Percent Free Prostate-specific Antigen Research Articles

An NMR-based metabolic signature to identify clinically significant prostate cancer in patients undergoing biopsy.

Despite clinical suspicion of prostate cancer (PCa), 20-25% of patients exhibit a tumor-negative biopsy result. To assess the serum metabolic profile of clinically significant (cs) compared to clinically insignificant (ci) PCa or benign (Be) patients. 1078 serum samples were analyzed. Nuclear magnetic resonance (NMR) spectroscopy was used to quantify 73 metabolites, Random Forest for model algorithm. We identified a 22-metabolite panel, which discriminated csPCa (ISUP 2-5, n=328) from ciPCa (ISUP 1, n=101) and benign patients (negative biopsy, n=649) with a higher performance when combined with the standard clinical parameters age, prostate specific antigen (PSA), and percentage free PSA (%fPSA) (AUC 0.84) than the clinical parameters alone (AUC 0.73). Our study further revealed significant dysregulations of the urea cycle and the choline pathway along with changes in tricarboxylic acid (TCA) cycle, cholesterol metabolism, and a significant increase of the inflammation marker GlycB in csPCa patients. In particular, ornithine and dimethylglycine were the 2 most important features to discriminate csPCa from Be+ciPCa with significantly higher ornithine and lower dimethylglycine levels in patients with csPCa (ornithine: 63.7 ± 26.5 µmol/l, dimethylglycine: 12.6 ± 6.3 µmol/l, p<0.001) compared to Be+ciPCa patients (ornithine: 50.3 ± 31.6 µmol/l, dimethylglycine: 14.9 ± 7.7 µmol/l). This study discovered a 22-metabolite panel to discriminate patients with csPCa from Be+ciPCa patients when combined with age, PSA, and %fPSA. It may therefore be used as supportive biomarker to reduce the number of unnecessary biopsies and also to identify novel therapeutic targets in the future.

Diagnostic properties of percent-free PSA as a predictor of prostate cancer in Thai men with total serum PSA level of 4-10 ng/ml

Objective: The percent-free prostate specific antigen (%fPSA) could enhance total PSA (tPSA) with regards to early prostate cancer detection by increasing its specificity. However, due to significant physiologic differences across races, the optimal cut-off level for %fPSA may vary. We aimed to determine optimal %fPSA cut-off level for Thai men aged between 50 to 80 years whose tPSA score ranged from 4-10 ng/mL and to evaluate its corresponding diagnostic properties, specifically sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). The secondary endpoint is the relationship between Gleason Grade Group and %fPSA value. Materials and Methods: A total of 184 male patients from age 50-80 years whose tPSA was between 4-10 ng/ml were enrolled onto the study. Their %fPSA were measured before undergoing transrectal ultrasonography (TRUS) guided prostate biopsy, which procured at least 10 cores. All histologic reports were reviewed and confirmed for further analysis. Results: Out of the 184 patients registered the final diagnoses were 31 (16.84%) were positive for prostate cancer and the other 153 (83.16%) had benign prostate hypertrophy (BPH). At %fPSA cut-off of ≤ 10%, the sensitivity would be 22.6%, specificity 95.4%, PPV 50.0% and NPV 85.9%. However, at a %fPSA cut-off of ≤ 20%, the sensitivity was 77.4%, specificity 32.7%, PPV 18.9%, and NPV 87.7%. The %fPSA value has a direct relationship with sensitivity and NPV whereas it is inversely proportional to specificity and PPV. Lower %fPSA is associated with higher risk of prostate cancer. The area under the curve (AUC) of ROC curve was 0.65. The incidence of prostate cancer among patients with Gleason Grade Groups 1, 2, 3, 4, and 5 were 41.94%, 32.26%, 16.13%, 6.45%, and 3.23% respectively. The mean %fPSA scores among those groups were 14.75%, 17.64%, 10.19% ,13.33%, and 15.65% respectively. Conclusion: The decision to undergo prostate biopsy in Thai males with a tPSA score between 4-10 ng/ml can be guided by %fPSA, which proved to be an effective and useful predictive tool. The cut-off level of %fPSA ≤ 20% had the highest diagnostic properties in Thai men in our study which yielded a sensitivity of 77.4%, specificity of 32.7%, PPV of 18.9%, and NPV 87.7%. If %fPSA was ≥ 30%, there was no risk of prostate cancer in this cohort. In addition, with regard to disease severity, we found that %fPSA level is not associated with the Gleason Grade Grouping.

Blood-Based DNA Methylation Analysis by Multiplexed OBBPA-ddPCR to Verify Indications for Prostate Biopsies in Suspected Prostate Cancer Patients.

