Elevated Prostate-specific Antigen Research Articles

The Prevalence of Prostate Cancer in Organ Donors With Increased Prostate-Specific Antigen

Elevated PSA levels were found in 139 kidney donors out of a total of 472 donors from our Transplant Centre tested between 2009 and 2022, representing 29,4%. We analyzed these kidney donors with elevated prostate specific antigen (PSA) levels, at mean age 47,3 years. PSA values ranged from 2.8 to 160.4 ng/ml, mean 13,9ng/ml), proper range <2.5 ng/ml. Prostate hist-pat examination was performed in 38/139 - 27% donors. 14 cases of prostate cancer (Pca) were found, Gleason 3+3 in 8 cases, 3+4 in four cases (one donor disqualification), one case Gleason 4+3 (donor disqualification), one case Gleason 4+5 (donor disqualification). There were 33 patients who met the criteria, age ≥50 years and PSA level > 10 mg/mL; of these, prostate hist-pat was performed in 24 cases, Pca was found in 10/42% cases. There were no difference between donors ≥ 50 years old, PSA>10 ng/ml with and without pathomorphological diagnosis of Pca in respect of age (mean 60,4 vs. 60,6 years), creatinine clearance according to the Cockroft-Gaulta formula (mean 101,6 vs. 94,8 ml/min) and PSA levels (mean 34,1 vs. 29,3 ng/ml). Among other donors with Pca three were <50 years with PSA >10 ng/ml and one was ≥ 50 years and PSA< 8 ng/ml. Kidneys from donors with prostate cancer were transplanted into 19 recipients, 10 men, nine women, follow-up time 1-10 years. There was no case of prostate cancer transmission. One of the recipients died of neoplasm – breast cancer. ConclusionsDonors ≥ 50 years old, PSA>10 ng/ml have higher risk of Pca. Accepting donors with Pca (Gleason 3+3, and 3+4) possesses minimal risk of transmission. All donors ≥ 50 years and also younger with increased PSA require further diagnostic procedure (e.g. DRE, USG, eventually histological examination).

Determinants of receipt of prostate cancer screening among men living with HIV enrolled in an urban HIV Clinic in the United States over the period of 2000–2020

BackgroundProstate cancer is projected to account for the greatest proportion of cancer-related burden among men with HIV. However, incidence is reportedly lower than in men without HIV, potentially due to differences in screening. Factors influencing receipt of screening in men with HIV are unknown. We described receipt of prostate-specific antigen (PSA) testing and assessed factors for association with receipt of PSA test. MethodsDemographics, measures of HIV and related care, and non-HIV care were assessed for association with receipt of first PSA test in men ≥40 years old each calendar year in 2000–2020 using univariable and multivariable Poisson regression. Models were additionally stratified by calendar period to identify changes in determinants of PSA test as prostate cancer screening guidelines changed. ResultsMen (n = 2063) 72% Non-Hispanic Black, median age of 47 (IQR: 41, 53), contributed median of 4.7 years (IQR: 2.3, 10.0) of follow-up. Receipt of antiretroviral therapy (aIRR = 1.33; 95% CI: 1.14, 1.55), engagement in HIV care (aIRR = 2.09; 95% CI: 1.66, 2.62), history of testosterone-replacement therapy (aIRR = 1.34; 95% CI: 1.19, 1.50), urologist evaluation (aIRR = 1.66; 95% CI: 1.35, 2.05), and receipt of PSA test in preceding two years (no elevated PSA aIRR = 2.37; 95% CI: 2.16, 2.61; elevated PSA aIRR = 4.35; 95% CI: 3.24, 5.84) were associated with PSA testing in men aged 50 or older. Associations varied across calendar time. ConclusionFindings suggest men with greater interaction with healthcare are more likely to receive PSA test. Measures of control of HIV did not appear to influence the decision to screen.

Evaluation of the relationship between prostate volume and prostate specific antigen in patients diagnosed with benign prostatic hyperplasia

Aims: The aim of this study was to investigate the relationship between prostate volume and prostate specific antigen (PSA) levels in patients diagnosed with benign prostatic hyperplasia (BPH). In addition, it is aimed to show that BPH may be one of the causes of PSA elevation in patients without prostate cancer. Methods: Prostate volume was calculated in 60 BPH patients who underwent prostate magnetic resonance imaging (MRI) imaging in radiology department between December 1, 2023 and March 1, 2024 due to elevated PSA. The relationship between prostate volume and the tpsa and fpsa values of the patients in the last month was evaluated. Results: There was a positive correlation between age and total prostate specific antigen (tpsa) and free prostate specific antigen (fpsa) in patients with benign prostatic hyperplasia. However, the correlation between age and fpsa was stronger. Similarly, a positive correlation was found between prostate volume and tpsa and fpsa. The correlation between increased prostate volume and increased fpsa was also stronger. Conclusion: In our study, a positive correlation was found between prostate volume and tpsa and fpsa in patients diagnosed with BPH. It was determined that one of the reasons for the increase in PSA values may be the increase in prostate volume.

