Hermans Tom J N, Voskuilen Charlotte S, van der Heijden Michiel S, Schmitz-Dräger Bernd J, Kassouf Wassim, Seiler Roland, Kamat Ashish M, Grivas Petros, Kiltie Anne E, Black Peter C, van Rhijn Bas W G
Department of Surgical Oncology (Urology), Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
Department of Medical Oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
Urol Oncol. 2018 Sep;36(9):413-422. doi: 10.1016/j.urolonc.2017.10.014. Epub 2017 Nov 8.
Approximately half of patients who undergo radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) will succumb to metastatic disease. We summarize the evidence for neoadjuvant radiation (NAR), chemo (NAC), and immunotherapy (checkpoint inhibition) prior to RC for MIBC.
Data were obtained by a search of PubMed, ClinicalTrials.gov, and Cochrane databases for English language articles published from 1925 up to 2017.
NAC usage has increased over the last decade, while NAR is rarely administered. Although NAR results in downstaging, its impact on survival is inconclusive. Based on level I evidence, cisplatin-based NAC (CB-NAC) is considered standard of care in cT2-4aN0M0 MIBC. NAC results in a 6% absolute 10-year overall survival (OS) benefit. In-depth analyses of key randomized controlled trials showed that failure to correct for uniform staging, surgical variation, and patient selection compromises the ability to identify factors predictive of response to NAC. The benefit appears to be restricted to patients downstaged to ypT1N0 or less. In these patients, 5-year OS is 80% to 90%. Regarding a number needed to treat of 17, most patients with cT2-4aN0M0 MIBC will be exposed to toxicity without benefit. Possible approaches to reduce overtreatment are suggested in this article and include patient selection, the chosen NAC regimen, and emerging molecular data to predict responsiveness to NAC. Neoadjuvant immunotherapy with checkpoint inhibitors is a promising future perspective currently under investigation.
Past studies on NAR show inconclusive results and NAR is rarely administered. Instead, CB-NAC is advised in eligible patients with cT2-4aN0M0 MIBC prior to RC. In the near future, predictive biomarkers will be the key to tailor the use of CB-NAC and reduce harm to nonresponders.
因肌层浸润性膀胱癌（MIBC）接受根治性膀胱切除术（RC）的患者中，约有一半会死于转移性疾病。我们总结了MIBC患者在RC术前接受新辅助放疗（NAR）、化疗（NAC）和免疫治疗（检查点抑制）的证据。
通过检索PubMed、ClinicalTrials.gov和Cochrane数据库，获取1925年至2017年发表的英文文章数据。
在过去十年中，NAC的使用有所增加，而NAR很少应用。尽管NAR可使肿瘤降期，但其对生存率的影响尚无定论。基于I级证据，以顺铂为基础的NAC（CB-NAC）被认为是cT2-4aN0M0 MIBC的标准治疗方案。NAC可使10年总生存率（OS）绝对提高6%。对关键随机对照试验的深入分析表明，未能校正统一分期、手术差异和患者选择会影响识别NAC反应预测因素的能力。这种益处似乎仅限于降期至ypT1N0或更低分期的患者。在这些患者中，5年OS率为80%至90%。考虑到需治疗人数为17，大多数cT2-4aN0M0 MIBC患者将遭受毒性而无益处。本文提出了减少过度治疗的可能方法，包括患者选择、所选的NAC方案以及预测NAC反应性的新出现的分子数据。使用检查点抑制剂进行新辅助免疫治疗是目前正在研究的一个有前景的未来方向。
过去关于NAR的研究结果尚无定论，且NAR很少应用。相反，建议符合条件的cT2-4aN0M0 MIBC患者在RC术前使用CB-NAC。在不久的将来，预测性生物标志物将是调整CB-NAC使用并减少对无反应者伤害的关键。
