Accuracy Of Prostate-specific Antigen Research Articles

Abstract A064: Prediction of positive prostate biopsy is significantly improved in Black and Hispanic men when serum PVT1 exon 9 copy number is combined with serum prostate specific antigen

Abstract Background Men of African ancestry (moAA) experience the highest incidence and mortality rates of prostate Cancer (PCa) in the United States, where 1 in 8 men are expected to be diagnosed with the disease in their lifetime. Yet, most biomarkers used in PCa screening today, which are based on prostate specific antigen (PSA), are developed and validated in predominantly White populations with weak or nonexistent validation in moAA, making moAA more likely to be subjected to unnecessary prostate biopsies. To reduce this disparity in PCa detection and management, there is a critical need for new biomarkers that target the unique genetic make-up of moAA. We recently showed that plasmacytoma variant translocation 1 (PVT1), exons 4A, 4B, and 9 are overexpressed in the prostate tissues and detected in higher copy numbers in serum of moAA with PCa. In this study, we investigated the predictive power of these potential biomarkers in detecting PCa across different racial populations. Methodology Forty serum samples from White, Hispanic, and Black men, 50 percent of whom had PCa, were analyzed to obtain copy numbers for PVT1 exons 4A, 4B, and 9. Seven logistic regression models were developed to predict PCa using single biomarkers, all pairwise combinations of biomarkers and all three biomarkers. The median area under the receiver operator characteristic curve (AUC) was used to measure the predictive accuracy of each model after a repeated, stratified k-fold cross validation. Model accuracy was first evaluated using data from all races and then for just the Black and Hispanic subpopulation. Our best performing models were compared with PSA as a predictor of PCa. We also evaluated the predictive accuracy of composite models that combined our biomarkers with PSA. Results In predicting PCa for all races, our model with only PVT1 exon 9 achieved the highest median AUC of 0.71, which was better than the AUC of 0.63 obtained with just PSA. When PSA and PVT1 exon 9 were combined, the median AUC increased to 0.75. Combining all three biomarkers with PSA increased the median AUC to 0.813. For the Black and Hispanic subpopulation, PVT1 exon 9 achieved the highest AUC of 0.92 which was significantly higher than the median AUC of 0.63 achieved with PSA. No significant change in AUC was observed when the PVT1 biomarkers were combined with PSA. Conclusion Our results show that PVT1 exon 9 is more accurate than PSA in predicting PCa, achieving near perfect accuracy within the Black and Hispanic subpopulation. Whereas combining PSA with PVT1 biomarkers improved the performance of PSA for all races, no significant improvement in PSA’s performance was observed in Black and Hispanic subpopulations. Thus, PVT1 exon 9 may hold the key to reducing disparity in PCa detection among moAA while improving the predictive accuracy of PSA for the general population Citation Format: Emmanuel Owusu Asante-Asamani, Dinuka Sewandi De Silva, Gargi Pal, Michael Liss, Robin Leach, Olorunseun Ogunwobi. Prediction of positive prostate biopsy is significantly improved in Black and Hispanic men when serum PVT1 exon 9 copy number is combined with serum prostate specific antigen [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr A064.

Abstract A065: Serum PVT1 exons 4A and 4B copy numbers are better predictors of high-grade prostate cancer in Black and Hispanic men than serum prostate specific antigen

Abstract Background Men of African ancestry (moAA) experience the highest incidence and mortality rates of prostate Cancer (PCa) in the United States, where 1 in 8 men are expected to be diagnosed with the disease in their lifetime. Yet, most biomarkers used in PCa screening today, which are based on prostate specific antigen (PSA), are developed and validated in predominantly White populations with weak or nonexistent validation in moAA, making moAA more likely to be subjected to unnecessary prostate biopsies. To reduce this disparity in PCa detection and management, there is a critical need for new biomarkers with demonstrated usefulness in moAA. We recently showed that plasmacytoma variant translocation 1 (PVT1), exons 4A, 4B, and 9 are overexpressed in the prostate tissues and detected in higher copy numbers in serum of moAA with PCa. In this study, we investigated the predictive power of these potential biomarkers in detecting high-grade PCa across different racial populations. Methodology Forty serum samples from White, Hispanic, and Black men, 50% of whom had PCa with 25% showing high-grade PCa, were analyzed to obtain copy numbers for PVT1 exons 4A, 4B, and 9. Seven logistic regression models were developed to predict PCa using individual PTV1 biomarkers, all pairwise combinations of biomarkers and all three biomarkers. The median area under the receiver operator characteristic curve (AUC) was used to measure the predictive accuracy of each model after a repeated, stratified k-fold cross validation. Model accuracy was first evaluated using data from all races and then for just the Black and Hispanic subpopulation. Our best performing models were compared with PSA as a predictor of PCa. We also evaluated the predictive accuracy of composite models that combined our biomarkers with PSA. Results In predicting high-grade PCa for all races, PSA had a median AUC of 0.58. All our PVT1 biomarkers had an AUC greater than 0.64, which was better than PSA. When PSA and PVT1 exon 4B were combined, the median AUC of PSA increased to 0.67, other PTV1 biomarkers did not improve the AUC of PSA. For the Black and Hispanic subpopulation, PVT1 exon 4A achieved the highest median AUC of 0.92 which was significantly higher than the median AUC of 0.33 achieved with PSA. The model with Exon 4A and Exon 4B as well as all three biomarkers achieved perfect discrimination (AUC of 1.0). We were also able to obtain perfect discrimination when PVT1 exon 4A was combined with PSA (AUC: 1.0). Conclusion Our results show that PVT1 exon 4A is more accurate than PSA in predicting high-grade PCa in Black and Hispanic subpopulations, achieving perfect discrimination when combined with PSA. Significant improvement in PSA’s predictability is observed in all races when combined with PTV1 exon 4B. Thus, PVT1 exon 4A and PVT1 exon 4B may hold the key to reducing disparity in high-grade PCa detection among moAA while improving the predictive accuracy of PSA for the general population. Citation Format: Emmanuel Owusu Asante-Asamani, Dinuka S.H. Sewandi De Silva, Gargi Pal, Michael Liss, Robin Leach, Olorunseun O. Ogunwobi. Serum PVT1 exons 4A and 4B copy numbers are better predictors of high-grade prostate cancer in Black and Hispanic men than serum prostate specific antigen [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr A065.

