Prostate-specific Antigen Testing Research Articles

Organized prostate cancer screening program: a proposal from the Italian Society of Urology (SIU).

To contrast opportunistic PCa screening, the European Union Council suggested extending screening programs to PCa by recommending the implementation of a stepwise approach in the EU Countries to evaluate the feasibility and effectiveness of an organized program based on PSA testing in combination with additional MRI as a follow-up test. The objective of this expert-based document is to propose an organized PCa screening program according to the EU Council recommendations. The Italian Society of Urology (SIU) developed a team of experts with the aim to report 1) the most recent epidemiologic data about incidence, prevalence, and mortality of PCa; 2) the most important risk factors to identify categories of men with an increased risk to eventually develop the disease; 3) the most relevant studies presenting data on population-based screening; and 4) the current recommendations of the leading International Guidelines. According to previous evidence, the Panel proposed some indications to develop a new organized PCa screening program for asymptomatic men with a life-expectancy of at least fifteen years. The SIU Panel strongly supports the implementation of a pilot, organized PCa screening program inviting asymptomatic men in the age range of 50-55 years. Invited men who are already performing opportunistic screening will be randomized to continue opportunistic screening or to cross into the organized protocol. Men with PSA level ≤3 ng/mL and familiarity for PCa received a DRE as well as all those with PSA levels >3 ng/mL. All other men with PSA levels greater than 3 ng/mL proceed to secondary testing represented by mpMRI. Men with Prostate Imaging-Reporting and Data System (PI-RADS) lesions 3 and PSAD 0.15 ng/mL/cc or higher as well as those with PI-RADS 4-5 lesions proceed to targeted plus systematic prostate biopsy. The primary outcome of the proposed pilot PCa screening program will be the detection rate of clinically significant PCa defined as a tumor with a ISUP Grade Group ≥2. Main secondary outcomes will be the detection rate of aggressive PCa (ISUP Grade Group ≥4); the detection rate of insignificant PCa (ISUP Grade Group 1); the number of unnecessary prostate biopsy avoided, the metastasis-free survival, and the overall survival. Men will be invited over a one-year period. Preliminary analyses will be planned 2 and 5 years after the baseline enrollment. According to the recent EU Council recommendations on cancer screening, pilot studies evaluating the feasibility and effectiveness of PCa screening programs using PSA as the primary and mpMRI as the secondary screening test in selected cohorts of patients must be strongly promoted by scientific societies and supported by national governments.

Risk of Biochemical Recurrence and Metastasis in Prostate Cancer Patients Treated with Radical Prostatectomy After a 10-year Disease-free Interval

Background and objectiveProstate-specific antigen (PSA) testing is used to follow up prostate cancer (PCa) patients treated with radical prostatectomy (RP). Research on PSA thresholds for identifying PCa patients with biochemical recurrence (BCR) who are at a higher risk of progression yielded inconclusive results. This study aims to investigate the risk of late BCR in PCa patients treated with RP and long postoperative (120 mo) undetectable PSA follow-up, and to identify prognostic factors for late BCR within this patient cohort. MethodsPCa patients treated with curative RP (1992–2012) and free of BCR during the first 120 mo following RP were retrospectively identified within five European tertiary centers; BCR was defined as two consecutive PSA values of ≥0.2 ng/ml. Kaplan-Meier and Cox regression models tested for an association between BCR and patient or tumor characteristics. Key findings and limitationsThe study cohort consisted of 4639 patients, of whom 243 (5.2%) developed BCR at a medium follow-up of 147 mo. Of those with BCR, 23 (9.5%) subsequently developed metastatic progression. In Kaplan-Meier models, BCR-free survival differed according to advanced tumor status. In multivariable Cox regression models, pT stage (pT3a: hazard ratio [HR]: 1.46; pT3b: HR: 2.42), pathological Gleason score (pGS 3 + 4: HR: 1.71; pGS ≥4 + 3: HR: 2.47), surgical margin (R1/Rx: HR: 1.72), and pNx stage (pNx: HR: 0.72) represented independent predictors for BCR (all p < 0.05). Conversely, age, PSA at diagnosis, and year of surgery failed to achieve independent predictor status for BCR. Conclusions and clinical implicationsAmong PCa patients with an uneventful follow-up of at least 10 yr after RP, still one in 20 patients subsequently develop late BCR. Nevertheless, late BCR and subsequent progression to metastasis (0.3%) rates in patients with pT2 stage and pGS ≤3 + 4 were strikingly low, implicating that abandoning follow-up beyond an uneventful period of 10 yr is justifiable within this cohort of patients. Patient summaryIn this study, prostate cancer patients treated with a radical prostatectomy and at least 10 yr of uneventful prostate-specific antigen testing were identified within five European centers. Relying on these patients, the rate of subsequent late biochemical recurrence was calculated and risk factors were identified for biochemical recurrence following 10 yr of uneventful prostate-specific antigen testing.

