Prostate Specific Antigen Density Cutoff Research Articles

Risk factor analysis and optimal cutoff value selection of PSAD for diagnosing clinically significant prostate cancer in patients with negative mpMRI: results from a high-volume center in Southeast China

BackgroundMulti-parametric magnetic resonance imaging (mpMRI) is a diagnostic tool used for screening, localizing, and staging prostate cancer. Patients with Prostate Imaging Reporting and Data System (PI-RADS) score of 1 and 2 are considered negative mpMRI, with a lower likelihood of detecting clinically significant prostate cancer (csPCa). However, relying solely on mpMRI is insufficient to completely exclude csPCa, necessitating further stratification of csPCa patients using biomarkers.MethodsA retrospective study was conducted on mpMRI-negative patients who underwent prostate biopsy at the First Affiliated Hospital of Zhejiang University from January 2022 to June 2023. A total of 607 patients were included based on inclusion and exclusion criteria. Univariate and multivariate logistic regression analysis were performed to identify risk factors for diagnosing csPCa in patients with negative mpMRI. Receiver Operating Characteristic (ROC) curves were plotted to compare the discriminatory ability of different Prostate-Specific Antigen Density (PSAD) cutoff values for csPCa.ResultsAmong the 607 patients with negative mpMRI, 73 patients were diagnosed with csPCa. In univariate logistic regression analysis, age, PSA, f/tPSA, prostate volume, and PSAD were all associated with diagnosing csPCa in patients with negative mpMRI (P < 0.05), with PSAD being the most accurate predictor. In multivariate logistic regression analysis, f/tPSA, age, and PSAD were independent predictors of csPCa (P < 0.05). PSAD cutoff value of 0.20 ng/ml/ml has better discriminatory ability for predicting csPCa and is a significant risk factor for csPCa in multivariate analysis.ConclusionAge, f/tPSA, and PSAD are independent predictors of diagnosing csPCa in patients with negative mpMRI. It is suggested that patients with negative mpMRI and PSAD less than 0.20 ng/ml/ml could avoid prostate biopsy, as a PSAD cutoff value of 0.20 ng/ml/ml has better diagnostic performance than the traditional cutoff value of 0.15 ng/ml/ml.

Added Value of Prostate-specific Antigen Density in Selecting Prostate Biopsy Candidates Among Men with Elevated Prostate-specific Antigen and PI-RADS ≥3 Lesions on Multiparametric Magnetic Resonance Imaging of the Prostate: A Systematic Assessment by PI-RADS Score

BackgroundA significant proportion of patients with positive multiparametric magnetic resonance imaging (mpMRI; Prostate Imaging-Reporting and Data System [PI-RADS] scores of 3–5) have negative biopsy results. ObjectiveTo systematically assess all prostate-specific antigen density (PSAD) values and identify an appropriate cutoff for identification of patients with positive mpMRI who could potentially avoid biopsy on the basis of their PI-RADS score. Design, setting, and participantsThe study included a cohort of 1341 patients with positive mpMRI who underwent combined targeted and systematic biopsies. Outcome measurements and statistical analysisMultivariable logistic regression analysis (MVA) was used to assess the association between PSAD and the risk of clinically significant prostate cancer (csPCa, grade group ≥2) after adjusting for confounders. We used locally weighted scatterplot smoothing to explore csPCa risk according to PSAD and PI-RADS scores. PSAD utility was observed only for patients with PI-RADS 3 lesions, so we plotted the effect of each PSAD value as a cutoff for this subgroup in terms of biopsies saved, csPCa cases missed, and clinically insignificant PCa (ciPCa, grade group 1) cases not detected. Results and limitationsOverall, 667 (50%) csPCa cases were identified. On MVA, PSAD independently predicted csPCa (odds ratio 1.57; p < 0.001). For PI-RADS ≥4 lesions, the csPCa risk was ≥40% regardless of PSAD. Conversely, among patients with PI-RADS 3 lesions, csPCa risk ranged from 0% to 60% according to PSAD values, and a PSAD cutoff of 0.10 ng/ml/cm3 corresponded to a threshold probability of 10% for csPCa. Using this PSAD cutoff for patients with PI-RADS 3 lesions would have saved 32% of biopsies, missed 7% of csPCa cases, and avoided detection of 34% of ciPCa cases. Limitations include selection bias and the high experience of the radiologists and urologists involved. ConclusionsPatients with PI-RADS ≥4 lesions should undergo prostate biopsy regardless of their PSAD, while PSAD should be used to stratify patients with PI-RADS 3 lesions. Using a threshold probability of 10% for csPCa, our data suggest that the appropriate strategy is to avoid biopsy in patients with PI-RADS 3 lesions and PSAD <0.10 ng/ml/cm3. Our results also provide information to help in tailoring an appropriate strategy for every patient with positive mpMRI findings. Patient summaryWe investigated whether a cutoff value for PSAD (prostate-specific antigen density) could identify patients with suspicious prostate lesions on MRI (magnetic resonance imaging) who could avoid biopsy according to the PI-RADS score for their scan. We found that patients with PI-RADS ≥4 should undergo prostate biopsy regardless of their PSAD. A PSAD cutoff of 0.10 should be used to stratify patients with PI-RADS 3.

