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JAMA Oncol. 2016 Jul 1;2(7):882-9. doi: 10.1001/jamaoncol.2016.0097.

A Novel Urine Exosome Gene Expression Assay to Predict High-grade Prostate Cancer at Initial Biopsy.

Author information

  • 1Department of Urology, Columbia University, New York, New York.
  • 2Department of Pathology, Icahn School of Medicine at Mt Sinai, New York, New York.
  • 3Exosome Diagnostics, Cambridge, Massachusetts.
  • 4Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio.
  • 5Department of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • 6Division of Urologic Surgery, Washington University, St Louis, Missouri.
  • 7Delaware Valley Urology, Voorhees, New Jersey.
  • 8Division of Urologic Surgery, University of Michigan, Ann Arbor.
  • 9The Cancer Therapy and Research Center, University of Texas Health Science Center at San Antonio, San Antonio.
  • 10Department of Urology, University of California-San Francisco, San Francisco.

Abstract

IMPORTANCE:

Overdiagnosis and overtreatment of indolent prostate cancer (PCA) is a serious health issue in most developed countries. There is an unmet clinical need for noninvasive, easy to administer, diagnostic assays to help assess whether a prostate biopsy is warranted.

OBJECTIVE:

To determine the performance of a novel urine exosome gene expression assay (the ExoDx Prostate IntelliScore urine exosome assay) plus standard of care (SOC) (ie, prostate-specific antigen [PSA] level, age, race, and family history) vs SOC alone for discriminating between Gleason score (GS)7 and GS6 and benign disease on initial biopsy.

DESIGN, SETTING, AND PARTICIPANTS:

In training, using reverse-transcriptase polymerase chain reaction (PCR), we compared the urine exosome gene expression assay with biopsy outcomes in 499 patients with prostate-specific antigen (PSA) levels of 2 to 20 ng/mL. The derived prognostic score was then validated in 1064 patients from 22 community practice and academic urology clinic sites in the United States. Eligible participants included PCA-free men, 50 years or older, scheduled for an initial or repeated prostate needle biopsy due to suspicious digital rectal examination (DRE) findings and/or PSA levels (limit range, 2.0-20.0 ng/mL).

MAIN OUTCOMES AND MEASURES:

Evaluate the assay using the area under receiver operating characteristic curve (AUC) in discrimination of GS7 or greater from GS6 and benign disease on initial biopsy.

RESULTS:

In 255 men in the training target population (median age 62 years and median PSA level 5.0 ng/mL, and initial biopsy), the urine exosome gene expression assay plus SOC was associated with improved discrimination between GS7 or greater and GS6 and benign disease: AUC 0.77 (95% CI, 0.71-0.83) vs SOC AUC 0.66 (95% CI, 0.58-0.72) (P < .001). Independent validation in 519 patients' urine exosome gene expression assay plus SOC AUC 0.73 (95% CI, 0.68-0.77) was superior to SOC AUC 0.63 (95% CI, 0.58-0.68) (P < .001). Using a predefined cut point, 138 of 519 (27%) biopsies would have been avoided, missing only 5% of patients with dominant pattern 4 high-risk GS7 disease.

CONCLUSIONS AND RELEVANCE:

This urine exosome gene expression assay is a noninvasive, urinary 3-gene expression assay that discriminates high-grade (≥GS7) from low-grade (GS6) cancer and benign disease. In this study, the urine exosome gene expression assay was associated with improved identification of patients with higher-grade prostate cancer among men with elevated PSA levels and could reduce the total number of unnecessary biopsies.

PMID:
27032035
DOI:
10.1001/jamaoncol.2016.0097
[PubMed - in process]
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