Preanalytical stability of molecular forms of prostate-specific antigen in serum samples (PSA, free PSA, [-2]proPSA) and their impact on fPSA/tPSA ratio and PHI.

BACKGROUND: Prostate cancer is a common cancer in men. Detection methods include the measurement of biomarkers: prostate-specific antigen (PSA), free PSA, [-2]proPSA, and the calculated indices: fPSA/tPSA ratio and Prostate Health Index (PHI). Proper preanalytical conditions are crucial for precise measurement and failure to adhere to protocols or regulations can influence the diagnostic algorithm. We assessed the stability of the above-mentioned biomarkers, fPSA/tPSA ratio and PHI, under various pre-analytical conditions. METHODS: Serum samples from 45 males were collected and stored under specific conditions before tPSA, fPSA, and [-2]proPSA were measured. Subsequently, the fPSA/tPSA and PHI were calculated. RESULTS: tPSA, fPSA, and [-2]proPSA remained stable during the two freeze-thaw cycles. Storage at 4°C and 22°C resulted in stable tPSA concentrations. However, fPSA levels decreased and [-2]proPSA levels increased over time. The fPSA/tPSA ratio remained stable for 72 h, at which point a decrease was observed in the samples kept at 4°C and 22°C. A gradual increase in PHI was observed in the samples kept at 4°C and 22°C. CONCLUSIONS: All biomarkers remained stable during two freeze-thaw cycles. tPSA was the most stable analyte when stored at 4°C, as well as at RT. A gradual increase of [-2]proPSA and a slight decrease in fPSA were observed during the storage test. This led to a decrease in the fPSA/tPSA ratio and an elevation in the PHI. We therefore recommend measuring prostate biomarkers promptly following blood collection. IMPACT: Understanding the pre-analytical stability of prostate biomarkers helps prevent false positive results and improve the accuracy of diagnostics for prostate cancer.

Predictive value of kallikrein forms and ß-microseminoprotein in blood from patients with evidence of detectable levels of PSA after radical prostatectomy.

PURPOSE: To determine whether ß-microseminoprotein or any of the kallikrein forms in blood-free, total or intact PSA or total hK2-predict metastasis in patients with evidence of detectable levels of PSA in blood after radical prostatectomy. METHOD: We determined marker concentrations in blood from 173 men treated with radical prostatectomy and evidence of detectable levels of PSA in the blood (PSA ≥ 0.05) after surgery between 2014 and 2015 and at least 1 year after any adjuvant therapy. We used Cox regression to determine whether any marker was associated with metastasis using both univariate and multivariable models that included standard clinical predictors. RESULTS: Overall, 42 patients had metastasis, with a median follow-up of 67 months among patients without an event. The levels of intact and free PSA and free-to-total PSA ratio were significantly associated with metastasis. Discrimination was highest for free PSA (c-index: 0.645) and free-to-total PSA ratio (0.625). Only free-to-total PSA ratio remained associated with overall metastasis (either regional or distant) after including standard clinical predictors (p = 0.025) and increased discrimination from 0.686 to 0.697. Similar results were found using distant metastasis as an outcome (p = 0.011; c-index increased from 0.658 to 0.723). CONCLUSION: Our results provide evidence that free-to-total PSA ratio can risk stratifying patients with evidence of detectable levels of PSA in blood after RP. Further research is warranted on the biology of prostate cancer markers in patients with evidence of detectable levels of PSA in blood after radical prostatectomy. Our findings on the free-to-total ratio for predicting adverse oncologic outcomes need to be validated in other cohorts.

Can post-treatment free PSA ratio be used to predict adverse outcomes in recurrent prostate cancer?

