European Randomized Study Of Screening For Prostate Cancer Research Articles

Which men benefit from prostate cancer screening? Prostate cancer mortality by subgroup in the European Randomised Study of Screening for Prostate Cancer.

To evaluate whether a subgroup of men can be identified that would benefit more from screening than others. This retrospective cohort study was based on three European Randomised Study of Screening for Prostate Cancer (ERSPC) centres, Finland, the Netherlands and Sweden. We identified 126 827 men aged 55-69 years in the study who were followed for maximum of 16 years after randomisation. The primary outcome was prostate cancer (PCa) mortality. We analysed three age groups 55-59, 60-64 and 65-69 years and PCa cases within four European Association of Urology (EAU) risk groups: low, intermediate, high risk, and advanced disease. The hazard ratio (HR) for PCa mortality in the screening arm relative to the control arm for men aged 55-59 years was 0.96 (95% confidence interval [CI] 0.75-1.24) in Finland, 0.70 (95% CI 0.44-1.12) in the Netherlands and 0.42 (95% CI 0.24-0.73) in Sweden. The HR for men aged 60-64 years was 1.03 (95% CI 0.77-1.37) in Finland, 0.76 (95% CI 0.50-1.16) in the Netherlands and 0.97 (95% CI 0.64-1.48) in Sweden. The HR for men aged 65-69 years was 0.80 (95% CI 0.62-1.03) in Finland and 0.57 (95% CI 0.38-0.83) in the Netherlands, and this age group was absent in Sweden. In the EAU risk group analysis, PCa mortality rates were materially lower for men with advanced disease at diagnosis in all three countries: 0.67 (95% CI 0.56-0.82) in Finland, 0.28 (95% CI 0.18-0.44) in the Netherlands, and 0.48 (95% CI 0.30-0.78) in Sweden. We were unable to unequivocally identify the optimal age group for screening, as mortality reduction differed among centres and age groups. Instead, the screening effect appears to depend on screening duration, and the number and frequency of screening rounds. PCa mortality reduction by screening is largely attributable to stage shift.

Variation in harms and benefits of prostate‐specific antigen screening for prostate cancer by socio‐clinical risk factors: A rapid review

AbstractObjectiveTo analyse the latest evidence on the relative harms and benefits of screening and diagnostic pathways with close examination of (i) men aged 50 years or older, (ii) men whose ethnicity places them at higher risk and (iii) men with a family history.MethodsWe conducted a literature search using PubMed and Cochrane Central Register of Controlled Trials (CENTRAL) databases and other sources, from January 1990 to 25 January 2023. Two independent reviewers selected for randomised controlled trials (RCTs) and cohort studies which met our inclusion criteria.ResultsTwenty‐eight articles were selected, from six trials, including the Göteborg trial—reported separately from European Randomised Study of Screening for Prostate Cancer (ERSPC). Prostate‐specific antigen (PSA)‐based screening led to the increased detection of low‐grade cancer and reduction of advanced/metastatic disease but had contradictory effects on prostate cancer (PCa)‐specific mortality (no difference or reduced), possibly due to issues of contamination or compliance. Screening men from a relatively young age (50–55) reduced risk of PCa‐specific mortality in a subanalysis of an 18‐year follow‐up study and in a 17‐year cohort study from the main Göteborg trial. Moreover, one Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial analysis reported a trend of reduced risk of PCa‐specific mortality for men with a family history who were screened. [Correction added on 05 March 2024, after first online publication: “Cancer Screening Trial” has been added to the preceding sentence.] However, we did not find relevant studies for ethnicity.ConclusionUnder current UK practice, the choice to conduct a PSA test relies on a shared decision‐making approach guided by known risk factors. However, we found there was a lack of strong evidence on the harms and benefits of PSA screening by socio‐clinical risk factors and suggest further research is required to understand the long‐term impact of screening on high‐risk populations in the current diagnostic setting.

Navigating through the Controversies and Emerging Paradigms in Early Detection of Prostate Cancer: Bridging the Gap from Classic RCTs to Modern Population-Based Pilot Programs.

Over the last three decades, the European Randomized Study of Screening for Prostate Cancer (ERSPC) and the US-based Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening have steered the conversation around the early detection of prostate cancer. These two randomized trials assessed the effect of screening on prostate cancer disease-specific mortality. Elevated PSA levels were followed by a systematic sextant prostate biopsy. Standard repeat testing intervals were applied. After controversies from 2009 to 2016 due to contradicting results of the two trials, the results aligned in 2016 and showed that early PSA detection reduces prostate cancer-specific mortality. However, overdiagnosis rates of up to 50% were reported, and this sparked an intense debate on harms and benefits for almost 20 years. The balance between harms and benefits is highly debated and has initiated further research to investigate new ways of early detection. In the meantime, the knowledge and tools for the diagnostic algorithm improved. This is a continuously ongoing effort which focuses on individual risk-based screening algorithms that preserve the benefits of the purely PSA-based screening algorithms, while reducing the side effects. An important push towards investigating new techniques for early detection came from the European Commission on the 20th of September 2022. The European Commission published its updated recommendation to investigate prostate, lung, and gastric cancer early detection programs. This opened a new window of opportunity to move away from the trial setting to population-based early detection settings. With this review, we aim to review 30 years of historical evidence of prostate cancer screening, which led to the initiation of the 'The Prostate Cancer Awareness and Initiative for Screening in the European Union' (PRAISE-U) project, which aims to encourage the early detection and diagnosis of PCa through customized and risk-based screening programs.

