IsoPSA Performance Characteristics are Unaffected by 5-Alpha Reductase Inhibitors or Alpha-Blockers: Results From the IsoPSA Validation Study.

OBJECTIVE: To. determine the impact of 5-α reductase inhibitors or α-blockers on IsoPSA performance for the detection of actionable prostate cancer. MATERIALS AND METHODS: This is a secondary analysis of data from an institutional review board approved, prospective, multicenter(8-sites) study evaluating IsoPSA in men ≥ 50 years of age with a total PSA ≥ 4 ng/mL with planned prostate biopsy who met previously described inclusion and exclusion criteria. Analytic groups included (i)all subjects, (ii-iii)+/- 5-ARI use, (iv-v)+/- α-blocker use. The performance characteristics of IsoPSA in these groups were assessed by ROC curve, sensitivity, and specificity (SP) analysis. RESULTS: A total of 1385 men were recruited with 888 men included in final analysis. Actionable prostate cancer, defined as GG2+, was identified in a total of 316 patients with 40 and 217 patients reporting 5-ARI and α-blocker use respectively. Sensitivity to detect both prostate cancer and actionable cancer was similar between patient subsets (P >.05). SP was similar between patients regardless of 5-ARI(P >.05). Increased SP was noted in patients on α-blockers(GG1+: No-α-blocker: 0.360 vs α-blocker: 0.529, P <.05; GG2+: No-α-blocker: 0.40 vs α-blocker: 0.61, P <.05). ROC analysis demonstrates that IsoPSA performance is unaffected by 5-ARI or α-blocker use for prostate cancer and actionable cancer (GG2+) detection. CONCLUSION: The performance of IsoPSA for detecting any prostate cancer and clinically actionable prostate cancer is unaffected by commonly used medications (5-ARI and α-blockers) for symptoms of benign prostatic hyperplasia.

Clinical validation of IsoPSA, a single parameter, structure-focused assay for improved detection of prostate cancer: A prospective, multicenter study.

BACKGROUND: IsoPSA is a blood-based test that assesses prostate cancer (CaP) risk by partitioning and detecting cancer-specific structural isoforms of prostate specific antigen (PSA) with an aqueous 2- phase system. OBJECTIVE: To validate the diagnostic performance of IsoPSA for High-Grade CaP and Any CaP risk on biopsy in men age ≥ 50 with total PSA ≥ 4 ng/ml. DESIGN, SETTING, AND PARTICIPANTS: Prospective, multicenter study of 888 men scheduled for prostate biopsy at 8 academic and community sites between August 2015 and August 2020. INTERVENTION: IsoPSA test. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Receiver operating characteristic and likelihood ratio analysis used to validate diagnostic performance for previously established IsoPSA Index cutoffs for High-Grade CaP (Gleason Score ≥ 7) and Any CaP (Gleason Score ≥ 6), compare IsoPSA to total PSA and % free PSA, and evaluate subgroups (total PSA 4-10 ng/ml, total PSA > 10 ng/ml, biopsy naïve, prior negative biopsy). RESULTS AND LIMITATIONS: The disease prevalence was 35.6% (High-Grade CaP) and 58.9% (Any CaP). The area under the receiver operating characteristic curve was 0.783 (High-Grade CaP) and 0.770 (Any CaP). IsoPSA outperformed total PSA and % free PSA on area under the receiver operating characteristic curve, specificity, positive and negative predictive value at similar sensitivity. Using selected IsoPSA Index cutoffs, an estimated 46% (High-Grade CaP) and 42% (Any CaP) of biopsies could be avoided in low-risk patients. IsoPSA displayed statistically informative likelihood ratio-based predictive characteristics. IsoPSA maintained accuracy in clinically relevant subgroups. CONCLUSIONS: IsoPSA diagnostic performance and predictive value is validated for High-Grade CaP and Any CaP in men age ≥ 50 with total PSA ≥ 4 ng/ml undergoing diagnostic biopsy. IsoPSA outperforms total and % free PSA in discriminating the risk of prostate cancer on biopsy. PATIENT SUMMARY: IsoPSA has the potential to reduce unnecessary biopsies and improve the risk-benefit ratio for CaP early detection.

Clinical Validation of IsoPSA™, a Single Parameter, Structure Based Assay for Improved Detection of High Grade Prostate Cancer.