Current prostate carcinoma (PCa) biomarkers, including total prostate-specific antigen (tPSA), have unsatisfactory diagnostic sensitivity and specificity resulting in overdiagnosis and overtreatment. Previously, we described an optimised bias-based preamplification-digital droplet PCR (OBBPA-ddPCR) technique, which detects tumour DNA in blood-derived cell-free DNA (cfDNA) of cancer patients. The current study investigated the performance of newly developed OBBPA-ddPCR-based biomarkers. Blood plasma samples from healthy individuals (n = 90, controls) and PCa (n = 39) and benign prostatic hyperplasia patients (BPH, n = 40) were analysed. PCa and BPH patients had tPSA values within a diagnostic grey area of 2-15 ng/mL, for whom further diagnostic validation is most crucial. Methylation levels of biomarkers RASSF1A, MIR129-2, NRIP3, and SOX8 were found significantly increased in PCa patients compared to controls. By combining classical PCa risk factors (percentage of free PSA compared to tPSA (QfPSA) and patient's age) with cfDNA-based biomarkers, we developed PCa risk scores with improved sensitivity and specificity compared to established tPSA and QfPSA single-marker analyses. The diagnostic specificity was increased to 70% with 100% sensitivity for clinically significant PCa patients. Thus, prostate biopsies could be avoided for 28 out of 40 BPH patients. In conclusion, the newly developed risk scores may help to confirm the clinical decision and prevent unnecessary prostate biopsy.

An approach to diagnosis of prostate cancer using fuzzy logic

&lt;p&gt;&lt;span&gt;Early diagnosis of cancers is a major requirement for patients and a complicated job for the oncologist. If it is diagnosed early, it could have made the patient more likely to live. For a few decades, fuzzy logic emerged as an emphatic technique in the identification of diseases like different types of cancers. The recognition of cancer diseases mostly operated with inexactness, inaccuracy, and vagueness. This paper aims to design the fuzzy expert system (FES) and its implementation for the detection of prostate cancer. Specifically, prostate-specific antigen (PSA), prostate volume (PV), age, and percentage free PSA (%FPSA) are used to determine prostate cancer risk (PCR), while PCR serves as an output parameter. Mamdani fuzzy inference method is used to calculate a range of PCR. The system provides a scale of risk of prostate cancer and clears the path for the oncologist to determine whether their patients need a biopsy. This system is fast as it requires minimum calculation and hence comparatively less time which reduces mortality and morbidity and is more reliable than other economic systems and can be frequently used by doctors.&lt;/span&gt;&lt;/p&gt;

The risk of prostate cancer diagnosis in men with an elevated PSA but low IsoPSA.

292 Background: IsoPSA is a structure-based serum assay. Initial studies demonstrated that it outperformed total and percent-free PSA in detecting clinically significant prostate cancer (csPCa) (i.e., grade group (GG) ≥2) on biopsy. This led to an overall reduction in invasive testing and magnetic resonance imaging (MRI). We sought to compare the risk of csPCa in patients with an initially normal or high IsoPSA, thus assessing IsoPSA’s prospective predictive ability of csPCa. Methods: We performed a single-center retrospective review of patients (n=1578) who underwent IsoPSA testing from November 2016 to August 2022. Data was dichotomized into patients with normal (≤6) and high IsoPSA (&gt;6). We collected the outcomes of any follow-up IsoPSA, prostate biopsy, MRI, and diagnosis of prostate cancer. In the case of multiple follow-up tests, the most recent one was recorded. Results: The median follow-up time of 1578 patients who underwent IsoPSA testing was 24 months (IQR 16-29). Among 541 patients with an initial normal IsoPSA, 60 (11.1%) had a subsequent high IsoPSA, 23 (4.3%) had csPCa on a subsequent biopsy, and 48 (8.9%) had suspicious lesions on MRI (PI-RADS 4-5). Among 1037 patients with an initial high IsoPSA, 366 (35.3%) had csPCa on a subsequent biopsy and 342 (33%) had suspicious lesions on MRI. The sensitivity of IsoPSA to predict csPCa was 94.1%, and its negative predictive value was 89.3%. Conclusions: With 24-month follow-up, 4.3% of patients with normal IsoPSA developed csPCa, suggesting that a low baseline IsoPSA provides durable information about the 2-year risk of csPCa.[Table: see text]

Associations of HALP score with serum prostate-specific antigen and mortality in middle-aged and elderly individuals without prostate cancer.