From Screening to Mortality Reduction: An Overview of Empirical Data on the Patient Journey in European Randomized Study of Screening for Prostate Cancer Rotterdam After 21 Years of Follow-up and a Reflection on Quality of Life

BackgroundPrevious research quantified the effect of prostate-specific antigen (PSA)-based prostate cancer (PCa) screening on quality-adjusted life years using 11-yr follow-up data from the European Randomized Study of Screening for Prostate Cancer (ERSPC) extrapolated by the Microsimulation Screening Analysis (MISCAN). ERSPC data now matured to 21 yr of follow-up. ObjectiveTo provide an overview of the effect of PSA-based screening on tumour characteristics and PCa treatment using long-term, detailed, empirical ERSPC data. Design, setting, and participantsMen were included from the ERSPC Rotterdam who were randomised to a PSA-based screening (S) or control (C) arm. Outcome measurements and statistical analysisWe assessed the effects of PSA-based screening on the number of PCa diagnoses, tumour characteristics, treatments, and cumulative incidence of disease progression. We also evaluated the changes in tumour characteristics and treatments over time for both study arms. Results and limitationsAmong PCa patients in the S-arm, fewer patients were diagnosed with advanced tumour stages (T3/T4: 12% vs 23%; relative risk [RR] = 0.50; 95% confidence interval [CI] 0.44–0.57), less disease progression was observed, and less secondary treatment (30% vs 48%; RR = 0.61; 95% CI 0.57–0.66; p < 0.001) and less palliative treatment were needed (21% vs 55%; RR = 0.38; 95% CI 0.35–0.42) than among those in the C-arm. This was at the cost of overdiagnosis and increased local treatments (eg, radical prostatectomy: 32% vs 14%; RR = 2.18; 95% CI 1.92–2.48). Over time, the number of local treatments decreased, whereas expectant management strategies increased. The RRs of treatments were slightly different from those of the MISCAN. ConclusionsAfter 21 yr of follow-up, empirical data of the ERSPC showed that PSA-based screening reduces advanced PCa stages, disease progression, and extensive treatments at the cost of more overdiagnosis and probably more overtreatment. Our data showed reduced local treatments and increased expectant management strategies over time. Patient summaryProstate-specific antigen–based screening reduces the number of invasive prostate cancer treatments needed, however, at the cost of more overdiagnosis and probably more overtreatment. Limiting these costs remains crucial to benefit optimally from prostate cancer screening.

PROSTATE CANCER SCREENING USING THE PROSTATE-SPECIFIC ANTIGEN (PSA) TEST

We aimed to conduct a systematic review and meta-analysis on published literature extracted from PubMed/Medline, Google scholar, and Cochrane library. The results of the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial showed a statistically significant 29% prostate cancer mortality reduction for the men screened in the intervention arm and a 23% negative impact on the life-years gained because of quality of life. However, alternative prostate-specific antigen (PSA) screening strategies for the population may exist, optimizing the effects on mortality reduction, quality of life, over diagnosis, and costs.

Relationship Between Baseline Prostate-specific Antigen on Cancer Detection and Prostate Cancer Death: Long-term Follow-up from the European Randomized Study of Screening for Prostate Cancer

