Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia.
Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, University Hospital of Tours, Tours, France.
Urol Oncol. 2021 Mar;39(3):180-190. doi: 10.1016/j.urolonc.2020.12.019. Epub 2021 Jan 8.
The present systematic review aimed to identify prognostic values of tissue-based biomarkers in patients treated with neoadjuvant systemic therapy (NAST), including chemotherapy (NAC) and checkpoint inhibitors (NAI) for urothelial carcinoma of the bladder (UCB).
The PubMed, Web of Science, and Scopus databases were searched in August 2020 according to the PRISMA statement. Studies were deemed eligible if they compared oncologic or pathologic outcomes in patients treated with NAST for UCB with and without detected pretreatment tissue-based biomarkers.
Overall, 44 studies met our eligibility criteria. Twenty-three studies used immunohistochemistry (IHC), 19 - gene expression analysis, three - quantitative polymerase chain reaction (QT PCR), and two - next-generation sequencing (NGS). According to the currently available literature, predictive IHC-assessed biomarkers, such as receptor tyrosine kinases and DNA repair pathway alterations, do not seem to convincingly improve our prediction of pathologic response and oncologic outcomes after NAC. Luminal and basal tumor subtypes based on gene expression analysis showed better NAC response, while claudin-low and luminal-infiltrated tumor subtypes did not. In terms of NAI, PD-L1 seems to maintain value as a predictive biomarker, while the utility of both tumor mutational burden and molecular subtypes remains controversial. Specific genomic alterations in DNA repair genes have been shown to provide significant predictive value in patient treated with NAC. QT PCR quantification of specific genes selected through microarray analysis seems to classify cases regarding their NAC response.
We believe that the present systematic review may offer a robust framework that will enable the testing and validation of predictive biomarkers in future prospective clinical trials. NGS has expanded the discovery of molecular markers that are reflective of the mechanisms of the NAST response.
本系统评价旨在确定新辅助全身治疗（NAST），包括化疗（NAC）和检查点抑制剂（NAI）治疗膀胱癌（UCB）患者的组织生物标志物的预后价值。
根据 PRISMA 声明，于 2020 年 8 月检索 PubMed、Web of Science 和 Scopus 数据库。如果研究比较了接受 NAST 治疗 UCB 的患者有无检测到预处理组织生物标志物的肿瘤学或病理结果，则认为其符合入选标准。
总体而言，44 项研究符合入选标准。23 项研究使用免疫组织化学（IHC），19 项 - 基因表达分析，3 项 - 定量聚合酶链反应（QT PCR），2 项 - 下一代测序（NGS）。根据目前的文献，预测性 IHC 评估的生物标志物，如受体酪氨酸激酶和 DNA 修复途径改变，似乎并不能令人信服地改善我们对 NAC 后病理反应和肿瘤学结果的预测。基于基因表达分析的腔型和基底型肿瘤亚型显示出更好的 NAC 反应，而 Claudin-low 和腔浸润型肿瘤亚型则没有。在 NAI 方面，PD-L1 似乎仍然是一种有价值的预测生物标志物，而肿瘤突变负担和分子亚型的效用仍存在争议。在接受 NAC 治疗的患者中，DNA 修复基因的特定基因组改变已被证明具有显著的预测价值。通过微阵列分析选择的特定基因的 QT PCR 定量似乎可以对 NAC 反应进行分类。
我们认为，本系统评价可以提供一个稳健的框架，使预测生物标志物在未来的前瞻性临床试验中得到测试和验证。NGS 扩大了对反映 NAST 反应机制的分子标志物的发现。