Anatomic endoscopic enucleation of the prostate using a novel hybrid thulium:yttrium-aluminium-garnet laser generator: surgical technique and clinical outcomes.

We aim to report here the first clinical series of patients treated with AEEP using a novel hybrid thulium:yttrium-aluminium-garnet (Tm:YAG) laser generator (RevoLix HTL, LISA Laser Products, Germany), i.e. capable of emitting both in pulsated and continuous-wave. We included 39 consecutive patients who underwent hybrid Tm:YAG AEEP (hybrid ThuLEP) at a single center starting from July 2022 and were followed-up until 3months after surgery. Complete baseline, intraoperative, and follow-up demographic and clinical data were collected. The International Prostatic Symptoms Score (IPSS) questionnaire was used to quantify urinary symptoms at baseline and during follow-up. Post-operative follow-up further included a PSA test, uroflowmetry with post-void residual volume (PVR) measurement. Clavien-Dindo classification was used to classify complications. Median (IQR) age at surgery and prostate volume were 68 (IQR 63-74) years and 85 (60-105) cc. Both en-bloc or two-lobes technique enucleation were performed according to the intraoperative and endoscopic anatomy, with a median operative time of 85 (63-108) minutes. Bladder catheter was removed in all cases on postoperative day two. Intraoperative bleeding requiring conversion to bipolar enucleation was observed in two patients. After discharge, one patient developed arm phlebitis which was treated with anticoagulants leading to new onset haematuria requiring short term catheterisation (Clavien-Dindo grade II) and two more patients had a single episode of acute urinary retention (Clavien-Dindo grade I). Median pre- vs postoperative Qmax and IPSS were 8.0 (7.0-9.4) vs. 25.0 (22.5-32.5) ml/s and 22 (20-28) vs. 1 (0-2), whereas PVR decreased from 70 (50-115) to 0 (0-26) ml. Hybrid ThuLEP is a feasible and effective surgical procedure for the management of benign prostatic obstruction.

The Circulating miR-107 as a Potential Biomarker Up-Regulated in Castration-Resistant Prostate Cancer.

Prostate cancer (PCa) is a prevalent malignancy in men globally. Current diagnostic methods like PSA testing have limitations, leading to overdiagnosis and unnecessary treatment. Castration-resistant prostate cancer (CRPC) emerges in some patients receiving androgen deprivation therapy (ADT). This study explores the potential of circulating microRNA-107 (miR-107) in liquid biopsies as a prognosis tool to differentiate CRPC from non-castration-resistant PCa (NCRPC). We designed a case-control study to evaluate circulating miR-107 in serum as a potential prognosis biomarker. We analyzed miR-107 expression in liquid biopsies and found significantly higher levels (p < 0.005) in CRPC patients, compared to NCRPC. Notably, miR-107 expression was statistically higher in the advanced stage (clinical stage IV), compared to stages I-III. Furthermore, CRPC patients exhibited significantly higher miR-107 levels (p < 0.05), compared to NCRPC. These findings suggest that miR-107 holds promise as a non-invasive diagnostic biomarker for identifying potential CRPC patients.

