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Objective: To evaluate whether a subgroup of men can be identified that would benefit more from screening than others. Materials and Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Population‐based organised repeated screening for prostate cancer has been found to reduce disease‐specific mortality, but with substantial overdiagnosis leading to overtreatment. Although only very few countries have implemented a screening programme on a national level, individual prostate‐specific antigen (PSA) testing is common. This opportunistic testing may have little favourable impact, while stressing the side‐effects. The classic early detection protocols as were state‐of‐the‐art in the 1990s applied a PSA and digital rectal examination threshold for sextant systematic prostate biopsy, with a fixed interval for re‐testing, and limited indication for expectant management. In the three decades since these trials were started, different important improvements have become available in the cascade of screening, indication for biopsy, and treatment. The main developed aspects include: better identification of individuals at risk (using early/baseline PSA, family history, and/or genetic profile), individualised re‐testing interval, optimised and individualised starting and stopping age, with gradual invitation at a fixed age rather than invitation of a wider range of age groups, risk stratification for biopsy (using PSA density, risk calculator, magnetic resonance imaging, serum and urine biomarkers, or combinations/sequences), targeted biopsy, transperineal biopsy approach, active surveillance for low‐risk prostate cancer, and improved staging of disease. All these developments are suggested to decrease the side‐effects of screening, while at least maintaining the advantages, but Level 1 evidence is lacking. The knowledge gained and new developments on early detection are being tested in different prospective screening trials throughout Europe. In addition, the European Union‐funded PRostate cancer Awareness and Initiative for Screening in the European Union (PRAISE‐U) project will compare and evaluate different screening pilots throughout Europe. Implementation and sustainability will also be addressed. Modern screening approaches may reduce the burden of the second most frequent cause of cancer‐related death in European males, while minimising side‐effects. Also, less efficacious opportunistic early detection may be indirectly reduced. [ABSTRACT FROM AUTHOR]

Objectives: To compare the performance of currently available biopsy decision support tools incorporating magnetic resonance imaging (MRI) findings in predicting clinically significant prostate cancer (csPCa). Patients and Methods: We retrospectively included men who underwent prostate MRI and subsequent targeted and/or systematic prostate biopsies in two large European centres. Available decision support tools were identified by a PubMed search. Performance was assessed by calibration, discrimination, decision curve analysis (DCA) and numbers of biopsies avoided vs csPCa cases missed, before and after recalibration, at risk thresholds of 5%–20%. Results: A total of 940 men were included, 507 (54%) had csPCa. The median (interquartile range) age, prostate‐specific antigen (PSA) level, and PSA density (PSAD) were 68 (63–72) years, 9 (7–15) ng/mL, and 0.20 (0.13–0.32) ng/mL2, respectively. In all, 18 multivariable risk calculators (MRI‐RCs) and dichotomous biopsy decision strategies based on MRI findings and PSAD thresholds were assessed. The Van Leeuwen model and the Rotterdam Prostate Cancer Risk Calculator (RPCRC) had the best discriminative ability (area under the receiver operating characteristic curve 0.86) of the MRI‐RCs that could be assessed in the whole cohort. DCA showed the highest clinical utility for the Van Leeuwen model, followed by the RPCRC. At the 10% threshold the Van Leeuwen model would avoid 22% of biopsies, missing 1.8% of csPCa, whilst the RPCRC would avoid 20% of biopsies, missing 2.6% of csPCas. These multivariable models outperformed all dichotomous decision strategies based only on MRI‐findings and PSAD. Conclusions: Even in this high‐risk cohort, biopsy decision support tools would avoid many prostate biopsies, whilst missing very few csPCa cases. The Van Leeuwen model had the highest clinical utility, followed by the RPCRC. These multivariable MRI‐RCs outperformed and should be favoured over decision strategies based only on MRI and PSAD. [ABSTRACT FROM AUTHOR]