OBJECTIVES: To assess whether free PSA ratio (FPSAR) at biochemical recurrence (BCR) can predict metastasis, castrate-resistant prostate cancer (CRPC), and cancer-specific survival (CSS), following therapy for localised disease. PATIENTS AND METHODS: A single-centre retrospective cohort study (NCT03927287) including a discovery cohort composed of patients with an FPSAR after radical prostatectomy (RP) or radiotherapy (RT) between 2000 and 2017. For validation, an independent Biobank cohort of patients with BCR after RP was tested. Using a defined FPSAR cut-off, the metastasis-free-survival (MFS), CRPC-free survival, and CSS were compared. Multivariable Cox models determined the association between post-treatment FPSAR, metastases, and CRPC. RESULTS: Overall, 822 patients (305 RP- and 363 RT-treated patients and 154 Biobank patients) were analysed. In the RP cohort, a total of 272/305 (89.1%) and 33/305 (10.9%) had a FPSAR test incidentally and reflexively, respectively. In the RT cohort, 155/363 (42.7%) and 208/263 (57.3%) had a FPSAR test incidentally and reflexively, respectively. However, in the prospective Biobank RP cohort, FPSAR testing was done on all samples of patients diagnosed with BCR. A FPSAR cut-off of 0.10 was determined using receiver operating characteristic analyses in both the RP and RT cohorts. A FPSAR of <0.10 resulted in longer median MFS (14.8 vs 9.3 years and 14.8 vs 13 years, respectively), and longer median CRPC-free survival (median not reached vs 9.9 years and 20.7 vs 13.8 years, respectively). Multivariable analyses showed that a FPSAR of ≥0.10 was associated with increased metastasis in the RP cohort (hazard ratio [HR] 1.915, 95% confidence interval [CI] 1.241-2.955) and RT cohort (HR 1.754, 95% CI 1.112-2.769), and increased CRPC in the RP cohort (HR 2.470, 95% CI 1.493-4.088). Findings were validated in the Biobank cohort. CONCLUSIONS: A post-treatment FPSAR of ≥0.10 is associated with more aggressive disease, suggesting a potentially novel role for this biomarker.

Systematic Differences Between Total and Free Prostate-Specific Antigen Immunoassays: Comparison Using Passing and Bablok Regression.

Recent studies have shown that there are systematic differences among total and free prostate-specificantigen (PSA) immunoassays. In this study we analyzedintermethod differences in total PSA (tPSA) and free PSA(fPSA) measurement using ARCHITECT i2000SR (Abbott Diagnostics) and COBAS E601 (Roche Diagnostics). A number of 160 blood samples were tested for tPSA and 50 samples for fPSA (selecting only sampleswith tPSA: 4.1-10.0 µg/L). Passing-Bablok regression analysis was used to compare the two analytical methods fortPSA, fPSA and percentage of fPSA (%fPSA). A strong correlation was noticed between ARCHITECT i2000SR and COBAS E601 for tPSA, fPSA and %fPSA (r between 0.94 and 0.99). Concentrations of tPSA and fPSA measured by COBAS E601 were higher thanthose measured by ARCHITECT i2000SR with a bias of 0.8 µg/L for tPSA and 0.14 µg/L for fPSA. Analyzing therelative difference between methods for fPSA and %fPSA, COBAS E601 exceed a 10% relative difference limit. Our study confirms that there are differences in measured concentrations of tPSA and fPSA byvarious commercial methods. Because clinical judgment on subsequent diagnostic procedures, such as prostatebiopsy, is based on tPSA and fPSA results, tests harmonization should be a priority.

[Epigenetic markers of early diagnostics of prostate cancer.]

The last 25 years, the prostate specific antigen (PSA) of the serum is used to diagnose prostate cancer. The experience of applying the PSA test showed its inconsistency as a diagnostic marker due to low cancerspecificity. Along with this, the next wave of biomarkers of prostate cancer appeared, which may supplement or, in due course, replace PSA due to higher sensitivity and cancerspecificity. This expanding panel of biomarkers was supplemented, basically, with new genomic technologies, which allowed to look impartially at cancer biology. Such efforts gave several notable success stories, quickly moving biomarkers from the laboratory table to clinical practice. The bulk of biomarker research focuses on early diagnosis of the disease, rather than on predictions that will allow for the prevention of the disease. This article examines the current state of biomarker studies of prostate cancer, including the revolutionary significance of the PSA test and its impact on early detection of prostate cancer, recent advances in biomarker detection, and a further developmental vector that improves the clinical management of this disease.

Current biomarkers for diagnosing of prostate cancer.

Prostate cancer (PCa) is mostly detected by prostate-specific antigen (PSA) as one of the most widely used tumor markers. But PSA is limited with its low specificity. The prostate health index (phi) can improve specificity over percent free and total PSA and correlates with aggressive cancer. The urinary PCA3 also shows its utility to detect PCa but its correlation with aggressiveness and the low sensitivity at high values are limitations. While the detection of alterations of the androgen-regulated TMPRSS2 and ETS transcription factor genes in tissue of ˜50% of all PCa patients was one research milestone, the urinary assay should only be used in combination with PCA3. Both US FDA-approved markers phi and PCA3 perform equally.

