Prostate-based biofluids for the detection of prostate cancer: A comparative study of the diagnostic performance of cell-sourced RNA biomarkers.
BACKGROUND
Prostate cancer (PCa) diagnosis requires improvement with the aid of more accurate biomarkers. Postejaculate urethral washings (PEUW) could be a physiological equivalent to urine obtained following rectal prostatic massage, the current basis for the prostate cancer antigen 3 (PCA3) test. The aim of this study was to investigate if PEUW contained prostate-based material, evidenced by the presence of prostate specific antigen (PSA), and to evaluate the diagnostic performance of PEUW-based biomarkers.


METHODS
Male patients referred for elevated serum PSA or abnormal digital rectal examination provided ejaculate and PEUW samples. PSA, PCA3, and β2-microglobulin (β2M) were quantified in ejaculate and PEUW and compared with absolute and clinically significant (according to D'Amico criteria) PCa presence, as determined by biopsies. Diagnostic performance was determined and compared with serum PSA using receiver operating characteristic analysis.


RESULTS
From 83 patients who provided PEUW samples, paired analysis with ejaculate samples was possible for 38 patients, while analysis in an unpaired, extended cohort was possible for 62 patients. PSA and PCA3 were detected in PEUW, normalized to β2M, and PCA3:PSA was calculated. In predicting absolute PCa status, PCA3:β2M in ejaculate [area under the curve (AUC) 0.717] and PEUW (AUC 0.569) were insignificantly better than PCA3:PSA (AUC 0.668 and 0.431, respectively) and comparable with serum PSA (AUC 0.617) with similar trends observed for the extended cohort. When considering clinically significant PCa presence, serum PSA in the comparison (AUC 0.640) and extended cohorts (AUC 0.665) was comparable with PCA3: β2M (AUC 0.667) and PCA3:PSA (AUC 0.605) in ejaculate, with lower estimates for PEUW in the comparison (PCA3: β2M AUC 0.496; PCA3:PSA AUC 0.342) and extended (PCA3: β2M AUC 0.497; PCA3:PSA AUC 0.469) cohorts. The statistical analysis was limited by sample size.


CONCLUSIONS
PEUW contains prostatic material, but has limited diagnostic accuracy when considering cell-derived DNA analysis. PCA3-based markers in ejaculate are comparable to serum PSA and digital rectal examination-urine markers.
The University of Queensland, Division of Surgery, School of Medicine, Brisbane, QLD, Australia; The University of Queensland, Centre for Clinical Research, Brisbane, QLD, Australia; The University of Queensland, Centre for Advanced Imaging, Brisbane, QLD, Australia; Department of Urology, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.
Matthew J
MJ
Roberts
The University of Queensland, Centre for Clinical Research, Brisbane, QLD, Australia.
Renee S
RS
Richards
The University of Queensland, Centre for Clinical Research, Brisbane, QLD, Australia.
Clement W K
CW
Chow
Research School of Population Health, The Australian National University, Canberra, Australia; School of Agricultural, Computational and Environmental Sciences, University of Southern Queensland, Toowoomba, Australia; College of Medicine, Qatar University, Doha, Qatar.
Suhail A R
SA
Doi
The University of Queensland, Centre for Advanced Imaging, Brisbane, QLD, Australia.
Horst Joachim
HJ
Schirra
Department of Environmental Health Sciences, University Medical Centre Freiburg, Freiburg, Germany.
Marion
M
Buck
Aquesta Pathology, Brisbane, QLD, Australia.
Hemamali
H
Samaratunga
Anatomical Pathology, Pathology Queensland, Brisbane, QLD, Australia.
Joanna
J
Perry-Keene
Anatomical Pathology, Pathology Queensland, Brisbane, QLD, Australia.
Diane
D
Payton
Department of Urology, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.
John
J
Yaxley
The University of Queensland, Centre for Clinical Research, Brisbane, QLD, Australia.
Martin F
MF
Lavin
The University of Queensland, Centre for Clinical Research, Brisbane, QLD, Australia; Department of Urology, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia; Edith Cowan University, Joondalup, Western Australia, Australia.
Robert A
RA
Gardiner
Biomarker; Ejaculate; Prostate Cancer; Prostate Cancer Antigen 3; Prostate Specific Antigen; mRNA
Cancer Res. 2000 Jul 1;60(13):3650-4
10910081
Nucleic Acids Res. 2001 May 1;29(9):e45
11328886
Am J Surg Pathol. 2005 Sep;29(9):1228-42
16096414
Clin Cancer Res. 2007 Sep 1;13(17):5103-8
17785564
Br J Cancer. 2008 Aug 5;99(3):491-501
18648369
PLoS One. 2009;4(3):e4995
19319183
Korean J Urol. 2011 Feb;52(2):79-89
21379423
Stat Med. 2012 Oct 15;31(23):2676-86
22307964
BJU Int. 2013 Oct;112(6):717-28
22759214
Eur Urol. 2014 Mar;65(3):534-42
23201468
PLoS One. 2013 Jun 24;8(6):e67514
23826311
Cancers (Basel). 2010 Jun 04;2(2):1125-54
24281110
Endocr Relat Cancer. 2014 Aug;21(4):L17-21
24859988
Eur Urol. 2014 Dec;66(6):1109-15
25168616
J Clin Oncol. 2014 Dec 20;32(36):4066-72
25385735
Cancer Epidemiol Biomarkers Prev. 2015 Jan;24(1):268-75
25392181
Nat Rev Urol. 2014 Dec;11(12):688-701
25403245
Eur Urol. 2015 Sep;68(3):464-70
25454615
Eur Urol. 2015 Jun;67(6):1112-1121
25466942
Prostate. 2015 Apr 1;75(5):539-49
25597828
Biomark Med. 2015;9(2):77-80
25689895
Eur J Nucl Med Mol Imaging. 2015 Jul;42(8):1284-94
25975367
Nat Cell Biol. 2015 Sep;17(9):1145-57
26302406
J Urol. 2016 Feb;195(2):313-20
26327354
Prostate Cancer Prostatic Dis. 2015 Dec;18(4):370-5
26345389
J Clin Oncol. 2016 Jun 20;34(18):2182-90
26884580
Eur Urol Focus. 2015 Sep;1(2):200-206
28723434
J Clin Oncol. 1994 Dec;12(12):2634-9
7527455
Br J Urol. 1996 Sep;78(3):414-8
8881953
Urol Clin North Am. 1997 May;24(2):283-291
9126225
Urol Clin North Am. 1997 May;24(2):293-7
9126226
JAMA. 1998 Sep 16;280(11):969-74
9749478