With the new policy recommendation in 2022 to explore the possibilities of screening for prostate cancer by the European Commission, the landscape for prostate cancer early detection is evolving. In line with this recommendation, the PRAISE-U project aims to evaluate the early detection and diagnosis of prostate cancer through customised and risk-based screening programmes, with the goal to align protocols across European Union member states. This systematic review is part of the PRAISE-U project, with the goal to review the policy, medical guideline recommendations, and the current level of opportunistic screening presented in the scientific literature on prostate cancer early detection from 2016 to 2023 in European Union member states. An extensive literature search was performed on 1 June 2023 in a large number of databases, including Embase.com, Medline (Ovid), Web of Science Core Collection, Google Scholar, and Policy Commons. We identified 318 articles (qualitative, quantitative, and reviews), of which 41 were included in the full-text screening. Seventeen articles were ultimately identified as eligible for inclusion. The included articles revealed significant variations towards PSA-based early detection policies for prostate cancer in nine European countries. Despite official recommendations, opportunistic screening was prevalent across all nine countries regardless of recommendations for or against PSA-based early detection. This systematic review suggests that the current early detection policies are not fit for purpose. High levels of opportunistic screening and overdiagnosis persist, prompting policy recommendations for standardised guidelines, informed decision making, and increased awareness to improve efficiency and effectiveness in early detection. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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Objective: To evaluate the feasibility of multivariable risk stratification for early prostate cancer (PCa) detection in a primary healthcare diagnostic facility with regard to its effects on the referral rate and subsequent PCa diagnoses compared to a PSA threshold of 3.0 ng/mL as the current referral indicator. Patients and Methods: In 2014, the Erasmus MC Cancer Institute and the primary healthcare diagnostic facility STAR‐SHL (located in Rotterdam city centre) initiated this observational study, in which general practitioners (GPs) could refer men who wished to undergo PCa screening to STAR‐SHL for consultation by specially trained personnel. Referral recommendations to secondary healthcare were based on the outcome of application of the Rotterdam Prostate Cancer Risk Calculator (RPCRC) and were compared to the current Dutch GPs' PSA referral threshold of 3.0 ng/mL. For data collection on PCa diagnoses, the study cohort was linked to the Dutch nationwide pathology databank (PALGA). Results: Between January 2014 and February 2021, 507 men were referred for consultation and in 495 men prostate‐specific antigen (PSA) was tested. The median (interquartile range) follow‐up from consultation to PALGA linkage was 43 (25–65) months. In total, 279 men (56%) had a PSA level ≥3.0 ng/mL, of whom 68% (95% confidence interval [95% CI] 63–74) were considered at low risk according to the RPCRC. Within 1 year after consultation, one of these men (0.52%; 95% CI 0.092–2.9) was diagnosed with clinically significant (cs)PCa (i.e., International Society of Urological Pathology Grade Group ≥2). Thereafter, another four (2.1%; 95% CI 0.82–5.3) low‐risk men were diagnosed with csPCa. Of the high‐risk men who were biopsied within 1 year after consultation (n = 61), 77% (95% CI 65–86) were diagnosed with PCa and 49% (95% CI 37–61) with csPCa. Conclusion: In a primary healthcare diagnostic facility, the RPCRC could reduce up to 68% of referrals to secondary healthcare, as compared to a PSA referral threshold of 3.0 ng/mL. Deploying the RPCRC in this setting resulted in a high csPCa detection rate in those men biopsied. This strategy can be considered safe since the observational data showed low proportions of csPCa among men at low risk. [ABSTRACT FROM AUTHOR]