Development and Validation of an 18-Gene Urine Test for High-Grade Prostate Cancer

Benefits of prostate cancer (PCa) screening with prostate-specific antigen (PSA) alone are largely offset by excess negative biopsies and overdetection of indolent cancers resulting from the poor specificity of PSA for high-grade PCa (ie, grade group [GG] 2 or greater). To develop a multiplex urinary panel for high-grade PCa and validate its external performance relative to current guideline-endorsed biomarkers. RNA sequencing analysis of 58 724 genes identified 54 markers of PCa, including 17 markers uniquely overexpressed by high-grade cancers. Gene expression and clinical factors were modeled in a new urinary test for high-grade PCa (MyProstateScore 2.0 [MPS2]). Optimal models were developed in parallel without prostate volume (MPS2) and with prostate volume (MPS2+). The locked models underwent blinded external validation in a prospective National Cancer Institute trial cohort. Data were collected from January 2008 to December 2020, and data were analyzed from November 2022 to November 2023. Protocolized blood and urine collection and transrectal ultrasound-guided systematic prostate biopsy. Multiple biomarker tests were assessed in the validation cohort, including serum PSA alone, the Prostate Cancer Prevention Trial risk calculator, and the Prostate Health Index (PHI) as well as derived multiplex 2-gene and 3-gene models, the original 2-gene MPS test, and the 18-gene MPS2 models. Under a testing approach with 95% sensitivity for PCa of GG 2 or greater, measures of diagnostic accuracy and clinical consequences of testing were calculated. Cancers of GG 3 or greater were assessed secondarily. Of 761 men included in the development cohort, the median (IQR) age was 63 (58-68) years, and the median (IQR) PSA level was 5.6 (4.6-7.2) ng/mL; of 743 men included in the validation cohort, the median (IQR) age was 62 (57-68) years, and the median (IQR) PSA level was 5.6 (4.1-8.0) ng/mL. In the validation cohort, 151 (20.3%) had high-grade PCa on biopsy. Area under the receiver operating characteristic curve values were 0.60 using PSA alone, 0.66 using the risk calculator, 0.77 using PHI, 0.76 using the derived multiplex 2-gene model, 0.72 using the derived multiplex 3-gene model, and 0.74 using the original MPS model compared with 0.81 using the MPS2 model and 0.82 using the MPS2+ model. At 95% sensitivity, the MPS2 model would have reduced unnecessary biopsies performed in the initial biopsy population (range for other tests, 15% to 30%; range for MPS2, 35% to 42%) and repeat biopsy population (range for other tests, 9% to 21%; range for MPS2, 46% to 51%). Across pertinent subgroups, the MPS2 models had negative predictive values of 95% to 99% for cancers of GG 2 or greater and of 99% for cancers of GG 3 or greater. In this study, a new 18-gene PCa test had higher diagnostic accuracy for high-grade PCa relative to existing biomarker tests. Clinically, use of this test would have meaningfully reduced unnecessary biopsies performed while maintaining highly sensitive detection of high-grade cancers. These data support use of this new PCa biomarker test in patients with elevated PSA levels to reduce the potential harms of PCa screening while preserving its long-term benefits.

Abdominal CT metrics in 17,646 patients reveal associations between myopenia, myosteatosis, and medical phenotypes: a phenome-wide association study

BackgroundDeep learning facilitates large-scale automated imaging evaluation of body composition. However, associations of body composition biomarkers with medical phenotypes have been underexplored. Phenome-wide association study (PheWAS) techniques search for medical phenotypes associated with biomarkers. A PheWAS integrating large-scale analysis of imaging biomarkers and electronic health record (EHR) data could discover previously unreported associations and validate expected associations. Here we use PheWAS methodology to determine the association of abdominal CT-based skeletal muscle metrics with medical phenotypes in a large North American cohort. MethodsAn automated deep learning pipeline was used to measure skeletal muscle index (SMI; biomarker of myopenia) and skeletal muscle density (SMD; biomarker of myosteatosis) from abdominal CT scans of adults between 2012-2018. A PheWAS was performed with logistic regression using patient sex and age as covariates to assess for associations between CT-derived muscle metrics and 611 common EHR-derived medical phenotypes. PheWAS P values were considered significant at a Bonferroni corrected threshold (α=0.05/1222). Findings17,646 adults (mean age, 56 years +/- 19 [SD]; 57.5% women) were included. CT-derived SMI was significantly associated with 268 medical phenotypes; SMD with 340 medical phenotypes. Previously unreported associations with the highest magnitude of significance included higher SMI with decreased cardiac dysrhythmias (OR [95%CI], 0.59 [0.55-0.64]; P<0.0001), decreased epilepsy (OR, 0.59 [0.50-0.70]; P<0.0001), and increased elevated prostate-specific antigen (OR, 1.84 [1.47-2.31]; P<0.0001), and higher SMD with decreased decubitus ulcers (OR, 0.36 [0.31-0.42]; P<0.0001), sleep disorders (OR, 0.39 [0.32-0.47]; P<0.0001), and osteomyelitis (OR, 0.43 [0.36-0.52]; P<0.0001). InterpretationPheWAS methodology reveals previously unreported associations between CT-derived biomarkers of myopenia and myosteatosis and EHR medical phenotypes. The high-throughput PheWAS technique applied on a population scale can generate research hypotheses related to myopenia and myosteatosis and can be adapted to research possible associations of other imaging biomarkers with hundreds of EHR medical phenotypes.