The association between the Hemoglobin, Albumin, Lymphocyte, and Platelet (HALP) score and serum prostate-specific antigen (PSA) and all-cause mortality remains underexplored. We aimed to investigate the relationship between HALP score and these outcomes among middle-aged and elderly individuals without prostate cancer (PCa). This cross-sectional study included participants aged 40 years and older from National Health and Nutrition Examination Survey (NHANES) 2001-2010. HALP score was calculated using the formula: HALP score = (Hemoglobin × Albumin × Lymphocytes)/Platelets. High PSA level was defined as a percentage free PSA (%fPSA) less than or equal to 25% and a total PSA (tPSA) level equal to or higher than 4.0 ng/mL. Mortality data were obtained through December 30, 2019 by linking to the National Death Index. Among 7,334 participants, 6,826 were classified as having low PSA level, while 508 were categorized as having high PSA level. Logistic regression revealed lower odds of high PSA level with higher HALP quartiles (P trend<0.001). Among 508 participants with high PSA level, over a median follow-up period of 10.13 years (IQR: 5.42-13.17 years), a total of 268 all-cause deaths were recorded. Cox regression analysis showed that participants in the highest HALP quartile had the lowest risk of all-cause mortality (HR = 0.527, 95% CI: 0.368-0.754) in participants with high PSA level. Restricted cubic spline analysis indicated a non-linear and negative correlation between HALP score and all-cause mortality, with an inflection point at 43.98 (P for non-linearity = 0.009). Random survival forest analysis ranked HALP score as the most significant predictor for all-cause mortality. Our study highlights that the HALP score the HALP score is associated with high PSA level and all-cause mortality among middle-aged and elderly individuals without PCa. Further research is warranted to validate these findings and elucidate underlying mechanisms.

The Value of the Prostate Health Index and Derived Indexes in the Diagnosis of Prostate Cancer with PI-RADS-3 Lesions

Introduction: The purpose of this article was to evaluate the diagnostic value of prostate health index (PHI) and its derivatives in prostate cancer (PCa) with prostate imaging reporting and data system (PI-RADS)-3 lesions. Methods: Patients with benign prostatic hyperplasia (BPH) (n = 155) were included in the BPH group, while all patients with PCa (n = 49) were enrolled in the PCa group. Between the groups, the serum concentrations of total prostate-specific antigen (TPSA), percent-free prostate-specific antigen (%fPSA), prostate health index (PHI), prostate health index density (PHID), and prostate-specific antigen density (PSAD) were compared. Results: On average, 49 (24%) of 204 men had PCa on biopsy, with 81.63% of those cases being clinically serious. Age, prostate volume, TPSA, and PSAD did not significantly differ between the PCa group and the BPH group. In contrast, [-2]pro prostate-specific antigen (p2PSA) (17.10 ± 4.77 vs. 13.93 ± 3.22, p < 0.001), PHI (33.88 ± 8.81 vs. 25.83 ± 5.63, p < 0.001), and PHID (0.52 ± 0.15 vs. 0.38 ± 0.11, p < 0.001) showed a statistically significant difference between the two groups. Compared to conventional PSA, PHI (AUC = 0.786, 95% CI: 0.705–0.867) and PHID (AUC = 0.763, 95% CI: 0.684–0.843) were considerably better predictors of all PCa. The TPSA, %fPSA, p2PSA, PHI, PHID, and PSAD areas under the receiver operating characteristic for clinically significant PCa (csPCa) were 0.587, 0.650, 0.696, 0.823, 0.796, and 0.614, respectively. Out of all the various parameters, PHI and PHID performed very well in this cohort’s biopsy outcome prediction. Conclusion: PHI offers the best diagnostic value for detecting PCa in cases of PI-RADS-3 lesions. Additionally, PHID raised the possibility of csPCa PI-RADS-3 lesions. However, more investigation is required to confirm our results by using multicenter collaboration.

Time to stop reporting estimates of any prostate cancer risk with percentage of free prostate-specific antigen.

Time to stop reporting estimates of any prostate cancer risk with percentage of free prostate-specific antigen.

Relationship between Proclarix and the Aggressiveness of Prostate Cancer.