Abstract 38: External Quality Assessment for Prostate Specific Antigen Test Accuracy: A Needs Assessment of Nigerian Tertiary Hospitals

Abstract Purpose: Prostate cancer is a major cause of death in African men, and the accuracy of prostate specific antigen (PSA) test results is important to ensure patients have access to accurate early diagnosis and treatment. External Quality Assessment (EQA) is an established framework to improve the quality of PSA results. We aimed to determine the need for implementing an EQA program for PSA in Nigeria. Methods: We used mixed-method design to collect data from 6 tertiary hospitals across the six regions in Nigeria. We conducted an online survey using a structured questionnaire developed from the International Standard Organization (ISO) 15189 checklist for accreditation of diagnostic laboratories. Responses were analyzed to obtain descriptive categorical data that was analyzed on Microsoft Excel. Using an in-depth interview guide, 12 respondents (6 Urologists and 6 Chemical Pathologists) from sampled hospitals were interviewed virtually. Responses were recorded and transcribed and relevant themes were identified and generated from the transcribed data. Results: Five of six laboratories sampled (83%) reported conducting repeat PSA testing. No sampled lab (0%) was enrolled in an EQA program for PSA. Eleven of the twelve respondents confirmed occasional disparities between PSA results and patient’s clinical status. They gave the impact of an erroneous PSA result on patient care as: extra unnecessary cost to the patient due to repeat testing; delay in decision making and initiating appropriate treatment; unnecessary invasive procedures. Training of lab staff, adoption of standard operating procedures and quality measures for EQA were considered opportunities to encourage PSA EQA practice while lack of funds for EQA programs, weak logistics for distribution of EQA samples and results, poor staff motivation and commitment were mentioned as barriers to effective practice uptake. Conclusion: There is a clear need for the implementation of an EQA program for PSA in Nigeria. This will reduce the incidence of incongruous PSA results, thus promoting better clinician approach to disease treatment and better patient outcomes especially in resource-constrained environments. Citation Format: Ifeyinwa Nnakenyi, Tonia Onyeka, Ngozi Idemili-Aronu1, Justus Onu, Echezona Ezeanolue. External Quality Assessment for Prostate Specific Antigen Test Accuracy: A Needs Assessment of Nigerian Tertiary Hospitals [abstract]. In: Proceedings of the 11th Annual Symposium on Global Cancer Research; Closing the Research-to-Implementation Gap; 2023 Apr 4-6. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(6_Suppl):Abstract nr 38.

Abstract 4172: Serum PVT1 exon 9 copy number is a better predictor of positive prostate biopsy in Black and Hispanic men than serum prostate specific antigen