Correlation Between Serum Prostatic Specific Antigen and Prostatic Volume in Prostatic Hyperplasia

Background Prostate specific antigen (PSA) is a serine protease produced by the prostate epithelium and per urethral glands in male. Serum PSA elevation occurs as a result of disruption of normal prostatic architecture that allows PSA to diffuse into prostatic tissue and gain access to the circulation.  Prostatic hyperplasia is a progressive condition characterized by prostate enlargement accompanied by lower urinary tract symptoms (LUTS). MethodsThe objective is to investigate the correlation between serum PSA levels and trans abdominal USG prostate volume in clinically diagnosed cases with prostatic hyperplasia. This is a hospital based study conducted in the Department of Radiology and Medicine at Bharatpur Hospital. All cases diagnosed clinically underwent USG by radiologist and serum PSA estimation was done in the lab by Elisa method. 150 cases were studied. ResultsAge of 51-60 years with a percentage of 29.30%, consisted of 67 patients with a volume of 20.00-39.99 cc (44.7%), 87 patients with PSA levels of &lt;2.6 ng/mL (58.0%), prostate volume is 20.00-&gt; 80 cc at the age of 51-60 years, PSA levels &lt;2.6-&gt;20 ng / mL at the age of 51-60 years and value of p = 0,000 (p&lt;0.05) and the value of r = 107.57, implying that prostate volume and PSA levels has a significant and strong correlation.Conclusions There is a significant association between prostate volume and PSA levels in BPH patients in our study, with p = 0,000 and r =107.59 showing a strong positive correlation.

A Community-Based Prostate Cancer Screening and Education Program for Asian American Men in Medically Underserved Communities.

This study analyzed data from a community-based prostate cancer (PCa) education and screening program (Prostate Outreach Project; POP) to enhance PCa-related knowledge among medically underserved Asian American men. It also examined PCa screening history, clinical abnormalities based on prostate-specific antigen (PSA) tests and digital rectal examination (DRE) results, and follow-up and PCa diagnosis rates. Participants-521 Asian men (251 Vietnamese, 142 Chinese, and 128 South Asians)-were offered PCa screening using PSA tests and/or DRE and an educational session on PCa. Of these men, 277 completed PCa-related knowledge surveys before and after viewing an educational video. Significant between-group differences in PCa-related knowledge were found at pre-assessment (p < 0.001) but not at post-assessment (p = 0.11), at which time all groups showed improved PCa-related knowledge. Most participants (77.9%) had never received PCa screening, but Vietnamese men had the lowest previous screening rate (17.3%). Chinese men had elevated PSA values and the highest abnormal DRE rates. Of the 125 men with abnormal screening outcomes, only 15.2% had adequate follow-up. Of the 144 men diagnosed with PCa in POP, 11.1% were Asians (seven Chinese, six Vietnamese, and three South Asian). Despite the ethnic heterogeneity among Asian men, a community outreach program may successfully enhance their PCa-related knowledge.

Presacral Schwannoma Resembling Lymph Node Metastasis in a Patient with Locally Advanced Prostate Cancer

Introduction: SSchwannomas originating in the pelvic region are rare and present diagnostic challenges when they coexist with malignancies. Case Presentation: A 58-year-old man with urinary frequency and an elevated prostate-specific antigen level underwent preoperative imaging. T2-weighted magnetic resonance imaging (MRI) of the prostate identified an irregular hypointense lesion with extracapsular invasion, as well as a presacral nodule resembling lymph node metastasis. The presacral nodule exhibited an intermediate signal intensity on the apparent diffusion coefficient map that was derived from diffusion-weighted images. Dynamic contrast-enhanced MRI revealed persistent enhancement in the presacral node, while the prostate tumor exhibited strong early enhancement followed by washout. Pathological and laparoscopic findings confirmed the coexistence of locally advanced prostate cancer and pelvic schwannoma. Conclusions: MRI is useful not only in detecting prostate cancer but also in differentiating lymph node metastases from schwannoma.

Abstract 3751: Diagnostic assessment of Filamin A (FLNA) as a serum biomarker for identification of benign prostatic hyperplasia vs aggressive prostate cancer in a prospective Mexican cohort