PURPOSE: Current prostate specific antigen markers to detect prostate cancer are limited by low specificity for high grade disease. IsoPSA™ is a blood based, structure focused assay which predicts risk by partitioning the isoforms of prostate specific antigen that are linked to cancer in an aqueous 2-phase reagent system. We validated the clinical performance of this assay for identifying high grade disease in a new contemporary biopsy cohort. MATERIALS AND METHODS: We performed a multicenter prospective validation in 271 men scheduled for prostate biopsy at a total of 7 academic and community centers who were enrolled between May 2017 and March 2018. Blood samples were obtained for assay prior to biopsy. The discrimination power of the assay to detect high grade prostate cancer (Gleason 7 or greater) was evaluated by ROC analysis and compared to prior results. Clinical performance was further improved by comparison with multiparametric magnetic resonance imaging-ultrasound vs transrectal ultrasound guided biopsies. RESULTS: The assay AUC was 0.784 for high grade vs low grade cancer/benign histology, which was superior to the AUCs of total prostate specific antigen and percent free prostate specific antigen. If 1,000 patients were biopsied, the assay would have reduced the number of unnecessary biopsies from 705 to 402 (43%) with only 22 missed high grade cancers, of which 7 would have been Gleason sum 4 + 3 or higher. Subset analysis of multiparametric magnetic resonance imaging guided biopsy produced a substantial improvement of the AUC to 0.831. CONCLUSIONS: Validation of the structure based IsoPSA assay demonstrated statistical concordance with previously reported results and verified its superior performance vs concentration based prostate specific antigen and the free-to-total prostate specific antigen ratio. The assay improvement in detecting high grade prostate cancer using multiparametric magnetic resonance imaging-ultrasound guided biopsy may help define a new diagnostic paradigm.

The Single-parameter, Structure-based IsoPSA Assay Demonstrates Improved Diagnostic Accuracy for Detection of Any Prostate Cancer and High-grade Prostate Cancer Compared to a Concentration-based Assay of Total Prostate-specific Antigen: A Preliminary Report.

BACKGROUND: IsoPSA is a serum-based assay that predicts prostate cancer (PCa) risk by partitioning isoforms of prostate-specific antigen (PSA) with an aqueous two-phase reagent. OBJECTIVES: To determine the diagnostic accuracy of IsoPSA in identifying the presence or absence of PCa and the presence of high-grade disease in a contemporary biopsy cohort. DESIGN, SETTING, AND PARTICIPANTS: Multicenter prospective study of 261 men scheduled for prostate biopsy at five academic and community centers in the USA enrolled between August 2015 and December 2016. INTERVENTION: Performance of the IsoPSA assay. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Discrimination power was evaluated using receiver operating characteristic (ROC) analysis. The outcome of the IsoPSA assay was transformed into risk probability using logistic regression. Decision curve analysis (DCA) was used to compare the net benefit of IsoPSA against other clinical protocols. RESULTS AND LIMITATIONS: The overall prevalence was 53% for any PCa and 34% for high-grade PCa. The area under the ROC curve was 0.79 for any cancer versus none and 0.81 for high-grade PCa versus low-grade PCa/benign histology. In this preliminary study, DCA revealed a superior net benefit of IsoPSA against no biopsy, all biopsy, and the modified Prostate Cancer Prevention Trial Risk Calculator 2.0. At a cutoff selected to recommend biopsy, IsoPSA demonstrated a 48% reduction in false-positive biopsies; at a cutoff selected to identity men at low risk of high-grade disease, there was a 45% reduction in the false-positive rate. CONCLUSION: The structure-based IsoPSA assay outperformed concentration-based PSA measurement, and provided a net benefit against other protocols. Once validated, clinical use of IsoPSA could significantly reduce unnecessary biopsies while identifying patients needing treatment. PATIENT SUMMARY: The IsoPSA assay outperformed prostate-specific antigen in predicting the overall risk of prostate cancer and the risk of clinically significant cancer in a preliminary study. The IsoPSA assay could assist in determining the need for prostate biopsy for patients.

Herbal and complementary medicine in chronic prostatitis.

Chronic prostatitis is a very common and poorly understood condition with significant impact on quality of life. The etiology of prostatitis can be multifactorial and can present with a variety of symptoms. Given the lack of proven efficacy of conventional therapies such as antibiotics, many patients have turned to phytotherapy and other alternative treatments. This review will cover the alternative therapies commonly used in prostatitis with an emphasis on those with published data. These treatments include phytotherapy (quercetin, bee pollen) and physical therapy. Complementary therapies have shown the potential to help men with prostatitis, particularly when allopathic therapies have failed.

Concealed penis.

A small phallus causes great concern regarding genital adequacy. A concealed penis, although of normal size, appears small either because it is buried in prepubic tissues, enclosed in scrotal tissue penis palmatus (PP), or trapped due to phimosis or a scar following circumcision or trauma. From July 1978 to January 2001 we operated upon 92 boys with concealed penises; 49 had buried penises (BP), while PP of varying degrees was noted in 14. Of 29 patients with a trapped penis, phimosis was noted in 9, post-circumcision cicatrix (PCC) in 17, radical circumcision in 2, and posttraumatic scarring in 1. The BP was corrected at 2-3 years of age by incising the inner prepuce circumferentially, degloving the penis to the penopubic junction, dividing dysgenetic bands, and suturing the dermis of the penopubic skin to Buck's fascia with nonabsorbable sutures. Patients with PP required displacement of the scrotum in addition to correction of the BP. Phimosis was treated by circumcision. Patients with a PCC were recircumcised carefully, preserving normal skin, but Z-plasties and Byars flaps were often required for skin coverage. After radical circumcision and trauma, vascularized flaps were raised to cover the defect. Satisfactory results were obtained in all cases although 2 patients with BP required a second operation. The operation required to correct a concealed penis has to be tailored to its etiology.