BackgroundThe European Association of Urology guidelines recommend a risk-based strategy for prostate cancer screening based on the first prostate-specific antigen (PSA) level and age. ObjectiveTo analyze the impact of the first PSA level on prostate cancer (PCa) detection and PCa-specific mortality (PCSM) in a population-based screening trial (repeat screening every 2–4 yr). Design, setting, and participantsWe evaluated 25589 men aged 55–59 yr, 16898 men aged 60–64 yr, and 12936 men aged 65–69 yr who attended at least one screening visit in the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial (screening arm: repeat PSA testing every 2–4 yr and biopsy in cases with elevated PSA; control arm: no active screening offered) during 16-yr follow-up (FU). Outcome measurements and statistical analysisWe assessed the actuarial probability for any PCa and for clinically significant (cs)PCa (Gleason ≥7). Cox proportional-hazards regression was performed to assess whether the association between baseline PSA and PCSM was comparable for all age groups. A Lorenz curve was computed to assess the association between baseline PSA and PCSM for men aged 60–61 yr. Results and limitationsThe overall actuarial probability at 16 yr ranged from 12% to 16% for any PCa and from 3.7% to 5.7% for csPCa across the age groups. The actuarial probability of csPCa at 16 yr ranged from 1.2–1.5% for men with PSA <1.0 ng/ml to 13.3–13.8% for men with PSA ≥3.0 ng/ml. The association between baseline PSA and PCSM differed marginally among the three age groups. A Lorenz curve for men aged 60–61 yr showed that 92% of lethal PCa cases occurred among those with PSA above the median (1.21 ng/ml). In addition, for men initially screened at age 60–61 yr with baseline PSA <2 ng/ml, further continuation of screening is unlikely to be beneficial after the age of 68–70 yr if PSA is still <2 ng/ml. No case of PCSM emerged in the subsequent 8 yr (up to age 76–78 yr). A limitation is that these results may not be generalizable to an opportunistic screening setting or to contemporary clinical practice. ConclusionsIn all age groups, baseline PSA can guide decisions on the repeat screening interval. Baseline PSA of <1.0 ng/ml for men aged 55–69 yr is a strong indicator to delay or stop further screening. Patient summaryIn prostate cancer screening, the patient’s baseline PSA (prostate-specific antigen) level can be used to guide decisions on when to repeat screening. The PSA test when used according to current knowledge is valuable in helping to reduce the burden of prostate cancer.

A Detailed Evaluation of the Effect of Prostate-specific Antigen–based Screening on Morbidity and Mortality of Prostate Cancer: 21-year Follow-up Results of the Rotterdam Section of the European Randomised Study of Screening for Prostate Cancer

BackgroundConsidering the long natural history of prostate cancer (PCa), long-term results of the European Randomised Study of Screening for PCa (ERSPC) are crucial. ObjectiveTo provide an update on the effect of prostate-specific antigen (PSA)-based screening on PCa-specific mortality (PCSM), metastatic disease, and overdiagnosis in the Dutch arm of the ERSPC. Design, setting, and participantsBetween 1993 and 2000, a total of 42376 men, aged 55–74 yr, were randomised to a screening or a control arm. The main analysis was performed with men aged 55–69 yr (n = 34831). Men in the screening arm were offered PSA-based screening with an interval of 4 yr. Outcome measurements and statistical analysisIntention-to-screen analyses with Poisson regression were used to calculate rate ratios (RRs) of PCSM and metastatic PCa. Results and limitationsAfter a median follow-up of 21 yr, the RR of PCSM was 0.73 (95% confidence interval [CI]: 0.61–0.88) favouring screening. The numbers of men needed to invite (NNI) and needed to diagnose (NND) to prevent one PCa death were 246 and 14, respectively. For metastatic PCa, the RR was 0.67 (95% CI: 0.58–0.78) favouring screening. The NNI and NND to prevent one metastasis were 121 and 7, respectively. No statistical difference in PCSM (RR of 1.18 [95% CI: 0.87–1.62]) was observed in men aged ≥70 yr at the time of randomisation. In the screening arm, higher rates of PCSM and metastatic disease were observed in men who were screened only once and in a selected group of men above the screening age cut-off of 74 yr. ConclusionsThe current analysis illustrates that with a follow-up of 21 yr, both absolute metastasis and mortality reduction continue to increase, resulting in a more favourable harm-benefit ratio than demonstrated previously. These data do not support starting screening at the age of 70–74 yr and show that repeated screening is essential. Patient summaryProstate-specific antigen–based prostate cancer screening reduces metastasis and mortality. Longer follow-up shows fewer invitations and diagnoses needed to prevent one death, a positive note towards the issue of overdiagnosis.

MiR-20b-5p is a novel biomarker for detecting prostate cancer.