Abstract Prostate cancer (PCa) exhibits a significant health risk to aging men, in which effective diagnosis of high gleason (Gleason &amp;gt;7) cancers is of critical need. Currently, the main screening tool utilized for detection of prostate cancer is prostate specific antigen (PSA), however, PSA exhibits limited utility in men with benign prostatic hyperplasia (BPH) due to inherent elevated PSA as the result of an enlarged prostate, resulting in increasing unnecessary biopsies. In Mexico, there is currently a higher incidence of aggressive PCa due to the risk within the overall population as well as the need for increased screening tools. Since, there is a critical unmet need to evaluate novel PCa diagnostic test that could serve as a reflex test within the screening paradigm, we evaluated the recently developed test, pSTATEdx, which measures the cleaved portion of Filamin A (FLNA) via IP-MRM mass spectrometry in conjunction with the patients age, to determine the overall risk of aggressive prostate cancer. In the current study, we analyzed a prospective cohort from Mexico City and Guadalajara evaluating 34 BPH and 44 PCa in men exhibiting symptoms with PSA levels between 4-10 ng/mL, who were all referred for 12 core prostate biopsies due to suspicion of prostate cancer. Additionally, we assessed 41 non-diseased men as controls who had PSA below 1.5 ng/mL, who were not assessed further. Comparison of non-diseased controls with BPH/PCa men exhibited an AUC of 0.99, PPV 0.96, NPV 0.89, OR 118, and P value 2 e-20, thus demonstrating that pSTATEdx had significant utility in assessing prostate health independent of PSA. In comparison with previously published data, FLNA mean levels were 24 ng/mL in previously published American study cohort and 55 ng/mL in the Mexican BPH/PCa cohort with a P value of &amp;lt;0.001. Assessment of patient populations revealed that there was superior diagnostic performance of FLNA for patients between PSA 4-7, which represents an increased unmet need for biopsy decision support. Analysis of BPH compared to all PCa exhibited a sensitivity of 0.94 and specificity of 0.53, PPV 0.64, NPV of 0.91, and OR of 16.4. Diagnostic analysis of BPH compared to high gleason PCa exhibited a sensitivity of 1, specificity of 0.21, PPV 0.38, NPV of 1, and OR of inf in this pilot study. This assessment revealed promising insight that aggressive PCa was not missed using pSTATEdx. pSTATEdx demonstrated diagnostic utility in prevention of unnecessary biopsies in the Mexican population as a reflex test to those patients with PSA levels between 4-7 as well as demonstrated that aggressive prostate cancers were not missed with the risk score. Additional studies are planned in the future to expand the utility of pSTATEdx in Latin America. Citation Format: Arturo Rodriguez, Arturo Mendoza, Matthew Rosenburg, José de J. Castaneda, Alejandro A. Melgar, Bernardo Ciseros, Adrian G. Gangemi, Nischal M. Chand, Poornima Tekumalla, Greg Miller, Anjan Thakurta, Diego Banuelos, Juan J. Real, Diego A. Joya, Alejandro Romero, Juan D. Farias, Eduardo Cabeza, Hector H. Remess, Julio J. Delgado, Hector M. Sanchez, Ignacio Barragan, Mabel Rodriguez, Barbara Garcia, David A. Sanchez, Juan Izquierdo, Elizabeth M. Lopez, Juan Hanao, Jeronimo G. Frusch, Niven R. Narain, Michael A. Kiebish. Diagnostic assessment of Filamin A (FLNA) as a serum biomarker for identification of benign prostatic hyperplasia vs aggressive prostate cancer in a prospective Mexican cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3751.

Abstract 4801: Clinical polygenic model to stratify risk of any, metastatic, and fatal prostate cancer in a randomized controlled trial of precision screening

Abstract Introduction: Lifetime risk of prostate cancer (PCa) is strongly associated with three factors: ancestry, family history, and genetics. We previously developed a polygenic hazard score (PHS) for PCa comprised of 290 common genetic variants (PHS290). When accounting for family history and ancestry (self-reported or genetically determined), PHS290 remained a powerful independent predictor of age at PCa diagnosis, metastatic PCa diagnosis, and PCa death. Additional variants associated with PCa susceptibility or benign elevation of prostate-specific antigen (PSA) have since been published. Here, we evaluate their impact on lifetime risk predictions for metastatic and fatal PCa and develop an updated polygenic score. This score will inform the design of the Prostate Cancer, Genetic Risk, and Equitable Screening Study (ProGRESS, ClinicalTrials.gov ID NCT05926102), a nationwide randomized controlled trial evaluating precision PCa screening in the VA healthcare system. Methods: We utilized a machine learning approach to update the PHS. Over 450 variants associated with PCa, aggressive PCa, benign prostatic hyperplasia, or benign PSA elevation were evaluated for inclusion. First, we identified pairs of variants with highly correlated genotype (defined as R2 &amp;gt; 0.95) and utilized univariable Cox proportional hazards models (using age at diagnosis of PCa) to exclude one variant from each pair. We then evaluated all remaining candidate variants for inclusion in a new PHS using a LASSO-regularized Cox proportional hazards model. We combined the new PHS with clinical predictors (ancestry and family history) to create a comprehensive, quantitative polygenic score in a diverse, population-based cohort of n=590,750 (Million Veteran Program). Both self-reported and genetic ancestry (based on 2,309 ancestry informative markers) were assessed. We estimated hazard ratios (HRs) to compare men with high versus low polygenic score and evaluated absolute predictions of any, metastatic, and fatal PCa. Results: The updated polygenic score included 356 variants, as well as family history and genetic ancestry. When comparing the highest to the lowest quintile of the population for polygenic score, the HRs for any PCa, metastatic PCa, and fatal PCa were 5.6, 5.8, and 5.2 respectively. These HRs are all greater than those achieved with PHS290, which yielded 5.2, 4.9, and 4.4 respectively. Risk stratification improved within each ancestry group, including within the &amp;gt;100,000 participants of African ancestry—a group known to have elevated risk of fatal PCa. Absolute risk prediction was accurate for both metastatic and fatal PCa. Conclusion: The polygenic score accurately predicts risk of metastatic and fatal PCa in multiple ancestry groups. A clinical polygenic model has potential utility for precision PCa screening and will now be evaluated prospectively in the ProGRESS trial. Citation Format: Anna M. Dornisch, Roshan Karunamuni, Kara N. Maxwell, Julie Lynch, Isla P. Garraway, Adam Kibel, Charles A. Brunette, Morgan E. Danowski, Kyung M. Lee, Scott L. DuVall, J M. Gaziano, Brent S. Rose, Richard L. Hauger, Jason L. Vassy, Tyler M. Seibert. Clinical polygenic model to stratify risk of any, metastatic, and fatal prostate cancer in a randomized controlled trial of precision screening [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4801.