Proclarix is a CE-marked test that provides the risk of clinically significant prostate cancer (csPCa), ranging from 0% to 100%, based on the serum measurement of Thrombospondin-1, cathepsin D, prostate-specific antigen (PSA), and percentage of free PSA in addition to age. We hypothesize that Proclarix could be correlated with PCa aggressiveness. We analyzed the association of this new biomarker with four surrogates of aggressiveness: grade group (GG) in the biopsy, clinical stage, risk of biochemical recurrence after primary treatment of localized PCa, and pathology in the surgical specimen. This is a retrospective study from 606 men with suspicion of PCa [PSA of ≥3.0ng/mL and/or abnormal digital rectal examination (DRE)], in whom Proclarix was assessed (0-100%). The GG was defined by the International Society of Urological Pathology categories. The TNM was used for clinical staging (cT based on DRE, whereas cN and cM were established with computed tomography and 99-technetium bone scintigraphy). The risk of biochemical recurrence of localized PCa after primary treatment was defined by combining PSA, GG, and cT. Finally, an unfavorable pathology in a surgical specimen was defined as GG> 2 or pT≥ 3. The median age of the cohort was 67yearsold, with a median PSA of 7ng/mL and a rate of abnormal DRE of 23.3%. CsPCa was detected in 254 men (41.9%), with a median Proclarix of 60.1% compared with 37.3% obtained in patients with insignificant PCa and 20.7% in men without PCa. Among patients with GG > 3, Proclarix was significantly higher (58.2%) than in those with GG of 3 or lower (33.1%, p< 0.001). Men with localized tumors exhibited a Proclarix median of 37.3% compared with those with advanced disease (60.1%, p< 0.001). Proclarix levels among 197 patients with low and intermediate risk of biochemical recurrence were 24.9% and 35.0%, respectively, significantly lower compared with patients with high-risk disease (58.7%, p< 0.001). Unfavorable pathology was observed in 35 patients out of the 79 who underwent radical prostatectomy, with a Proclarix median of 35.7% compared with 23.7% obtained in patients with favorable pathology (p= 0.013). Proclarix and magnetic resonance imaging were independent predictors of the four surrogates of aggressiveness analyzed. There is a correlation between Proclarix and the aggressiveness of PCa.

Risk Stratification of Low-risk Prostate Cancer: Individualizing Care in the Era of Active Surveillance.

While active surveillance is the preferred management for most men with low-risk prostate cancer, a subset may harbor more aggressive disease. In this review we examine the evidence underlying an accurate and nuanced assessment of oncologic risk in these men. We performed a nonsystematic literature review current to January 2023 on PubMed for articles relating to clinical, pathological, molecular, and imaging-based modalities available for risk assessment in men with low-risk prostate cancer. Relevant articles were reviewed by the authors and evidence was summarized. Many tools are available to personalize clinical decision-making for men with low-risk prostate cancer. Total volume of cancer, PSA density, and presence of ductal components have been consistently and strongly associated with current or future evidence of higher-grade disease. PSA kinetics, Prostate Imaging Reporting & Data System 4/5 lesions on MRI, perineural invasion, germline mutations, and genomic classifiers all appear to be associated with an increased risk, although are not as extensively validated. Race, percent free PSA, and other serum biomarkers such as Prostate Health Index and 4Kscore do not appear to be associated with long-term elevated risk. Long-term prognosis for men diagnosed with low-risk prostate cancer is excellent. There are many factors which should be routinely integrated into the initial management decision as well as determining intensity and frequency of active surveillance. Development of comprehensive multivariable instruments to guide clinical decisions is encouraged.

MP55-14 IsoPSA PERFORMANCE CHARACTERISTICS ARE NOT IMPACTED BY 5-ALPHA REDUCTASE INHIBITORS OR ALPHA-BLOCKERS

You have accessJournal of UrologyCME1 Apr 2023MP55-14 IsoPSA PERFORMANCE CHARACTERISTICS ARE NOT IMPACTED BY 5-ALPHA REDUCTASE INHIBITORS OR ALPHA-BLOCKERS Jason Scovell, Mark Stovsky, Aimee Kestranek, and Eric Klein Jason ScovellJason Scovell More articles by this author , Mark StovskyMark Stovsky More articles by this author , Aimee KestranekAimee Kestranek More articles by this author , and Eric KleinEric Klein More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003308.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: IsoPSA is a structure-based test linked to tumor biology that has demonstrated improved performance characteristics over PSA and percent free PSA to identify clinically actionable prostate cancer (GG2+). Medications for benign prostatic hyperplasia (BPH) including 5-α reductase inhibitors (5ARIs) and α-blockers are commonly used in the patient population undergoing prostate cancer screening. The relationship between 5-ARIs and PSA levels is well established. We sought to determine the impact that common BPH medications have on IsoPSA performance. METHODS: This is a secondary analysis of data from an institutional review board (IRB) approved, prospective, multicenter study evaluating IsoPSA in men≥50 years of age with a total PSA ≥ 4ng/ml with planned prostate biopsy who met previously described inclusion/exclusion criteria. Analytic groups included (i) all subjects, (ii-iii) +/- 5-ARI use, (iv-v) +/- α-blocker use. Sensitivity and specificity analysis were performed and receiver operating curves (ROC) were evaluated. RESULTS: A total of 1,385 men were recruited from a multi-center (8 sites), prospective, nonrandomized cohort with 888 men included in final analysis. Actionable prostate cancer, defined as GG2 or greater, was identified in a total of 316 patients (35.6%). In this cohort, 40 patients reported 5-ARI use and 217 reported α-blocker use. At the pre-determined IsoPSA threshold (5.25 all cancer; 6.0 GG2+) sensitivity to detect both all prostate cancer and actionable cancer was similar between all patients enrolled and patients on either 5-ARIs or α-blockers (All: 0.90 vs 5-ARI: 0.94 vs α-blocker: 0.85; p>0.05). Specificity was similar between patients regardless of 5-ARI (No 5-ARI: 0.46 vs 5-ARI: 0.45, p>0.05). Increased specificity was noted in patients on α-blockers (No α-blocker: 0.40 vs α-blocker: 0.61, p<0.05). There were no additional differences in FP, FN, FP, FN, LR (+/-), PPV, or NPV rates between all sub-cohorts. ROC analysis demonstrates excellent performance of IsoPSA regardless of 5-ARI or α-blocker use for both the detection of all prostate cancer and for actionable cancer (Figure 1). CONCLUSIONS: Common BPH medications (5-ARI and α-blockers) do not negatively impact IsoPSA performance characteristics for the detection of prostate cancer including clinically actionable prostate cancer. Source of Funding: Cleveland Diagnostics funded the initial study of IsoPSA © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e769 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jason Scovell More articles by this author Mark Stovsky More articles by this author Aimee Kestranek More articles by this author Eric Klein More articles by this author Expand All Advertisement PDF downloadLoading ...

