保留膀胱与根治切除在高级别非肌层浸润性膀胱癌中的疗效对比 -- 基于队列研究的 meta 分析

原文： 2019 年发布于 Frontiers in Oncology 215 卷第 2 期 3781-3791  浏览量：165次 原文链接

作者单位： The Danish Cancer Society Research Center, Copenhagen, Denmark Centre for Epidemiology and Screening, Department of Public Health, University of Copenhagen, Copenhagen, Denmark. Electronic address: mp@sund.ku.dk. Department of Epidemiology, Lazio Regional Health Service, Rome, Italy Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden. Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany. Centre for Epidemiology and Screening, Department of Public Health, University of Copenhagen, Copenhagen, Denmark. Unit of Cancer Epidemiology, Città della Salute e della Scienza University Hospital and Center for Cancer Prevention, Turin, Italy. Occupational and Environmental Medicine, Department of Public Health and Clinical Medicine, Umea University, Umea, Sweden. Norwegian Institute of Public Health, Oslo, Norway. Department of Landscape Architecture and Spatial Planning, Norwegian University of Life Sciences, Ås, Norway. Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden. Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden. Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden. Aging Research Center, Department of Neurobiology Care Science and Society, Karolinska Institute, Stockholm, Sweden. The Danish Cancer Society Research Center, Copenhagen, Denmark. Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, UK. MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, UK Department for Determinants of Chronic Diseases, National Institute for Public Health and the Environment, Bilthoven, The Netherlands Department of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, UK Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands Swiss Tropical and Public Health Institute, Basel, Switzerland University of Basel, Basel, Switzerland. MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, UK. Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK. Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden Agency for Preventive and Social Medicine, Bregenz, Austria. Agency for Preventive and Social Medicine, Bregenz, Austria. Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA. Swiss Tropical and Public Health Institute, Basel, Switzerland University of Basel, Basel, Switzerland Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA. Epidemiology and Prevention Unit, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. Unit of Epidemiology & Medical Statistics, Department of Diagnostics and Public Health, University of Verona, Verona, Italy. Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany Unit of Epidemiology, Regional Health Service, Grugliasco, Italy. Environmental Health Reference Centre, Regional Agency for Environmental Prevention of Emilia-Romagna, Modena, Italy. Department of Epidemiology, Lazio Regional Health Service, Rome, Italy. Institute de Salut Global Barcelona, Barcelona, Spain CIBER Epidemiología y Salud Pública, Madrid, Spain Universitat Pompeu Fabra, Barcelona, Spain. Public Health Department of Gipuzkoa, BioDonostia Research Institute, San Sebastian, Spain Consortium for Biomedical Research in Epidemiology and Public Health, Madrid, Spain. Division of Epidemiology and Biostatistics, School of Public Health, University of Illinois at Chicago, Chicago, IL, USA. Institute de Salut Global Barcelona, Barcelona, Spain CIBER Epidemiología y Salud Pública, Madrid, Spain. Centre for Atmospheric and Instrumentation Research, University of Hertfordshire, Hatfield, UK. Swiss Tropical and Public Health Institute, Basel, Switzerland University of Basel, Basel, Switzerland. Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands National Institute for Public Health (RIVM), Bilthoven, The Netherlands. MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, UK Molecular and Epidemiology Unit, Human Genetics Foundation, Turin, Italy. Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands. The Danish Cancer Society Research Center, Copenhagen, Denmark Department of Environmental Science, Aarhus University, Roskilde, Denmark.

归属分类：膀胱肿瘤治疗及预后证据

DOI： 10.1080/21681805.2020.1773527

关键词：扩散加权成像特异度

BACKGROUND: The activity of PD-1/PD-L1 inhibitors in the treatment of advanced bladder cancer (BC) is promising for many patients. However, a subset of patients do not benefit from treatment, thus leading to an effort to better identify predictive molecular biomarkers of response. OBJECTIVE: To conduct a systematic review of the literature on predictive molecular biomarkers associated with response to PD-1 and PD-L1 inhibitors in advanced bladder cancer, defined as locally-advanced, unresectable, or metastatic (mBC) disease. METHODS: A search of the literature was performed using Embase (1947 - January 2019), Medline (1946 - January 2019), and EBM Reviews for Cochrane Central Register of Controlled Trials (as of December 2018). Studies examining the association of molecular biomarkers with clinical outcome in BC treated with PD-1 or PD-L1 monotherapy were included. Outcomes of interest were overall survival (OS), cancer-specific survival (CSS), progression-free survival (PFS), duration of response, and objective response rate (ORR). RESULTS: Using the study search criteria, 899 unique abstract citations were found, of which 834 did not meet the eligibility criteria. Full text of the remaining 65 citations were screened, and 50 studies excluded, including 18 review articles. Eight additional studies from the bibliography of the review papers were included, making a total of 23 studies. Five PD-1 / PD-L1 antibodies have been tested in BC immunohistochemistry (IHC). These studies used different expression scoring criteria and generally had poor ability to discriminate likelihood for response. Overall, the data suggests CD8(+) T cell infiltration is necessary to mediate an antitumor immune response, but other immune cell populations, such as neutrophils may suppress T cell-mediated immunity and efficacy of PD-1/PD-L1 blockade. An IFNγ signature is a promising predictor, but there needs to be consensus on the optimal gene panel composition, and prospective validation. Tumor mutation burden (TMB) is a promising predictor in six studies reporting on 1200 patients, but there is not a consensus on the optimal definition of `high TMB`. Detection of T cell receptor (TCR) clonal expansion has only been conducted in small studies and so its predictive value remains inconclusive. Epithelial-mesenchymal transformation (EMT) and transforming growth factor β (TGFβ) are associated with poor prognosis and possibly intrinsic resistance to PD-1/PD-L1 checkpoint blockade, but more work needs to be done to build upon and confirm the initial findings. CONCLUSIONS: Currently no molecular biomarker is sufficiently mature for routine clinical use, while some candidates, or a combination show great promise and need further study.