Potential survival benefits from treating aggressive (Gleason score, ≥7) early-stage prostate cancer are undermined by harms from unnecessary prostate biopsy and overdiagnosis of indolent disease.
To evaluate the a priori primary hypothesis that combined measurement of PCA3 and TMPRSS2:ERG (T2:ERG) RNA in the urine after digital rectal examination would improve specificity over measurement of prostate-specific antigen alone for detecting cancer with Gleason score of 7 or higher. As a secondary objective, to evaluate the potential effect of such urine RNA testing on health care costs.
Prospective, multicenter diagnostic evaluation and validation in academic and community-based ambulatory urology clinics. Participants were a referred sample of men presenting for first-time prostate biopsy without preexisting prostate cancer: 516 eligible participants from among 748 prospective cohort participants in the developmental cohort and 561 eligible participants from 928 in the validation cohort.
Urinary PCA3 and T2:ERG RNA measurement before prostate biopsy.
Presence of prostate cancer having Gleason score of 7 or higher on prostate biopsy. Pathology testing was blinded to urine assay results. In the developmental cohort, a multiplex decision algorithm was constructed using urine RNA assays to optimize specificity while maintaining 95% sensitivity for predicting aggressive prostate cancer at initial biopsy. Findings were validated in a separate multicenter cohort via prespecified analysis, blinded per prospective-specimen-collection, retrospective-blinded-evaluation (PRoBE) criteria. Cost effects of the urinary testing strategy were evaluated by modeling observed biopsy results and previously reported treatment outcomes.
Among the 516 men in the developmental cohort (mean age, 62 years; range, 33-85 years) combining testing of urinary T2:ERG and PCA3 at thresholds that preserved 95% sensitivity for detecting aggressive prostate cancer improved specificity from 18% to 39%. Among the 561 men in the validation cohort (mean age, 62 years; range, 27-86 years), analysis confirmed improvement in specificity (from 17% to 33%; lower bound of 1-sided 95% CI, 0.73%; prespecified 1-sided P = .04), while high sensitivity (93%) was preserved for aggressive prostate cancer detection. Forty-two percent of unnecessary prostate biopsies would have been averted by using the urine assay results to select men for biopsy. Cost analysis suggested that this urinary testing algorithm to restrict prostate biopsy has greater potential cost-benefit in younger men.
Combined urinary testing for T2:ERG and PCA3 can avert unnecessary biopsy while retaining robust sensitivity for detecting aggressive prostate cancer with consequent potential health care cost savings.
JAMA oncology. 2017 May 18 [Epub ahead of print]
Martin G Sanda, Ziding Feng, David H Howard, Scott A Tomlins, Lori J Sokoll, Daniel W Chan, Meredith M Regan, Jack Groskopf, Jonathan Chipman, Dattatraya H Patil, Simpa S Salami, Douglas S Scherr, Jacob Kagan, Sudhir Srivastava, Ian M Thompson, Javed Siddiqui, Jing Fan, Aron Y Joon, Leonidas E Bantis, Mark A Rubin, Arul M Chinnayian, John T Wei, and the EDRN-PCA3 Study Group , Mohamed Bidair, Adam Kibel, Daniel W Lin, Yair Lotan, Alan Partin, Samir Taneja
Department of Urology, Emory University School of Medicine, Atlanta, Georgia., Department of Biostatistics, The University of Texas, MD Anderson Cancer Center, Houston, Texas., Department of Biostatistics, Rollins School of Public Health, Emory University, Atlanta, Georgia., Department of Urology, University of Michigan, Ann Arbor, Michigan5Michigan Center for Translational Pathology, Department of Pathology, University of Michigan, Ann Arbor, Michigan., Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland., Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts., Hologic Inc, San Diego, California., Hofstra North Shore-LIJ School of Medicine, The Arthur Smith Institute for Urology, New Hyde Park, New York., Department of Urology, Weill-Cornell Medical Center, New York, New York., Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland., University of Texas Health Sciences Center - San Antonio, Texas., Michigan Center for Translational Pathology, Department of Pathology, University of Michigan, Ann Arbor, Michigan., Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, California., Department of Pathology, Weill-Cornell Medical Center, New York, New York., Department of Urology, University of Michigan, Ann Arbor, Michigan., San Diego Clinical Trials, San Diego, California., Brigham and Women's Hospital, Boston, Massachusetts., University of Washington Medical Center, Seattle., University of Texas Southwestern Medical Center, Dallas., Johns Hopkins Hospital, Baltimore, Maryland., New York University School of Medicine, New York.