Prostate Specific Antigen as a Tumor Marker in Prostate Cancer: Biochemical and Clinical Aspects.

In this chapter the use of prostate specific antigen (PSA) as a tumor marker for prostate cancer is discussed. The chapter provides an overview of biological and clinical aspects of PSA. The main drawback of total PSA (tPSA) is its lack of specificity for prostate cancer which leads to unnecessary biopsies. Moreover, PSA-testing poses a risk of overdiagnosis and subsequent overtreatment. Many PSA-based markers have been developed to improve the performance characteristics of tPSA. As well as different molecular subforms of tPSA, such as proPSA (pPSA) and free PSA (fPSA), and PSA derived kinetics as PSA-velocity (PSAV) and PSA-doubling time (PSADT). The prostate health index (phi), PSA-density (PSAD) and the contribution of non PSA-based markers such as the urinary transcripts of PCA3 and TMPRSS-ERG fusion are also discussed. To enable further risk stratification tumor markers are often combined with clinical data (e.g. outcome of DRE) in so-called nomograms. Currently the role of magnetic resonance imaging (MRI) in the detection and staging of prostate cancer is being explored.

Stability of [-2]Pro-PSA in whole blood and serum: analysis for optimal measurement conditions.

BACKGROUND: The clinical usefulness of [-2]pro-PSA (where PSA is prostate-specific antigen) in prostate cancer diagnosis has been emphasized in recent studies. To determine proper blood sample handling conditions for [-2]pro-PSA evaluation, we analyzed the preanalytical stability of [-2]pro-PSA. METHODS: Blood samples from 22 Japanese males were stored under various conditions before total PSA (tPSA), free PSA, and [-2]pro-PSA concentrations were measured, and the preanalytical stability of [-2]pro-PSA and the changes in the Prostate Health Index (phi) were assessed. RESULTS: [-2]Pro-PSA was stable in serum for at least 24 hr at both room temperature (RT) and at 4°C. However, [-2]pro-PSA levels in whole blood increased rapidly over time, particularly at RT. Mean recovery (%) of [-2]pro-PSA in whole blood at RT was >110% at 1 hr after drawing of blood. The phi tended to increase over time in a pattern similar to the change in[-2]pro-PSA. CONCLUSIONS: Preanalytical stability was lower for [-2]pro-PSA than for free PSA or tPSA. Whole-blood [-2]pro-PSA increased in a time-dependent manner, particularly at RT. Thus, whole blood samples collected at RT should be centrifuged within 1 hr after drawing. The [-2]pro-PSA in serum is stable for at least 24 hr at both RT and at 4°C.

Lectin-nanoparticle concept for free PSA glycovariant providing superior cancer specificity.

BACKGROUND: Using lectins to target cancer-associated modifications of PSA glycostructure for identification of clinically significant prostate cancers, e.g., Gleason score (GS) ≥ 7, from benign and indolent cancers (GS 6), is highly promising yet technically challenging. From previous findings to quantify increased PSA fucosylation in urine, we set out to construct a robust, specific test concept suitable for plasma samples. METHODS: Macrophage galactose-binding lectin (MGL) coupled to 100 nm Eu3 + -nanoparticles was used to probe PSA captured from cancer cell lines, seminal plasma, and plasma samples from 249 patients with a clinical suspicion of prostate cancer onto 3 mm dense spots of free PSA antibody fab fragments. Results were compared to four kallikrein tests: tPSA, fPSA, iPSA and hK2. RESULTS: The fPSAMGLglycovariant provided superior discrimination of the GS ≥ 7 and benign + GS 6 groups (p 0.0003) compared to fPSA (NS). The corresponding AUC in ROC analysis was 0.70 compared to 0.66 for tPSA. In contrast to all four kallikrein tests, the fPSAMGLGV was independent of prostate gland volume. Using a logistic regression analysis the fPSAMGLGV significantly improved on the four-kallikrein model. CONCLUSIONS: Due to Eu-nanoparticles and a dense fPSA capture spot, the fPSAMGL glycovariant identifies an fPSA subform with the highest cancer specificity compared to the four conventional kallikreins.

