Spermine Measuring Device Evaluation Protocol
Spermine Measuring Device Evaluation Protocol
Prostate gland is a clinically important male sexual organ and its main function is for the
 production of semen. Globally, it is the second most common cancer in men globally and is
 also the fifth cancer cause for death in male. Despite the improvement in the understanding
 of prostate cancer, the current usage of serum prostate specific antigen (PSA) as a
 diagnostic marker is still not ideal. Many patients with elevated PSA and then subjected to
 prostate biopsy were found to have no prostate cancer. Therefore, there is a need to discover
 new biological markers to improve the current situation in diagnosis and also management of
 prostate cancer. In our recent studies, urinary spermine levels have been shown to correlate
 well with prostate cancer diagnosis and cancer aggressiveness.

 Due to its nature, it could provide a more convenient and non-invasive method for detecting
 prostate cancer. In order to further improve the accessibility of the test, a simple urine
 measuring device has been designed to allow more simple and practical usage of the test in
 clinical setting.The purpose of this study was to evaluate the accuracy of this newly
 designed urine measuring device for urinary spermine in predicting your prostatic biopsy
 result.
Prostate cancer (PC) is highly prevalent worldwide and is currently the 3rd most commonly
 diagnosed prostate cancer in Hong Kong male population with more than 2000 new cases
 diagnosed per year. Depending on the clinical staging and also the patients' condition,
 different treatments, including curative surgery or radiotherapy, palliative androgen
 deprivation therapy, could be offered to patients and will good response. However, current
 there are only one biological marker, PSA, for the monitoring of the disease progress and
 treatment response. While PSA testing provided a reasonable assessment of the disease status
 and progress, it is an invasive blood test and maybe less convenience for some patients.
 Therefore, there is a need for exploring newer markers for the monitoring of the treatment
 response and disease progress is needed.

 One example of such cancer biomarkers are natural polyamines. Interests on these analytes
 have been starting in 1971 when Russell reported a considerable increase of urinary
 polyamines such as putrescine (Put), spermidine (Spd) and spermine (Spm) in patients with
 various types of solid tumors and leukaemias. Afterwards, polyamine studies focusing on
 specific cancers continued, like cervical cancer, colorectal cancer and breast cancer, etc.

 In our recent study, we have explored the potential roles of urinary polyamines as prostate
 cancer biomarkers were evaluated. Patients with prostate cancer (PCa), benign prostatic
 hyperplasia (BPH) patients and healthy controls (HC) showing PSA>4.0ng/ml were enrolled in
 the study. Their urine samples were obtained, and the urinary levels of Put, Spd, Spm were
 determined by ultra-high-performance liquid chromatography coupled with triple quadrupole
 mass spectrometer (UPLC-MS/MS). Receiver operating characteristics (ROC) curve and Student's
 t- test were used to evaluate their diagnostic accuracies. Among the three biogenic
 polyamines, Spm had demonstrated a good diagnostic performance when comparing their levels in
 PCa patients with BPH patients (1.47 in PCa vs 5.87 in BPH; p<0.0001). The results were in
 accordance with transrectal ultrasound prostatic biopsy (TRUSPB) results, with an area under
 curve (AUC) value of 0.83±0.03. Therefore, urinary Spm could have a potential to serve as a
 novel PCa diagnostic biomarker, which in turn could help to address the limited sensitivity
 and specificity problem of serum PSA test. In our further work, we have confirmed that
 spermine is a good marker for the detection of prostate cancer and also showed good
 correlation with cancer grading.

 However, the current measurement of spermine required the use of liquid chromatography (LCM)
 in laboratory, which might limit its clinical usage. Therefore, a simple spermine measuring
 device (SMD) has been designed for easier daily usage, such as simple cancer screening and
 also combined evaluation with serum PSA level. The SMD is a simple device, with automatic
 urine aspiration and also spermine level assessment. First about 30 cc urine will be freshly
 collected by a prepared collection device. Then the cap of the SMD will be removed and the
 aspiration tip of the device will be immersed into the urine specimen. After firmly pressed
 on the device, a small sample of urine will be aspirated into the SMD. The device will then
 automatically assess the urine spermine level. The result will then be read at a indicator
 window after about 5 minutes. If the level was below a pre-set cutoff, i.e. suggestive of
 having increase risk of prostate cancer, the indicator window will turn into red colour.

 However, if the spermine level is higher than the cutoff value, i.e. low risk of having
 cancer, the indicator window will turn blue. However, the kit has not been validated in
 clinical urine sample. Therefore, we would like to perform an evaluation the accuracy of this
 SMD with the laboratory measured spermine level by LCM, as well as the pathology result from
 prostate biopsy.
Inclusion Criteria:

 -  Adult Chinese male patients with age > 18 years old

 -  Clinical indicated for prostate cancer detection and has serum PSA level done within 8
 weeks of urine test.

 Exclusion Criteria:

 -  Patient with recent urinary tract infection within 6 weeks prior to urine collection.

 -  Patient with recent urethral instrumentation, such as Foley catheter insertion,
 cystoscopy etc., within 6 weeks prior to urine collection.

 -  Patient with consumption of 5 alpha reductase inhibitors in past 6 months.

 -  Patient refused or unable to provide consent for the study