Prostate specific antigen-age volume score in predicting prostate cancer among the Indonesian population

Link of Video Abstract: https://youtu.be/ZNusQRjFEH0 Introduction: Several methods have been explored to increase the effectiveness of prostate-specific antigen (PSA) for prostate cancer screening. A lower prostate-specific antigen-age volume (PSA-AV) score is associated with higher cancer risk. This study aimed to evaluate the value of PSA-AV scores in the detection of prostate cancer among the Indonesian population. Methods: A retrospective study was conducted on 844 prostate biopsies performed at our center between January 2015 and December 2019. The score of PSA-AV was derived by multiplication of the patient's age and prostate volume and then division with PSA level. A ROC curve analysis was conducted to determine the cutoff for the PSA-AV score. The sensitivities and specificities of the PSA-AV score were contrasted with total PSA, PSA density, and age-adjusted PSA. Results: The mean age of the patient was 63.63±8.6 years, with a mean PSA of 16.3±13.9 ng/mL and a mean volume of 42.7±16.0 cm3. Among 844 biopsies, 25.5% tested positive for prostate cancer. Prostate cancer patients had significantly higher mean age, PSA levels, and positive digital rectal examinations (P&lt;0.05). In predicting prostate cancer, the PSA-AV score demonstrated a higher AUC of 0.772, surpassing the AUC of 0.762 achieved by the total PSA. The analysis identified a cutoff of 700 for the PSA-AV score, which showed significant sensitivity (94%) and sufficient specificity (8.4%). These values outperformed the total PSA cutoff of 4 ng/mL (sensitivity 91.6%; specificity 5.4%), PSA density cutoff of 0.15 (sensitivity 85.1%; specificity 30.0%), and age-adjusted PSA cutoff (sensitivity 88.4%; specificity 11.8%). The superiority of the PSA-AV score of &lt;700 was more prominent in the subgroup analysis of patients below 70 years of age and those with a low-moderate prostate volume (&lt;60 cm3). Conclusions: The PSA-AV score demonstrated superior sensitivities and specificities compared to total PSA, PSA density, and age-adjusted PSA. Therefore, it is recommended to utilize a PSA-AV score of &lt;700, particularly for men below 70 years of age with low-moderate prostate volumes (&lt; 60 cm3).

Prediction of Significant Prostate Cancer in Equivocal Magnetic Resonance Imaging Lesions: A High-volume International Multicenter Study

BackgroundDecision of performing prostate biopsy in men with Prostate Imaging Reporting and Data System (PI-RADS) 3 findings in prostate magnetic resonance imaging (MRI) is challenging as they have a low but still relevant risk of harboring significant prostate cancer (sPC). ObjectiveTo identify clinical predictors of sPC in men with PI-RADS 3 lesions in prostate MRI and to analyze the hypothetical effect of incorporating prostate-specific antigen density (PSAD) into biopsy decision. Design, setting, and participantsWe analyzed a retrospective multinational cohort from ten academic centers comprising 1476 men who underwent a combined prostate biopsy (MRI targeted plus systematic biopsy) between February 2012 and April 2021 due to a PI-RADS 3 lesion in prostate MRI. Outcome measurements and statistical analysisThe primary outcome was the detection of sPC (ISUP ≥2) in a combined biopsy. Predictors were identified by a regression analysis. Descriptive statistics were applied to evaluate the hypothetical effect of involving PSAD into biopsy decision. Results and limitationsOf all patients, 273/1476 (18.5%) were diagnosed with sPC. MRI-targeted biopsy diagnosed fewer sPC cases than combined strategy: 183/1476 (12.4%) versus 273/1476 (18.5%), p < 0.01. Age (odds ratio [OR] 1.10 [95% confidence interval {CI}: 1.05–1.15], p < 0.001), prior negative biopsy (OR 0.46 [0.24–0.89], p = 0.022), and PSAD (p < 0.001) were found to be independent predictors of sPC. Applying a PSAD cutoff of 0.15, 817/1398 (58.4%) biopsies would have been avoided at the cost of missing sPC in 91 (6.5%) men. Limitations were the retrospective design, heterogeneity of the study cohort due to the long inclusion period, and no central revision of MRI. ConclusionsAge, previous biopsy status, and PSAD were found to be independent predictors of sPC in men with equivocal prostate MRI. Implementation of PSAD into biopsy decision can avoid unnecessary biopsies. Clinical parameters such as PSAD need validation in a prospective setting. Patient summaryIn this study, we looked for clinical predictors of significant prostate cancer in men with Prostate Imaging Reporting and Data System 3 lesions in prostate magnetic resonance imaging. We identified age, previous biopsy status, and especially prostate-specific antigen density as independent predictors.