Methylated DNA Markers in Voided Urine for the Identification of Clinically Significant Prostate Cancer.

Non-invasive assays are needed to better discriminate patients with prostate cancer (PCa) to avoid over-treatment of indolent disease. We analyzed 14 methylated DNA markers (MDMs) from urine samples of patients with biopsy-proven PCa relative to healthy controls and further studied discrimination of clinically significant PCa (csPCa) from healthy controls and Gleason 6 cancers. To evaluate the panel, urine from 24 healthy male volunteers with no clinical suspicion for PCa and 24 men with biopsy-confirmed disease across all Gleason scores was collected. Blinded to clinical status, DNA from the supernatant was analyzed for methylation signal within specific DNA sequences across 14 genes (HES5, ZNF655, ITPRIPL1, MAX.chr3.6187, SLCO3A1, CHST11, SERPINB9, WNT3A, KCNB2, GAS6, AKR1B1, MAX.chr3.8028, GRASP, ST6GALNAC2) by target enrichment long-probe quantitative-amplified signal assays. Utilizing an overall specificity cut-off of 100% for discriminating normal controls from PCa cases across the MDM panel resulted in 71% sensitivity (95% CI: 49-87%) for PCa detection (4/7 Gleason 6, 8/12 Gleason 7, 5/5 Gleason 8+) and 76% (50-92%) for csPCa (Gleason ≥ 7). At 100% specificity for controls and Gleason 6 patients combined, MDM panel sensitivity was 59% (33-81%) for csPCa (5/12 Gleason 7, 5/5 Gleason 8+). MDMs assayed in urine offer high sensitivity and specificity for detection of clinically significant prostate cancer. Prospective evaluation is necessary to estimate discrimination of patients as first-line screening and as an adjunct to prostate-specific antigen (PSA) testing.

UroLift to preserve seminal parameters in young male with LUTS from BPH.

Prostatic urethral lift has been an effective ejaculation sparing treatment for benign prostatic hypertrophy. The aim of this study was to evaluate the effect on male semen parameters. Between July 2014 and January 2022, 20 young men with urinary symptoms of BPH, unresponsive to drug treatment and motivated to preserve ejaculation for eventual paternity, underwent UroLift. Semen analysis was performed before and 6month after surgery with evaluation of pH, volume, sperm concentration, total motility, vitality and morphology according to WHO 2011. All underwent digital rectal examination, transrectal prostate ultrasound to measure prostate volume, PSA, uroflowmetry, cystoscopy and urodynamics test if necessary. Objective and subjective urinary function was scheduled at 1, 3, 6, 12month than yearly with UFM, IPSS, IIEF-5, and MSHQ-EjD-SF. At a mean follow-up of 36month (range 12 to 63), no retroejaculation or changes in seminal parameters occurred. Mean age was 44.5 (range 36.5 to 48) years. Mean operative time was 15 (range 10 to 20)min and 2.5 (range 2 to 4) implants per patients were used. At 6month there were no difference in terms of total sperm count, volume, pH, motility, vitality, morphology, liquefaction, leucocytes (p = 0.9; p = 0.8; p = 0.7; p = 1; p = 1; p = 1; p = 0,2; p = 0.5). At last, Q-max increased by 64.4% (p = 0.001), post-void residual volume decreased by 66.6% (p = 0.016), and IPSS decreased by 60% (p < 0.001). IIEF and MSHQ-EjD-SF were preserved (p = 0.14, p = 0.4). UroLift appears safe technique to correct LUTS from BPH in young men desirous to preserve seminal analysis.

Targeted Prostate Health Checks, a novel system to identify men with prostate cancer-A pilot study.