Comparisons of the diagnostic accuracy across prostate health index, prostate health index density, and percentage free prostate-specific antigen for clinically significant prostate cancer: a prospective diagnostic study.

As the novel serum biomarkers, it has not been clearly clarified that the diagnostic accuracy of prostate health index (PHI) and prostate health index density (PHID) are superior to that of percentage free prostate-specific antigen (%fPSA) in detection of clinically significant prostate cancer (csPCa), especially in the gray zone. Therefore, this study aimed to compare the diagnostic value of PHI, PHID, and %fPSA for csPCa in the patients with prostate-specific antigen (PSA) >4 ng/mL and those with PSA within 4-10 ng/mL. In this study, the serum samples and clinicopathological features were prospectively obtained from the patients who underwent prostate biopsy between September 2019 and December 2020. According to the inclusion criteria, the patients with total PSA (tPSA) >4 ng/mL, prostate magnetic resonance imaging or ultrasound clearly suggesting an occupying lesion were enrolled in this study. The patients with Gleason score ≥7 indicated csPCa. The receiver operating characteristic curves and the area under the curve (AUC) values were used to assess the diagnostic performance. Among the 296 patients (mean age 67.5 years, median tPSA 7.94 ng/mL) included in this study, there were 54 in the csPCa group (mean age 70.4 years, median tPSA 11.0 ng/mL) and 242 in the non-csPCa group (mean age 66.8 years, median tPSA 7.67 ng/mL). Based on the PSA level, there were 198 patients with PSA within the gray zone, which included 40 patients in the csPCa group and 158 in the non-csPCa group. In all patients, the sensitivity of PHID for detecting csPCa was 96.30%, and the specificity was 33.06% with the cut-off value of 0.51. Moreover, both PHID and PHI did better in the diagnosis of csPCa (AUC: 0.880 and 0.867, respectively) compared with other PSA derivative markers. Similarly, in the patients with PSA level in the gray zone, the diagnostic accuracy of PHID and PHI in predicting csPCa (AUC: 0.788 and 0.777, respectively) were better than other PSA derivative markers. PHID presented the better diagnostic accuracy in predicting csPCa in patients with PSA in the gray zone than other PSA derivative markers, which could be a promising biomarker for making the biopsy strategy.

Do PHI and PHI density improve detection of clinically significant prostate cancer only in the PSA gray zone?

Prostate health index (PHI) is a predictive biomarker of positive prostate biopsy. The majority of evidence refers to its use in the PSA gray zone (4-10ng/mL) and negative digital rectal exam (DRE). We aim to evaluate and compare the predictive accuracy of PHI and PHI density (PHId) with PSA, percentage of free PSA and PSA density, in a wider range of patients for the detection of clinically significant prostate cancer (csPCa). Multicenter prospective study that included patients suspicious of harboring prostate cancer. Non-probabilistic convenience sampling, where men who attended the urology consultation were tested for PHI before prostate biopsy. To evaluate and compare diagnostic accuracy AUC and decision curve analysis (DCA) were calculated. All these procedures were performed for the overall sample and the following subsamples: PSA<4ng/ml; PSA 4-10ng/ml; PSA 4-10ng/ml plus negative DRE and PSA>10ng/ml. Among the 559 men included, 194 (34.7%) were diagnosed of csPCa. PHI and PHId outperfomed PSA in all subgroups. PHI best diagnostic performance was found in PSA 4-10ng/ml with negative DRE (sensitivity 93.33, NPV 96.04). Regarding AUC, significant differences were found between PHId and PSA in the subgroup of PSA 4-10ng/ml, whatever DRE status. In DCA, PHI density shows the highest net benefit. PHI and PHId outperfom PSA in csPCa detection, not only in the PSA grey zone with negative DRE, but also in a wider range of PSA values. There is an urgent need of prospective studies to established a validated threshold and its incorporation in risk calculators.