Prostate cancer (PCa) is the second most frequently diagnosed solid tumor and the fifth leading cause of cancer mortality among men worldwide. The prostate specific antigen (PSA) test for PCa remains controversial. Therefore, the development of more effective non-invasive biomarkers for PCa is necessary. The present study evaluated the diagnostic value of microRNA (miR)-20b-5p in PCa. Tissue miR-20b-5p expression levels and their correlation with clinical parameters were assessed using The Cancer Genome Atlas (TCGA) datasets, and the diagnostic value of the miR-20b-5p expression levels in PCa tissues was assessed using receiver operating characteristic curve analysis. Reverse transcription-quantitative PCR (RT-qPCR) was used to assess the relative expression levels of miR-20b-5p in PCa tissues compared with benign prostate hyperplasia (BPH) tissues. In addition, miR-20b-5p expression levels in PCa cell lines and non-tumorigenic prostate epithelial cells were compared. In this study, exosomes were extracted from the prostatic fluid as a source of liquid biopsy for the detection of PCa. The prostatic fluid exosomal miR-20b-5p expression levels between patients with PCa and the biopsy-negative patients were compared, and the diagnostic efficiency of prostatic fluid exosomal miR-20b-5p expression levels in PCa was compared with PSA and with the European Randomized Study of Screening for Prostate Cancer (ERSPC) risk calculator. The mechanism by which miR-20b-5p may function in PCa was assessed using bioinformatic analysis and validation experiments. miR-20b-5p was expressed at a markedly higher level in PCa tissues compared with normal prostate tissues with high diagnostic efficiency (area under the curve: 0.826). The expression levels of miR-20b-5p were also significantly higher in PCa tissues compared with BPH tissues; similarly, miR-20b-5p was more highly expressed in PCa cells compared with non-tumorigenic prostate epithelial cells. Prostatic fluid exosomal miR-20b-5p expression levels in patients with PCa were significantly higher compared with confirmed to be biopsy-negative, and the diagnostic performance of miR-20b-5p was superior to PSA and ERSPC risk calculator. The results of RT-qPCR and western blotting following transfection of DU145 cells with miR-20b-5p mimics and inhibitor showed that miR-20b-5p reduced the expression of retinoblastoma-associated protein 1 (RB1). Therefore, RB1 may be a significant target gene for miR-20b-5p. In conclusion, the present study demonstrated that miR-20b-5p was upregulated in PCa at the tissue and cellular levels, as well as in prostatic fluid exosomes. Therefore, miR-20b-5p may be a promising early diagnostic biomarker for PCa and an important tool to guide the decision-making of prostate biopsy.

Detailed Evaluation of Androgen Deprivation Overtreatment in Prostate Cancer Patients Compared to the European Association of Urology Guidelines Using Long-term Data from the European Randomised Study of Screening for Prostate Cancer Rotterdam

BackgroundGuidelines on androgen deprivation therapy (ADT) for prostate cancer (PCa) arise from a critical appraisal of scientific evidence, which is a costly effort. Despite these efforts and the side effects of ADT, guidelines may not always be adhered to. ObjectiveTo determine ADT overtreatment in PCa patients compared to the European Association of Urology (EAU) guidelines, and to identify predictors and physicians’ motivations for this overtreatment. Design, setting, and participantsMen were included from the European Randomised study of Screening for Prostate Cancer (ERSPC) Rotterdam who were diagnosed with PCa between 2001 and 2019, and received ADT <1 yr after diagnosis. Outcome measurements and statistical analysisPatients were categorised into the concordant ADT or discordant ADT group following the EAU guidelines. Physicians’ motivations for discordancy were reported. Multivariable logistic regression was performed to identify predictors for guideline-discordant ADT including the nonlinear fit of the year of diagnosis. Results and limitationsOf 3608 PCa patients, 1037 received ADT <1 yr after diagnosis. Adherence improved gradually over the study period, resulting in overall discordancy of 15%. A patient diagnosed in 2011 had 3.3 times lower risk on guideline-discordant ADT than a patient diagnosed in 2004 (odds ratio [OR] 0.30; 95% confidence interval [CI] 0.18–0.50). The most common reason for discordancy was unwillingness or unfitness for curative treatment of asymptomatic patients. Age (OR 1.19; 95% CI 1.15–1.24) and Gleason score ≥4 + 3 (OR 1.70; 95% CI 1.06–2.74) were associated with guideline-discordant ADT. ConclusionsIn a Dutch cohort, slow adaptation of the EAU guidelines on ADT for PCa patients between 2001 and 2019 resulted in overall overtreatment of 15%, mostly in asymptomatic patients who were unfit or unwilling for curative treatment. Clear, structured presentation, or integration of these tailored guidelines into the electronic health record might accelerate the adaptation of future guidelines. Patient summarySlow adaptation of the guidelines on hormonal therapy resulted in overtreatment in 15% of prostate cancer patients, mostly in asymptomatic patients who were unfit or unwilling for curative treatment.