The objective of this study is to report the pilot phase of the Targeted Prostate Health Check programme that aims to identify men in the Surrey and Sussex region who have prostate cancer and who failed to be detected during the Covid era. Men aged 50 to 70, or 45 to 70 if Black or with a family history of prostate cancer, were identified from participating general practitioner (GP) records. Short message service (SMS) texts invited men to visit www.talkprostate.co.uk for information on prostate cancer and give consent to prostate-specific antigen (PSA) checks coordinated by a third-party virtual healthcare provider. Elevated age-related PSA levels, or levels below age-related thresholds but at 3ng/mL or more, triggered referral to a rapid access urology clinic. GPs were informed of the results. From 1842 text messages inviting 1549 people, 544 men consented to a PSA check. From 500 phlebotomy appointments, 485 (30% of invited men) took the PSA test of whom 68 (14%) were referred with an elevated PSA. After clinical review with multiparametric magnetic resonance imaging (mp-MRI), 22 patients underwent transperineal biopsies, and prostate cancer was detected in 18 men of whom 17 (95%) had clinically significant cancer. Our Targeted Prostate Cancer Health Check system identifies men at risk without burdening primary care. Awareness on prostate cancer risk was raised in 1549 invited men, half of whom were further educated via the registration website. One third of invited men were checked in whom clinically significant prostate cancer was found in 3.5%.

Risk-adapted early detection program for prostate cancer2.0-position paper of the German Society of Urology 2024

Despite the proven effectiveness of organized PSA-based screening in reducing prostate cancer-related mortality, there is currently no program in Germany covered by statutory health insurance. In accordance with the EU Council Decision (2022/0290(NLE)), the German Society of Urology (DGU) has developed aconcept for risk-adapted prostate cancer early detection. Based on aliterature review of current screening studies, an algorithm for PSA-based prostate cancer early detection was developed. Risk-adapted prostate cancer screening involves PSA testing in the age group of 45-70years, followed by PSA-based individual risk stratification and stepwise expansion of diagnostics through magnetic resonance imaging (MRI) to biopsy. While initially up to 2.6million men will undergo PSA testing, areduction in these initial examinations to fewer than 200,000 men per year will occur from year four onwards. The presented algorithm provides clear recommendations for risk-adapted PSA-based early detection for prostate cancer for urologists and patients. The goal is to improve diagnosis of clinically significant prostate cancer, while reducing overdiagnosis and overtreatment.

Evaluation of a multigenomic liquid biopsy (PROSTest) for prostate cancer detection and follow-up in a Caribbean population

IntroductionThe PROSTest is a novel machine learning-based liquid biopsy assay that functions as a diagnostic and prognostic tool in prostate cancer (PCa). The algorithm outcome (scored 0–100) has a cutoff of >50 to indicate PCa. In this study, we evaluated the screening utility of the test in comparison with the commonly used PSA test. Materials and Methods509 men (median age: 62 [40–88]), predominantly Afro-Caribbean (n=449, 88.2 %) were enrolled in this study at a referral centre for prostatic cancer screening and management. These included 417 symptomatic patients with urinary tract (UT) problems, of which 12 were diagnosed with PCa, 53 with benign prostatic hyperplasia (BPH) and 352 were free from prostatic diseases, prior to PROSTest (Cohort 1). The remaining 92 of the 509, with relatively young age (median 49 and range 40–75 years) were screened with the PROSTest first and included 28 with UT symptoms and 64 asymptomatic but with a family history of cancer (Cohort 2). PROSTest and PSA was performed on all subjects. ResultsIn Cohort 1, the PROSTest was positive in 11 (91.7 %) PCa, 9 (17.0 %) of BPH, and 29 (8.2 %) of subject with UT symptoms but no disease. In Cohort 2, PROSTest was positive in 4 of 28 (14.3 %) symptomatic patients and in 5 of 64 (7.8 %) asymptomatic subjects. A total of 111 individuals (from both cohorts) were identified as "at risk" (PSA >4 ng/mL). Sixteen of 111 (14.4 %) were PROSTest-positive. Thirty-nine percent (43/111) have completed a 1-year follow-up. Of the 43 with elevated PSA, 2 out of 2 (100 %) who were also PROSTest-positive, were diagnosed with PCa. ConclusionPROSTest is a more sensitive and specific biomarker than PSA in the diagnosis and, potentially, screening for PCa. The seemingly false positive PROSTest results in BPH or symptomatic UT require a longer follow-up of these patients.

