Pilot study: performance of the Progensa PCA3 test in post-oxytocin urine specimens

Prostate cancer (PCa) is the most frequent malignancy diagnosed in the Western
male population. Although the routine use of serum prostate-specific antigen
(PSA) testing has undoubtedly increased PCa detection, one of its main
drawbacks has been its lack of specificity, which results in a high negative
biopsy rate. Furthermore, there is objective indication that PSA-based
(opportunistic) screening has led to the diagnosis of clinically insignificant
prostate tumours, i.e. in the absence of screening these tumours would not have
been diagnosed within the patient*s lifetime, which results in over-treatment.

PCA3 (Prostate CAncer gene 3) is a new prostate specific gene that is highly
overexpressed in prostate cancer tissue. This gene was identified at the
experimental urology laboratory in Nijmegen in 1999. Since 2006, the Progensa®
PCA3-test is a clinically available urine test that is indicated to aid in the
decision to take repeat prostate biopsies. Levels of PCA3 can be measured in
the urine after digital rectal examination (DRE). A DRE is necessary to shed
enough cells to provide informative specimens. The informative rate for
specimens collected absent a DRE is low (75.9%), compared to 96,7% when a DRE
is performed.

We hypothesize that oxytocin nasal spray can be used instead of a DRE to
mobilize prostate cells into the urethra. Oxytocin nasal spray is used in the
clinical setting to promote nursing. In several studies, oxytocin nasal spray
is used for the molecular analysis of nipple fluid for breast cancer screening.
Oxytocin nasal spray increases the yield of nipple aspirate fluid by causing
rhythmic contractions of the myoepithelial cells around the acini of the
breast. In these studies, no oxytocin side-effects were reported.
Embryologically, the prostate in the male may be viewed as corresponding to the
uterus in the female. Oxytocin blood levels are increased during and after
ejaculation in humans (Carmichael et al 1987); oxytocin is found to contract
the prostate. If our hypothesis is correct, oxytocin could replace the DRE in
the future to shed enough cells for PCA3 measurement.

The primary objective is to determine the yield of prostate cells in the urine
specimen after oxytocin nasal spray, using a urine specimen with no
manipulation as a reference method.

A prospective pilot study will be conducted to determine the yield of prostate
cells in urine collected before and after oxytocin nasal spray administration.
Ten healthy male subjects will be included. Urine specimens without
manipulation will be collected from all subjects. Subsequently, all subjects
will be administered 4 IE (=1 spray) of oxytocin in both nostrils. 5 minutes
after administration, subjects will provide again a urine specimen. The urine
specimen will be processed and tested for the amount of PSA mRNA with the
Progensa® PCA3-test at Laboratory Experimental Urology (RUNMC). PCA3 mRNA and
the PCA3 score will not be measured.

We will administer 4 IE (=1 spray) in each nostril of all subjects.

Both the risk and the burden of participation are minimal. No serious side
effects of oxytocin nasal spray are reported. Side effects are seen only
seldomly(>=1/10.000, <1/1.000): allergic skin reactions, headache and nausea.
The burden is also minimal: administration of oxytocine and collect two urine
samples.

Using the Progensa PCA3 Assay, only the amount of PSA mRNA will be measured
.The amount of PCA3 mRNA will not be measured, thus the PCA3 score will not be
calculated. Therefore, this study will not give any information about the
health status/risk of having prostate cancer of the subjects.