Urinary Molecular Pathology for Patients with Newly Diagnosed Urothelial Bladder Cancer

No AccessJournal of UrologyAdult Urology1 Oct 2021Urinary Molecular Pathology for Patients with Newly Diagnosed Urothelial Bladder CancerThis article is commented on by the following:Editorial CommentEditorial Comment Ruiyun Zhang, Jingyu Zang, Feng Xie, Yue Zhang, Yiqiu Wang, Ying Jing, Yi Zhang, Zhaoxiong Chen, Akezhouli Shahatiaili, Mei-Chun Cai, Zhixin Zhao, Pan Du, Shidong Jia, Guanglei Zhuang, and Haige Chen Ruiyun ZhangRuiyun Zhang Department of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China Equal study contribution. More articles by this author , Jingyu ZangJingyu Zang State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China Equal study contribution. More articles by this author , Feng XieFeng Xie Huidu Shanghai Medical Sciences Ltd, Shanghai, China Equal study contribution. Financial and/or other relationship with Huidu Shanghai Medical Sciences Ltd. More articles by this author , Yue ZhangYue Zhang Huidu Shanghai Medical Sciences Ltd, Shanghai, China Financial and/or other relationship with Huidu Shanghai Medical Sciences Ltd. More articles by this author , Yiqiu WangYiqiu Wang Department of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China More articles by this author , Ying JingYing Jing State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China More articles by this author , Yi ZhangYi Zhang Shanghai Key Laboratory of Gynecologic Oncology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China More articles by this author , Zhaoxiong ChenZhaoxiong Chen CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Center for Quantitative Biology, Peking University, Beijing, China More articles by this author , Akezhouli ShahatiailiAkezhouli Shahatiaili Department of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China More articles by this author , Mei-Chun CaiMei-Chun Cai State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China More articles by this author , Zhixin ZhaoZhixin Zhao Huidu Shanghai Medical Sciences Ltd, Shanghai, China Financial and/or other relationship with Huidu Shanghai Medical Sciences Ltd. More articles by this author , Pan DuPan Du Huidu Shanghai Medical Sciences Ltd, Shanghai, China Financial and/or other relationship with Huidu Shanghai Medical Sciences Ltd. More articles by this author , Shidong JiaShidong Jia Huidu Shanghai Medical Sciences Ltd, Shanghai, China Financial and/or other relationship with Huidu Shanghai Medical Sciences Ltd. More articles by this author , Guanglei ZhuangGuanglei Zhuang http://orcid.org/0000-0003-3088-177X Department of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China More articles by this author , and Haige ChenHaige Chen ‡Correspondence: Department of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Rd, Pudong New District, Shanghai200127, China telephone: 86-13801796126; E-mail Address: [email protected] Department of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001878AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Next-generation sequencing (NGS)-based profiling of both urinary tumor DNA (utDNA) and circulating tumor DNA (ctDNA) shows promise for noninvasive detection and surveillance of urothelial bladder cancer (UBC). However, the analytical performance of these assays remains undefined in the real-world setting. Here, we sought to evaluate the concordance between tumor DNA (tDNA) profiling and utDNA or ctDNA assays using a UBC patient cohort from the intended-use population. Materials and Methods: Fifty-nine cases with pathologically confirmed disease and matching tissue/urine pairs were prospectively enrolled. Baseline peripheral blood mononuclear cell and plasma specimens were collected during clinic visits. The PredicineCARETM NGS assay was applied for ultra-deep targeted sequencing and somatic alteration identification in tDNA, utDNA and ctDNA. Results: Diverse quantitative metrics including cancer cell fraction, variant allele frequency and tumor mutation burden were invariably concordant between tDNA and utDNA, but not ctDNA. The mutational landscapes captured by tDNA or utDNA were highly similar, whereas a considerable proportion of ctDNA aberrations stemmed from clonal hematopoiesis. Using tDNA-informed somatic events as reference, utDNA assays achieved a specificity of 99.3%, a sensitivity of 86.7%, a positive predictive value of 67.2%, a negative predictive value of 99.8% and a diagnostic accuracy of 99.1%. Higher