Circulating Tumor DNA Assessment for Treatment Monitoring Adds Value to PSA in Metastatic Castration-Resistant Prostate Cancer.

Enzalutamide after abiraterone progression is commonly used in metastatic castration-resistant prostate cancer despite a low rate of clinical benefit. Analyzing IMbassador250, a phase III trial assessing enzalutamide with or without atezolizumab after abiraterone, we hypothesized that baseline and early changes in circulating tumor DNA (ctDNA) tumor fraction (TF) may identify patients more likely to exhibit survival benefit from enzalutamide. ctDNA was quantified from plasma samples using a tissue-agnostic assay without buffy coat sequencing. Baseline ctDNA TF, changes in ctDNA TF from baseline to cycle 3 day 1 (C3D1), and detection at C3D1 alone were compared with overall response rate, radiographic progression-free survival (rPFS), median OS (mOS), and 50% reduction in PSA. ctDNA TF detection at baseline and/or C3D1 was associated with shorter rPFS and OS in 494 evaluable patients. Detection of ctDNA TF at C3D1, with or without detection at cycle 1 day 1, was associated with worse rPFS and mOS than lack of detection. When ctDNA TF and PSA response at C3D1 were discordant, patients with (ctDNA TF undetected/PSA not reduced) had more favorable outcomes than (ctDNA TF detected/PSA reduced; mOS 22.1 vs. 16 months; P < 0.001). In a large cohort of patients with metastatic castration-resistant prostate cancer receiving enzalutamide after abiraterone, we demonstrate the utility of a new tissue-agnostic assay for monitoring molecular response based on ctDNA TF detection and dynamics. ctDNA TF provides a minimally invasive, complementary biomarker to PSA testing and may refine personalized treatment approaches.

National Trends in PSA Cancer Screening With Parallel Investigation of Colorectal Cancer Screening: An Analysis of the CDC Behavioral Risk Factor Surveillance System From 2012 to 2022

Introduction/BackgroundFrom 2012 to 2022 there have been numerous revisions in the United States Preventative Task Force guidelines for prostate cancer screening, including advising against PSA testing to allowing shared-decision making for men aged 55 to 69. We sought to observe trends in PSA testing rates in relation to the changing guidelines. Conversely, colorectal cancer screening recommendations remained consistent for patients aged 50-75 and we sought to use this as a comparison to observe the effect of differing guidelines. MethodsThe Centers for Disease Control Behavioral Risk Factor Surveillance System is a national database of surveys on health-related behaviors and preventive medical services. We extracted responses from 2012 to 2022 regarding both prostate and colorectal cancer screening. Our primary variable of interest was prostate cancer screening while colorectal cancer screening served as a positive control. ResultsProstate cancer screening decreased among respondents from 70.1% in 2012 to 59.7% in 2022. However, there was a significant rebound in prostate cancer screening prevalence in 2022. In contrast, colorectal cancer screening rates steadily increased from 70.7% in 2012 to 78% in 2022. The annual percentage of men who had received prostate cancer screening was statistically different year to year. ConclusionsTrends in the rate of screening for prostate and colorectal cancer appeared to adapt to the updated recommendations. However, further investigation regarding lower income levels, minority groups, and uninsured men are essential to address the social and racial disparities seen in prostate cancer screening. Efforts to promote shared-decision making may improve effective cancer screening.

PSA screening for prostate cancer in the United States: 30years of controversy.

In 1994, the United States approved the Prostate-Specific Antigen (PSA) test as a screening tool for prostate cancer. It did so despite the test's inherent weakness: not being prostate cancer specific. Subsequent randomized trials yielded conflicting results as to its benefits. Medical guideline organizations are concerned that PSA screening results in the diagnosis and treatment of clinically indolent prostate cancer. Nevertheless, PSA screening is prevalent in North America and Europe with PSA screening increasing in other regions. We provide a critical review of the major factors that led to the prevalence of PSA screening in the United States despite the debate about its benefits. Public advocacy in favor of the test and failure of the medical community to appreciate its inherent weakness led to widespread adoption. These factors persist today. Other countries need to carefully analyze the utility of the PSA test before adopting it.