Abstract Background: Men of African ancestry (moAA) experience the highest incidence and mortality rates of prostate Cancer (PCa) in the United States, where 1 in 8 men are expected to be diagnosed with the disease in their lifetime. Yet, most biomarkers used in PCa screening today, which are based on prostate specific antigen (PSA), are developed and validated in predominantly White populations with weak or nonexistent validation in moAA, making moAA more likely to be subjected to unnecessary prostate biopsies. To reduce this disparity in PCa detection and management, there is a critical need for new biomarkers that target the unique genetic make-up of moAA. We recently showed that plasmacytoma variant translocation 1 (PVT1), exons 4A, 4B, and 9 are overexpressed in the prostate tissues and detected in higher copy numbers in serum of moAA with PCa. In this study, we investigated the predictive power of these potential biomarkers in detecting PCa across different racial populations. Methodology: Forty serum samples from White, Hispanic, and Black men, 50 percent of whom had PCa, were analyzed to obtain copy numbers for PVT1 exons 4A, 4B, and 9. Seven logistic regression models were developed to predict PCa using single biomarkers, all pairwise combinations of biomarkers and all three biomarkers. The median area under the receiver operator characteristic curve (AUC) was used to measure the predictive accuracy of each model after a repeated, stratified k-fold cross validation. Model accuracy was first evaluated using data from all races and then for just the Black or Hispanic subpopulation. Our best performing models were compared with PSA as a predictor of PCa. We also evaluated the predictive accuracy of composite models that combined our biomarkers with PSA. Results: In predicting PCa for all races, our model with only PVT1 exon 9 achieved the highest median AUC of 0.71, which was better than the AUC of 0.63 obtained with just PSA. When PSA and PVT1 exon 9 were combined, the median AUC increased to 0.75. Combining all three biomarkers with PSA increased the median AUC to 0.813. For the Black or Hispanic subpopulation, PVT1 exon 9 achieved the highest AUC of 0.92 which was significantly higher than the median AUC of 0.63 achieved with PSA. No significant change in AUC was observed when the PVT1 biomarkers were combined with PSA. Conclusion: Our results show that PVT1 exon 9 is more accurate than PSA in predicting PCa, achieving near perfect accuracy within the Black or Hispanic subpopulation. Whereas combining PSA with PVT1 biomarkers improved the performance of PSA for all races, no significant improvement in PSA’s performance was observed in Black or Hispanic subpopulation. Thus, PVT1 exon 9 may hold the key to reducing disparity in PCa detection among moAA while improving the predictive accuracy of PSA for the general population. Citation Format: Emmanuel Owusu Asante-Asamani, Sobana Handi D. De Silva, Gargi Pal, Micheal Liss, Robin J. Leach, Olorunseun O. Ogunwobi. Serum PVT1 exon 9 copy number is a better predictor of positive prostate biopsy in Black and Hispanic men than serum prostate specific antigen. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4172.

The Diagnostic Accuracy of Prostate-Specific Antigen and Digital Rectal Examination in the Diagnosis of Prostate Cancer at the University of Benin Teaching Hospital.

To assess and compare the diagnostic accuracy of prostate-specific antigen (PSA) and digital rectal examination (DRE) in the diagnosis of prostate cancer. It was a prospective, comparative study carried out over a period of 14 months at the University of Benin Teaching Hospital, Benin City. It involved male patients ≥50 years who presented at the urology clinic with lower urinary tract symptoms (due to prostatic disease), PSA > 4 ng/mL and or abnormal DRE findings. They had serum total PSA determined. Patients were recruited for prostate biopsy and samples sent for histopathological assessment. Histopathology was determined by a histopathologist dedicated to the study. Using a researcher-administered, structured proforma, data were collected, collated and subjected to statistical analysis for assessment and comparative analysis of the diagnostic accuracy of PSA and DRE. The study involved 94 patients; they were all Nigerians. The age range of the study population was 50-85 years, with a mean age of 70.4 ± 8.6 years. Most (89.4%) of the patients were exposed to formal education. PSA of the study population ranged between 2.5 and 840 ng/mL. For patients with carcinoma of the prostate (CaP), median PSA value was 79.2 ng/mL, whereas patients with benign prostatic disease had a median PSA value of 16.0 ng/mL. The difference in median PSA value between the two groups was statistically significant (P < 0.001). In this study, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy of PSA was 97.2%, 12.1%, 40.7%, 87.5% and 44.7%, respectively. However, a sensitivity, specificity, PPV, NPV and diagnostic accuracy of DRE was 88.9%, 70.7%, 65.3%, 91.1% and 77.7%, respectively. Combination of PSA and DRE had sensitivity, specificity, PPV, NPV and diagnostic accuracy of 91.7%, 91.4%, 86.8%, 94.6% and 91.5%, respectively. In this study, 36 (38.3%) patients had CaP whereas 57 (60.6%) patients had benign prostatic disease and 1 (1.1%) patient had high-grade prostatic intraepithelial neoplasia. The study revealed a low specificity, high sensitivity and low diagnostic accuracy of PSA in diagnosis of CaP. However, sensitivity, specificity, and diagnostic accuracy of DRE were high but not sufficient in diagnosis of CaP. A combination of PSA and DRE had a higher sensitivity, specificity and diagnostic accuracy in diagnosis of prostate cancer.

EE299 Budget Impact Analysis of Sentinel Prostate Test Versus Current Diagnostic Strategy for Men with Suspicion of Prostate Cancer in the US

miR Sentinel™ Prostate Cancer Test (Sentinel) is a small non-coding RNA-based, non-invasive urine test designed to detect and risk-classify prostate cancer (PCa) with predictive accuracy over 90%. Current care for men suspected for PCa with prostate-specific antigen (PSA)>3ng/mL involves transrectal ultrasound-guided biopsy (TRUSB) with/without magnetic resonance imaging (MRI). Due to poor PSA accuracy, unnecessary biopsies are performed leading to increased costs and biopsy-related complications. MRI further increases costs, access to equipment is limited, and performance varies. This analysis assessed the clincial and budget effects of using Sentinel in biopsy-naïve men 45 and older with elevated PSA.