Abstract 7090: A scaled proteomic discovery study for prostate cancer diagnostic signatures using Proteograph workflow with trapped ion mobility mass spectrometry

Abstract Background and Aims: The low cancer specificity of serum Prostate-Specific Antigen (PSA), the principal biomarker for prostate cancer detection, leads to a high frequency of unwarranted prostate biopsies. To alleviate this deficit, we executed a proteomic discovery study seeking PSA reflex signatures using the Proteograph™ Product Suite, a multi-nanoparticle-based deep plasma/serum proteomics workflow (Seer, Inc.), with timsTOF Pro mass spectrometry (Bruker) to interrogate over 900 serum specimens from patients that underwent prostate biopsy due to elevated PSA and/or abnormal digital rectal exam. Methods: Our study followed rigorous design principles including uniform collection, randomization and blinding of specimens, all of which were processed with the Proteograph Product Suite. Liquid chromatography-mass spectrometry (LC-MS) analyses leveraged the Bruker timsTOF Pro MS platform utilizing 30-minute reversed-phase chromatography and a label-free dia-PASEF (data independent acquisition - parallel accumulation serial fragmentation) data acquisition method. Peptides deriving from a chosen subset of specimens designed to maximize peptide diversity were pooled, fractionated and analyzed using DDA (data-dependent acquisition)-PASEF to build a spectral reference library. Results: The DIA-NN algorithm was employed through the cloud-based Proteograph Analysis Suite (PAS) to search LC-MS data. Leveraging our study-specific spectral library proteomic depth achieved was approximately 3600 protein groups identified (median) per patient serum specimen and more than 4400 in at least 25% of samples across the study. Customized machine learning workflows and the SeerML pipeline were used to identify and assess diagnostic power of new proteomic signatures. Conclusions: Our data demonstrate the remarkable proteomic depth achievable in a scaled patient serum specimen discovery study using a combination of Proteograph and timsTOF platforms. This significant effort revealed serum proteomic signatures with increased diagnostic performance over that provided by PSA blood measurement and traditional patient-associated metadata alone, providing a foundation for future clinical tests aimed to reduce the current high frequency of unnecessary prostate biopsy. Citation Format: Mark Flory, Matthew Chang, Jessie May Cartier, Jane Lange, Travis Moore, James McGann, Ryan Kopp, Michael Liss, Robin Leach, Brenna Albracht, James Dai, Michael Krawitzky, Eltaher Elgierari, Jessica Chu, Paul Pease, Max Mahoney, Shadi Ferdosi, Ryan Benz, Khatereh Motamedchaboki, Asim Siddiqui, Mahdi Zamanighomi, Amir Alavi, Harendra Guturu, Daniel Hornburg, Serafim Batzoglou. A scaled proteomic discovery study for prostate cancer diagnostic signatures using Proteograph workflow with trapped ion mobility mass spectrometry [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7090.

Serum Prostat-Spesifik Antijen Düzeyi 2,5-10 Ng/Ml Arasındaki Erkeklerde İki Kadeh Testinin Prostat Biyopsisi ve Asemptomatik Prostat İnflamasyonu Varlığı ve Derecesiyle İlişkisinin Araştırılması

Objective: Prostate-specific antigen (PSA) is a marker used to detect prostate cancer. When high PSA values are detected, a prostate biopsy is performed considering the possibility of prostate cancer. PSA elevation is not specific to prostate cancer, but may also be caused by conditions such as benign prostatic hyperplasia (BPH), urinary tract infection, and chronic prostatitis. Prostate cancer is not detected in approximately 66% of patients undergoing a biopsy, and patients are exposed to unnecessary biopsy and biopsy complications. Chronic prostatitis is detected in approximately 40% of these biopsies. The two-glass test is based on examining urine before and after rectal examination, which is used in diagnosing chronic prostatitis. In this study, we aimed to reveal the two-glass test’s effectiveness in predicting the incidence of prostatitis and inflammation in patients with a PSA value of 2.5-10 ng/ml and who underwent prostate needle biopsy.&#x0D; &#x0D; Methods: Fifty-two male patients, aged between 50 and 78 years, with PSA values between 2.5 and 10 ng/ml, who applied to our clinic were included in the study. EPS-two-glass test and prostate biopsy were applied to all patients. EPS; is a sample obtained by removing the fluid from the urethra after a prostate massage; VB-3; shows the urine produced by taking about 10 ml of urine voided after massage. EPS and VB3 detect prostate infection. Under the microscope, ≥10 leukocytes were considered significant for prostate inflammation. According to the pathology results, the patients were divided into 3 groups; prostate cancer, BPH, and chronic prostatitis. The chronic prostatitis group was classified according to the histopathological calcification described by Nickel.&#x0D; &#x0D; Results: In this study, the ratio of chronic prostatitis was found to be 38%. VB3 positivity was found to be statistically significant in the chronic prostatitis group compared to the other groups (p = 0.028). Although there was no statistically significant difference between the prevalence of inflammation and PSA elevation, PSA was found to be higher in the multifocal inflammation subgroup than in the focal inflammation patient group.&#x0D; &#x0D; Conclusion: The relationship between chronic prostatitis and PSA elevation remains a mystery. Although no statistical relationship was found between inflammation and PSA elevation in this study, the significant correlation between chronic prostatitis and VB3 positivity reinforces the possibility of this relationship. We believe that our results will form the basis for further studies to avoid unnecessary biopsies.