Head-to-head comparison of prostate health index and urinary PCA3 for predicting cancer at initial or repeat biopsy.

PURPOSE: We performed a head-to-head comparison of the PHI (Prostate Health Index) and PCA3. MATERIALS AND METHODS: We evaluated PHI and PCA3 performance in 211 patients undergoing initial (116) or repeat (95) prostate biopsy. Multivariable logistic regression analysis was done using the AUC to test the accuracy of PHI and PCA3 for predicting prostate cancer in the overall population and in each setting. Decision curve analysis was used to compare the clinical benefit of different models. RESULTS: Overall, the AUC of the PHI (0.70) was significantly higher than the AUC of PCA3 (0.59), total prostate specific antigen (0.56) and free-to-total prostate specific antigen (0.60) (p = 0.043, 0.002 and 0.037, respectively). PHI was more accurate than PCA3 for predicting prostate cancer in the initial setting (AUC 0.69 vs 0.57) and in the repeat setting (AUC 0.72 vs 0.63), although no statistically significant difference was observed. Including PCA3 in the base multivariable model (prostate specific antigen plus free-to-total prostate specific antigen plus prostate volume) did not increase predictive accuracy in either setting (AUC 0.79 vs 0.80 and 0.75 vs 0.76, respectively). Conversely, including PHI in the base multivariable model improved predictive accuracy by 5% (AUC 0.79 to 0.84) and 6% (AUC 0.75 to 0.81) in the initial and repeat prostate biopsy settings, respectively. On decision curve analysis the highest net benefit was observed when PHI was added to the base multivariable model. CONCLUSIONS: PHI and PCA3 provide a significant increase in sensitivity and specificity compared to all other examined markers and they may help guide biopsy decisions. PCA3 does not increase the accuracy of predicting prostate cancer when PHI is assessed.

SRD5A1 and SRD5A2 are associated with treatment for benign prostatic hyperplasia with the combination of 5α-reductase inhibitors and α-adrenergic receptor antagonists.

PURPOSE: Common treatments for benign prostatic hyperplasia include 5α-reductase inhibitors and α-adrenergic receptor antagonists. However, these treatments can only partially decrease the risk of benign prostatic hyperplasia progression. SRD5A1 and SRD5A2 are 5α-reductase inhibitor targets. We investigated the association between drug efficacy and single nucleotide polymorphisms in the SRD5A1 and SRD5A2 genes in a Chinese population. MATERIALS AND METHODS: We genotyped 11 tagging single nucleotide polymorphisms in the SRD5A1 and SRD5A2 genes in a total of 426 benign prostatic hyperplasia cases and 1,008 controls from Xinhua Hospital, Shanghai, People's Republic of China. Cases were treated with type II 5α-reductase inhibitors and α-adrenergic receptor antagonists. We tested the association of tagging single nucleotide polymorphisms with benign prostatic hyperplasia risk/progression, clinical characteristics at baseline, including the I-PSS (International Prostate Symptom Score) and total prostate volume, and changes in clinical characteristics after treatment. RESULTS: The 11 tagging single nucleotide polymorphisms were not significantly associated with benign prostatic hyperplasia risk or progression (each p >0.05). In the SRD5A1 gene rs6884552 and rs3797177 were significantly associated with baseline I-PSS (p = 0.04 and 0.003, respectively). In the SRD5A2 gene rs523349 (V89L) and rs9332975 were significantly associated with baseline total prostate volume (p = 0.01 and 0.001, respectively). In SRD5A1 rs166050 was significantly associated with the posttreatment change in total prostate volume (p = 0.04). In SRD5A2 rs523349 and rs612224 were significantly associated with the posttreatment I-PSS change (p = 0.03 and 0.009, respectively). CONCLUSIONS: SRD5A1 and SRD5A2 single nucleotide polymorphisms are significantly associated with the clinical characteristics of benign prostatic hyperplasia and the efficacy of benign prostatic hyperplasia treatment.

[Immuno-analytical characteristics of PSA and derived biomarkers (total PSA, free PSA, p2PSA)]. / Caractéristiques immuno-analytiques du PSA et des biomarqueurs dérivés (PSA total, PSA libre et P2ProPSA).