Systematic review and meta-analysis of the diagnostic accuracy of prostate-specific antigen (PSA) for the detection of prostate cancer in symptomatic patients

BackgroundProstate-specific antigen (PSA) is a commonly used test to detect prostate cancer. Attention has mostly focused on the use of PSA in screening asymptomatic patients, but the diagnostic accuracy of PSA for prostate cancer in patients with symptoms is less well understood.MethodsA systematic database search was conducted of Medline, EMBASE, Web of Science, and the Cochrane library. Studies reporting the diagnostic accuracy of PSA for prostate cancer in patients with symptoms were included. Two investigators independently assessed the titles and abstracts of all database search hits and full texts of potentially relevant studies against the inclusion criteria, and data extracted into a proforma. Study quality was assessed using the QUADAS-2 tool by two investigators independently. Summary estimates of diagnostic accuracy were calculated with meta-analysis using bivariate mixed effects regression.ResultsFive hundred sixty-three search hits were assessed by title and abstract after de-duplication, with 75 full text papers reviewed. Nineteen studies met the inclusion criteria, 18 of which were conducted in secondary care settings with one from a screening study cohort. All studies used histology obtained by transrectal ultrasound-guided biopsy (TRUS) as a reference test; usually only for patients with elevated PSA or abnormal prostate examination. Pooled data from 14,489 patients found estimated sensitivity of PSA for prostate cancer was 0.93 (95% CI 0.88, 0.96) and specificity was 0.20 (95% CI 0.12, 0.33). The area under the hierarchical summary receiver operator characteristic curve was 0.72 (95% CI 0.68, 0.76). All studies were assessed as having a high risk of bias in at least one QUADAS-2 domain.ConclusionsCurrently available evidence suggests PSA is highly sensitive but poorly specific for prostate cancer detection in symptomatic patients. However, significant limitations in study design and reference test reduces the certainty of this estimate. There is very limited evidence for the performance of PSA in primary care, the healthcare setting where most PSA testing is performed.

Increased Body Mass Index Is a Risk Factor for Poor Clinical Outcomes after Radical Prostatectomy in Men with International Society of Urological Pathology Grade Group 1 Prostate Cancer Diagnosed with Systematic Biopsies

Introduction: The association between obesity and clinically significant prostate cancer (PCa) is still a matter of debate. In this study, we evaluated the effect of body mass index (BMI) on the prediction of pathological unfavorable disease (UD), positive surgical margins (PSMs), and biochemical recurrence (BCR) in patients with clinically localized (≤cT2c) International Society of Urological Pathology (ISUP) grade group 1 PCa at biopsy. Methods: 427 patients with ISUP grade group 1 PCa who have undergone radical prostatectomy and BMI evaluation were included. The outcome of interest was the presence of UD (defined as ISUP grade group ≥3 and pT ≥3a), PSM, and BCR. Results: Statistically significant differences resulted in comparing BMI with prostate-specific antigen (PSA) and serum testosterone levels (both p < 0.0001). Patients with UD and PSM had higher BMI values (p < 0.0001 and p = 0.006, respectively). BCR-free survival was significantly decreased in patients with higher BMI values (p < 0.0001). BMI was an independent risk factor for BCR and PSM. Receiver-operating characteristic analysis testing PSA accuracy in different BMI groups, showed that PSA had a reduced predictive value (area under the curve [AUC] = 0.535; 95% confidence interval [CI] = 0.422–0.646), in obese men compared to overweight (AUC = 0.664; 95% CI = 0.598–0.725) and normal weight patients (AUC = 0.721; 95% CI = 0.660–0.777). Conclusion: Our findings show that increased BMI is a significant predictor of UD and PSM at RP in patients with preoperative low-to intermediate-risk diseases, suggesting that BMI evaluation may be useful in a clinical setting to identify patients with favorable preoperative disease characteristics harboring high-risk PCa.

Correlations between whole body volumetric parameters of 68Ga-PSMA PET/CT and biochemical-histopathological parameters in castration-naive and resistant prostate cancer patients.

