LAUSR

Simple Summary Prostate cancer remains one of the leading causes of death in men in the United States. The commonly utilized method of diagnosing prostate cancer is via the digital rectal examination and serum PSA assay, which is usually followed by biopsy of the prostate gland to evaluate the extent of the cancer. While serum PSA assay has been used for many years by urologists across the globe to diagnose prostate cancer, a falsely elevated level due to conditions (BPH or prostatitis) other than cancer could cause the patient to undergo prostate gland biopsy, which is invasive and poses a greater risk of complications. To overcome these issues, we evaluated whether urinary PSA, which is secreted from the prostate gland into the urine could have predictive value in differentiating aggressive prostate cancer from indolent disease. In this study, we analyzed more than 400 samples for serum and urinary PSA, and found that urinary PSA had a higher predictive power in differentiating aggressive prostate cancer, and could serve a better surrogate tumor biomarker in capitulating the tissue milieus for the purpose of detecting aggressive prostate cancer. Furthermore, combining the ratio between serum to urine PSA enhanced the performance of both biomarkers in predicting aggressive prostate diseases. These studies support the role of urinary PSA, in combination with serum, for detecting aggressive prostate cancer. Abstract Serum PSA, together with digital rectal examination and imaging of the prostate gland, have remained the gold standard in urological practices for the management of and intervention for prostate cancer. Based on these adopted practices, the limitations of serum PSA in identifying aggressive prostate cancer has led us to evaluate whether urinary PSA levels might have any clinical utility in prostate cancer diagnosis. Utilizing the Access Hybritech PSA assay, we evaluated a total of n = 437 urine specimens from post-DRE prostate cancer patients. In our initial cohort, PSA tests from a total of one hundred and forty-six (n = 146) urine specimens were obtained from patients with aggressive (Gleason Score ≥ 8, n = 76) and non-aggressive (Gleason Score = 6, n = 70) prostate cancer. A second cohort, with a larger set of n = 291 urine samples from patients with aggressive (GS ≥ 7, n = 168) and non-aggressive (GS = 6, n = 123) prostate cancer, was also utilized in our study. Our data demonstrated that patients with aggressive disease had lower levels of urinary PSA compared to the non-aggressive patients, while the serum PSA levels were higher in patients with aggressive prostate disease. The discordance between serum and urine PSA levels was further validated by immuno-histochemistry (IHC) assay in biopsied tumors and in metastatic lesions (n = 62). Our data demonstrated that aggressive prostate cancer was negatively correlated with the PSA in prostate cancer tissues, and, unlike serum PSA, urinary PSA might serve a better surrogate for capitulating tissue milieus to detect aggressive prostate cancer. We further explored the utility of urine PSA as a cancer biomarker, either alone and in combination with serum PSA, and their ratio (serum to urine PSA) to predict disease status. Comparing the AUCs for the urine and serum PSA alone, we found that urinary PSA had a higher predictive power (AUC= 0.732) in detecting aggressive disease. Furthermore, combining the ratios between serum to urine PSA with urine and serum assay enhanced the performance (AUC = 0.811) in predicting aggressive prostate disease. These studies support the role of urinary PSA in combination with serum for detecting aggressive prostate cancer.