Prostate-specific antigen (PSA) is the recommended tumor marker for individual screening and follow-up of prostate cancer. This paper reviews main structural and physiological data about prostate specific antigen isoforms: total PSA, free PSA, [-2]proPSA (also named p2PSA). It describes the pre-, per- and post-analytical conditions for these different parameters. It presents the interpretation of results and derived calculated indices (free/total PSA ratio, Prostate Health Index or PHI) for the management of prostate cancer (initial diagnosis and follow-up).

The Potentiality of Prostate-Specific Antigen as a Prognostic Biomarker in Breast Cancer.

Background Serum prostate-specific antigen (PSA) is a well-established marker that can be measured as an indicator for screening, diagnosing, and managing prostate cancer due to its advanced tissue specificity. Numerous studies have revealed that free PSA is the predominant molecular form of PSA in breast cancer cases. In contrast, total PSA is prevalent in benign breast tumor cases and healthy females. This case-control study aims to measure PSA levels among individuals with breast cancer in order to establish PSA as a prognostic biomarker. Methods The study involved 150 female subjects between the ages of 18 and 70 and was conducted between 2013 and 2014. The subjects were then categorized into three groups: those with malignant breast cancer, those with benign breast tumors, and the control group with no history of malignant or benign breast tumors. Participants were asked to complete a lifestyle questionnaire and interview using hospital medical records to establish past and pertinent patient medical history. These cases were acquired from the 7th of October Hospital's surgery department and Benghazi Central Hospital's oncology clinic in Libya. Sandwich-type ELISA's were used for PSA quantitation, while the Wilcoxon Rank-Sum test was used to identify statistically significant differences between total PSA and free PSA measurements within each patient group. Results This study did not reveal significant statistical differences in total PSA levels between breast cancer cases and control groups (p=0.200), or between breast cancer and fibroadenoma patients (p=0.472). However, there was a significant difference in F-PSA levels between breast cancer and fibroadenoma cases (p=0.0001). Neither total-PSA (p=0.200) nor F-PSA (p=0.262) levels showed significant differences between breast cancer cases and controls. This study paved the way for further investigations into PSA's role in breast cancer. Despite its limitations, it offers an opportunity to delve deeper into understanding PSA's potential role and use in breast cancer. Conclusion A comprehensive statistical analysis revealed a positive correlation between F-PSA levels and breast cancer diagnosis. The findings suggest that PSA may serve as a prognostic biomarker for breast cancer. This may contribute to improved customized treatment approaches, offering precise and accurate risk assessments, understanding breast cancer biology, and improving health outcomes for patients with breast cancer.

Technical Note: Newly Reformulated Total and Free PSA Immunoassay on Cobas e411 Analyzer Is Virtually Free from Biotin Interference.

OBJECTIVE: Total and free prostate specific antigens (PSA) have been used as diagnostic markers for monitoring progress of therapy in patients with prostate cancer as well as for screening purpose. Roche total and free PSA immunoassay utilizes biotinylated antibody in assay design. As a result, both assays are affected by elevated serum biotin levels. Recently, Roche reformulated these assays to reduce biotin interference. We evaluated biotin interference in these products. MATERIALS AND METHODS: We prepared three serum pools with one pool containing high amount of total PSA. Then aliquots of each serum pool were further supplemented with various concentrations of biotin (100-1500 ng/mL) followed by measuring both total and free PSA using Roche total and free PSA immunoassay and Cobas e411 analyzer. RESULTS: We observed no significant interference of biotin in both total and free PSA assays up to biotin concentration of 1200 ng/mL. CONCLUSION: We concluded that newly reformulated total and free PSA immunoassays are virtually free from biotin interference.

Measurement of total and free prostate specific antigen (PSA) in human serum samples using an ultra-microanalytical system.

