Portal de Periódicos da CAPES

Racial Variation in the Utility of Urinary Biomarkers PCA3 and T2ERG in a Large Multicenter Study

2017; Lippincott Williams & Wilkins; Volume: 198; Issue: 1 Linguagem: Inglês

10.1016/j.juro.2017.01.058

1527-3792

Padraic O’Malley, Daniel P. Nguyen, Bashir Al Hussein Al Awamlh, Guojiao Wu, Ian M. Thompson, Martin G. Sanda, Mark A. Rubin, John T. Wei, Richard Lee, Paul J. Christos, Christopher E. Barbieri, Douglas S. Scherr,

Urinary Bladder and Prostate Research

No AccessJournal of UrologyAdult Urology1 Jul 2017Racial Variation in the Utility of Urinary Biomarkers PCA3 and T2ERG in a Large Multicenter Study Padraic G. O'Malley, Daniel P. Nguyen, Bashir Al Hussein Al Awamlh, Guojiao Wu, Ian M. Thompson, Martin Sanda, Mark Rubin, John T. Wei, Richard Lee, Paul Christos, Christopher Barbieri, and Douglas S. Scherr Padraic G. O'MalleyPadraic G. O'Malley Department of Urology, Weill Cornell Medical College and New York Presbyterian Hospital, New York, New York , Daniel P. NguyenDaniel P. Nguyen Department of Urology, Universität Bern, Bern, Switzerland , Bashir Al Hussein Al AwamlhBashir Al Hussein Al Awamlh Department of Urology, Weill Cornell Medical College and New York Presbyterian Hospital, New York, New York , Guojiao WuGuojiao Wu Department of Healthcare Policy and Research, Weill Cornell Medical College and New York Presbyterian Hospital, New York, New York , Ian M. ThompsonIan M. Thompson Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, Texas , Martin SandaMartin Sanda Department of Urology, Emory University School of Medicine, Atlanta, Georgia , Mark RubinMark Rubin Department of Pathology, Weill Cornell Medical College and New York Presbyterian Hospital, New York, New York , John T. WeiJohn T. Wei Department of Urology, University of Michigan, Livonia, Michigan , Richard LeeRichard Lee Department of Urology, Weill Cornell Medical College and New York Presbyterian Hospital, New York, New York , Paul ChristosPaul Christos Department of Healthcare Policy and Research, Weill Cornell Medical College and New York Presbyterian Hospital, New York, New York , Christopher BarbieriChristopher Barbieri Department of Urology, Weill Cornell Medical College and New York Presbyterian Hospital, New York, New York , and Douglas S. ScherrDouglas S. Scherr Department of Urology, Weill Cornell Medical College and New York Presbyterian Hospital, New York, New York View All Author Informationhttps://doi.org/10.1016/j.juro.2017.01.058AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: To our knowledge it is unknown whether urinary biomarkers for prostate cancer have added utility to clinical risk calculators in different racial groups. We examined the utility of urinary biomarkers added to clinical risk calculators for predicting prostate cancer in African American and nonAfrican American men. Materials and Methods: Demographics, PCPT (Prostate Cancer Prevention Trial) risk scores, data on the biomarkers data PCA3 (prostate cancer antigen 3) and T2ERG (transmembrane protease serine 2 and v-ets erythroblastosis virus E26 oncogene homolog gene fusion), and biopsy pathology features were prospectively collected on 718 men as part of EDRN (Early Detection Research Network). Utility was determined by generating ROC curves and comparing AUC values for the baseline multivariable PCPT model and for models containing biomarker scores. Results: PCA3 and T2ERG added utility for the prediction of prostate cancer and clinically significant prostate cancer when combined with the PCPT Risk Calculator. This utility was seen in nonAfrican American men only for PCA3 (AUC 0.64 increased to 0.75 for prostate cancer and to 0.69–0.77 for clinically significant prostate cancer, both p <0.001) and for T2ERG (AUC 0.64–0.74 for prostate cancer, p <0.001, and 0.69–0.73 for clinically significant prostate cancer, p = 0.029). African American men did not have an added benefit with the addition of biomarkers, including PCA3 (AUC 0.75–0.77, p = 0.64, and 0.65–0.66, p = 0.74) and T2ERG (AUC 0.75–0.74, p = 0.74, and 0.65–0.64, p = 0.88), for prostate cancer and clinically significant prostate cancer, respectively. Limitations include the small number of African American men (72). The post hoc subgroup analysis nature of the study limited findings to being hypothesis generating. Conclusions: As novel biomarkers are discovered, clinical utility should be established across demographically diverse cohorts. References 1 : Prostate-cancer mortality at 11 years of follow-up. N Engl J Med2012; 366: 981. Google Scholar 2 : Cancer statistics, 2014. CA Cancer J Clin2014; 64: 9. Google Scholar 3 : Do prostate cancer risk models improve the predictive accuracy of PSA screening? A meta-analysis. Ann Oncol2015; 26: 848. Google Scholar 4 : Association of insurance and race/ethnicity with disease severity among men diagnosed with prostate cancer, National Cancer Database 2004-2006. Cancer Epidemiol Biomarkers Prev2010; 19: 2437. Google Scholar 5 : Multiple regions within 8q24 independently affect risk for prostate cancer. Nat Genet2007; 39: 638. Google Scholar 6 : Hidden barriers between knowledge and behavior: the North Carolina prostate cancer screening and treatment experience. Cancer2007; 109: 1599. Google Scholar 7 : Can urinary PCA3 supplement PSA in the early detection of prostate cancer?. J Clin Oncol2014; 32: 4066. Google Scholar 8 : Urine TMPRSS2:ERG plus PCA3 for individualized prostate cancer risk assessment. Eur Urol2015; 70: 45. Google Scholar 9 : Urinary biomarkers for prostate cancer. Curr Opin Urol2015; 25: 77. Google Scholar 10 : Urine TMPRSS2:ERG fusion transcript