With the aim of developing a noninvasive test for detection of clinically significant prostate cancer, we investigated the potential of capturing cells from urine by microfiltration coupled with analysis of DNA-methylation biomarkers.
In this prospective study, urine from men suspected of prostate cancer and scheduled for transrectal ultrasonography-guided biopsy of the prostate was collected before (n=99) or after (n=58) digital rectal examination (DRE), or from a urethral catheter (n=7). Cells were isolated from whole-volume urine voids using a filtration device containing a membrane filter with a pore size of 8 μm. Ten additional men provided repeated (4-5) urine-cell samples through self-collection prior to biopsy. Cellular DNA was analysed for 5 methylation biomarkers using droplet digital PCR.
One hundred and seventeen patients (71%) were diagnosed with prostate cancer. Across all tumor grades, the sensitivity of urine-DNA testing was 81% and 60% for post- and pre-DRE samples, respectively. In a prediction model including PSA, age and the result of the urine-DNA analysis for detection of high-grade disease (Gleason score ≥ 7), an area-under-the-curve of 0.95 (95% CI, 0.90-1.00) was obtained for post-DRE samples. Analysis of repeat samples demonstrated substantial intraindividual variation in the shedding of cancerous cells into the urine.
Capture of cells from urine by microfiltration provides a novel tool for noninvasive detection of prostate cancer, with high sensitivity for high-grade disease. Repeated sampling may increase sensitivity, particularly for cases where urine is obtained without prior physical manipulation of the prostate.
The Journal of urology. 2018 Apr 24 [Epub ahead of print]
Louise Katrine Larsen, Jørn Skibsted Jakobsen, Ahmad Abdul-Al, Per Guldberg
Danish Cancer Society Research Center, Copenhagen, Denmark., Department of Urology, Herlev Hospital, University of Copenhagen, Herlev, Denmark., Danish Cancer Society Research Center, Copenhagen, Denmark. Electronic address: .