Silina Linda, Maksut Fatlinda, Bernard-Pierrot Isabelle, Radvanyi François, Créhange Gilles, Mégnin-Chanet Frédérique, Verrelle Pierre
French League Against Cancer Team, CNRS UMR144, Curie Institute and PSL Research University, 75005 Paris, France.
CNRS UMR 9187, INSERM U1196, Curie Institute, PSL Research University and Paris-Saclay University, Rue H. Becquerel, 91405 Orsay, France.
Cancers (Basel). 2020 Dec 30;13(1):87. doi: 10.3390/cancers13010087.
Bladder cancer is among the top ten most common cancer types in the world. Around 25% of all cases are muscle-invasive bladder cancer, for which the gold standard treatment in the absence of metastasis is the cystectomy. In recent years, trimodality treatment associating maximal transurethral resection and radiotherapy combined with concurrent chemotherapy is increasingly used as an organ-preserving alternative. However, the use of this treatment is still limited by the lack of biomarkers predicting tumour response and by a lack of targeted radiosensitising drugs that can improve the therapeutic index, especially by limiting side effects such as bladder fibrosis. In order to improve the bladder-preserving treatment, experimental studies addressing these main issues ought to be considered (both in vitro and in vivo studies). Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for systematic reviews, we conducted a literature search in PubMed on experimental studies investigating how to improve bladder cancer radiotherapy with different radiosensitising agents using a comprehensive search string. We made comments on experimental model selection, experimental design and results, formulating the gaps of knowledge still existing: such as the lack of reliable predictive biomarkers of tumour response to chemoradiation according to the molecular tumour subtype and lack of efficient radiosensitising agents specifically targeting bladder tumour cells. We provided guidance to improve forthcoming studies, such as taking into account molecular characteristics of the preclinical models and highlighted the value of using patient-derived xenografts as well as syngeneic models. Finally, this review could be a useful tool to set up new radiation-based combined treatments with an improved therapeutic index that is needed for bladder preservation.
膀胱癌是全球十大最常见的癌症类型之一。所有病例中约25%为肌层浸润性膀胱癌，对于无转移的此类病例，金标准治疗方法是膀胱切除术。近年来，将最大经尿道切除术、放疗与同步化疗相结合的三联疗法越来越多地被用作一种保留器官的替代方案。然而，这种治疗方法的应用仍受到限制，一方面缺乏预测肿瘤反应的生物标志物，另一方面缺乏可提高治疗指数的靶向放射增敏药物，尤其是缺乏能减少膀胱纤维化等副作用的药物。为了改进保留膀胱的治疗方法，应该考虑针对这些主要问题开展实验研究（包括体外和体内研究）。按照系统评价和Meta分析的首选报告项目（PRISMA）指南进行系统评价，我们在PubMed上进行了文献检索，以查找使用综合检索词研究如何用不同放射增敏剂改善膀胱癌放疗的实验研究。我们对实验模型选择、实验设计和结果进行了评论，指出了仍然存在的知识空白：例如缺乏根据分子肿瘤亚型对放化疗的肿瘤反应的可靠预测生物标志物，以及缺乏专门针对膀胱肿瘤细胞的有效放射增敏剂。我们为改进后续研究提供了指导，例如考虑临床前模型的分子特征，并强调使用患者来源的异种移植模型以及同基因模型的价值。最后，本综述可能是建立具有更高治疗指数的新的基于放疗的联合治疗方法的有用工具，而这正是保留膀胱所需要的。