Prostate specific antigen (PSA) is a serine protease used for the screening of prostate cancer. The total portion of PSA (tPSA) can be found in its free form (fPSA), or bound to other proteins forming a stable complex. A heterogeneous sandwich-type UltraMicro Enzyme-Linked ImmunoSorbent Assay (UMELISA) has been developed for the measurement of tPSA and fPSA in human serum samples. Strips coated with a high affinity monoclonal antibody (MAb) directed against PSA are used as solid phase, to ensure the specificity of the assay. Biotinylated MAbs specific for tPSA and fPSA ensured sensitivity, given the high affinity binding to streptavidin. The assay was completed in 1.5 h, with a measuring range 0.019-20 µg/L (tPSA), and 0.009-20 µg/L (fPSA). The intra- and inter-assay CV were lower than 9%. Recovery percentages were 96-105%. High correlations were found between the values of the UMELISA PSA standards and the International Reference Standards 96/670 (R2 = 0.9996) and 96/688 (R2 = 0.9989). The assay did not recognize any of the interfering molecules tested. Regression analysis of serum samples showed a good correlation with Roche Elecsys total PSA (n = 631, R2 = 0.986, ρc = 0.992), BioMérieux VIDAS TPSA (n = 631, R2 = 0.989, ρc = 0.993) and Roche Elecsys free PSA (n = 164, R2 = 0.973, ρc = 0.979), all with a relative difference below 15%, and a p < 0.001. A retrospective study of the use of UMELISA PSA in Cuba was carried out. The analytical performance characteristics of UMELISA PSA support its use for the quantification of tPSA and fPSA in human serum samples in a single kit, making it an affordable diagnostic assay available to Cuban Public Health System and developing countries. Between the years 2014-2020, more than 3 million Cuban patients have benefited from the test for free.

The Impact of Cell-free Plasma DNA on Metastatic and Nonmetastatic Prostate Cancer.

Intorductuion: Increased cell-free DNA (cfDNA) is observed in many diseases such as cancer, myocardial infarction, and autoimmune diseases. It has the ability to alter the receptor cell phenotype, triggering events related to malignant transformation. AIMS: Our study aims at assessing the use of cell-free plasma DNA in the diagnosis of metastatic and non-metastatic prostate cancer. METHODS: The study included 180 subjects who were classified into four groups: Group I (GI) included 50 perfect health subjects as the control group, Group II (GII) included 40 patients with prostatitis, group III (GIII) included 40 patients with benign prostatic hyperplasia (BPH) and Group IV (GIV) included 50 patients with pre-operative prostate cancer (PC). Evaluation of the plasma level of circulating cell-free DNA by real-time PCR and measurement of total PSA (tPSA) and free to total PSA percent (f/tPSA%) were carried out for all groups. RESULTS: Our study revealed that the level of tPSA was significantly higher in prostate cancer patients, while levels of f/t PSA were found to be significantly lower. The level of cfDNA was significantly higher in prostate cancer patients (399.9±88.6ng/ul) when compared to that of group I (12.1±1.5ng/ul) (p<0.01), group II (14.7±2.4 ng/ul) (p<0.01), and group III (26.6±45.6 ng/ul) (p<0.01) respectively. CONCLUSION: There was a statistically significant difference in yields of cfDNA between metastatic and non-metastatic groups (P=0.03) with a higher level in the metastatic group.

Screening for prostate cancer: a study on the free and total prostate specific antigen.

BACKGROUND: A variety of biomarkers have been developed to monitor growth of cancerous diseases and to detect them at an early stage. Prostate-specific antigen (PSA) is a valuable prostate cancer biomarker that is now widely used for population screening, diagnosis, and monitoring of patients with prostate cancer. Other factors than prostate cancer can cause elevation of PSA levels therefore, free prostate specific antigen measurements in serum have been proposed in order to improve the specificity of laboratory identification of prostate cancer. AIM: The aim of our study was to evaluate the diagnostic significance of both total PSA and Free PSA in discriminating prostate cancer from other prostate diseases. MATERIALS AND METHODS: Our study group consisted of 1201 males admitted at outpatient clinic aged between 35 and 84 years old (mean age 63 years). All laboratory measurements were performed on serum samples. The data were statistically analyzed by using descriptive statistics for Windows. RESULTS: The mean total PSA concentration evaluated among 1038 patients was 16.17 ng/mL whereas only Free PSA concentration was evaluated in 163 serum samples and resulted in a mean value of 2.67 ng/ml. In order to calculate the correlation between total and free PSA, data among 69 /1038 patients were further analyzed through statistical program software package for data analysis. CONCLUSIONS: Measuring serum free PSA concentrations along with PSA concentrations may provide higher accuracy for detecting prostate cancer and might eliminate unnecessary biopsies in the men with PSA of more than 4.0 ng/mL.

Is serum PSA a predictor of male hypogonadism? Testing the hypothesis.