Use of IsoPSA with prostate MRI PIRADS score in biopsy decision making in patients with elevated PSA.

388 Background: IsoPSA is prospectively validated to be superior to PSA and percent free PSA in predicting prostate cancer (PCa) as well as clinically significant prostate cancer. We sought to evaluate the use of IsoPSA in combination with prostate magnetic resonance imaging (MRI) and the prostate imaging reporting and data systems (PIRADS) on predicting either benign/indolent or csPCA at biopsy. Methods: This was a single center retrospective review of prospectively collected patient data that included all patients who underwent IsoPSA testing, preoperative prostate MRI and prostate biopsy from 2019-2021. Chi Squared analysis was used to assess for associations between a binary classification of low (&lt;6) or elevated (&gt;6) IsoPSA index, in combination with PIRADS scores in predicting either indolent/benign or csPCa at biopsy. Logistic regression was used to explore independent predictors of csPCa. Receiver Operating Curve (ROC) analysis was completed with areas under the curve (AUC) for IsoPSA and PIRADS scores, both alone and in combination. Predictive probabilities were assessed using combinations of IsoPSA thresholds and PIRADS scores. Results: 207 patients met inclusion criteria. Among patients with a negative MRI, low IsoPSA index was associated with a lower chance of csPCa compared to those with elevated IsoPSA (2% vs 15%, p&lt;0.018). For those with a PIRADS 4-5 lesion, elevated IsoPSA index was associated with a higher chance of csPCa at biopsy compared to a low IsoPSA index (49% vs 19%, p=0.05). On multivariate analysis, elevated IsoPSA and PIRADS 4-5 were independent predictors of csPCa (p&lt;0.001). Similarly, low IsoPSA index and negative MRI were independent predictors of benign/indolent disease at biopsy (p&lt;0.001). Using predictive probabilities, the combination of PIRADS 4-5 with elevated IsoPSA was associated with the highest risk of csPCa (48%) and the highest AUC (0.83) for predicting csPCa. This AUC value was superior to either marker alone (0.76, 0.76) and total PSA alone (0.57) (p&lt;0.001). Conclusions: The combination of elevated IsoPSA with adverse PIRADS score (4-5) is associated with a 48% predicted probability of csPCa at biopsy with an AUC of 0.83, which was more accurate than either marker alone. A low IsoPSA in combination with a negative MRI resulted in a 98% chance of benign/indolent disease at biopsy. These findings may prove useful for the practicing Urologist and may help guide discussions regarding the need for biopsy when interpreting various IsoPSA/PIRADS combinations. [Table: see text]

Evaluation and multi-institutional validation of a novel urine biomarker lncRNA546 to improve the diagnostic specificity of prostate cancer in PSA gray-zone.

Background and objectivesProstate specific antigen (PSA) is currently the most commonly used biomarker for prostate cancer diagnosis. However, when PSA is in the gray area of 4-10 ng/ml, the diagnostic specificity of prostate cancer is extremely low, leading to overdiagnosis in many clinically false-positive patients. This study was trying to discover and evaluate a novel urine biomarker long non-coding RNA (lncRNA546) to improve the diagnostic accuracy of prostate cancer in PSA gray-zone.MethodsA cohort study including consecutive 440 participants with suspected prostate cancer was retrospectively conducted in multi-urology centers. LncRNA546 scores were calculated with quantitative real-time polymerase chain reaction. The area under the receiver operating characteristic curve (AUROC), decision curve analysis (DCA) and a biopsy-specific nomogram were utilized to evaluate the potential for clinical application. Logistic regression model was constructed to confirm the predictive power of lncRNA546.ResultsLncRNA546 scores were sufficient to discriminate positive and negative biopsies. ROC analysis showed a higher AUC for lncRNA546 scores than prostate cancer antigen 3 (PCA3) scores (0.78 vs. 0.66, p<0.01) in the overall cohort. More importantly, the AUC of lncRNA546 (0.80) was significantly higher than the AUCs of total PSA (0.57, p=0.02), percentage of free PSA (%fPSA) (0.64, p=0.04) and PCA3 (0.63, p<0.01) in the PSA 4-10 ng/ml cohort. A base model constructed by multiple logistic regression analysis plus lncRNA546 scores improved the predictive accuracy (PA) from 79.8% to 86.3% and improved AUC results from 0.862 to 0.915. DCA showed that the base model plus lncRNA546 displayed greater net benefit at threshold probabilities beyond 15% in the PSA 4-10 ng/ml cohort.ConclusionLncRNA546 is a promising novel biomarker for the early detection of prostate cancer, especially in the PSA 4-10 ng/ml cohort.