MP43-08 ACTIVE SURVEILLANCE FOR PROSTATE CANCER: UPTAKE OVER TIME AND THE IMPACT OF AN ORGANIZED PROTOCOL

You have accessJournal of UrologyCME1 May 2022MP43-08 ACTIVE SURVEILLANCE FOR PROSTATE CANCER: UPTAKE OVER TIME AND THE IMPACT OF AN ORGANIZED PROTOCOL Sebastiaan Remmers, and Monique Roobol Sebastiaan RemmersSebastiaan Remmers More articles by this author , and Monique RoobolMonique Roobol More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002609.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The European Randomized Study of Screening for Prostate Cancer (ERSPC) showed that PSA-based screening coincides with overdiagnosis and overtreatment. Active Surveillance (AS) was initiated to reduce the harm of overtreatment. However, the rate of uptake of AS is highly heterogeneous around the world. Here, we look at the uptake of AS over time. Specifically, we assessed whether the initiation of an organized protocol increased the rate of men opting for AS and looked at differences between screening and clinical setting. METHODS: Data include diagnoses in the period 1993-2013 in men aged ≤70 yr diagnosed within ERSPC Rotterdam and eligible for AS according to the Prostate cancer Research International: Active Surveillance (PRIAS) pre-MRI criteria (Gleason 6, PSA <10 ng/ml, ≤cT2a). The number of PRIAS eligible men was compared against all men with low-risk disease in both arms of the trial and we assessed the choice of initial treatment for PRIAS eligible men before and after 2006 (the year PRIAS was initiated). RESULTS: In the study period, 962 men in the screening (S-) arm and 265 men in the control (C-) arm were diagnosed with cT1c/cT2a Gleason 6 disease (Tab/Fig). The percentage of PRIAS eligible men in this group is very different: 91% in the S-arm and 63% in the C-arm, reflecting lead time (lower PSA and tumor load). In the 90s and before PRIAS was initiated (i.e. <2006), 22% of all PRIAS eligible men in the S- arm opted for AS and 77% for radical prostatectomy (RP) / radiotherapy (RT); in the C- arm 27% opted for AS and 68% for RP/RT. From 2006 (initiation of PRIAS) till 2013 63% of the PRIAS eligible men in the S-arm opted for AS and 34% for RP/RT; in the C- arm 47% of the PRIAS eligible men opted for AS and 47% for RP/ RT. A difference most likely due to (although eligible for AS according to the PRIAS criteria) higher PSA values at diagnosis in the C- arm (median 6.2 ng/ml) than in the S-arm (median 3.9 ng/ml). CONCLUSIONS: In conclusion, PSA-based screen-detected low risk PCa is in general suitable for an AS approach. The initiation and awareness of an organized protocol for AS has increased the uptake in men diagnosed with low-risk PCa, but there is certainly still room for improvement. Since (opportunistic) early detection practices are ubiquitous, next to avoiding overdiagnosis, the use of AS in clinical practice should be strongly encouraged. Source of Funding: No © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e743 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sebastiaan Remmers More articles by this author Monique Roobol More articles by this author Expand All Advertisement PDF DownloadLoading ...

Improving the Early Detection of Clinically Significant Prostate Cancer in Men in the Challenging Prostate Imaging-Reporting and Data System 3 Category

BackgroundProstate Imaging-Reporting and Data System (PI-RADS) category 3 is a challenging scenario for detection of clinically significant prostate cancer (csPCa) and some tools can improve the selection of appropriate candidates for prostate biopsy. ObjectiveTo assess the performance of the European Randomized Study of Screening for Prostate Cancer (ERSPC) magnetic resonance imaging (MRI) model, the new Proclarix test, and prostate-specific antigen density (PSAD) in selecting candidates for prostate biopsy among men in the PI-RADS 3 category. Design, setting, and participantsWe conducted a head-to-head prospective analysis of 567 men suspected of having PCa for whom guided and systematic biopsies were scheduled between January 2018 and March 2020 in a single academic institution. A PI-RADS v.2 category 3 lesion was identified in 169 men (29.8%). Outcome measurement and statistical analysiscsPCa, insignificant PCa (iPCa), and unnecessary biopsy rates were analysed. csPCa was defined as grade group ≥2. Receiver operating characteristic (ROC) curves, decision curve analysis curves, and clinical utility curves were plotted. Results and limitationsPCa was detected in 53/169 men (31.4%) with a PI-RADS 3 lesion, identified as csPCa in 25 (14.8%) and iPCa in 28 (16.6%). The area under the ROC curve for csPCa detection was 0.703 (95% confidence interval [CI] 0.621–0.768) for Proclarix, 0.657 (95% CI 0.547–0.766) for the ERSPC MRI model, and 0.612 (95% CI 0.497–0.727) for PSAD (p = 0.027). The threshold with the highest sensitivity was 10% for Proclarix, 1.5% for the ERSPC MRI model, and 0.07 ng/ml/cm3 for PSAD, which yielded sensitivity of 100%, 91%, and 84%, respectively. Some 21.3%, 26.2%, and 7.1% of biopsies would be avoided with Proclarix, PSAD, and the ERSPC MRI model, respectively. Proclarix showed a net benefit over PSAD and the ERSPC MRI model. Both Proclarix and PSAD reduced iPCa overdetection from 16.6% to 11.3%, while the ERSPC MRI model reduced iPCa overdetection to 15.4%. ConclusionsProclarix was more accurate in selecting appropriate candidates for prostate biopsy among men in the PI-RADS 3 category when compared to PSAD and the ERSPC MRI model. Proclarix detected 100% of csPCa cases and would reduce prostate biopsies by 21.3% and iPCa overdetection by 5.3%. Patient summaryWe compared three methods and found that the Proclarix test can optimise the detection of clinically significant prostate cancer in men with a score of 3 on the Prostate Imaging-Reporting and Data System for magnetic resonance imaging scans.

