Development and Evaluation of a Rapid Urinary Test for PSA and Zinc in Prostate Cancer Diagnosis: Findings from a Prospective Study

BACKGROUND: Due to the ongoing debate regarding the validity of serum PSA as a screening method for prostate cancer (PCa), clinical research in recent years has focused on evaluating alternative biomarkers. A previous study by our group demonstrated the potential of urinary Zinc and urinary PSA as reliable biomarkers for PCa diagnosis. Rapid tests are innovative diagnostic tools since they provide rapid results with simple interpretation that can be read by non-specialized personnel making it suitable for decentralization towards local structures. OBJECTIVE: The aim of this study is to assess the use of urinary rapid tests based on PSA and Zinc to improve the early diagnosis of prostate cancer in combination with standard parameters of care (SOC) as PSA, digital examination (DRE), age and multiparametric magnetic resonance (mpMRI). METHODS: 45 ml urine sample were collected after prostatic massage from 248 men eligible for prostatic biopsy according to standard clinical parameters such as serum PSA level, abnormal DRE and suspected mpMRI. Quantification of urinary PSA (uPSA) and urinary Zinc (uZinc) was performed by a device combining lateral flow immunoassay and colorimetric dip-stick assay, with consequent confirmation by ELISA assay and by colorimetric vitro assay respectively. Five logistic regression models were created to determine the diagnostic performance of SOC, uPSA, uZinc, Urine model (uPSA+uZinc) and SOC+urine. Then, four logistic models were designed to predict diagnostic accuracy of MRI, MRI+SOC, MRI+urine, SOC+MRI+urine. The receiver operating characteristic (ROC) curves (AUC) assessed the discriminative power of the logistic models. RESULTS: 232 subjects were included in the study, 136 of them were diagnosed with PCa. The uPSA and uZinc were optimized to return an intensity scale from 0 to 4, inversely related to the quantity of analyte present in the sample. The rapid test showed a strong correlation with the commercial methods and uPSA levels were strongly associated to clinical stage, D’Amico risk group and Gleason score with higher intensity scores linked to more advance stages of PCa while uZinc intensity had a slightly weaker association. Urine model achieved an AUC of 0.720 while the SOC+urine had the highest AUC of 0.766 with p=0.0058. AUC of MRI+urine was of 0.835 while SOC+MRI+urine obtained an AUC of 0.835 with p=0.0022 and 0.0011 respectively. A decision-making algorithm was created to integrate the urinary test into clinical routine with targeted men being those with serum PSA ranging from 5 to 9 ng/ml, negative DRE and PIRADS ≤ 3. Based on the algorithm, 45 subjects were candidates for urine testing with 49% of them having a score 2 requiring biopsy and 51% of individuals were eligible for follow-up. 41% of biopsies were positive while only 13% of the follow-up group had PCa with ISUP score <2. CONCLUSIONS: The results demonstrated that rapid tests for uPSA and uZinc could boost early clinical detection of prostatic neoplastic transformation, plus being a precious tool in detection and monitoring sparing useless and invasive procedure in cancer-free subjects especially when used in combination with age, serum PSA, DRE and mpMRI.