The Incidence of Extreme Serum Prostate Specific Antigen Levels During the COVID-19 Pandemic

ObjectiveThe COVID-19 pandemic resulted in decreased prostate specific antigen (PSA) testing for prostate cancer screening and its impact remains uncharacterized. Our objective was to compare incident PSA testing rates, PSA levels, and prostate cancer treatment rates before and during the pandemic after the state of emergency (SoE) was declared. Materials and MethodsThis was a population-based, retrospective cohort study among men 50-80 years of age in Ontario, Canada undergoing incident PSA testing from November 23, 2018 to July 9, 2021. Working backwards and forwards from the date of the province-wide SoE (March 17, 2020), 30-day time periods were constructed during which incident PSA testing rates were measured. Our primary outcome was the rate of incident PSA testing. Secondary endpoints included comparison of incident PSA levels and prostate cancer treatment rates. ResultsWe identified 835,402 men who underwent incident PSA testing. There was a 20% decrease in PSA testing after the SoE (RR = 0.80,95% CI: 0.800.81, P < .001). There was a higher proportion of extreme PSA levels after the SoE with a higher proportion of patients with a PSA >20 ng/mL (rate ratio = 1.63,95% CI: 1.54-1.73, P < .0001) and >100 ng/mL (rate ratio = 1.98,95% CI: 1.77-2.20, P < .0001). This effect was highest for those aged 50-59 years. More patients required active treatment (5,201,59.5% prior to the pandemic vs. 5,072,64.2%, P < .001 after the SoE declaration). ConclusionsThe COVID-19 SoE resulted in patients experiencing a 2-fold increase in the risk of having an extreme PSA level and higher odds of treatment. Future studies are needed to assess the impact on the rates of advanced prostate cancer and cancer-specific mortality.

Prostate-Specific Antigen Screening and Prostate Cancer Mortality: An Emulation of Target Trials in US Medicare.

No consensus about the effectiveness of prostate-specific antigen (PSA) screening exists among clinical guidelines, especially for the elderly. Randomized trials of PSA screening have yielded different results, partly because of variations in adherence, and it is unlikely that new trials will be conducted. Our objective was to estimate the effect of annual PSA screening on prostate cancer (PC) mortality in Medicare beneficiaries age 67-84 years. This is a large-scale, population-based, observational study of two screening strategies: annual PSA screening and no screening. We used data from 537,599 US Medicare (2001-2008) beneficiaries age 67-84 years who had a good life expectancy, no previous PC, and no PSA test in the 2 years before baseline. We estimated the 8-year PC mortality and incidence, treatments for PC, and treatment complications of PSA screening. In men age 67-74 years, the estimated difference in 8-year risk of PC death between PSA screening and no screening was -2.3 (95% CI, -4.1 to -1.1) deaths per 1,000 men (a negative risk difference favors screening). Treatment complications were more frequent under PSA screening than under no screening. In men age 75-84 years, risk difference estimates were closer to zero. Our estimates suggest that under conventional statistical criteria, annual PSA screening for 8 years is highly compatible with reductions of PC mortality from four to one fewer PC deaths per 1,000 screened men age 67-74 years. As with any study using real-world data, the estimates could be affected by residual confounding.

Association of Prostate-Specific Antigen With Age, Digital Rectal Examination, and Lower Urinary Tract Symptoms in the Lebanese Population: A Cross-Sectional Study.