MP53-12 HOW DO PSA-BASED MARKERS PREDICT CLINICALLY SIGNIFICANT PROSTATE CANCER (CSPCA) ON PROSTATE BIOPSY INDEPENDENT OF PROSTATE SIZE

You have accessJournal of UrologyCME1 May 2022MP53-12 HOW DO PSA-BASED MARKERS PREDICT CLINICALLY SIGNIFICANT PROSTATE CANCER (CSPCA) ON PROSTATE BIOPSY INDEPENDENT OF PROSTATE SIZE Max Kuster, Michelle Ou, Jacob Gaines, Eric Macdonald, and Simon Hall Max KusterMax Kuster More articles by this author , Michelle OuMichelle Ou More articles by this author , Jacob GainesJacob Gaines More articles by this author , Eric MacdonaldEric Macdonald More articles by this author , and Simon HallSimon Hall More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002628.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Both PSA density (PSAD) and PSA based makers (4k and PHI) are used to guide prostate biopsy decisions. In this study we examined the correlation between percent free PSA (%fPSA) and PSAD, as well as their potential combined use in determining csPCa risk. METHODS: We identified 331 patients from an IRB-approved prostate MRI database without a prior diagnosis of prostate cancer, who had an mpMRI, %fPSA and PSAD at the time of imaging, and a subsequent prostate biopsy within 1.5 years. The relationship between %fPSA and PSAD was analyzed using Pearson correlation. Logistic regression and ROC curves were used to test the diagnostic ability of %fPSA, PSAD, and %fPSA + PSAD. Detection rates of csPCa, defined as Gleason grade (GG) group ≥2, were compared among cohorts. RESULTS: The Pearson correlation coefficient for %fPSA and PSAD was -.349 (p < .001). ROC analysis predicting csPCa yielded an AUC of .712 for PSAD, .638 for %fPSA, and .718 for the combined PSAD+%fPSA model. We noted that there were “outliers” in terms of low %fPSA and low PSAD and vice versa. As such, we analyzed low risk (Cohort 1: %fPSA>20 and PSAD <0.15, N=54) and high risk (Cohort 2: %fPSA<10 and PSAD>0.15, N=79) groups against the restrictive associated “outlier” groups (Cohort 3: %fPSA>20 & PSAD>0.15, N=14 and Cohort 4: %fPSA<10 & PSAD<0.15, N=7). The low-risk cohort showed a csPCa rate of 25.9% while the high-risk cohort showed a rate of 74.7%, a significantly higher rate (p < .001). Cohort 3 showed a significantly higher csPCa rate and average GG group (78.6% and 2.64) than Cohort 1 (25.9% and 1.04, both p < .001). There were no significant differences in csPCa between the two low-%fPSA cohorts (2 and 4), the two high-PSAD cohorts (2 and 3), the two low-PSAD cohorts (1 and 4), or the two outlier cohorts (3 and 4). CONCLUSIONS: This analysis notes an inverse correlation between PSAD and %fPSA and may explain the ability of PSA-based markers utilizing %fPSA to predict cancer risk independent of prostate size. The higher AUC of PSAD compared with %fPSA and the negligible change in diagnostic efficacy when adding %fPSA to a PSAD-based model suggest that PSAD is a more powerful metric than %fPSA for the prediction of csPCa. Source of Funding: none © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e899 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Max Kuster More articles by this author Michelle Ou More articles by this author Jacob Gaines More articles by this author Eric Macdonald More articles by this author Simon Hall More articles by this author Expand All Advertisement PDF DownloadLoading ...

Label-Free Determination of PSA and Free PSA Using MA-SERS

Prostate cancer is one of the compelling types of cancer diagnosed in men. Development of screening analytical methods, which provide fast and reliable results is, thus, demanding. Currently applied methods are usually based on the determination of serum prostate-specific antigen (PSA), where several limitations were identified. However, scientific reports have shown a direct correlation between the percentage of free PSA and prostate volume, and indirect correlation between the unfavorable course of the disease of prostate cancer and the percentage of free PSA in men with elevated PSA levels. Parallel analysis of PSA and free PSA presents an interesting alternative. Here, we present a new analytical method for a parallel analysis of PSA and free PSA in a whole human blood based on MA-SERS. The method is based on magnetic Fe3O4@Ag nanocomposite functionalized using anti-PSA. The method can distinguish between levels of PSA and free PSA within a single analytical run with limits of detection of 0.62 ng/ml for PSA and 0.49 ng/ml for free PSA, respectively.