A west African ancestry-associated SNP on 8q24 predicts a positive biopsy in African American men with suspected prostate cancer following PSA screening.

African American (AA) men have the highest incidence and mortality rates of prostate cancer (PCa) among all racial groups in the United States. While race is a social construct, for AA men, this overlaps with west African ancestry. Many of the PCa susceptibility variants exhibit distinct allele frequencies and risk estimates across different races and contribute substantially to the large disparities of PCa incidence among races. We previously reported that a single-nucleotide polymorphism (SNP) in 8q24, rs7824364, was strongly associated with west African ancestry and increased risks of PCa in both AA and Puerto Rican men. In this study, we determined whether this SNP can predict biopsy positivity and detection of clinically significant disease (Gleason score [GS] ≥ 7) in a cohort of AA men with suspected PCa. SNP rs7824364 was genotyped in 199 AA men with elevated total prostate-specific antigen (PSA) (>2.5 ng/mL) or abnormal digital rectal exam (DRE) and the associations of different genotypes with biopsy positivity and clinically significant disease were analyzed. The variant allele carriers were significantly over-represented in the biopsy-positive group compared to the biopsy-negative group (44% vs. 25.7%, p = 0.011). In the multivariate logistic regression analyses, variant allele carriers were at a more than a twofold increased risk of a positive biopsy (odds ratio [OR] = 2.14, 95% confidence interval [CI] = 1.06-4.32). Moreover, the variant allele was a predictor (OR = 2.26, 95% CI = 1.06-4.84) of a positive biopsy in the subgroup of patients with PSA < 10 ng/mL and normal DRE. The variant allele carriers were also more prevalent in cases with GS ≥ 7 compared to cases with GS < 7 and benign biopsy. This study demonstrated that the west African ancestry-specific SNP rs7824364 on 8q24 independently predicted a positive prostate biopsy in AA men who were candidates for prostate biopsy subsequent to PCa screening.

Flare phenomenon visualized by 99mTc-bone scintigraphy has prognostic value for patients with metastatic castration-resistant prostate cancer.

This study aimed to determine the prognostic value of the flare phenomenon in patients with metastatic castration-resistant prostate cancer (mCRPC) using the bone scan index (BSI) derived from 99mTc-methylenediphosphonate (MDP) bone scintigraphy images. We categorized 72 patients from the PROSTAT-BSI registry with mCRPC who were followed-up for 2years after starting docetaxel chemotherapy to groups based on pre-chemotherapy BSI values of < 1, 1-4, and > 4. We assessed the effects of the flare phenomenon (defined as a > 10% increase in the BSI within 3months of starting chemotherapy, followed by > 10% improvement within the next 3months) on survival using Kaplan-Meier curves and Cox proportional hazard analyses. The flare phenomenon was found in 26 (36%) of the 72 patients. Prostate-specific antigen (PSA), alkaline phosphatase (ALP), and hemoglobin (Hb) levels steadily increased, then deteriorated in patients with and without flare, respectively. Elevated BSI and PSA values at 3months after starting therapy and the absence of abiraterone or/and enzalutamide therapy led to poor 2-year overall survival (OS) in the group without flare. In contrast, no influence was noticeable in the group with flare. The results of multivariable analyses that included only factors associated with PSA and BSI showed that increased baseline BSI (hazard ratio [HR], 1.39; 95% confidence interval [CI], 1.04-1.86; P = 0.023) and PSA (HR, 7.15; 95% CI 2.13-24.04; P = 0.0015) values could be independent risk factors for patients with mCRPC without flare. However, these factors lost significance during flare. The risk for all-cause death was significantly higher among patients with BSI > 4 without, than with flare. The results of univariable analyses indicated that flare positively impacted survival (HR, 0.24; 95% CI 0.06‒0.91; P = 0.035). Multivariable analysis did not identify any factors that could predict outcomes. Favorable prognosis, with fewer disturbances from other factors such as the use of abiraterone or/and enzalutamide, PSA changes, and BSI, was attainable in cases when the mCRPC patient demonstrated flare phenomenon. Follow-up bone scintigraphy at least every 3months could help to determine the prognosis of patients with bone metastasis of mCRPC.

Association between patient ethnicity and prostate cancer diagnosis following a prostate-specific antigen test: a cohort study of 730,000 men in primary care in the UK