Predictors of clinically significant prostate cancer in biopsy-naïve and prior negative biopsy men with a negative prostate MRI: improving MRI-based screening with a novel risk calculator.

Purpose:A pre-biopsy decision aid is needed to counsel men with a clinical suspicion for clinically significant prostate cancer (csPCa), despite normal prostate magnetic resonance imaging (MRI).Methods:A risk calculator (RC) for csPCa (International Society of Urological Pathology grade group (ISUP) ⩾ 2) presence in men with a negative-MRI (Prostate Imaging–Reporting and Data System (PI-RADS) ⩽ 2) was developed, and its performance was compared with RCs of the European Randomized Study of Screening for Prostate Cancer (ERSPC), Prostate Biopsy Collaborative Group (PBCG), and Prospective Loyola University mpMRI (PLUM). All biopsy-naïve and prior negative biopsy men with a negative-MRI followed by systematic prostate biopsy were included from October 2015 to September 2021. The RC was developed using multivariable logistic regression with the following parameters: age (years), family history of PCa (first- or second-degree family member), ancestry (African Caribbean/other), digital rectal exam (benign/malignant), MRI field strength (1.5/3.0 Tesla), prior negative biopsy status, and prostate-specific antigen (PSA) density (ng/ml/cc). Performance of RCs was compared using receiver operating characteristic (ROC) curve analysis.Results:A total of 232 men were included for analysis, of which 18.1% had csPCa. Parameters associated with csPCa were family history of PCa (p < 0.0001), African Caribbean ancestry (p = 0.005), PSA density (p = 0.002), prior negative biopsy (p = 0.06), and age at biopsy (p = 0.157). The area under the curve (AUC) of the developed RC was 0.76 (95% CI 0.68–0.85). This was significantly better than the RCs of the ERSPC (AUC: 0.59; p = 0.001) and PBCG (AUC: 0.60; p = 0.002), yet similar to PLUM (AUC: 0.69; p = 0.09).Conclusion:The developed RC (Prostate Biopsy Cohort Amsterdam (‘PROBA’ RC), integrated predictors for csPCa at prostate biopsy in negative-MRI men and outperformed other widely used RCs. These findings require external validation before introduction in daily practice.

An analysis of three different prostate cancer risk calculators applied prior to prostate biopsy: A Turkish cohort validation study.

The study aimed to investigate the best-performing of three risk calculators (RCs) for the Turkish population in predicting cancer-free status and high-risk prostate cancer (PCa) in patients undergoing transrectal ultrasound-guided prostate biopsy. The electronic medical records of 527 patients who underwent prostate biopsy for the first time due to PSA of 0.3-50ng/dl and/or cancer suspicion at digital rectal examination (DRE) between January 2017 and December 2020 were retrieved retrospectively. The predictive power of the RCs in the biopsy and the surgical cohort was calculated by two urologists using European Randomised Study of Screening for Prostate Cancer (ERSPC) RC, the North American Prostate Cancer Prevention Trial-RC (PCPT-RC), and the Prostate Biopsy Collaborative Group (PBCG)-RC. All three RCs were successful in predicting PCa and high-risk disease at ROC analysis (p<0.0001). Of these three nomograms, PBCG-RC outperformed PCPT-RC 2.0 and ERSPC-RH in predicting benign pathology outcomes at biopsy. A better performance of PBCG-RC was also observed in terms of prediction of high-risk disease at biopsy. Using any of the available RCs prior to biopsy is of greater assistance to prostate-specific antigen and DRE than examination alone. The study results show that PBCG-RC performed before biopsy has a higher predictive power than the other two RCs.

Predicting high-grade prostate cancer at initial biopsy: clinical performance of the ExoDx (EPI) Prostate Intelliscore test in three independent prospective studies

BackgroundThe ability to discriminate indolent from clinically significant prostate cancer (PC) at the initial biopsy remains a challenge. The ExoDx Prostate (IntelliScore) (EPI) test is a noninvasive liquid biopsy that quantifies three RNA targets in urine exosomes. The EPI test stratifies patients for risk of high-grade prostate cancer (HGPC; ≥ Grade Group 2 [GG] PC) in men ≥ 50 years with equivocal prostate-specific antigen (PSA) (2–10 ng/mL). Here, we present a pooled meta-analysis from three independent prospective-validation studies in men presenting for initial biopsy decision.MethodsPooled data from two prospective multi-site validation studies and the control arm of a clinical utility study were analyzed. Performance was evaluated using the area under the receiver-operating characteristic curve (AUC), negative predictive value (NPV), positive predictive value (PPV), sensitivity, and specificity for discriminating ≥ GG2 from GG1 and benign pathology.ResultsThe combined cohort (n = 1212) of initial-biopsy subjects had a median age of 63 years and median PSA of 5.2 ng/mL. The EPI AUC (0.70) was superior to PSA (0.56), Prostate Cancer Prevention Trial Risk Calculator (PCPT-RC) (0.62), and The European Randomized Study of Screening for Prostate Cancer (ERSPC) (0.59), (all p-values <0.001) for discriminating GG2 from GG1 and benign histology. The validated cutoff of 15.6 would avoid 23% of all prostate biopsies and 30% of “unnecessary” (benign or Gleason 6/GG1) biopsies, with an NPV of 90%.ConclusionsEPI is a noninvasive, easy-to-use, urine exosome–RNA assay that has been validated across 3 independent prospective multicenter clinical trials with 1212 subjects. The test can discriminate high-grade (≥GG2) from low-grade (GG1) cancer and benign disease. EPI effectively guides the biopsy-decision process independent of PSA and other standard-of-care factors.

