Afferi Luca, Moschini Marco, Cumberbatch Marcus G, Catto James W, Scarpa Roberto M, Porpiglia Francesco, Mattei Agostino, Sanchez-Salas Rafael, Esperto Francesco
Department of Urology, Luzerner Kantonsspital, Lucerne, Switzerland.
Department of Urology, Luzerner Kantonsspital, Lucerne, Switzerland -
Minerva Urol Nefrol. 2020 Jun;72(3):265-278. doi: 10.23736/S0393-2249.20.03786-8. Epub 2020 Apr 16.
The European Organization for Research and Treatment of Cancer (EORTC) and the Spanish Urological Club for Oncological Treatment (CUETO) scoring systems show limited accuracy for the prediction of disease recurrence and progression of non-muscle-invasive bladder cancer (NMIBC). This aspect is even more relevant in the category of HR NMIBC. Biomarkers might potentially help to further categorize the outcomes of these patients. Therefore, we sought to review the evidence available on tissue-based, urinary, and serum biomarkers for the prediction of recurrence, progression, and survival in HR NMIBC.
A systematic literature review without time restrictions was performed using PubMed/EMBASE, Web of Science, SCOPUS, and the Cochrane Libraries. The search was filtered for articles in the English, Italian, German, French, and Spanish languages, involving patients with more than 18 years of age. Relevant papers on tissue-based, serum and urinary biomarkers related to the prediction of oncological outcomes for high-risk bladder cancer patients were included in the analyses.
Overall, 71 studies were eligible for inclusion in this review. The majority of the investigations performed so far focused on immunohistochemical analyses on tumoral tissue. Overall, p53 was the most studied biomarker, but results regarding its prognostic and predictive role were contradictory. Ki67 seems to be a promising biomarker in the prediction of recurrence. Recently, PD-L1 has been associated with the prediction of recurrence free survival and of treatment-refractory disease. Markers developed un urine samples are focused on commercially available kits, which currently do not unequivocally show strongly superior levels of accuracy to cytology. However, they have demonstrated to be potentially helpful in the prediction of recurrence. Blood-based biomarkers represent an emerging reality with promising future applications.
Despite a long history of attempts to discover accurate biomarkers predicting oncological outcomes for HR NMIBC, contradictory or uncertain findings render the adoption of this ancillary techniques in clinical practice still unlikely. Future attempts should be directed to the development of prospective trials and the definition of standardized cut-off levels to render findings worthy of comparison.
欧洲癌症研究与治疗组织（EORTC）和西班牙肿瘤治疗泌尿学俱乐部（CUETO）的评分系统在预测非肌肉浸润性膀胱癌（NMIBC）的疾病复发和进展方面准确性有限。这一情况在高危NMIBC类别中更为突出。生物标志物可能有助于进一步对这些患者的预后进行分类。因此，我们试图回顾关于基于组织、尿液和血清生物标志物预测高危NMIBC复发、进展和生存的现有证据。
使用PubMed/EMBASE、科学网、Scopus和Cochrane图书馆进行了无时间限制的系统文献综述。搜索筛选了英文、意大利文、德文、法文和西班牙文的文章，涉及年龄超过18岁的患者。分析纳入了与高危膀胱癌患者肿瘤学预后预测相关的基于组织、血清和尿液生物标志物的相关论文。
总体而言，71项研究符合纳入本综述的条件。迄今为止进行的大多数研究集中在肿瘤组织的免疫组化分析上。总体而言，p53是研究最多的生物标志物，但其预后和预测作用的结果相互矛盾。Ki67似乎是预测复发的有前景的生物标志物。最近，PD-L1与无复发生存期和治疗难治性疾病的预测相关。基于尿液样本开发的标志物集中在商用试剂盒上，目前这些试剂盒在准确性上并未明确显示出明显优于细胞学检查的水平。然而，它们已被证明在预测复发方面可能有帮助。基于血液的生物标志物是一个新兴领域，具有广阔的未来应用前景。
尽管长期以来一直试图发现准确预测高危NMIBC肿瘤学预后的生物标志物，但相互矛盾或不确定的结果使得在临床实践中采用这种辅助技术仍然不太可能。未来的尝试应致力于开展前瞻性试验并确定标准化的临界值，以使研究结果值得比较。