BackgroundBlack men have higher prostate-specific antigen (PSA) levels and higher prostate cancer incidence and mortality than White men, while Asian men tend to have lower prostate cancer incidence and mortality than White men. Much of the evidence comes from the USA, and information from UK populations is limited.MethodsThis retrospective cohort study used data on patients registered at general practices in England contributing to the Clinical Practice Research Datalink (CPRD) Aurum dataset. Those eligible were men aged 40 and over with a record of ethnicity and a PSA test result recorded between 2010 and 2017 with no prior cancer diagnosis.The aim was to assess the incidence of prostate cancer following a raised PSA test result in men from different ethnic groups. Additionally, incidence of advanced prostate cancer was investigated. Cancer incidence was estimated from multi-level logistic regression models adjusting for potential confounding factors.Results730,515 men with a PSA test were included (88.9% White). Black men and men with mixed ethnicity had higher PSA values, particularly for those aged above 60 years. In the year following a raised PSA result (using age-specific thresholds), Black men had the highest prostate cancer incidence at 24.7% (95% CI 23.3%, 26.2%); Asian men had the lowest at 13.4% (12.2%, 14.7%); incidence for White men was 19.8% (19.4%, 20.2%). The peak incidence of prostate cancer for all groups was in men aged 70–79. Incidence of prostate cancer diagnosed at an advanced stage was similar between Black and White men.ConclusionsMore prostate cancer was diagnosed in Black men with a raised PSA result, but rates of advanced prostate cancer were not higher in this group. In this large primary care-based cohort, the incidence of prostate cancer in men with elevated PSA levels increases with increasing age, even when using age-adjusted thresholds, with Black men significantly more likely to be diagnosed compared to White or Asian men. The incidence of advanced stage prostate cancer at diagnosis was similar for Black and White men with a raised PSA result, but lower for Asian men.

Filamin A Is a Prognostic Serum Biomarker for Differentiating Benign Prostatic Hyperplasia from Prostate Cancer in Caucasian and African American Men.

Prostate cancer represents a significant health risk to aging men, in which diagnostic challenges to the identification of aggressive cancers remain unmet. Prostate cancer screening is driven by the prostate-specific antigen (PSA); however, in men with benign prostatic hyperplasia (BPH) due to an enlarged prostate and elevated PSA, PSA's screening utility is diminished, resulting in many unnecessary biopsies. To address this issue, we previously identified a cleaved fragment of Filamin A (FLNA) protein (as measured with IP-MRM mass spectrometry assessment as a prognostic biomarker for stratifying BPH from prostate cancer and subsequently evaluated its expanded utility in Caucasian (CA) and African American (AA) men. All men had a negative digital rectal examination (DRE) and PSA between 4 and 10 ng/mL and underwent prostate biopsy. In AA men, FLNA serum levels exhibited diagnostic utility for stratifying BPH from patients with aggressive prostate cancer (0.71 AUC and 12.2 OR in 48 men with BPH and 60 men with PCa) and outperformed PSA (0.50 AUC, 2.2 OR). In CA men, FLNA serum levels also exhibited diagnostic utility for stratifying BPH from patients with aggressive prostate cancer (0.74 AUC and 19.4 OR in 191 men with BPH and 109 men with PCa) and outperformed PSA (0.46 AUC, 0.32 OR). Herein, we established FLNA alone as a serum biomarker for stratifying men with BPH vs. those with high Gleason (7-10) prostate cancers compared to the current diagnostic paradigm of using PSA. This approach demonstrates clinical actionability of FLNA alone without the requirement of prostate volume measurement as a test with utility in AA and CA men and represents a significant opportunity to decrease the number of unnecessary biopsies in aggressive prostate cancer diagnoses.

Repeated Prostate Cancer Screening Using Prostate-Specific Antigen Testing and Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) has been proposed to enhance the benefit-to-harm ratio of prostate cancer screening, but data on repeated screening outcomes are lacking. To describe outcomes of prostate-specific antigen (PSA)-based screening with MRI and prostate biopsies at repeat screening. This secondary analysis examined the population-based, screen-by-invitation STHLM3-MRI randomized clinical trial, which recruited Swedish men aged 50 to 74 years. Men were eligible for repeat screening at 2 to 3 years if they had PSA levels of 1.5 ng/mL or greater at trial inclusion, were randomized to the MRI-targeted group (including screening using biomarkers and MRI), and were not diagnosed with prostate cancer after the first screening round. Repeat screening was performed between November 10, 2021, and February 20, 2023. Data analysis was performed between May and August 2023. Participants underwent blood sampling, including PSA testing. A biparametric MRI scan was performed if PSA levels were 3 ng/mL or greater, and men with lesions with a Prostate Imaging-Reporting and Data System (PI-RADS) score of 3 or greater were referred for targeted and systematic biopsies. The primary outcome was clinically significant prostate cancer (Gleason score of ≥3 + 4). Secondary outcomes included the proportion of men with clinically insignificant cancer (Gleason score of 6), the number of elevated PSA tests, MRI scans, and biopsy procedures. Of 7609 men from the first screening round, 2078 (27.3%) were eligible for and were invited for rescreening. Among the invitees, 1500 (72.2%) participated. Their median age was 67 (IQR, 61-72) years. Of 1094 men with PSA levels between 1.5 and 2.9 ng/mL in the first screening round, 326 (29.8%) had levels of 3 ng/mL or greater in the second round. Overall, 667 men (44.5%) had PSA levels of 3 ng/mL or greater: 617 underwent MRI (92.5%), revealing 51 (7.6%) with equivocal lesions (PI-RADS score of 3) and 33 (4.9%) with suspicious lesions (PI-RADS score of ≥4). Only 10 of 383 men (2.6%) with a prior negative MRI result had a lesion with a PI-RADS score of 4 or greater. Among the 1500 rescreened men, 48 (3.2%) had a Gleason score of 3 + 4 or greater, including 19 (1.3%) with a score of 4 + 3 or greater and 11 (0.7%) with a score of 6. In this secondary analysis of the STHLM3-MRI randomized clinical trial, cancer detection during the second screening round in biennial PSA and MRI-based prostate cancer screening was limited, and the detection of low-grade tumors remained low. A substantial proportion of men exhibited elevated PSA levels during rescreening, and a considerable portion of MRI scans performed lacked lesions suggestive of cancer. Future studies should explore strategies to reduce MRI-related resource use. ClinicalTrials.gov Identifier: NCT03377881.

