Personalized Prediction of Tumor Response and Cancer Progression on Prostate Needle Biopsy (2009)

No AccessJournal of UrologyAdult Urology1 Jul 2009Personalized Prediction of Tumor Response and Cancer Progression on Prostate Needle Biopsyis accompanied byPhase II Trial of Capecitabine and Weekly Docetaxel for Metastatic Castrate Resistant Prostate Cancer Michael J. Donovan, Faisal M. Khan, Gerardo Fernandez, Ricardo Mesa-Tejada, Marina Sapir, Valentina Bayer Zubek, Douglas Powell, Stephen Fogarasi, Yevgen Vengrenyuk, Mikhail Teverovskiy, Mark R. Segal, R. Jeffrey Karnes, Thomas A. Gaffey, Christer Busch, Michael Haggman, Peter Hlavcak, Stephen J. Freedland, Robin T. Vollmer, Peter Albertsen, Jose Costa, and Carlos Cordon-Cardo Michael J. DonovanMichael J. Donovan Aureon Laboratories, Inc., New York, New York , Faisal M. KhanFaisal M. Khan Aureon Laboratories, Inc., New York, New York , Gerardo FernandezGerardo Fernandez Aureon Laboratories, Inc., New York, New York , Ricardo Mesa-TejadaRicardo Mesa-Tejada Aureon Laboratories, Inc., New York, New York Yonkers and Herbert Irving Comprehensive Cancer Center, Columbia University, New York, New York , Marina SapirMarina Sapir Aureon Laboratories, Inc., New York, New York , Valentina Bayer ZubekValentina Bayer Zubek Aureon Laboratories, Inc., New York, New York , Douglas PowellDouglas Powell Aureon Laboratories, Inc., New York, New York , Stephen FogarasiStephen Fogarasi Aureon Laboratories, Inc., New York, New York , Yevgen VengrenyukYevgen Vengrenyuk Aureon Laboratories, Inc., New York, New York , Mikhail TeverovskiyMikhail Teverovskiy Aureon Laboratories, Inc., New York, New York , Mark R. SegalMark R. Segal Center for Bioinformatics and Molecular Biostatistics, University of California-San Francisco, San Francisco, California , R. Jeffrey KarnesR. Jeffrey Karnes Mayo Clinic, Rochester, Minnesota , Thomas A. GaffeyThomas A. Gaffey Mayo Clinic, Rochester, Minnesota , Christer BuschChrister Busch University Hospital at Uppsala, Uppsala, Sweden , Michael HaggmanMichael Haggman University Hospital at Uppsala, Uppsala, Sweden , Peter HlavcakPeter Hlavcak University Hospital at Uppsala, Uppsala, Sweden , Stephen J. FreedlandStephen J. Freedland Durham Veterans Affairs and Duke University Medical Center, Durham, North Carolina , Robin T. VollmerRobin T. Vollmer Durham Veterans Affairs and Duke University Medical Center, Durham, North Carolina , Peter AlbertsenPeter Albertsen University of Connecticut Health Science Center, Farmington, Connecticut , Jose CostaJose Costa Aureon Laboratories, Inc., New York, New York Yale University School of Medicine, New Haven, Connecticut , and Carlos Cordon-CardoCarlos Cordon-Cardo Aureon Laboratories, Inc., New York, New York Yonkers and Herbert Irving Comprehensive Cancer Center, Columbia University, New York, New York View All Author Informationhttps://doi.org/10.1016/j.juro.2009.02.135AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: To our knowledge in patients with prostate cancer there are no available tests except clinical variables to determine the likelihood of disease progression. We developed a patient specific, biology driven tool to predict outcome at diagnosis. We also investigated whether biopsy androgen receptor levels predict a durable response to therapy after secondary treatment. Materials and Methods: We evaluated paraffin embedded prostate needle biopsy tissue from 1,027 patients with cT1c-T3 prostate cancer treated with surgery and followed a median of 8 years. Machine learning was done to integrate clinical data with biopsy quantitative biometric features. Multivariate models were constructed to predict disease progression with the C index to estimate performance. Results: In a training set of 686 patients (total of 87 progression events) 3 clinical and 3 biopsy tissue characteristics were identified to predict clinical progression within 8 years after prostatectomy with 78% sensitivity, 69% specificity, a C index of 0.74 and a HR of 5.12. Validation in an independent cohort of 341 patients (total of 44 progression events) yielded 76% sensitivity, 64% specificity, a C index of 0.73 and a HR of 3.47. Increased androgen receptor in tumor cells in the biopsy highly significantly predicted resistance to therapy, ie androgen ablation with or without salvage radiotherapy, and clinical failure (p <0.0001). Conclusions: Morphometry reliably classifies Gleason pattern 3 tumors. When combined with biomarker data, it adds to the hematoxylin and eosin analysis, and prostate specific antigen values currently used to assess outcome at diagnosis. Biopsy androgen receptor levels predict the likelihood of a response to therapy after recurrence and may guide future treatment decisions. References 1 : Cancer statistics, 2008. CA Cancer J Clin2008; 58: 71. Google Scholar 2 : A randomized trial comparing radical prostatectomy with watchful waiting in early prostate cancer. N Engl J Med2002; 347: 781. Google Scholar 3 : Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med2005; 352: 1977. 