PD13-04 PROSTATE CANCER SPECIFIC MORTALITY IN THE ERSPC TRIAL: WHAT IS THE ROLE OF SCREENING RESULT AND ADHERENCE

PD13-04 PROSTATE CANCER SPECIFIC MORTALITY IN THE ERSPC TRIAL: WHAT IS THE ROLE OF SCREENING RESULT AND ADHERENCE

Enhancement of prostate cancer diagnosis by machine learning techniques: an algorithm development and validation study.

To investigate the value of machine learning(ML) in enhancing prostate cancer(PCa) diagnosis. Consecutive systematic prostate biopsies performed from Jan 2003-June 2017 were used as the training cohort, and prospective biopsies performed from July 2017-November 2019 were used as validation cohort. Men were included if PSA was 0.4-50 ng/mL, and information of digital rectal examination (DRE), Transrectal ultrasound(TRUS) prostate volume, TRUS abnormality were known. Clinically significant PCa(csPCa) was defined as Gleason 3 + 4 or above cancers. Area-under-curve (AUC) of receiver-operating characteristics (ROC) was compared between PSA, PSA density, European Randomized Study of Screening for Prostate Cancer (ERSPC) risk calculator (ERSPC-RC), and various ML techniques using PSA, DRE and TRUS information. ML techniques used included XGBoost, LightGBM, Catboost, Support vector machine (SVM), Logistic regression (LR), and Random Forest (RF), where cost sensitive learning was applied. Training and validation cohorts included 3881 and 778 consecutive men, respectively. RF model performed better than other ML techniques and PSA, PSA density and ERSPC-RC for prediction of PCa or csPCa in the validation cohort. In csPCa prediction, AUC of PSA, PSA density, ERSPC-RC and RF was 0.71, 0.80, 0.83 and 0.88 respectively. At 90-95% sensitivity for csPCa, RF model achieved a negative predictive value (NPV) of 97.5-98.0% and avoided 38.3-52.2% unnecessary biopsies. Decision curve analyses (DCA) showed RF model provided net clinical benefit over PSA, PSA density and ERSPC-RC. By using the same clinical parameters, ML techniques performed better than ERSPC-RC or PSA density in csPCa predictions, and could avoid up to 50% unnecessary biopsies.

Assessment of prostate-specific antigen screening: an evidence-based report by the German Institute for Quality and Efficiency in Health Care.

Prostate-specific antigen (PSA) testing increases prostate cancer diagnoses and reduces long-term disease-specific mortality, but also results in overdiagnoses and treatment-related harms. To systematically assess the benefits and harms of population-based PSA screening and the potential net benefit to inform health policy decision-makers in Germany. We performed a protocol-guided comprehensive literature search according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. All steps were performed by one or two investigators; any discrepancies were resolved by consensus. To allow subgroup analyses for identifying the optimal screening parameters, the eight national trials conducted under the umbrella of the European Randomised study of Screening for Prostate Cancer (ERSPC) were included as individual trials. We included a total 11 randomised controlled trials (RCTs) with a total of 416 000 study participants. For all-cause mortality, we found neither benefit nor harm. PSA screening was associated with a reduced risk of both prostate cancer mortality and the development of metastases. For the outcomes of health-related quality of life, adverse effects and the consequences of false-negative screening results there was no difference; however, this was due to the lack of eligible RCT data. Finally, PSA screening was associated with large numbers of overdiagnoses with adverse downstream consequences of unnecessary treatment (e.g. incontinence, erectile dysfunction) and large numbers of false-positive PSA tests leading to biopsies associated with a small but not negligible risk of complications. Limitations of this assessment include the clinical heterogeneity and methodological limitations of the underlying studies. The benefits of PSA-based prostate cancer screening do not outweigh its harms. We failed to identify eligible screening studies of newer biomarkers, PSA derivatives or modern imaging modalities, which may alter the balance of benefit to harm. In the present study, we reviewed the evidence on the PSA blood test to screen men without symptoms for prostate cancer. We found that the small benefits experienced by some men do not outweigh the harms to many more men.