To evaluate the relationship between whole body volumetric (Wbv) results of 68Ga-PSMA PET/CT with biochemical and histopathological parameters. One hundred twenty-one prostate cancer patients who underwent 68Ga-PSMA PET/CT between January 2018 and December 2019 were included. Imaging was conducted for staging upon new diagnosis with moderate- and high-risk disease and for confirming the progression of castration resistance. The relationships between the Wbv 68Ga-PSMA PET/CT parameters and prostate-specific antigen (PSA) levels, PSA doubling time and Gleason score (GS) were evaluated. The median GS and mean PSA levels were similar between the castration-naive and resistant patients. The PSA levels were positively correlated with MTVwb (p: 0.009, r: 0.286) and TLPwb (p: 0.002, r: 0.344). Gleason scores were positively correlated with MTVwb (p: 0.050, r: 0.216), TLPwb (p: 0.007, r: 0.296) and highest standard uptake value (HSUV) max (p: 0.047, r: 0.220). In the castration-naive group, Gleason scores (from p < 0.001 to p = 0.04 and r = 0.331 to 0.549) and PSA levels (from p = 0.002 to p = 0.045 and from r = 0.323 to 0.473) correlated with all 68Ga-PSMA-PET/CT parameters. PSA doubling time was negatively correlated with whole-body metabolic tumour volume (MTVwb) (p: 0.050, r: 0.232) and whole-body total lesion PSMA (TLPwb) (p: 0.026, r: 0.262). The MTVwb, TLPwb and HSUVpeak values of the patients with biochemical recurrence (BR) of 0-6months (n = 18) were higher than those with BR > 2years (n = 35) (p = 0.046, 0.047 and 0.042, respectively). Wbv 68Ga-PSMA PET/CT results were correlated with PSA levels and Gleason scores. The correlation was relatively stronger in the castration-naive group. The prognostic accuracy of PSA in the resistant group may be weaker than in the naive group. The difference in volumetric parameters of patients with short BR compared to long BR supports the idea that 68Ga-PSMA PET/CT can distinguish patients with rapid relapse from others.

PSA-based machine learning model improves prostate cancer risk stratification in a screening population.

The majority of prostate cancer diagnoses are facilitated by testing serum Prostate Specific Antigen (PSA) levels. Despite this, there are limitations to the diagnostic accuracy of PSA. Consideration of patient demographic factors andbiochemical adjuncts to PSA may improve prostate cancer risk stratification. We aimed to develop a contemporary, accurate and cost-effective model based on objective measures to improve the accuracy of prostate cancer risk stratification. Data were collated from a local institution and combined with patient data retrieved from the Prostate, Lung, Colorectal and Ovarian Cancer screening Trial (PLCO) database. Using a dataset of 4548 patients, a machine learning model was developed and trained usingPSA, free-PSA, age andfree-PSA to total PSA (FTR) ratio. The model was trained on a dataset involving 3638 patients and was then tested on a separate set of 910 patients. The model improved prediction for prostate cancer (AUC 0.72) compared to PSA alone (AUC 0.63), age (AUC 0.52), free-PSA (AUC 0.50) and FTR alone (AUC 0.65). When an operating point is chosen such that the sensitivity of the model is 80% the specificity of the model is 45.3%. The benefit in AUC secondary to the model was related to sample size, with AUC of 0.64 observed when a subset of the cohort was assessed. Development of a dense neural network modelimproved the diagnostic accuracy in screening for prostate cancer. These results demonstrate an additional utility of machine learning methods in prostate cancer risk stratification when using biochemical parameters.

Smoking reduces PSA accuracy for detection of prostate cancer: results from an Italian cross-sectional study.

The aim of our study is to evaluate the diagnostic accuracy of prostate-specific antigen (PSA) according to the smoking status in a cohort of European men undergoing prostate biopsy. From 2008 onwards, we consecutively enrolled, at a single institution in Italy, men undergoing 12 core transrectal ultrasound-guided prostate needle biopsy. Demographic, clinical and histopathological data were collected. We excluded men who had PSA >30 ng/mL. Patients were classified in three groups: non-smokers, smokers and former smokers. Receiver-operator characteristics (ROC) curve analysis were used to compare predictive properties of PSA across smoking categories for the final histopathological diagnosis of prostate cancer. 872 patients were enrolled. with a median age and PSA of 67 years (IQR: 61/74) and 6.2 ng/mL (IQR: 4.4/9.7) respectively.402/872 patients (46%) were non-smokers; 151 of 872 were smokers (17%) and 319 of 872 were former smokers (36%); 374 of 872 (43%) had cancer on biopsy. PSA accuracy for smokers (AUC= 0.47, P=0.490) was lower when compared to non-smokers (AUC=0.59, P=0.003) and former smokers (AUC=0.59, P=0.005). In a cohort of Italian men undergoing prostate biopsy, the performance accuracy of PSA, as a predictor of prostate cancer, is lower in smokers. Although the molecular link behind our findings is still unknown, our study firstly showed that the PSA accuracy for PCa diagnosis is significantly influential by smoking.

Прогностическое значение простатспецифического антигена при определении показаний к первичной биопсии предстательной железы