preoperative utDNA or tDNA abundance correlated with worse relapse-free survival. Actionable variants including FGFR3 alteration and ERBB2 amplification were identified in utDNA. Conclusions: Urine-based molecular pathology provides a valid and complete genetic profile of bladder cancer, and represents a faithful surrogate for genotyping and monitoring newly diagnosed UBC. References 1. : Bladder cancer. Nat Rev Dis Primers 2017; 3: 17022. Google Scholar 2. : Advances in bladder cancer biology and therapy. Nat Rev Cancer 2021; 21: 104. Google Scholar 3. : Liquid biopsy biomarkers in bladder cancer: a current need for patient diagnosis and monitoring. Int J Mol Sci 2018; 19: 2514. 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Google Scholar Support: This work was supported by the National Natural Science Foundation of China (81672514, 81902562), Shanghai Natural Science Foundation (16ZR1420300, 18410720400, 19431907400), Ren Ji Hospital Research Funding Projects (RJZZ18-020, PYIII-17-017, PY2018-IIC-02), Shanghai Jiao Tong University School of Medicine Research Funding Projects (TM201708) and Foundation of Shanghai Hospital Development Center (SHDC12015125). © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsRelated articlesJournal of UrologyAug 11, 2021, 12:00:00 AMEditorial CommentJournal of UrologyAug 11, 2021, 12:00:00 AMEditorial Comment Volume 206Issue 4October 2021Page: 873-884Supplementary Materials Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.Keywordshigh-throughput nucleotide sequencingcirculating tumor DNAurineliquid biopsyurinary bladder neoplasmsAcknowledgmentsThe author would like to thank Bonnie King and Jianjun Yu for proofreading.MetricsAuthor Information Ruiyun Zhang Department of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China Equal study contribution. More articles by this author Jingyu Zang State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China Equal study contribution. More articles by this author Feng Xie Huidu Shanghai Medical Sciences Ltd, Shanghai, China Equal study contribution. Financial and/or other relationship with Huidu Shanghai Medical Sciences Ltd. More articles by this author Yue Zhang Huidu Shanghai Medical Sciences Ltd, Shanghai, China Financial and/or other relationship with Huidu Shanghai Medical Sciences Ltd. More articles by this author Yiqiu Wang Department of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China More articles by this author Ying Jing State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China More articles by this author Yi Zhang Shanghai Key Laboratory of Gynecologic Oncology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China More articles by this author Zhaoxiong Chen CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Center for Quantitative Biology, Peking University, Beijing, China More articles by this author Akezhouli Shahatiaili Department of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China More articles by this author Mei-Chun Cai State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China More articles by this author Zhixin Zhao Huidu Shanghai Medical Sciences Ltd, Shanghai, China Financial and/or other relationship with Huidu Shanghai Medical Sciences Ltd. More articles by this author Pan Du Huidu Shanghai Medical Sciences Ltd, Shanghai, China Financial and/or other relationship with Huidu Shanghai Medical Sciences Ltd. More articles by this author Shidong Jia Huidu Shanghai Medical Sciences Ltd, Shanghai, China Financial and/or other relationship with Huidu Shanghai Medical Sciences Ltd. More articles by this author Guanglei Zhuang Department of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China More articles by this author Haige Chen Department of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China ‡Correspondence: Department of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, 160 Pujian Rd, Pudong New District, Shanghai200127, China telephone: 86-13801796126; E-mail Address: [email protected] More articles by this author Expand All Support: This work was supported by the National Natural Science Foundation of China (81672514, 81902562), Shanghai Natural Science Foundation (16ZR1420300, 18410720400, 19431907400), Ren Ji Hospital Research Funding Projects (RJZZ18-020, PYIII-17-017, PY2018-IIC-02), Shanghai Jiao Tong University School of Medicine Research Funding Projects (TM201708) and Foundation of Shanghai Hospital Development Center (SHDC12015125). 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