Advanced strain elastography is a reliable approach for prostate cancer detection in patients with elevated PSA levels

This study aimed to examine the validity and reproducibility of strain elastography (SE) for detecting prostate cancer (PCa) in patients with elevated prostate-specific antigen (PSA) levels. The study included 107 patients with elevated PSA levels. All eligible patients underwent transrectal ultrasound (TRUS) with real-time elastography (RTE) to detect suspicious lesions. Two readers independently evaluated the lesions and assigned a strain ratio and elastography score to each lesion. Histopathology was used as a reference standard to estimate the validity of RTE in predicting malignant lesions. An intraclass correlation (ICC) was performed to detect reliability of the strain ratios and elastography scores. TRUS-guided biopsy detected malignancies in 64 (59.8%) patients. TRUS with RTE revealed 122 lesions. The strain ratio index (SRI) cut-off values to diagnose malignancy were 4.05 and 4.35, with sensitivity, specificity, and accuracy of 94.7%, 91.3%, and 93.4%, respectively. An elastography score > 3 was the best cut-off value for detecting malignancy. According to readers, the sensitivity, specificity, and accuracy were 91.3–94.7%, 89.5–93.4%, and 91.3–90.9%, respectively. Excellent inter-reader agreement was recorded for SRI and elastography scores, with ICC of 0.937 and 0.800, respectively. SE proves to be an efficient tool for detecting PCa with high accuracy in patients with elevated PSA levels.

(213) Assessing Primary Care Physicians Awareness of 5-Alpha Reductase Inhibitors for Men with Benign Prostatic Hyperplasia

Abstract Introduction Primary care physicians (PCPs) commonly prescribe 5-alpha-reductase inhibitors (5-ARIs) for the management of benign prostatic hyperplasia (BPH). 5-ARIs can affect prostate-specific antigen (PSA) kinetics by decreasing PSA levels by approximately half, and therefore delay the early detection of prostate cancer (PCa). Objective To determine PCPs’ level of awareness and indications for urology referral in patients treated with 5-ARIs. Methods After IRB approval, an anonymous survey was emailed to affiliated PCPs at an academic urban institution. Questions focused on residency graduation year, patient volume, knowledge of 5-ARIs and their effects on PSA, role of 5-ARIs in PCa prevention, and indications for prostate biopsy referral. PCPs were stratified by residency graduation year before or after 2010, or medical specialty of Family Medicine or Internal Medicine. Survey responses were summarized with descriptive statistics and responses between groups (residency graduation year or medical specialty) were compared using Chi-squared test. Results A total of 182 PCPs were emailed, of which 30 responded (16.5% response rate). Thirteen PCPs (43.3%) graduated residency before 2010 and 17 (56.7%) after 2010. Sixteen PCPs (53.3%) were Family Medicine physicians and 14 (46.7%) were Internists. The majority of PCPs reported that every 6 months, they saw at least one patient with BPH (96.7%), ordered at least one PSA test (86.7%), and referred at least one patient for a prostate biopsy (56.7%). Forty percent of PCPs were not aware of the suppressive effects of 5-ARIs on PSA, 70.0% would not refer a patient for a prostate biopsy who is taking 5-ARIs and has an elevated corrected PSA, 70.0% were not sure or thought that 5-ARIs may decrease the risk of high-grade PCa, and 43.3% were not sure or thought that 5-ARIs are approved for the prevention of PCa. There were no significant differences in the knowledge of 5-ARIs and their effects on PSA, role of 5-ARIs in PCa prevention, or indications for prostate biopsy referral between PCPs who graduated residency before 2010 and after 2010, or between PCPs who were Family Medicine physicians and Internists (p&amp;gt;0.05 for all). Conclusions There is a general lack of awareness amongst PCPs on the knowledge of 5-ARIs and indications for biopsy referral in patients treated with 5-ARIs. An educational opportunity exists to optimize usage of 5-ARIs and avoid delaying PCa detection. Disclosure No.

Multi-drug-resistant Escherichia coli in adult male patients with enlarged prostate attending general hospitals in Benue state.

The aim of this study was to investigate multi-drug-resistant (MDR) Escherichia coli in urine of adult male patients with enlarged prostate. Three hundred and sixty-eight samples of urine and blood were collected. Escherichia coli was isolated, purified, and identified and prostate-specific antigen (PSA) was determined. Multi-drug resistance test and specific drug resistance genes were assessed. Prevalence of Escherichia coli was high (38.5%) in patients with PSA of 60-79ngml-1 and 60% were MDR. The isolates showed highest resistance to tetracycline (53.3.0%) and least to cephalosporins (5%). They had intL and gyrA genes, which are integron, and quinolone resistance genes and sul1 and sul2 which are sulphonamide resistance-associated genes. Levofloxacin, ertapenem, and Augmentin (100% susceptibilities) were considered choice drugs for treatment of Escherichia coli infection in patients with elevated PSA.