Freehand transperineal prostate biopsy with a coaxial needle under local anesthesia: Experience from a single institution in Malaysia

BackgroundFreehand transperineal prostate biopsy (TPPBx) using a coaxial needle technique offers an alternative to probe-mounted freehand or template-guided techniques in the diagnosis of prostate cancer (PCa). It only requires the same equipment used for transrectal ultrasound-guided (TRUS) biopsy. Our study is the first in Malaysia to report this experience and its outcomes. We aim to determine PCa detection rate and pain tolerability of freehand TPPBx utilizing a coaxial needle under local anesthesia (LA). MethodsInstitutional review board approval was obtained from National Medical Research Register (NMRR ID-21-02052-VIL). We retrospectively reviewed the medical records of patients who underwent TPPBx between August 2020 and April 2022. Records were reviewed for patients’ characteristics, prostate volume, prostate-specific antigen (PSA) results, biopsy results and pain tolerability. Data was analyzed to determine PCa and clinically significant prostate cancer (csPCa) detection rate. LA was achieved using perineal skin infiltration and a periprostatic nerve block. The commonly used standard side-firing transrectal ultrasound with its Prostate Biplane Transducer was used as an imaging guide. The principles of the Ginsburg protocol were followed. Pain tolerability was assessed using a visual analog scale. ResultsA total of 55 patients with elevated PSA levels underwent freehand TPPBx under LA. The mean age was 67.3 years, the median PSA was 14.2 ng/mL, and the median PSA density (PSAD) was 0.33 ng/mL/cc. The optimal PSAD cutoff for predicting csPCa was 0.35 ng/mL/cc (area under the curve [AUC], 0.792; sensitivity, 87.5%; specificity, 69.2%). PCa was detected in 24 patients (43.6%), of whom 16 (29.1%) had csPCa. The median pain scores during LA infiltration and biopsy were four and two, respectively, which were significant different (P < 0.05). TPPBx exhibited an infection rate of zero. ConclusionThe PCa detection rate and patient tolerability of freehand TPPBx using a coaxial needle are similar to those of a contemporary published series. The use of existing equipment that is used for TRUS biopsy allows for widespread use and transition from TRUS biopsy.

Prostate-specific Antigen Density Cutoff of 0.15 ng/ml/cc to Propose Prostate Biopsies to Patients with Negative Magnetic Resonance Imaging: Efficient Threshold or Legacy of the Past?

BackgroundA prostate-specific antigen density (PSAd) cutoff of 0.15 ng/ml/cc is a commonly recommended threshold to identify patients with negative prostate magnetic resonance imaging (MRI) who should proceed to a prostate biopsy. We were unable to find any study that explicitly examined the properties of this threshold compared with others. ObjectiveTo investigate whether the 0.15 cutoff is justified for selecting patients at risk of harboring high-grade cancer (Gleason score ≥3 + 4) despite negative MRI. Design, setting, and participantsA cohort of 8974 prostate biopsies provided by the Prostate Biopsy Collaborative Group (PBCG) was included in the study. Outcome measurements and statistical analysisLocally weighted scatterplot smoothing was used to investigate whether there was a change in the risk of high-grade cancer around this value. We examined whether the use of this cutoff in patients with negative MRI corresponds to a reasonable threshold probability for a biopsy (defined as a 10% risk of high-grade disease). To do so, we applied the negative likelihood ratio of MRI, calculated from eight studies on prostate MRI, to the risk curve derived from the PBCG. Results and limitationsThere was no discontinuity in the risk of high-grade prostate cancer at a PSAd cutoff of 0.15. This cutoff corresponded to a probability of high-grade disease ranging from 2.6% to 10%, depending on MRI accuracy. Using 10% as threshold probability, the corresponding PSAd cutoff varied between 0.15 and 0.38, with the threshold increasing for greater MRI accuracy. Possible limitations include difference between studies on MRI and the use of ultrasound to measure prostate volume. ConclusionsThe 0.15 cutoff to recommend prostate biopsies in patients with negative MRI is justified only under an extreme scenario of poor MRI properties. We recommend a value of at least ≥0.20. Our results suggest the need for future studies to look at how to best identify patients who need prostate biopsies despite negative MRI, likely by using individualized risk prediction. Patient summaryIn this study, we investigated whether the commonly used prostate-specific antigen density cutoff of 0.15 is justified to identify patients with negative magnetic resonance imaging (MRI) who should proceed to a prostate biopsy. We found that this cutoff is appropriate only in case of very poor MRI quality, and a higher cutoff (≥0.20) should be used for the average MRI.

Prediction of a novel prostate-specific antigen density cutoff value and use of transrectal ultrasound-guided prostate biopsy for diagnosis of prostate cancer in Thailand

Objective: The measurement of prostate-specific antigen density (PSAD) is a noninvasive and inexpensive practice, which may improve the accurate diagno- sis of prostate cancer. The incidence of prostate cancer in Thailand is relatively low compared with that in Western countries. Therefore, a blanket adoption of the Western cutoff value (PSAD 0.15 ng/ml/cm3) is inapplicable and can lead to unnecessary biopsies. The aim of this study was to determine an optimal PSAD cutoff value for effective diagnosis in Thai men. Materials and Methods: We retrospectively studied transrectal ultrasound-guided prostate biopsies from 542 men with intermediate PSA concentrations ranging from 4 to 10 ng/ml, carried out from January 2011 to January 2017. The area under the receiver operating characteristic curve (AuROC) was used to evaluate the efficacy of PSAD for the diagnosis of prostate cancer. Results: In Thai men who had intermediate PSA concentrations, the AuROC was higher for PSAD in comparison to that of PSA (0.692 vs 0.544). The AuROC using the PSAD cutoff value = 0.20 ng/ml/cm3 was higher than that using the PSAD cutoff value = 0.15 ng/ml/cm3 (0.652 vs 0.626). The sensitivity, specificity, positive predictive value, and negative predictive values were 67.33%, 62.13%, 29.95%, and 89.15%, respectively. Conclusion: PSAD improved the diagnosis of prostate cancer in Thai men with intermediate PSA concentrations. The optimal cutoff value was 0.20 ng/ml/cm3.