In response to the rising incidence of indolent, low-risk prostate cancer (PCa) due to increased prostate-specific antigen (PSA) screening in the 1990s, active surveillance (AS) emerged as a treatment modality to combat overtreatment by delaying or avoiding unnecessary definitive treatment and its associated morbidity. AS consists of regular monitoring of PSA levels, digital rectal exams, medical imaging, and prostate biopsies, so that definitive treatment is only offered when deemed necessary. This paper provides a narrative review of the evolution of AS since its inception and an overview of its current landscape and challenges. Although AS was initially only performed in a study setting, numerous studies have provided evidence for the safety and efficacy of AS which has led guidelines to recommend it as a treatment option for patients with low-risk PCa. For intermediate-risk disease, AS appears to be a viable option for those with favourable clinical characteristics. Over the years, the inclusion criteria, follow-up schedule and triggers for definitive treatment have evolved based on the results of various large AS cohorts. Given the burdensome nature of repeat biopsies, risk-based dynamic monitoring may further reduce overtreatment by avoiding repeat biopsies in selected patients. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to externally validate the Rotterdam Prostate Cancer Risk Calculator (RPCRC)-3/4 and RPCRC-MRI within a Dutch clinical cohort. Methods: Men subjected to prostate biopsies, between 2018 and 2021, due to a clinical suspicion of prostate cancer (PCa) were retrospectively included. The performance of the RPCRC-3/4 and RPCRC-MRI was analyzed in terms of discrimination, calibration and net benefit. In addition, the need for recalibration and adjustment of risk thresholds for referral was investigated. Clinically significant (cs) PCa was defined as Gleason score ≥ 3 + 4. Results: A total of 1575 men were included in the analysis. PCa was diagnosed in 63.2% (996/1575) of men and csPCa in 41.7% (656/1575) of men. Use of the RPCRC-3/4 could have prevented 37.3% (587/1575) of all MRIs within this cohort, thereby missing 18.3% (120/656) of csPCa diagnoses. After recalibration and adjustment of risk thresholds to 20% for PCa and 10% for csPCa, use of the recalibrated RPCRC-3/4 could have prevented 15.1% (238/1575) of all MRIs, resulting in 5.3% (35/656) of csPCa diagnoses being missed. The performance of the RPCRC-MRI was good; use of this risk calculator could have prevented 10.7% (169/1575) of all biopsies, resulting in 1.2% (8/656) of csPCa diagnoses being missed. Conclusion: The RPCRC-3/4 underestimates the probability of having csPCa within this Dutch clinical cohort, resulting in significant numbers of csPCa diagnoses being missed. For optimal performance of a risk calculator in a specific cohort, evaluation of its performance within the population under study is essential. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the impact of intra‐operative neurovascular structure‐adjacent frozen‐section examination (NeuroSAFE) on the rate of nerve‐sparing surgery (NSS) and oncological outcome in a large radical prostatectomy (RP) cohort. Patients and methods: Between January 2016 and December 2020, 1756 prostate cancer patients underwent robot‐assisted RP, of whom 959 (55%) underwent this with NeuroSAFE and 797 (45%) without (control cohort). In cases where NeuroSAFE showed tumour in the margin, a secondary resection was performed. The effect of NeuroSAFE on NSS and positive surgical margin (PSM) status was analysed using logistic regression. Cox regression was used to identify predictors of biochemical recurrence‐free survival (BCRFS). Results and limitations: Patients in the NeuroSAFE cohort had a higher tumour grade (P < 0.001) and clinical stage (P < 0.001) than those in the control cohort. NeuroSAFE enabled more frequent NSS for both pT2 (93% vs 76%; P < 0.001) and pT3 disease (83% vs 55%; P < 0.001). In adjusted analysis, NeuroSAFE resulted in more frequent unilateral (odds ratio [OR] 3.90, 95% confidence interval (CI) 2.90–5.30; P < 0.001) and bilateral (OR 5.22, 95% CI 3.90–6.98; P < 0.001) NSS. While the PSM rate decreased from 51% to 42% in patients with pT3 stage disease (P = 0.031), NeuroSAFE was not an independent predictor of PSM status (OR 0.85, 95% CI 0.68–1.06; P = 0.2) in the entire cohort. Patients who underwent NeuroSAFE