymphoepithelioma/like histotypes, programmed cell-death ligand 1 (PD-L1) expression and high levels of activate T cells have been associated with higher response rate. In the metastatic setting, only 30% of patient may respond to ICI. A panel of biomarkers for patient selection is an actual need since the correlation between response and PD-L1 expression seem inconsistent across clinical trials, with some exceptions. Molecular characterization of BC, tumor mutation burden and immune-gene expression profiling might introduce new molecular biomarkers, hopefully transferable into the clinical-pathological practice.
在过去几年中，已对各阶段膀胱癌（BC）患者使用免疫检查点抑制剂（ICI）进行免疫治疗的疗效展开了研究。本文旨在评估BC患者使用新型药物的新治疗选择，阐明涵盖从非肌层浸润性（NMIBC）到肌层浸润性（MIBC）膀胱癌所有疾病阶段的基于ICI的治疗方法，并以转移性MIBC作为总结。在卡介苗（BCG）无反应的原位癌患者中，派姆单抗最近已获批准。在新辅助治疗中，两项临床试验的结果似乎确定了高反应性肿瘤的病理和基因组特征。鳞状细胞和淋巴上皮瘤样组织学类型、程序性细胞死亡配体1（PD-L1）表达以及高水平的活化T细胞与更高的反应率相关。在转移性情况下，只有30%的患者可能对ICI有反应。由于不同临床试验中反应与PD-L1表达之间的相关性似乎不一致（有一些例外情况），因此目前实际需要一组用于患者选择的生物标志物。BC的分子特征、肿瘤突变负荷和免疫基因表达谱分析可能会引入新的分子生物标志物，有望应用于临床病理实践。