Predictive value of PSA density in the diagnosis of prostate cancer in lebanese men.

Being the second most common cancer in men, prostate cancer detection relies on laboratory tests, imaging, and surgical procedures, although biopsy remains the mainstay in diagnosis of prostate cancer. No clear cut-off of prostate specific antigen density (PSAD) for suspecting prostate cancer has been established in the Lebanese population. Our primary objective was to evaluate the diagnostic strength of the PSAD value versus total prostate specific antigen (tPSA) level in the Lebanese men in correlation with biopsy outcome to avoid unnecessary prostate biopsy. A retrospective study of 347 patients with history of prostate biopsy done for cancer suspicion included tPSA, prostate volume, and prostate density values and results of prostate biopsy. Data was collected from Bahman hospital and statistical analysis of the mean values of tPSA, prostate volume and PSAD in different age groups was done. Significance of the results was tested using. On average, patients with negative biopsies were younger and they had lower tPSA levels, lower PSAD values and larger prostate volume compared to patients with positive biopsies. A PSAD cutoff of 0.185 ng/ml2 revealed the highest predictive strength for prostate cancer (6 times risk) compared with other parameters. These findings were mainly referred to patients with PSA > 10 ng/ml. A multifactorial approach must be conducted including all parameters in order to decide upon the need for prostate biopsy. PSAD proved to be a good marker in favor or against a prostate biopsy with a cut-off of 0.185 ng/ml2, especially in patients with tPSA level higher to 10 ng/ml. A multicenter study was recommended for better and more reliable results and more precise cut-offs.

PSA density in the diagnosis of prostate cancer in the Chinese population: results from the Chinese Prostate Cancer Consortium.

We performed this study to investigate the diagnostic performance of prostate-specific antigen density (PSAD) in a multicenter cohort of the Chinese Prostate Cancer Consortium. Outpatients with prostate-specific antigen (PSA) levels ≥4.0 ng ml−1 regardless of digital rectal examination (DRE) results or PSA levels <4.0 ng ml−1 and abnormal DRE results were included from 18 large referral hospitals in China. The diagnostic performance of PSAD and the sensitivity and specificity for the diagnosis of prostate cancer (PCa) and high-grade prostate cancer (HGPCa) at different cutoff values were evaluated. A total of 5220 patients were included in the study, and 2014 (38.6%) of them were diagnosed with PCa. In patients with PSA levels ranging from 4.0 to 10.0 ng ml−1, PSAD was associated with PCa and HGPCa in both univariate (odds ratio [OR] = 45.15, P < 0.0001 and OR = 25.38, P < 0.0001, respectively) and multivariate analyses (OR = 52.55, P < 0.0001 and OR = 26.05, P < 0.0001, respectively). The areas under the receiver operating characteristic curves (AUCs) of PSAD in predicting PCa and HGPCa were 0.627 and 0.630, respectively. With the PSAD cutoff of 0.10 ng ml−2, we obtained a sensitivity of 88.7% for PCa, and nearly all (89.9%) HGPCa cases could be detected and biopsies could be avoided in 20.2% of the patients (359/1776 cases). Among these patients who avoided biopsies, only 30 cases had HGPCa. We recommend 0.10 ng ml−2 as the proper cutoff value of PSAD, which will obtain a sensitivity of nearly 90% for both PCa and HGPCa. The results of this study should be validated in prospective, population-based multicenter studies.

The Use of Multiparametric Magnetic Resonance Imaging for Follow-up of Patients Included in Active Surveillance Protocol. Can PSA Density Discriminate Patients at Different Risk of Reclassification?

The objective of this study was to test Prostate Imaging Reporting and Data System (PI-RADS) classification on multiparametric magnetic resonance imaging (mpMRI) and MRI-derived prostate-specific antigen density (PSAD) in predicting the risk of reclassification in men in active surveillance (AS), who underwent confirmatory or per-protocol follow-up biopsy. Three hundred eighty-nine patients in AS underwent mpMRI before confirmatory or follow-up biopsy. Patients with negative (-) mpMRI underwent systematic random biopsy. Patients with positive (+) mpMRI underwent targeted fusion prostate biopsies+ systematic random biopsies. Different PSAD cutoff values were tested (< 0.10, 0.10-0.20,≥ 0.20). Multivariable analyses assessed the risk of reclassification, defined as clinically significant prostate cancer of grade group 2 or more, during follow-up according to PSAD, after adjusting for covariates. One hundred twenty-seven (32.6%) patients had mpMRI(-); 72 (18.5%) had PI-RADS 3, 150 (38.6%) PI-RADS 4, and 40 (10.3%) PI-RADS 5 lesions. The rate of reclassification to grade group 2 PCa was 16%, 22%, 31%, and 39% for mpMRI(-) and PI-RADS 3, 4, and 5, respectively, in case of PSAD< 0.10 ng/mL2; 16%, 25%, 36%, and 44%, in case of PSAD 0.10 to 0.19 ng/mL2; and 25%, 42%, 55%, and 67% in case of PSAD≥0.20 ng/mL2. PSAD≥ 0.20 ng/mL2 (odds ratio [OR], 2.45; P= .007), PI-RADS 3 (OR, 2.47; P= .013), PI-RADS 4 (OR, 2.94; P< .001), and PI-RADS 5 (OR, 3.41; P= .004) were associated with a higher risk of reclassification. PSAD≥ 0.20 ng/mL2 may improve predictive accuracy of mpMRI results for reclassification of patients in AS, whereas PSAD< 0.10 ng/mL2 may help selection of patients at lower risk of harboring clinically significant prostate cancer. However, the risk of reclassification is not negligible at any PSAD cutoff value, also in the case of mpMRI(-).