had better BCRFS compared to the control cohort (hazard ratio 0.62, 95% CI 0.45–0.84; P = 0.002). This study is limited by its comparison with a historical cohort and lack of functional outcomes. Conclusions: NeuroSAFE enables more unilateral and bilateral NSS without negatively affecting surgical margin status and biochemical recurrence. This validation study provides a comprehensive overview of the implementation, evaluation and intra‐operative decision making associated with NeuroSAFE in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Men diagnosed with localized prostate cancer (PCa) on active surveillance (AS) have shown to cope with anxiety caused by living with an 'untreated cancer' and different factors can influence the tolerance level for anxiety in these patients. The present study analyzes Italian (Milan) and Dutch (Rotterdam) men prospectively included in the Prostate cancer International Active Surveillance (PRIAS) trial, aiming to explore whether socio-demographic factors (i.e. age, relationship status, education, nationality) may be relevant factors in conditioning the level of anxiety at AS entry and over time.Methods: Italian and Dutch men participating in the IRB-approved PRIAS study, after signing an informed consent, filled in the Memorial Anxiety Scale for PCa (MAX-PC) at multiple time points after diagnosis. A linear mixed model was used to assess the relationship between the level of patient's anxiety and time spent on AS, country of origin, the interaction between country and time on AS, patients' relationship status and education, on PCa anxiety during AS.Results: 823 MAX-PC questionnaires were available for Italian and 307 for Dutch men, respectively. Median age at diagnosis was 64 years (IQR 60-70 years) and did not differ between countries. On average, Dutch men had a higher total MAX-PC score than Italian men. However, the level of their anxiety decreased over time. Dutch men on average had a higher score on the PCa anxiety sub-domain, which did not decrease over time. Minimal differences were observed in the sub-domains PSA anxiety and fear of recurrence.Conclusion: Significant differences in PCa anxiety between the Italian and Dutch cohorts were observed, the latter group of men showing higher overall levels of anxiety. These differences were not related to the socio-demographic factors we studied. Although both PRIAS-centers are dedicated AS-centers, differences in PCa-care organization (e.g. having a multidisciplinary team) may have contributed to the observed different level of anxiety at the start and during AS. Trial registration This study is registered in the Dutch Trial Registry ( www.trialregister.nl ) under NL1622 (registration date 11-03-2009), 'PRIAS: Prostate cancer Research International: Active Surveillance-guideline and study for the expectant management of localized prostate cancer with curative intent'. [ABSTRACT FROM AUTHOR]

Aims: Invasive cribriform and intraductal carcinoma (IDC) are associated with adverse outcome in prostate cancer patients, with the large cribriform pattern having the worst outcome in radical prostatectomies. Our objective was to determine the impact of the large and small cribriform patterns in prostate cancer biopsies. Methods and results: Pathological revision was carried out on biopsies of 1887 patients from the European Randomised Study of Screening for Prostate Cancer. The large cribriform pattern was defined as having at least twice the size of adjacent benign glands. The median follow‐up time was 13.4 years. Hazard ratios for metastasis‐free survival (MFS) and disease‐specific survival (DSS) were calculated using Cox proportional hazards regression. Any cribriform pattern was found in 280 of 1887 men: 1.1% IDC in grade group (GG) 1, 18.2% in GG2, 57.1% in GG3, 55.4% in GG4 and 59.3% in GG5; the large cribriform pattern was present in 0, 0.5, 9.8, 18.1 and 17.3%, respectively. In multivariable analyses, small and large cribriform patterns were both (P < 0.005) associated with worse MFS [small: hazard ratio (HR) = 3.04, 95% confidence interval (CI) = 1.93–4.78; large: HR = 3.17, 95% CI = 1.68–5.99] and DSS (small: HR = 4.07, 95% CI = 2.51–6.62; large: HR = 4.13, 95% CI = 2.14–7.98). Patients with the large cribriform pattern did not have worse MFS (P = 0.77) or DSS (P = 0.96) than those with the small cribriform pattern. Conclusions: Both small and large cribriform patterns are associated with worse MFS and DSS in prostate cancer biopsies. Patients with the large cribriform pattern on biopsy have a similar adverse outcome as those with the small cribriform pattern. [ABSTRACT FROM AUTHOR]