stratifies prostate cancer risk in men with elevated serum PSA. Sci Transl Med2011; 3: 94ra72. Google Scholar 11 : Assessing prostate cancer risk: results from the Prostate Cancer Prevention Trial. J Natl Cancer Inst2006; 98: 529. Google Scholar 12 : Molecular markers for cancer prognosis and treatment: have we struck gold?. Cancer Lett2012; 327: 142. Google Scholar 13 : Prospective multi-institutional study evaluating the performance of prostate cancer risk calculators. J Clin Oncol2011; 29: 2959. Google Scholar 14 : External validation of the Prostate Cancer Prevention Trial risk calculator in a screened population. Urology2006; 68: 1152. Google Scholar 15 : Evaluating the PCPT risk calculator in ten international biopsy cohorts: results from the Prostate Biopsy Collaborative Group. World J Urol2012; 30: 181. Google Scholar 16 : Racial variation in insulin-like growth factor-1 and binding protein-3 concentrations in middle-aged men. Cancer Epidemiol Biomarkers Prev1999; 8: 1107. Google Scholar 17 : Generalizability of associations from prostate cancer genome-wide association studies in multiple populations. Cancer Epidemiol Biomarkers Prev2009; 18: 1285. Google Scholar 18 : The use of PCA3 in the diagnosis of prostate cancer. Nat Rev Urol2009; 6: 255. Google Scholar 19 : PCA3 molecular urine assay correlates with prostate cancer tumor volume: implication in selecting candidates for active surveillance. J Urol2008; 179: 1804. Link, Google Scholar 20 : uPM3, a new molecular urine test for the detection of prostate cancer. Urology2004; 64: 311. Google Scholar 21 : DD3PCA3 RNA analysis in urine–a new perspective for detecting prostate cancer. Eur Urol2004; 46: 182. Google Scholar 22 : The time-resolved fluorescence-based PCA3 test on urinary sediments after digital rectal examination; a Dutch multicenter validation of the diagnostic performance. Clin Cancer Res2007; 13: 939. Google Scholar 23 : The added value of percentage of free to total prostate-specific antigen, PCA3, and a kallikrein panel to the ERSPC Risk Calculator for prostate cancer in prescreened men. Eur Urol2014; 66: 1109. Google Scholar 24 : Prospective multicentre evaluation of PCA3 and TMPRSS2-ERG gene fusions as diagnostic and prognostic urinary biomarkers for prostate cancer. Eur Urol2014; 65: 534. Google Scholar 25 : Combining urinary detection of TMPRSS2:ERG and PCA3 with serum PSA to predict diagnosis of prostate cancer. Urol Oncol2013; 31: 566. Google Scholar 26 : Urinary TMPRSS2:ERG and PCA3 in an active surveillance cohort: results from a baseline analysis in the Canary Prostate Active Surveillance Study. Clin Cancer Res2013; 19: 2442. Google Scholar 27 : Performance of the Genomic Evaluators of Metastatic Prostate Cancer (GEMCaP) tumor biomarker for identifying recurrent disease in African American patients. Cancer Epidemiol Biomarkers Prev2014; 23: 1677. Google Scholar 28 : Immunohistological Analysis of ABCD3 expression in Caucasian and African American prostate tumors. Biomed Res Int2015; 2015: 132981. Google Scholar 29 : Pathological examination of radical prostatectomy specimens in men with very low risk disease at biopsy reveals distinct zonal distribution of cancer in black American men. J Urol2014; 191: 60. Link, Google Scholar © 2017 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 198Issue 1July 2017Page: 42-49Supplementary Materials Advertisement Copyright & Permissions© 2017 by American Urological Association Education and Research, Inc.Keywordshumanbiomarkersgene fusiontumorprostatic neoplasmsprostate cancer antigen 3African AmericansAcknowledgmentsDr. Scott Tomlins provided insight into urinary T2ERG and optimization of interpretation.MetricsAuthor Information Padraic G. O'Malley Department of Urology, Weill Cornell Medical College and New York Presbyterian Hospital, New York, New York More articles by this author Daniel P. Nguyen Department of Urology, Universität Bern, Bern, Switzerland More articles by this author Bashir Al Hussein Al Awamlh Department of Urology, Weill Cornell Medical College and New York Presbyterian Hospital, New York, New York More articles by this author Guojiao Wu Department of Healthcare Policy and Research, Weill Cornell Medical College and New York Presbyterian Hospital, New York, New York More articles by this author Ian M. Thompson Department of Urology, University of Texas Health Science Center at San Antonio, San Antonio, Texas Financial interest and/or other relationship with Exosome. More articles by this author Martin Sanda Department of Urology, Emory University School of Medicine, Atlanta, Georgia Financial interest and/or other relationship with Metamark, Hologic and Exosome. More articles by this author Mark Rubin Department of Pathology, Weill Cornell Medical College and New York Presbyterian Hospital, New York, New York More articles by this author John T. Wei Department of Urology, University of Michigan, Livonia, Michigan More articles by this author Richard Lee Department of Urology, Weill Cornell Medical College and New York Presbyterian Hospital, New York, New York More articles by this author Paul Christos Department of Healthcare Policy and Research, Weill Cornell Medical College and New York Presbyterian Hospital, New York, New York More articles by this author Christopher Barbieri Department of Urology, Weill Cornell Medical College and New York Presbyterian Hospital, New York, New York More articles by this author Douglas S. Scherr Department of Urology, Weill Cornell Medical College and New York Presbyterian Hospital, New York, New York More articles by this author Expand All Advertisement PDF downloadLoading ...