Liquid biomarkers for early detection of prostate cancer and summary of available data for their use in African-American men.

Several liquid biomarker tests have been developed to account for the limitations of prostate specific antigen (PSA) screening prior to prostate biopsy. African ancestry is an established risk factor for prostate cancer (PCa) and must be particularly considered when evaluating patients with liquid biomarkers. While multiple tests have been developed over decades of exploration, recent advances can help patients and physicians incorporate data into a broader clinical context. We sought to review currently available liquid biomarker tests in a practical, clinically directed fashion with particular focus on performance in men with African ancestry. We reviewed discovery and validation studies and highlight important considerations for each test. We discuss the advantages and limitations of percent free PSA, Prostate Health Index, Progensa® PCA3, ExoDx® Prostate Test, SelectMDx®, 4Kscore® Test, and Mi-Prostate Score and summarize salient studies on their use. A literature review of evidence specifically for men with African ancestry was conducted and available studies were summarized. Liquid biomarkers can be useful tools for aiding in risk stratification prior to prostate biopsy. Use of such tests should be individualized based on a thorough knowledge of supporting evidence and the goals of the patient and physician. Further study should prioritize evaluation of such biomarkers in men with African ancestry.

Frequency of Prostate Cancer in Men with Low Percent Free Prostate Specific Antigen in the Serum

Introduction: Prostate cancer is the utmost communal type of cancer in adult men. Assessment of serum total prostate specific antigen (PSA) is broadly cast-off as a screening assistance in the prompt diagnosis of cancer of prostate. Irrespective of the prostate size or patient’s age, 25% cut off value is set or less free PSA level in percentage is suggested for cases with values of PSA amid 4.1 and 10 ng/ml; This helps in detecting prostate cancers in 95% of cases and prevent 20% of unnecessary biopsies. The greater the free PSA percentage, the less jeopardy of cancer. This analysis was designed to evaluate the incidence of prostate cancer in patients with a low percentage of free PSA. If the scale is found to be higher, aggressive strategies and early treatment can lead to good progress. Aim: To determine the frequency of prostate cancer in males with a low percentage of serum free PSA. Study Design: This is a descriptive, cross-sectional study lasting 6 months from July 2020 to December 2020 at the Urology Department of the Sindh Institute of Urology and Transplantation. Subject and method: 149 total individuals with symptoms of lower urinary tract were included in the research. All patients who came to the urology clinic (OPD); free PSA were examined with the same technique as the surgical patient and the result was recorded as proforma. Results: - The prostate cancer Incidence in males with decreased free serum PSA in percentage is noted in 128(85.91%) patients. Conclusions: Our study showed that prostate-specific free antigen plays an important role in the analysis of cancer of prostate. Keywords: Serum prostate specific antigen, Prostate cancer, percentage of free PSA

The Efficacy of Proclarix to Select Appropriate Candidates for Magnetic Resonance Imaging and Derived Prostate Biopsies in Men with Suspected Prostate Cancer.

PurposeTo analyze how Proclarix is valuable to appropriately select candidates for multiparametric magnetic resonance imaging (mpMRI) and derived biopsies, among men with suspected prostate cancer (PCa). Proclarix is a new marker computing the clinically significant PCa (csPCa) risk, based on serum thosmbospondin-1, cathepsin D, prostate-specific antigen (PSA) and percent free PSA, in addition to age, that has been developed in men with serum PSA 2 to 10 ng/mL, prostate volume ≥35 mL, and normal digital rectal examination (DRE).Materials and MethodsProclarix score (0%–100%) is analyzed in a prospective frozen serum collection of 517 correlative men scheduled for guided and/or systematic biopsies after mpMRI. Outcome variables were csPCa detection (grade group ≥2), insignificant PCa (iPCa) overdetection and avoided mpMRIs.ResultsThe area under the curve of Proclarix was 0.701 (95% CI 0.637–0.765) among 281 men with serum PSA 2 to 10 ng/mL, prostate volume ≥35 mL, and -normal DRE, and 0.754 (95% CI 0.701–0.807) in the others, p=0.038. Net benefit of Proclarix existed in all men. After selecting 10% threshold, Proclarix was integrated in an algorithm which also used the serum PSA level and DRE. A reduction of 25.4% of mpMRIs request was observed and 17.7% of prostate biopsies. Overdetection of iPCa was reduced in 18.2% and 2.6% of csPCa were misdiagnosed.ConclusionsProclarix is valuable in all men with suspected PCa. An algorithm integrating Proclarix score, serum PSA, and DRE can avoid mpMRI requests, unnecessary prostate biopsies and iPCa overdetection, with minimal loss of csPCa detection.