The utility of magnetic resonance imaging in prostate cancer diagnosis in the Australian setting

ObjectivesTo investigate the utility of Magnetic Resonance Imaging (MRI) for prostate cancer diagnosis in the Australian setting.Patients and methodsAll consecutive men who underwent a prostate biopsy (transperineal or transrectal) at Royal Melbourne Hospital between July 2017 to June 2019 were included, totalling 332 patients. Data were retrospectively collected from patient records. For each individual patient, the risk of prostate cancer diagnosis at biopsy based on clinical findings was determined using the European Randomized study of Screening for Prostate Cancer (ERSPC) risk calculator, with and without incorporation of MRI findings.ResultsMRI has good diagnostic accuracy for clinically significant prostate cancer. A PI‐RADS 2 or lower finding has a negative predictive value of 96% for clinically significant cancer, and a PI‐RADS 3, 4 or 5 MRI scan has a sensitivity of 93%. However, MRI has a false negative rate of 6.5% overall for clinically significant prostate cancers. Pre‐ biopsy MRI may reduce the number of unnecessary biopsies, as up to 50.0% of negative or ISUP1 biopsies have MRI PI‐RADS 2 or lower. Incorporation of MRI findings into the ERSPC calculator improved predictive performance for all prostate cancer diagnoses (AUC 0.77 vs 0.71, P = .04), but not for clinically significant cancer (AUC 0.89 vs 0.87, P = .37).ConclusionMRI has good sensitivity and negative predictive value for clinically significant prostate cancers. It is useful as a pre‐biopsy tool and can be used to significantly reduce the number of unnecessary prostate biopsies. However, MRI does not significantly improve risk predictions for clinically significant cancers when incorporated into the ERSPC risk calculator.

Clash of the calculators: External validation of prostate cancer risk calculators in men undergoing mpMRI and transperineal biopsy.

ObjectiveTo compare the accuracy of the European Randomized Study of Screening for Prostate Cancer (ERSPC) RC, MRI‐ERSPC‐RC, and Prostate Biopsy Collaborative Group (PBCG) RC in patients undergoing transperineal prostate biopsy.Patients and methodsWe identified 392 patients who underwent mpMRI before transperineal prostate biopsy across multiple public and private institutions between January 2017 and August 2019. The estimated probabilities of detecting PCa and significant PCa were calculated using the MRI‐ERSPC‐RC, ERSPC‐RC, and PBCG‐RC. Receiver operating characteristic (ROC) curves for each calculator were generated and the area underneath the curve (AUC) was compared. Calibration and clinical utility were assessed with calibration plots and decision curve analysis, respectively.ResultsPCa was detected in 285 patients (72.7%) with significant PCa found in 200 patients (51.1%). ROC curve analysis found the MRI‐ERSPC‐RC outperformed the ERSPC‐RC and PBCG‐RC. For the prediction of PCa, the AUC was 0.756, 0.696, and 0.675 for the MRI‐ERSPC‐RC, ERSPC‐RC, and PBCG‐RC, respectively. The AUC for the prediction of significant PCa was 0.803, 0.745, and 0.746 for the MRI‐ERSPC‐RC, ERSPC‐RC, and PBCG‐RC, respectively.ConclusionsOur study validated the ERSPC‐RC, MRI‐ERSPC‐RC, and PBCG‐RC in a cohort undergoing transperineal prostate biopsy with the MRI‐ERSPC‐RC performing the best. These RCs may enable improved shared decision making and help to guide patient selection for biopsy.

Impact of cancer screening on metastasis: A prostate cancer case study.

Trials of cancer screening present results in terms of deaths prevented, but metastasis is also a key endpoint that screening seeks to prevent. We developed a framework for projecting overall (de novo and progressive) metastases prevented in a screening trial using prostate cancer screening as a case study. Mechanistic simulation model in which screening shifts a fraction of cases that would be metastatic at diagnosis to being non-metastatic. This shift increases the incidence of non-overdiagnosed, organ-confined cases. We use estimates of the risk of metastatic progression for these cases to project how many progress to metastasis after diagnosis and tally the projected de novo and progressive metastatic cases with and without screening. We use data on stage shift from the European Randomized Study of Screening for Prostate Cancer (ERSPC) and data on the risk of metastatic progression from the Scandinavian Prostate Cancer Group-4 trial. We estimate the relative risk and absolute risk reductions in metastatic disease at diagnosis and compare these with reductions in overall metastases. Assuming no effect of screening beyond initial stage shift at diagnosis, the model projects a 43% reduction in metastasis at diagnosis but a 22% reduction in the cumulative probability of metastasis over 12 years in favor of screening. These results are consistent with the empirical findings from the ERSPC. Any reduction in metastatic disease at diagnosis under screening is likely to be an overly optimistic predictor of the impact of screening on overall metastasis and disease-specific mortality.