Reducing Unnecessary Prostate Multiparametric Magnetic Resonance Imaging by Using Clinical Parameters to Predict Negative and Indeterminate Findings.

We sought to develop a triage strategy to reduce negative and indeterminate multiparametric magnetic resonance imaging scans in patients at risk for prostate cancer. In this retrospective study we evaluated 865 patients with no prior prostate cancer diagnosis who underwent prostate multiparametric magnetic resonance imaging between 2009 and 2017. Age, prostate volume, prostate specific antigen and prostate specific antigen density were assessed as predictors of positive multiparametric magnetic resonance imaging, defined as PI-RADS™ (Prostate Imaging Reporting and Data System) version 2/Likert score 4 or greater. The cohort was split into a training cohort of 605 patients and a validation cohort of 260. The optimal threshold to rule out positive multiparametric magnetic resonance imaging was chosen to achieve a negative predictive value greater than 90%. All clinical variables were significant predictors of positive multiparametric magnetic resonance imaging (p <0.05). Prostate specific antigen density outperformed other parameters in diagnostic accuracy and did not significantly differ compared to a multivariate model (AUC=0.74 vs 0.75). At prostate specific antigen density greater than 0.078 ng/ml2 sensitivity, specificity, positive and negative predictive values were 94%, 29%, 22% and 95%, respectively, resulting in 25% fewer scans (64 of 260). In the multivariate model sensitivity, specificity, positive and negative predictive values were 85%, 32%, 22% and 91%, respectively, resulting in 29% fewer scans (75 of 260). Biopsies in men who would not have undergone multiparametric magnetic resonance imaging according to our proposed strategies revealed 2 clinically significant prostate cancers using prostate specific antigen density and 1 using the multivariate model. In patients at risk for prostate cancer applying a multivariate prediction model or a prostate specific antigen density cutoff of 0.078 ng/ml2 resulted in 25% to 29% fewer multiparametric magnetic resonance imaging scans performed while missing only a minimal number of clinically significant prostate cancers. Further prospective validation is required.

How to make clinical decisions to avoid unnecessary prostate screening in biopsy-naïve men with PI-RADs v2 score ≤ 3?

To determine whether patients can avoid systematic prostate biopsy (PBx) if their Prostate Imaging Reporting and Data System version 2 (PI-RADs v2) score is ≤ 3 and how we clinicians make decisions that can maximize benefit. We reviewed our prospectively maintained database of consecutive men who received transrectal ultrasound-guided 24-core biopsy as well as pre-biopsy multi-parametric magnetic resonance imaging (mp-MRI). Of the 1276 men who were performed PBx in our institution from 2012 to July 2018, 491 patients conformed to the criteria. Negative predictive value (NPV) of negative mp-MRI (defined as PI-RADs < 3) combined prostate-specific antigen density (PSAD) were calculated. Models based on PI-RADs v2 were developed to predict the absence of clinically significant prostate cancer (CSPCa) and prostate cancer (PCa). Nomograms as well as receiver operating curves (ROC) were established to estimate the discrimination. Calibration curves were used to assess the concordance between predictive value and true risk. Decision curves were made to measure the overall net benefit. Prostate cancer and CSPCa detection rates were 21.6%, 7.3% and 36.7%, 23.4% in PIRADs v2 < 3 cohort and PIRADs v2 = 3 cohort, respectively. Men with biopsy-proved CSPCa had higher prostate-specific antigen (PSA), lower prostate volume (PV) and higher PSAD (all p < 0.05 in the two cohorts) than patients with clinically insignificant prostate cancer (CIPCa) or negative results. NPV of negative mp-MRI for detection of PCa was much higher when the PSAD was less than 0.15 (p < 0.001) and 0.2 for CSPCa (p = 0.007). According to multivariate analysis, we developed the model comprising Age, PSAD and PI-RADs v2 to predict the absence of CSPCa and PCa. The area under the curve (AUC) of the model for non-CSPCa was 0.75 (95% CI 0.68-0.80, PSAD cutoff 0.20), better than 0.71 (95% CI 0.65-0.80, PSAD cutoff 0.15). As for model for non-PCa, the AUC was 0.76 (95% CI 0.70-0.80, PSAD cutoff 0.15), higher than 0.71(95% CI 0.67-0.78, PSAD cutoff 0.20). Internally validated calibration curves showed that the model might overestimated the risk of the absence of CSPCa when the threshold was between 53 and 72%, and if the threshold was between 72 and 87%, it might underestimate the risk. As for the absence of PCa, the model might overestimate the risk between 52 and 76%. Decision curves showed that a better clinical net benefit was met when the threshold was 55% for non-PCa and 70% for non-CSPCa. NPV of negative mp-MRI for detection of CSPCa and PCa was improved with decreasing PSAD. The nomograms based on PI-RADs v2, age and PSAD showed internally validated high discrimination and calibration for the absence of PCa and CSPCa. When the predictive value was greater than 70% for the absence of CSPCa and 55% for the absence of PCa, we could avoid unnecessary PBx to maximize net benefit.