Prostate cancer (PCa) is a leading cause of mortality in men worldwide. Prostate-specific antigen (PSA) testing is a standard method for PCa detection, yet its associationwith age, digital rectal examination (DRE) results, and lower urinary tract symptoms (LUTS) remains understudied, particularly in the Lebanese population. This study aimed to investigate the associationof PSA levels with age, DRE results, and LUTS severity among Lebanese men. A total of 725 men aged 55-70 years were recruited from a men's health campaign at Saint George Hospital University Medical Center in Lebanon. PSA levels, DRE results, andInternational Prostate Symptom Score(IPSS)were assessed. Statistical analysis included Kruskal-Wallis tests and Spearman's rho correlation coefficient. Participants exhibited a significant correlation between age and PSA levels (r = 0.138, p < 0.01). PSA levels varied significantly across age groups (p = 0.029), with higher mean PSA levels observed in older age groups. IPSS status correlated positively with PSA levels (r = 0.23, p < 0.001), indicating higher PSA levels associated with increased LUTS severity. Abnormal DRE findings were significantly associated with elevated PSA levels (p < 0.00), suggesting their potential as an indicator of prostate abnormalities. This study highlights the importance of age-specific reference ranges for PSA levels in the Lebanese population. Elevated PSA levels were associated with older age, increased LUTS severity, and abnormal DRE findings. These findings highlight the significance of integrating PSA testing with clinical assessments for PCa detection and risk stratification in Lebanon.

UPCARE: UrinaryExtracellularVesicles-DerivedProstateCancerAssessment forRisk Evaluation.

In the quest for efficient tumor diagnosis via liquid biopsy, extracellular vesicles (EVs) have shown promise as a source of potential biomarkers. This study addresses the gap in biomarker efficacy for predicting clinically significant prostate cancer (csPCa) between the Western and Chinese populations. We developed a urinary extracellular vesicles-based prostate score (EPS) model, utilizing the EXODUS technique for EV isolation from 598 patients and incorporating gene expressions of FOXA1, PCA3, and KLK3. Our findings reveal that the EPS model surpasses prostate-specific antigen (PSA) testing in diagnostic accuracy within a training cohort of 234 patients, achieving an area under the curve (AUC) of 0.730 compared to 0.659 for PSA (p=0.018). Similarly, in a validation cohort of 101 men, the EPS model achieved an AUC of 0.749, which was significantly better than PSA's 0.577 (p<0.001). Our model has demonstrated a potential reduction in unnecessary prostate biopsies by 26%, with only a 3% miss rate for csPCa cases, indicating its effectiveness in the Chinese population.

Unveiling potential: urinary exosomal mRNAs as non-invasive biomarkers for early prostate cancer diagnosis

BackgroundThis study investigated the use of urinary exosomal mRNA as a potential biomarker for the early detection of prostate cancer (PCa).MethodsNext-generation sequencing was utilized to analyze exosomal RNA from 10 individuals with confirmed PCa and 10 individuals without cancer. Subsequent validation through qRT-PCR in a larger sample of 43 PCa patients and 92 healthy controls revealed distinct mRNA signatures associated with PCa.ResultsNotably, mRNAs for RAB5B, WWP1, HIST2H2BF, ZFY, MARK2, PASK, RBM10, and NRSN2 showed promise as diagnostic markers, with AUC values between 0.799 and 0.906 and significance p values. Combining RAB5B and WWP1 in an exoRNA diagnostic model outperformed traditional PSA tests, achieving an AUC of 0.923, 81.4% sensitivity, and 89.1% specificity.ConclusionsThese findings highlight the potential of urinary exosomal mRNA profiling, particularly focusing on RAB5B and WWP1, as a valuable strategy for improving the early detection of PCa.

A Novel Liquid Biopsy Method Based on Specific Combinations of Vesicular Markers Allows Us to Discriminate Prostate Cancer from Hyperplasia.

Prostate cancer is the second most common cancer in males worldwide, and its incidence is rising. Early detection is crucial for improving the outcomes, but the current screening methods have limitations. While prostate-specific antigen (PSA) testing is the most widely used screening tool, it has poor specificity, leading to a high rate of false positives and unnecessary biopsies. The existing biopsy techniques are invasive and are associated with complications. The liquid biopsy methods that analyze the biomarkers in blood or other bodily fluids offer a non-invasive and more accurate alternative for detecting and characterizing prostate tumors. Here, we present a novel liquid biopsy method for prostate cancer based on the identification of specific proteins in the extracellular vesicles isolated from the blood of patients with prostate cancer. We observed that a specific combination of sEV proteins is a sensitive indicator of prostate cancer. Indeed, we found that the number of clusters expressed by specific combinations of either intra-vesicular (STAT3 and CyclinD1) or surface proteins (ERBB3, ALK, and CD81) allowed us to significantly discriminate the patients with prostate cancer from the individuals with hyperplasia. This new liquid biopsy method has the potential to improve prostate cancer screening by providing a non-invasive and more accurate diagnostic tool.