To investigate the diagnostic accuracy of PSA and its derivatives in detecting benign and malignant diseases of the prostate after an initial prostate biopsy. The current study analyzed 65 initial biopsies performed due to an elevated serum PSA level and compared them with the results of extended PSA testing with the use of PSA derivatives. The histological findings consistent with PCa were found in about 30% of initial biopsies performed due to elevated serum levels of total PSA. The incidence of histologically confirmed PCa increased with age, and 70-79 year old men were more likely to have it than 60-69 years old patients. PSA density in 85% of PCa cases exceeded that for benign prostatic hyperplasia (BPH). In all PCa patients, PHI and free /total PSA fraction were greater than 25 and less than 0.15, respectively. In most patients with BPH, the PHI and free /total PSA fraction did not exceed 25 and were greater than 0.15. 1. Initial biopsy triggered by elevated serum level of total PSA allows detection of PCa in about 30% of cases. 2. The age of 60 years and older should be regarded as a risk factor for PCa. The probability of malignant transformation of prostate epithelial cells in men over 70 years of age is greater than in 60-69-year-olds. 3. The density of PSA in men with morphologically verified PCa is statistically significantly greater than that in men with BPH and the threshold value in 85% of cases. 4. Determination of PHI and free/total PSA fraction can improve the accuracy of predicting malignant lesions of the prostate and adjust the indications for histological examination, reduce the number of unnecessary biopsies. 5. When defining indications for initial prostate biopsy in cases with serum PSA varying from 2 to 10 ng/ml, PSA derivatives should be used, including PSA density, prostate health index, and the free /total PSA fraction.

Emerging biomarkers in the diagnosis of prostate cancer.

Prostate cancer (PCa) is the second most common cancer in men worldwide. A large proportion of PCa are latent, never destined to progress or affect the patients’ life. It is of utmost importance to identify which PCa are destined to progress and which would benefit from an early radical treatment. Prostate-specific antigen (PSA) remains the most used test to detect PCa. Its limited specificity and an elevated rate of overdiagnosis are the main problems associated with PSA testing. New PCa biomarkers have been proposed to improve the accuracy of PSA in the management of early PCa. Commercially available biomarkers such as PCA3 score, Prostate Health Index (PHI), and the four-kallikrein panel are used with the purpose of reducing the number of unnecessary biopsies and providing information related to the aggressiveness of the tumor. The relationship with PCa aggressiveness seems to be confirmed by PHI and the four-kallikrein panel, but not by the PCA3 score. In this review, we also summarize new promising biomarkers, such as PSA glycoforms, TMPRSS2:ERG fusion gene, microRNAs, circulating tumor cells, androgen receptor variants, and PTEN gene. All these emerging biomarkers could change the management of early PCa, offering more accurate results than PSA. Nonetheless, large prospective studies comparing these new biomarkers among them are required to know their real value in PCa detection and prognosis.

Using Genetic and Epigenetic Markers to Improve Differential Diagnosis of Prostate Cancer and Benign Prostatic Hyperplasia by Noninvasive Methods in Mexican Patients.

Prostate cancer (PCa) is the most common malignancy in Mexican men. Serum prostate-specific antigen (PSA) is the usual noninvasive biomarker used for its detection. Its low specificity can increase the number of unnecessary prostate biopsies and the incidence of unpleasant complications for patients. The androgen-receptor gene (AR-CAG) repeat length and the percentage of promoter methylation (PPM) of genes glutathione-S-transferase P1 (GSTP1) and Ras association domain family 1 isoform A (RASSF1A) improve PCa detection. As an option for noninvasive assessment, we evaluated a combined analysis of all these biomarkers. A total of 186 patients scheduled for biopsy were included in the present study. PSA and AR-CAG repeats were analyzed in blood samples. The PPM of GSTP1 and RASSF1A genes was estimated in prostate tissue and urinary sediment cells (USCs) and plasma DNA using quantitative methylation-specific polymerase chain reaction. The predictive values for PCa and benign prostatic hyperplasia (BPH), logistic regression analysis, receiver operating characteristic curve, and decision curve analysis were used to assess the differential diagnosis. Statistically significant differences between PCa and BPH patients were observed for all biomarkers, with higher positive and negative predictive values when all biomarkers were included in the analysis, attaining USC values of 89.2% and 78.0%, respectively. The differential diagnosis accuracy of PSA (area under the curve, 0.59) increased to 0.70 and 0.68, respectively, when the combined analysis of PPM of RASSF1Aplasma or GSTP1AUSC and AR-CAG repeats was performed. Decision curve analysis showed the utility of the combined analysis to decrease the number of unnecessary biopsies. The results showed that combined analysis of the proposed biomarkers in plasma and USCs significantly increased the confidence for the differential diagnosis for PCa and BPH. This noninvasive practice might help in the early detection of PCa and patient follow-up, avoiding to some extent unnecessary prostate biopsies.

Does obesity modify prostate cancer detection in a European cohort?

IntroductionTo investigate prostate-specific antigen (PSA) accuracy and digital rectal examination (DRE) accuracy in detecting prostate cancer according to body mass index (BMI) in Spanish men with an indication of the first prostate biopsy.Material and methodsWe reviewed the clinical and histopathological data of 1,319 patients who underwent transrectal ultrasound-guided prostate needle biopsy. The patients were categorised according to the BMI as follows: <25 kg/m2 (normal weight); 25–29.9 kg/m2 (overweight); and ≥30 kg/m2 (obese). Receiver operator characteristic curves were used to assess PSA accuracy and DRE accuracy by calculating the area under the curve.ResultsThe obesity rate of the cohort was 14%. PSA accuracy for predicting prostate cancer in each BMI category was 0.52, 0.58 and 0.62, respectively (p = 0.01). After stratification by DRE findings, there was no difference in the performance accuracy of PSA in predicting the presence of cancer across BMI groups in abnormal DRE (p = 0.90). Serum PSA, DRE and BMI were strong predictors of prostate cancer diagnosis (odds ratio 1.07, 2.02 and 1.4, respectively; p <0.001). When the DRE was abnormal, a BMI ≥30 increased the risk of prostate cancer twice. With the addition of BMI to the model, the area under the curve of the combined PSA and DRE for diagnosing prostate cancer improved from 0.60 to 0.63.ConclusionsThe predictive value of PSA in predicting prostate cancer is not poorer in the obese population and the predictive value of an abnormal DRE in cancer detection is significantly modified by the patient’s BMI.