Performance characteristics of prostate-specific antigen density and biopsy primary Gleason score to predict biochemical failure in patients with intermediate prostate cancer who underwent radical prostatectomy.

BackgroundPrognosis for intermediate-risk prostate cancer (PCa) remains variable; therefore, we aimed to investigate high-risk factors for biochemical recurrence (BCR), and intermediate-risk PCa using radical prostatectomy to identify patients having equivalent BCR-free survival rates when compared to high-risk PCa.Patients and methodsA total of 441 medical records were analyzed, including those of 169 intermediate-risk and 272 high-risk PCa patients. Risk factors for time to BCR were tested and analyzed using Kaplan–Meier survival analysis, log-rank tests, and Cox proportion hazards models.ResultsIn the intermediate-risk group, prostate-specific antigen density (PSAD) and primary Gleason pattern were significant preoperative risk factors for BCR. Moreover, BCR-free survival of patients in the intermediate-risk group with a higher PSAD (>0.5 ng/mL/cm3) was comparable with that of patients in the high-risk group (P=0.735). When combining primary Gleason pattern 4 and 3 with PSAD cut-offs 0.3–0.7 ng/mL/cm3, we found that BCR-free survival of patients in the intermediate-risk group with a primary Gleason pattern 4 and PSAD >0.3 ng/mL/cm3 was comparable with that of patients in the high-risk group (P=0.463).ConclusionPSAD and primary Gleason pattern are potential risk factors associated with biochemical failure in intermediate-risk PCa patients after radical prostatectomy. Regarding significant differences in prognosis according to PSAD as well as primary Gleason pattern on biopsy, a subset of the intermediate-risk patients could be identified with outcomes that were equivalent to that of high-risk patients.

Prostate Specific Antigen Density as a Predictor of Clinically Significant Prostate Cancer When the Prostate Specific Antigen is in the Diagnostic Gray Zone: Defining the Optimum Cutoff Point Stratified by Race and Body Mass Index

We assessed the predictive value of prostate specific antigen density to detect clinically significant prostate cancer, defined as prostate cancer grade group 2 or greater, in a series of men undergoing prostate biopsy with prostate specific antigen 4 to 10 ng/ml. We sought to define an optimum cutoff point for prostate specific antigen density and assess how race and body mass index affects prostate specific antigen density performance. We analyzed data on 2,162 men, of whom 56% were African American, with serum prostate specific antigen 4 to 10 ng/ml who underwent prostate biopsy. We compared the AUC between prostate specific antigen and prostate specific antigen density to predict clinically significant and any prostate cancer vs no cancer. We calculated the negative predictive value of prostate specific antigen density cutoff points ranging from 0.05 to 0.15 by every 0.01 step. We a priori defined the optimal cutoff point of prostate specific antigen density as a negative predictive value of 95% and tested whether the cutoff was sensitive to body mass index and race by comparing the negative predictive value across strata. Median prostate specific antigen was 5.6 ng/ml (IQR 4.8-7) and median prostate specific antigen density was 0.15 ng/ml/cc (IQR 0.1-0.22). Prostate specific antigen density improved the performance of prostate specific antigen to detect significant cancer (AUC 0.58 to 0.68) and any cancer (AUC 0.55 to 0.69, each p <0.001). We identified a prostate specific antigen density cutoff point of less than 0.08 ng/ml/cc with a 96% negative predictive value for grade group 2 or greater. This was largely unchanged among different races and body mass indexes. Regardless of race or body mass index men with prostate specific antigen density less than 0.08 were unlikely to harbor grade group 2 or greater disease when prostate specific antigen was 4 to 10 ng/ml. If validated, prostate specific antigen density is a simple inexpensive and available tool that can be used to identify men who can likely forego prostate biopsies, thus reducing the over detection and morbidity of unnecessary biopsies.

Is prostate specific antigen (PSA) density necessary in selecting prostate cancer patients for active surveillance and what should be the cutoff in the Asian population?