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Google Scholar © 2009 by American Urological AssociationFiguresReferencesRelatedDetailsCited byTaneja S (2020) Re: Artificial Intelligence for Diagnosis and Grading of Prostate Cancer in Biopsies: A Population-Based, Diagnostic StudyJournal of Urology, VOL. 204, NO. 3, (620-621), Online publication date: 1-Sep-2020.Related articlesJournal of Urology18 May 2009Phase II Trial of Capecitabine and Weekly Docetaxel for Metastatic Castrate Resistant Prostate Cancer Volume 182Issue 1July 2009Page: 125-132 Advertisement Copyright & Permissions© 2009 by American Urological AssociationKeywordsreceptorsbiological markersprostatebiopsyandrogenprostatic neoplasmsAcknowledgmentsDrs. Vijay Aggarwal, Robert Shovlin, Jason Alter and Charles DiComo contributed to the manuscript. Dr. William M. Pottenger, Rutgers University performed the randomized training/test split of the data. Mark Clayton, and Drs. Stefan Hamann, Paola Capodieci and Ali Tabesh, Aureon Laboratories; Dr. Angelique W. Levi, Aureon Laboratories and Yale University School of Medicine; Dr. Mona Norberg, University Hospital at Uppsala, Dr. Jayakrishnan Jayachandran and Leah Gerber, Durham Veterans Affairs and Duke University Medical Center; and Judith Fine, University of Connecticut Health Science Center provided clinical database and technical support. The cohort was randomized and split at Rutgers University.Metrics Author Information Michael J. Donovan Aureon Laboratories, Inc., New York, New York Financial interest and/or other relationship with Aureon Laboratories. More articles by this author Faisal M. Khan Aureon Laboratories, Inc., New York, New York Financial interest and/or other relationship with Aureon Laboratories. More articles by this author Gerardo Fernandez Aureon Laboratories, Inc., New York, New York Financial interest and/or other relationship with Aureon Laboratories. More articles by this author Ricardo Mesa-Tejada Aureon Laboratories, Inc., New York, New York Yonkers and Herbert Irving Comprehensive Cancer Center, Columbia University, New York, New York Financial interest and/or other relationship with Aureon Laboratories. More articles by this author Marina Sapir Aureon Laboratories, Inc., New York, New York Financial interest and/or other relationship with Aureon Laboratories. More articles by this author Valentina Bayer Zubek Aureon Laboratories, Inc., New York, New York Financial interest and/or other relationship with Aureon Laboratories. More articles by this author Douglas Powell Aureon Laboratories, Inc., New York, New York Financial interest and/or other relationship with Aureon Laboratories. More articles by this author Stephen Fogarasi Aureon Laboratories, Inc., New York, New York Financial interest and/or other relationship with Aureon Laboratories. More articles by this author Yevgen Vengrenyuk Aureon Laboratories, Inc., New York, New York Financial interest and/or other relationship with Aureon Laboratories. More articles by this author Mikhail Teverovskiy Aureon Laboratories, Inc., New York, New York Financial interest and/or other relationship with Aureon Laboratories. More articles by this author Mark R. Segal Center for Bioinformatics and Molecular Biostatistics, University of California-San Francisco, San Francisco, California Financial interest and/or other relationship with Aureon Laboratories. More articles by this author R. Jeffrey Karnes Mayo Clinic, Rochester, Minnesota More articles by this author Thomas A. Gaffey Mayo Clinic, Rochester, Minnesota More articles by this author Christer Busch University Hospital at Uppsala, Uppsala, Sweden More articles by this author Michael Haggman University Hospital at Uppsala, Uppsala, Sweden More articles by this author Peter Hlavcak University Hospital at Uppsala, Uppsala, Sweden More articles by this author Stephen J. Freedland Durham Veterans Affairs and Duke University Medical Center, Durham, North Carolina Financial interest and/or other relationship with Aureon Laboratories. More articles by this author Robin T. Vollmer Durham Veterans Affairs and Duke University Medical Center, Durham, North Carolina More articles by this author Peter Albertsen University of Connecticut Health Science Center, Farmington, Connecticut Financial interest and/or other relationship with Sanofi, Bristol Meyers, Galaxo and Blue Cross Blue Shield. More articles by this author Jose Costa Aureon Laboratories, Inc., New York, New York Yale University School of Medicine, New Haven, Connecticut Financial interest and/or other relationship with Aureon Laboratories. More articles by this author Carlos Cordon-Cardo Aureon Laboratories, Inc., New York, New York Yonkers and Herbert Irving Comprehensive Cancer Center, Columbia University, New York, New York Financial interest and/or other relationship with Aureon Laboratories. More articles by this author Expand All Advertisement PDF downloadLoading ...