MP15-08 IS PSA DENSITY OR PSA (OR NEITHER) USEFUL TO PREDICT BIOPSY RECLASSIFICATION IN ACTIVE SURVEILLANCE PATIENTS?

You have accessJournal of UrologyProstate Cancer: Localized: Active Surveillance II1 Apr 2016MP15-08 IS PSA DENSITY OR PSA (OR NEITHER) USEFUL TO PREDICT BIOPSY RECLASSIFICATION IN ACTIVE SURVEILLANCE PATIENTS? Roghayeh Fazeli, Mufaddal Mamawala, Patricia Landis, Sacha Wolf, H. Ballentine Carter, and Bruce J Trock Roghayeh FazeliRoghayeh Fazeli More articles by this author , Mufaddal MamawalaMufaddal Mamawala More articles by this author , Patricia LandisPatricia Landis More articles by this author , Sacha WolfSacha Wolf More articles by this author , H. Ballentine CarterH. Ballentine Carter More articles by this author , and Bruce J TrockBruce J Trock More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2532AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prostate specific antigen (PSA) and PSA density (PSAD) are widely used to predict risk of biopsy progression in active surveillance (AS) patients. However, their relative prognostic accuracy has not been evaluated, nor has the incremental improvement they provide over other predictors. We compared the predictive accuracy of PSA and PSAD for biopsy reclassification and upgrading in prostate cancer patients managed by AS. METHODS The AS program at Johns Hopkins includes men with clinical stage T1c, PSAD < 0.15 ng/ml/mm3, biopsy Gleason score (GS) =6, <2 positive biopsy cores, =50% core involvement. Older men with low-risk tumors who did not meet all the criteria also entered due to patient preference. Biopsy reclassification is defined by >2 positive cores, >50% core involvement, or GS >7 (upgrading) at annual surveillance biopsy. Cox proportional hazards models of time to biopsy reclassification and upgrading evaluated PSA (PSA =2.5 vs. <2.5) and PSAD (PSAD =0.09 vs. <0.09), adjusted for age, number of positive cores, maximum core involvement, and year of diagnosis. Sub-analyses evaluated whether the effect of PSAD or PSA varied over time (before 2004 vs. 2004 -2014), or by prostate volume (= 45 mm3 vs. <45 mm3), or age at diagnosis (=65 vs. <65). RESULTS 1160 patients (median age 66) with at least 1 surveillance biopsy entered the AS program from 1995-2014. Median follow-up duration, time to reclassification, and time to upgrading were 4.8, 3.3, and 4.2 years, respectively. On multivariable analysis, risk of biopsy reclassification was associated with both binary PSAD, hazard ratio [HR]=1.35 (95% CI 1.1-1.6), p=0.003; and PSA, HR=1.59 (95% CI 1.17-2.15), p=0.003, as was risk of upgrading: PSAD, HR=1.53 (95% CI 1.14-2.06), p=0.004; and PSA, HR=1.71, (95% CI 1.08-2.71), p=0.023. Particularly strong significant associations for both PSAD and PSA were seen in men older than 65 who had prostate volume <45 mm3 (HR=2.40-3.59). However, adding PSA or PSAD to a base model with age, number of positive cores, and maximum tumor percentage gave only small increases in the c-index, except in men with prostate volume <45 (c-index increased from 0.613 to 0.646 for PSA and to 0.648 for PSAD). CONCLUSIONS Both PSAD and PSA have statistically significant predictive value for risks of biopsy reclassification and biopsy upgrading, with neither showing an advantage over the other. However, their utility for risk stratification is particularly important in men older than 65 with prostate volume <45 mm3. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e154-e155 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Roghayeh Fazeli More articles by this author Mufaddal Mamawala More articles by this author Patricia Landis More articles by this author Sacha Wolf More articles by this author H. Ballentine Carter More articles by this author Bruce J Trock More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Biomarkers in localized prostate cancer.

Biomarkers can improve prostate cancer diagnosis and treatment. Accuracy of prostate-specific antigen (PSA) for early diagnosis of prostate cancer is not satisfactory, as it is an organ- but not cancer-specific biomarker, and it can be improved by using models that incorporate PSA along with other test results, such as prostate cancer antigen 3, the molecular forms of PSA (proPSA, benign PSA and intact PSA), as well as kallikreins. Recent reports suggest that new tools may be provided by metabolomic studies as shown by preliminary data on sarcosine. Additional molecular biomarkers have been identified by the use of genomics, proteomics and metabolomics. We review the most relevant biomarkers for early diagnosis and management of localized prostate cancer.