BackgroundTo investigate the role of Prostate Specific Antigen density (PSAD) in selecting prostate cancer patients for active surveillance (AS) and to determine a cutoff PSAD in identifying adverse pathological outcomes.MethodsData from 287 patients who underwent radical prostatectomy for prostate cancer were retrospectively reviewed. Six different AS protocols, the University of Toronto; Royal Marsden; John Hopkins; University of California San Francisco (UCSF); Memorial Sloan Kettering Cancer Center (MSKCC) and Prostate Cancer Research International: Active Surveillance (PRIAS), were applied to the cohort. Pre-operative demographics and pathological outcomes were analysed. Statistical analyses on the predictive factors of adverse pathological outcomes and significance of PSAD were performed. A cutoff PSAD with best balance between sensitivity and specificity in identifying adverse pathological outcome was determined.ResultsPSAD predicted adverse pathological outcomes better than Prostate Specific Antigen (PSA) level alone. The PSAD was significantly lower (0.12–0.13 ng/dl/ml) in protocols including PSAD (the John Hopkins and PRIAS) compared with the other four protocols not including PSAD as a selection criteria (0.21–0.25 ng/dl/dl, P = 0.00). PSAD predicted adverse pathological outcomes in all protocols not incorporating PSAD as an inclusion criteria (P = 0.00–0.02). By the receiver operator characteristics curve analysis, it was found that a PSAD level of 0.19 ng/ml/ml had the best balance between sensitivity and specificity in predicting pathological adverse disease (Area under curve = 0.63, P = 0.004).ConclusionPSAD is necessary in selecting prostate cancer patients for active surveillance. It predicts adverse pathological outcomes in patients eligible for active surveillance better than PSA level alone. A PSAD cutoff at 0.19 ng/ml/ml has the best balance between sensitivity and specificity in predicting pathological adverse disease. We recommend using AS protocol incorporating PSAD as a selection criteria (in particular the PRIAS protocol with a cutoff PSAD at 0.2 ng/ml/ml) when recruiting prostate cancer patients for AS.

MRI Fusion-Targeted Transrectal Prostate Biopsy and the Role of Prostate-Specific Antigen Density and Prostate Health Index for the Detection of Clinically Significant Prostate Cancer in Southeast Asian Men

To test the hypothesis that targeted biopsy has a higher detection rate for clinically significant prostate cancer (csPCa) than systematic biopsy. We defined csPCa as any Gleason sum ≥7 cancer. In patients with Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions, to determine if factors, such as prostate-specific antigen density (PSAD) and prostate health index (PHI), can predict csPCa and help select patients for biopsy. We report the first series of targeted biopsies in Southeast Asian men, with comparison against systematic biopsy. Consecutive patients were registered into a prospective institutional review board-approved database in our institution. We reviewed patients who underwent biopsy from May 2016 to June 2017. Inclusion criteria for our study were patients with at least one PI-RADS ≥3, and who underwent both targeted and systematic biopsies in the same sitting. There were 115 patients in the study, of whom 74 (64.3%) had a previous negative systematic biopsy. Targeted biopsies detected significantly less Gleason 6 cancers than systematic biopsies (p < 0.01), and demonstrated significantly higher sensitivity, specificity, positive predictive value, and negative predictive value (NPV) for the detection of csPCa. For patients with PI-RADS 3 lesions, PHI and PSAD were found to be the best predictors for csPCa. PSAD <0.10 ng/mL/mL had an NPV of 93% and sensitivity of 92%, while allowing 20% of patients to avoid biopsy. PHI cutoff of <27 would allow 34% of patients to avoid biopsy, with both sensitivity and NPV of 100%. Targeted prostate biopsies were found to be significantly superior to systematic biopsies for the detection of csPCa, while detecting less Gleason 6 cancer. Usage of PSAD and PHI cutoff levels in patients with PI-RADS 3 lesions may enable a number of patients to avoid unnecessary biopsy.

Re-examining Prostate-specific Antigen (PSA) Density: Defining the Optimal PSA Range and Patients for Using PSA Density to Predict Prostate Cancer Using Extended Template Biopsy

To compare the predictive accuracy of prostate-specific antigen (PSA) density vs PSA across different PSA ranges and by prior biopsy status in a prospective cohort undergoing prostate biopsy. Men from a prospective trial underwent an extended template biopsy to evaluate for prostate cancer at 26 sites throughout the United States. The area under the receiver operating curve assessed the predictive accuracy of PSA density vs PSA across 3 PSA ranges (<4 ng/mL, 4-10 ng/mL, >10 ng/mL). We also investigated the effect of varying the PSA density cutoffs on the detection of cancer and assessed the performance of PSA density vs PSA in men with or without a prior negative biopsy. Among 1290 patients, 585 (45%) and 284 (22%) men had prostate cancer and significant prostate cancer, respectively. PSA density performed better than PSA in detecting any prostate cancer within a PSA of 4-10 ng/mL (area under the receiver operating characteristic curve [AUC]: 0.70 vs 0.53, P < .0001) and within a PSA >10 mg/mL (AUC: 0.84 vs 0.65, P < .0001). PSA density was significantly more predictive than PSA in detecting any prostate cancer in men without (AUC: 0.73 vs 0.67, P < .0001) and with (AUC: 0.69 vs 0.55, P < .0001) a previous biopsy; however, the incremental difference in AUC was higher among men with a previous negative biopsy. Similar inferences were seen for significant cancer across all analyses. As PSA increases, PSA density becomes a better marker for predicting prostate cancer compared with PSA alone. Additionally, PSA density performed better than PSA in men with a prior negative biopsy.

TRUS Biopsy Yield in Indian Population: A Retrospective Analysis.