Impact of Prostate-Specific Antigen Screening Pattern on Prostate Cancer Mortality Among Non-Hispanic Black and Non-Hispanic White Men: A Large, Urban Health System Cohort Analysis.

Randomized studies assessing the effect of PSA screening on mortality in non-Hispanic Black (NHB) men are lacking. We aimed to assess the association between PSA screening and survival among NHB men in comparison to non-Hispanic White (NHW) men in a racially diverse real-world North American population. The study cohort included 6378 men who self-identified as NHB or NHW and were diagnosed with prostate cancer (PCa). Patients received PSA screening and subsequent PCa treatment and follow-up at our institution. Patients were sorted based on PSA testing intensity for the 5 years prior to diagnosis, as follows: never, some (<1 test/y), and annual testing (1 test/y). The primary outcome was risk of prostate cancer-specific mortality (PCSM). Competing risk cumulative incidence curves estimated PCSM rates. Competing risk regression analyses examined the impact of PSA testing on PCSM. An interaction term was incorporated to assess the impact of race on the outcome. Median (IQR) age and PSA at diagnosis were 67 (60-73) years and 5.8 (4.4-9.6) ng/mL, respectively, and 2929 (46%) men were NHB (Kruskal-Wallis P values < .001). Annual PSA testing was more frequent in NHW (5%) than in NHB (3%) men (χ2 P value < .001). On cumulative incidence analysis, in the never, some, and annual PSA testing groups, the 10-year PCSM was respectively 12.3%, 5.8%, and 4.6% in NHW and 18.5%, 7%, and 1.2% in NHB patients (Gray's test P values < .001). At competing risk regression, PSA screening rate was associated with more favorable PCSM rates (HR: 0.47; 95% CI 0.33-0.68; P < .001). The interaction term for race did not show statistical significance (P = .2). PSA testing was associated with a reduced risk of PCSM in both NHB and NHW men diagnosed with PCa. Additionally, the positive impact of the screening rate seemed to be independent of race.

Development and validation of a predictive score for diagnosing prostate cancer in primary care.

Prostate cancer (PCa) represents the fifth cause of death in the male population worldwide. The prostate-specific antigen (PSA) test demonstrated poor accuracy to assess the presence of PCa. Thus, the PSA testing paradigm should be moved from the systematic screening approach to the early identification of men who are harbouring clinically significant disease. Accurate clinical-based tools to predict PCa should therefore be developed for general practice. We derived and validated a PCa predictive score using a primary care data source. Using the Italian Health Search Database, we formed a cohort of men aged 45-90 years in the period between 2002 and 2015. These patients were followed up until 31 December 2022. Those with less than a 5-year follow-up were excluded. The cohort was randomly divided into 'derivation' and 'validation' samples in a 1:1 ratio. Along with the demographic and clinical determinants forming the score, we investigated the role of PSA kinetics in the prediction accuracy. In a cohort of 529,082 men aged 45+ years, we identified 14,524 cases of PCa (incidence rate = 2.71 per 1000 person-years; 95% confidence interval = 2.67-2.80). The prediction accuracy of the PCa-HScore featured an explained variation of 12% and a discrimination power of 70%. The calibration slope was almost equal to 1 (p = 0.951, tested for equivalence against the 'perfect' slope) and the PSA kinetics did not improve the prediction accuracy. The PCa-HScore might guide the prescription of PSA and/or other clinical strategies in those men reporting certain levels of risk. A related decision support system could therefore be implemented in primary care.