Virus encoded circulatory miRNAs for early detection of prostate cancer.

BackgroundProstate cancer (PCa) is the most commonly diagnosed cancer and kills about 28,000 American men annually. Although progress has been made in understanding the molecular features of different forms of the disease, PCa is considered incurable when it becomes resistant to standard therapies. Prostate specific antigen (PSA) test has been a gold standard of diagnosis for PCa, however, it can result in lead to the unnecessary biopsies and treatment of indolent cancers due to the low specificity. Thus, the limitations of PSA screening for PCa have prompted much focus on strategies how to enhance the accuracy of PSA for distinction between aggressive and indolent cancers.DiscussionStudies of miRNAs in PCa patients have suggested differentially expressed miRNAs between healthy controls and those with PCa, providing potential biomarker candidates using body fluids including urine and blood. Virus infection has been considered to associate with PCa incidence. Virus infected PCa cells may shed extracellular vesicles and communicate with neighboring cells, which were not infected yet, however, no mechanistic approaches were performed to understand the biology. The miRNAs composition in the shedding extracellular vesicles, and its role in PCa are completely undefined. In the near future, new insights to connect between the viral derived miRNAs and PCa progression might provide an opportunity to diagnose, risk prediction and therapeutic strategies.SummaryThe goal of this debate article is to provide a short review on miRNAs, virus infection and viral encoded miRNAs in PCa, with a primary focus on circulating miRNAs as potential non-invasive biomarkers for PCa patients.

Use of statins and serum levels of Prostate Specific Antigen

ObjectivesTo quantify the effect of statins’ use on Prostate Specific Antigen (PSA) levels in patients referred to prostate biopsy and to determinate if the exposure to statins must be considered to improve the prostate cancer diagnostic accuracy of PSA. MethodsWe selected 551 subjects with PSA <10.0ng/mL, referred to ultrasound guided trans-rectal prostate biopsy and classified as cancer or non-cancer patients after biopsy. Information regarding statins’ use was obtained from clinical records. We used path analysis to quantify the direct (reflects the influence on PSA biology and metabolism) indirect (reflects the influence on PSA through the effect on the risk of prostate cancer) and total effects (net result of direct and indirect effects) of statins’ use on PSA. We used Receiver Operating Characteristic curves to assess the global predictive accuracy of models including PSA, age, body mass index, 5-α-reductase inhibitors, aspirin and statins’ use for distinguishing between prostate cancer and benign conditions. ResultsWe observed a negative total effect of statins on PSA levels (users vs. non-users: −0.633ng/mL; 95% CI: −1.087; −0.179), which corresponds to approximately 8.9% lower levels among statins’ users, mostly due to the direct effect (−0.588ng/mL; 95% CI: −1.034, −0.141) rather than that by the indirect effect (−0.045ng/mL; 95% CI: −0.152, 0.061). There were no statistically significant differences between the area under the curve corresponding to the models with or without statins (P=0.274). ConclusionIn patients referred to prostate biopsy, statins’ use contributed to lower Prostate Specific Antigen levels, but the clinical impact in these patients is low.

Age-Specific Cutoff Value for the Application of Percent Free Prostate-Specific Antigen (PSA) in Chinese Men with Serum PSA Levels of 4.0-10.0 ng/ml.

ObjectiveThe influence of age on the performance of percent free prostate-specific antigen (%fPSA) in diagnosing prostate cancer (PCa) in East Asians is controversial. We tested the diagnostic performance of %fPSA in a multi-center biopsy cohort in China and identified the proper age-specific cutoff values to avoid unnecessary biopsies.MethodsConsecutive patients with a prostate-specific antigen (PSA) level of 4.0–10.0 ng/ml or 10.1–20.0 ng/ml who underwent transrectal ultrasound-guided or transperineal prostate biopsy were enrolled from 22 Chinese medical centers from Jan 1, 2010 to Dec 31, 2013. The diagnostic accuracy of PSA and %fPSA was determined using the area under the receiver operating characteristic (ROC) curve (AUC). Age-specific cutoff values were calculated using ROC curve analysis.ResultsThe median %fPSA was much lower in younger patients compared with older patients with a PSA level of 4.0–10.0 ng/ml or 10.1–20.0 ng/ml. The AUC of %fPSA was higher than PSA only in older patients. In patients aged 50 to 59 years, %fPSA failed to improve the diagnosis compared with PSA in these two PSA ranges. Age-specific cutoff values were 24%, 27% and 32% for patients aged 60–69, 70–79 and ≥80 years, respectively, to reduce unnecessary biopsies in men with PSA levels of 4.0–10.0 ng/ml to detect 90% of all PCa.ConclusionsThe effectiveness of %fPSA is correlated with age in the Chinese population. Age-specific cutoff values would help avoid unnecessary biopsies in the Chinese population.