The reported cancer detection rate of Trans-Rectal Ultrasonography (TRUS) biopsies (TRUS biopsy yield) has been around 30 percent in western countries. However it is much lower in Asian countries, including India. Hence a larger proportion of patients in India undergo unnecessary biopsies. To find out the cancer detection rate of TRUS biopsy (TRUS biopsy yield) in contemporary Indian population. Also, to study the positive predictive values at different serum Prostate-Specific Antigen (PSA)/PSA Density (PSAD) cut off levels and suspicious Digital Rectal Examination (DRE) findings. This retrospective study was carried out in a tertiary care institute. All symptomatic patients who underwent TRUS guided biopsy for indication of raised serum PSA level (>4 ng/ml) or suspicious DRE findings (nodule, irregularity, hard consistency, immobile rectal mucosa) from January 2012 to December 2014 were included. For serum PSA range (4-10) ng/ml, TRUS guided biopsy was done in patients with percent free/total PSA < 25. Statistical analysis used were Chi-square test, Mann-Whitney U-test, Spearman's rank correlation analysis and Receiver-Operating Characteristic (ROC) curve. Out of the 235 patients included, 60 patients had malignancy (overall cancer detection rate= 25.53%). The cancer detection rate for PSA ranges of (4-10) and (10-20) ng/ml was as low as 5.95% and 13.16% respectively. Patients with malignant disease had significantly smaller prostate gland size than patients with benign disease (53.89 vs 63.06; p-value <0.05). On the other hand, cancer detection rate was 100% for PSA greater than 50ng/ml. The cancer detection rates were only upto 10% for PSA density ranges upto 0.25 ng/ml/cm3. The Area Under the Curve (AUC) for PSA and PSAD was 0.876 and 0.884 respectively. Only one patient (0.43%) had post-biopsy complication (acute bacterial prostatitis) requiring hospital admission. The current serum PSA and PSAD cut offs of 4 ng/ml and 0.15 ng/ml/cm3 need to be raised for Indian population to increase its positive predictive value. Prospective study validation of this finding is lacking.

Serum prostate-specific antigen as a tumor marker for its correlation with histopathological diagnosis of prostatomegaly

Background: Prostatomegaly is common in men past fifth decade of life and has been the most common cause of symptoms associated with lower urinary tract obstruction. The emergence of prostate-specific antigen (PSA) has come to rescue of clinicians at screening the prostate cancer by its raised value in serum. The further research over the PSA brought out few new indices which are sensitive in screening and suggesting prostate cancer such as the ratio between free and bound PSA, PSA density (PSAD), and PSA velocity. Objectives: The objective of this study is (1) to study serum PSA level and PSAD at the differentiation of benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia, and prostatic carcinoma (PCa) established at prostatic tissue diagnoses, (2) evaluation of the significance of total prostate-specific antigen (TPSA) level in the intermediate range of 4–10 ng/ml at assessment of benign versus malignant prostatomegaly at tissue diagnoses, and (3) to draw cutoff values of PSAD (0.15 vs. 0.18 ng/ml/cc) in suggesting benign versus malignant prostatomegaly at tissue diagnoses. Materials and Methods: Digital rectal examination was carried out in suspected clinical cases of prostatomegaly. One hundred and eight cases of prostatomegaly have undergone TPSA estimation prospectively by Vidas TPSA kit. PSAD was calculated as the ratio between TPSA and the volume of the prostate. The sample received for histopathological diagnoses were either sextant biopsy (25 specimens), transurethral resection of prostate (68 specimens), and prostatectomy (15 specimens). Results: TPSA was performed in total 108 patients of prostatomegaly, of which 35 (40.22%) cases had TPSA in the range of ≤4 ng/ml, 37 (34.25%) cases had TPSA in the range of 4.01–10 ng/ml, and 36 (33.33%) cases had TPSA in the range of >10 ng/ml. The mean PSAD cutoff of

Evaluation of prostatic cancer prevalence in patients with prostatic-specific antigen between 4 and 10 and normal digital rectal examination

Background:Prostate cancer is one of the most common male cancers. The prevalence of prostate cancer is different due to genetic and environmental factors. Diagnosis of prostate cancer is by biopsy due to prostate-specific antigen (PSA) and Digital Rectal Examination (DRE). Controversy about decision making for prostate biopsy in PSA between 4 and 10 and normal DRE, is one of the problems in this time. In this study we evaluated the prevalence of prostate cancer in males with PSA between 4 and 10 and normal DRE. We also evaluated the PSA density and percent of free PSA in patients with prostate cancer.Materials and Methods:A total of 121 males with PSA between 4 and 10 and normal DRE, were evaluated. Then, transrectal ultrasonography (TRUS) andprostate biopsy from 12 points of peripheral zone, was done. These data were analyzed by Chi-square, t-test and ANOVA and Roc curve.Results:In this study, the prevalence of prostate cancer in PSA between 4 and 10 and normal DRE, was evaluated, 29.8%. With use of Roc curve, PSA density cutoff point was calculated 0.12 and percent of free PSA cutoff point, was calculated, 18%.Conclusion:In males with PSA between 4 and 10 and normal DRE, PSA density smaller than 0.12-0.15, and percent of free PSA greater than 18%, the prevalence of prostate cancer is very few and we can safely ignore the TRUS and prostate biopsy in these males and eliminate its costs and side effects.