Noninvasive Detection of Clinically Significant Prostate Cancer Using Circulating Tumor Cells

No AccessJournal of UrologyAdult Urology1 Jan 2020Noninvasive Detection of Clinically Significant Prostate Cancer Using Circulating Tumor CellsThis article is commented on by the following:Editorial CommentEditorial Comment Lei Xu, Xueying Mao, Alistair Grey, Glenda Scandura, Tianyu Guo, Edwina Burke, Jacek Marzec, Semah Abdu, Elzbieta Stankiewicz, Caitlin R. Davies, Prabhakar Rajan, Karen Tipples, John Hines, Pui Ying Chan, Diane Campbell, Karen Wilkinson, Sakunthala Kudahetti, Jonathan Shamash, Tim Oliver, Daniel Berney, Greg Shaw, and Yong-Jie Lu Lei XuLei Xu Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, United Kingdom Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China Equal study contribution. More articles by this author , Xueying MaoXueying Mao Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, United Kingdom Equal study contribution. More articles by this author , Alistair GreyAlistair Grey Department of Urology, Barts Health National Health Service, United Kingdom Division of Surgery and Interventional Sciences, University College London, United Kingdom Department of Surgery and Cancer, Imperial College London, United Kingdom More articles by this author , Glenda ScanduraGlenda Scandura Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, United Kingdom More articles by this author , Tianyu GuoTianyu Guo Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, United Kingdom More articles by this author , Edwina BurkeEdwina Burke Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, United Kingdom More articles by this author , Jacek MarzecJacek Marzec Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, United Kingdom More articles by this author , Semah AbduSemah Abdu Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, United Kingdom More articles by this author , Elzbieta StankiewiczElzbieta Stankiewicz Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, United Kingdom More articles by this author , Caitlin R. DaviesCaitlin R. Davies Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, United Kingdom More articles by this author , Prabhakar RajanPrabhakar Rajan Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, United Kingdom Department of Urology, Barts Health National Health Service, United Kingdom Division of Surgery and Interventional Sciences, University College London, United Kingdom Department of Urology, University College London National Health Service Foundation Trust, London, United Kingdom More articles by this author , Karen TipplesKaren Tipples Department of Urology, Barts Health National Health Service, United Kingdom More articles by this author , John HinesJohn Hines Department of Urology, Barts Health National Health Service, United Kingdom Department of Urology, University College London National Health Service Foundation Trust, London, United Kingdom More articles by this author , Pui Ying ChanPui Ying Chan Department of Medical Oncology, Barts Health National Health Service, United Kingdom More articles by this author , Diane CampbellDiane Campbell Department of Urology, Barts Health National Health Service, United Kingdom More articles by this author , Karen WilkinsonKaren Wilkinson Department of Urology, Barts Health National Health Service, United Kingdom Department of Urology, University College London National Health Service Foundation Trust, London, United Kingdom More articles by this author , Sakunthala KudahettiSakunthala Kudahetti Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, United Kingdom More articles by this author , Jonathan ShamashJonathan Shamash Department of Medical Oncology, Barts Health National Health Service, United Kingdom More articles by this author , Tim OliverTim Oliver Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, United Kingdom More articles by this author , Daniel BerneyDaniel Berney Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, United Kingdom More articles by this author , Greg ShawGreg Shaw Department of Urology, Barts Health National Health Service, United Kingdom Division of Surgery and Interventional Sciences, University College London, United Kingdom Department of Urology, University College London National Health Service Foundation Trust, London, United Kingdom Financial interest and/or other relationship with ANGLE plc. More articles by this author , and Yong-Jie LuYong-Jie Lu ‡Correspondence: Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London , EC1M 6BQ, United Kingdom telephone: +44 (0)20 7882 3597; FAX: +44 (0)20 7882 3884; E-mail Address: [email protected] Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, United Kingdom First Affiliated Hospital and Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China Financial interest and/or other relationship with ANGLE plc. More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000475AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Prostate specific antigen testing results in unnecessary biopsy and over diagnosis with consequent overtreatment. Tissue biopsy is an invasive procedure associated with significant morbidity. More accurate noninvasive or minimally invasive diagnostic approaches should be developed to avoid unnecessary prostate biopsy and over diagnosis. We investigated the potential of using circulating tumor cell analysis in cancer diagnosis, particularly to predict clinically significant prostate cancer in prebiopsy cases. Materials and Methods: We enrolled 155 treatment naïve patients with prostate cancer and 98 before biopsy for circulating tumor cell enumeration. RNA was extracted from circulating tumor cells of 184 patients for gene expression analysis. The Kruskal-Wallis and Spearman rank tests, multivariate logistic regression and the random forest method were applied to assess the association of circulating tumor cells with aggressive prostate cancer. Results: Of patients with localized prostate cancer 54% were scored as having positive circulating tumor cells, which was associated with a higher Gleason score (p=0.0003), risk group (p <0.0001) and clinically significant prostate cancer (p <0.0001). In the prebiopsy group a positive circulating tumor cell score combined with prostate specific antigen predicted clinically significant prostate cancer (AUC 0.869). A 12-gene panel prognostic for clinically significant prostate cancer was also identified. When combining the prostate specific antigen level, the circulating tumor cell score and the 12-gene panel, the AUC of clinically significant prostate cancer prediction was 0.927. Adding those data to cases with available multiparametric magnetic resonance imaging data significantly increased prediction accuracy (AUC 0.936 vs 0.629). Conclusions: Circulating tumor cell analysis has the potential to significantly improve patient stratification by prostate specific antigen and/or multiparametric magnetic resonance imaging for biopsy and treatment. References 1. : Cancer statistics, 2014. CA Cancer J Clin 2014; 64: 9. Google Scholar 2. American Cancer Society: Cancer Facts & Figures 2016. Available at https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2016.html. Accessed July 22, 2019. Google Scholar 3. : American Cancer Society guideline for the early detection of prostate cancer: update 2010. CA Cancer J Clin 2010; 60: 70. Google Scholar 4. : Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med 2012; 367: 203. Google Scholar 5. : Outcomes in localized prostate cancer: National Prostate Cancer Register of Sweden follow-up study. J Natl Cancer Inst 2010; 102: 950. 