OBJECTIVE: Male hypogonadism (MH) is common among infertile men. Besides testosterone, limited MH biomarkers are available, while researchers have suggested the use of prostate-specific antigen (PSA) to help diagnose MH. Hence, we sought to evaluate the potential use of PSA to predict MH among relatively young men with infertility in Nigeria. METHODS: The study included 707 male partners (35-44 years) in infertile couples seeking infertility evaluation at a third-level care center in Nigeria. MH was diagnosed using standard guidelines. Receiver operating characteristic (ROC) and regression analyses explored the potential of serum free PSA (fPSA) and total PSA (tPSA) in predicting MH and MH-related clinical features. RESULTS: In all, 29.7% of the patients had MH (MH+ve). The MH+ve group had lower mean values of fPSA and tPSA than the group without MH (MH-ve). The best fPSA threshold of < 0.25 µg/L compared with the best tPSA threshold of < 0.74 µg/L had higher accuracy (area under the curve [AUC] 0.908 versus 0.866, respectively), sensitivity (87% versus 83%, respectively), and specificity (42% versus 37%, respectively) for MH diagnosis. After adjustment for confounders, fPSA level ≤ 0.25 µg/L was more likely to predict MH-related decreased libido (odds ratio [OR] 2.728, p<0.001) and erectile dysfunction (OR 3.925, p<0.001) compared with tPSA ≤ 0.74 µg/L in the MH+ve group. CONCLUSION: For MH diagnosis, fPSA and tPSA had good sensitivity but very poor specificity, although fPSA had better potential for MH diagnosis and association with MH-related clinical features than tPSA. Hence, fPSA could complement other biomarkers for MH diagnosis in men 35-44 years, although we recommend further studies to confirm these findings.

Evaluation of Phi Clinical Performance for the Detection of Prostate Cancer in Routine Clinical Practice.

Prostate Health Index (phi) and percent free PSA (%fPSA) are used in patients with a PSA concentration between 4-10 µg/L as an aid to distinguish prostate cancer (PCa) from benign conditions, and to assist in the decision of whether to proceed to biopsy. This study assesses the clinical performance and diagnostic accuracy of phi versus %fPSA in a cohort of Mayo Clinic's patients. Of 4065 phi orders received from May 2017-August 2018, concordance between phi and %fPSA results was evaluated on 2845 results with a total PSA within 4-10 µg/L. Retrospective chart review was performed on 201 Mayo Clinic patients, and %fPSA and phi results were compared with both the decision to biopsy and presence of PCa at biopsy. Receiver operating characteristic (ROC) curve analysis to evaluate the diagnostic accuracy of PSA, %fPSA and phi was performed. In this study 2.5% of the 2845 orders exhibited discordant PCa risk classifications between %fPSA and phi results. In the phi high risk category, 41.7% (versus 26.1% by %fPSA) of patients had biopsy and 100% (versus 66.6% by %fPSA) were positive for PCa. Phi exhibited the highest specificity and ROC area under the curve compared to %fPSA and PSA. phi was a better predictor than %fPSA for finding PCa at biopsy. These findings support continued utilization of phi in the evaluation of patients with a PSA in the 4-10 µg/L range.

Comparison of Three Assays for Total and Free PSA Using Hybritech and WHO Calibrations.

BACKGROUND/AIM: Lack of interchangeability between prostate-specific antigen (PSA) assays could have a clinical impact. We compared PSA assays from different manufacturers and calibrations. PATIENTS AND METHODS: A total of 233 men who underwent prostate biopsy (PSA: 2-10 ng/ml; Beckman Coulter Access® Hybritech® as reference) were enrolled. Total (tPSA) and free PSA (fPSA) were also measured using the Roche cobas® and the Abbott Architect® methods. RESULTS: Roche tPSA values were ≈1% higher than Beckman, while Abbott values were ≈5% lower. Roche had the highest diagnostic sensitivity (92%) compared to Beckman Coulter (87%) and Abbott (85%). Roche fPSA was ≈3% lower and Abbott ≈17% higher than that of Beckman. For the percentage of fPSA, Roche had the highest sensitivity (98%). CONCLUSION: Roche cobas® and Beckman Coulter Access® Hybritech® tPSA were almost interchangeable. While the agreement was acceptable for tPSA, this did not happen with fPSA and greater efforts for harmonization are required.