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Supported by Orchid Cancer Appeal, Cancer Research UK Grant No. C16420/A18066 and ANGLE plc, and the grant numbers of Orchid Cancer Appeal and ANGLE plc are not applicable. The funding source had no role in study design, data collection, analysis or interpretation or manuscript writing. No direct or indirect commercial, personal, academic, political, religious or ethical incentive is associated with publishing this article. © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsRelated articlesJournal of Urology3 Oct 2019Editorial CommentJournal of Urology3 Oct 2019Editorial Comment Volume 203Issue 1January 2020Page: 73-82Supplementary Materials Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.Keywordscirculatinggene expressionmagnetic resonance imagingprostatic neoplasmsneoplastic cellsprostatic specific antigenATCC® provided the PC3, LNCaP and VCaP PCa cell lines.MetricsAuthor Information Lei Xu Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, United Kingdom Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China Equal study contribution. More articles by this author Xueying Mao Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, United Kingdom Equal study contribution. More articles by this author Alistair Grey Department of Urology, Barts Health National Health Service, United Kingdom Division of Surgery and Interventional Sciences, University College London, United Kingdom Department of Surgery and Cancer, Imperial College London, United Kingdom More articles by this author Glenda Scandura Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, United Kingdom More articles by this author Tianyu Guo Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, United Kingdom More articles by this author Edwina Burke Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, United Kingdom More articles by this author Jacek Marzec Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, United Kingdom More articles by this author Semah Abdu Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, United Kingdom More articles by this author Elzbieta Stankiewicz Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, United Kingdom More articles by this author Caitlin R. Davies Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, United Kingdom More articles by this author Prabhakar Rajan Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, United Kingdom Department of Urology, Barts Health National Health Service, United Kingdom Division of Surgery and Interventional Sciences, University College London, United Kingdom Department of Urology, University College London National Health Service Foundation Trust, London, United Kingdom More articles by this author Karen Tipples Department of Urology, Barts Health National Health Service, United Kingdom More articles by this author John Hines Department of Urology, Barts Health National Health Service, United Kingdom Department of Urology, University College London National Health Service Foundation Trust, London, United Kingdom More articles by this author Pui Ying Chan Department of Medical Oncology, Barts Health National Health Service, United Kingdom More articles by this author Diane Campbell Department of Urology, Barts Health National Health Service, United Kingdom More articles by this author Karen Wilkinson Department of Urology, Barts Health National Health Service, United Kingdom Department of Urology, University College London National Health Service Foundation Trust, London, United Kingdom More articles by this author Sakunthala Kudahetti Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, United Kingdom More articles by this author Jonathan Shamash Department of Medical Oncology, Barts Health National Health Service, United Kingdom More articles by this author Tim Oliver Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, United Kingdom More articles by this author Daniel Berney Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, United Kingdom More articles by this author Greg Shaw Department of Urology, Barts Health National Health Service, United Kingdom Division of Surgery and Interventional Sciences, University College London, United Kingdom Department of Urology, University College London National Health Service Foundation Trust, London, United Kingdom Financial interest and/or other relationship with ANGLE plc. More articles by this author Yong-Jie Lu Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, United Kingdom First Affiliated Hospital and Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China ‡Correspondence: Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London , EC1M 6BQ, United Kingdom telephone: +44 (0)20 7882 3597; FAX: +44 (0)20 7882 3884; E-mail Address: [email protected] Financial interest and/or other relationship with ANGLE plc. More articles by this author Expand All The corresponding author certifies that, when applicable, a statement(s) has been included in the manuscript documenting institutional review board, ethics committee or ethical review board study approval; principles of Helsinki Declaration were followed in lieu of formal ethics committee approval; institutional animal care and use committee approval; all human subjects provided written informed consent with guarantees of confidentiality; IRB approved protocol number; animal approved project number. Supported by Orchid Cancer Appeal, Cancer Research UK Grant No. C16420/A18066 and ANGLE plc, and the grant numbers of Orchid Cancer Appeal and ANGLE plc are not applicable. The funding source had no role in study design, data collection, analysis or interpretation or manuscript writing. No direct or indirect commercial, personal, academic, political, religious or ethical incentive is associated with publishing this article. 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