Benchmark surveillance tests for detecting disease progression (eg, biopsies, endoscopies) in early‐stage chronic noncommunicable diseases (eg, cancer, lung diseases) are usually burdensome. For detecting progression timely, patients undergo invasive tests planned in a fixed one‐size‐fits‐all manner (eg, annually). We aim to present personalized test schedules based on the risk of disease progression, that optimize the burden (the number of tests) and the benefit (shorter time delay in detecting progression is better) better than fixed schedules, and enable shared decision making. Our motivation comes from the problem of scheduling biopsies in prostate cancer surveillance. Using joint models for time‐to‐event and longitudinal data, we consolidate patients' longitudinal data (eg, biomarkers) and results of previous tests, into individualized future cumulative‐risk of progression. We then create personalized schedules by planning tests on future visits where the predicted cumulative‐risk is above a threshold (eg, 5% risk). We update personalized schedules with data gathered over follow‐up. To find the optimal risk threshold, we minimize a utility function of the expected number of tests (burden) and expected time delay in detecting progression (shorter is beneficial) for different thresholds. We estimate these two in a patient‐specific manner for following any schedule, by utilizing a patient's predicted risk profile. Patients/doctors can employ these quantities to compare personalized and fixed schedules objectively and make a shared decision of a test schedule. [ABSTRACT FROM AUTHOR]

Introduction: Treatment choice for localized prostate cancer is complicated, as each treatment option comes with various pros and cons. It is well established that active surveillance (AS), may be ended with a change to curative treatment at the time of disease progression, but it is less clear whether secondary treatment after initial curative treatment is required. As part of the PIONEER project, we quantified the probabilities of treatment change. Methods: A cohort study based on PRIAS and ERSPC-Rotterdam data was conducted. Patients were followed up for 10 years or until the 31st of December 2017. The primary outcome was the incidence of treatment change following initial treatment (i.e., a change to curative treatment following AS or secondary treatment after initial RP/RT). Results: Over a period of 1 to 5 years after initial treatment, the cumulative incidence of treatment change ranged from 3.8% to 42.8% for AS, from 7.6% to 12.1% for radical prostatectomy (RP) and from no change to 5.3% for radiation therapy (RT). While the possibility of treatment change in AS is known, the numbers within a five-year period were substantial. For RP and RT, the rate of change to secondary treatment was lower, but still non-neglectable, with 5 (10)-year incidences up to 12% (20%) and 5% (16%), respectively. Conclusion: This is one of the first studies comparing the incidence of guideline-recommended treatment changes in men receiving different primary treatments (i.e., AS, RT, or RP) for localized prostate cancer (PCa). [ABSTRACT FROM AUTHOR]

Aims: Gleason pattern 4 (GP4) percentage, invasive cribriform and/or intraductal carcinoma (IC/IDC) and the presence of tertiary Gleason pattern 5 (TP5) in radical prostatectomy (RP) specimens all aid in the risk stratification of Grade Group (GG) 2 prostate cancer patients. However, it is unclear to what extent these pathological features are mutually related and what are their individual values if they are investigated simultaneously. The aims of this study were: (i) to determine the mutual relationships of the GP4 percentage, IC/IDC and TP5 in GG2 RP specimens; and (ii) to assess their prognostic value for biochemical recurrence‐free survival (BCRFS). Methods and results: Of 1064 RP specimens, 472 (44.4%) showed GG2 prostate cancer. Patients with ≥25% GP4 more frequently had IC/IDC (67.0% versus 43.9%; P < 0.001) and TP5 (20.6% versus 5.8%; P < 0.001) than those with <25% GP4. In unadjusted analysis, an increased GP4 percentage [hazard ratio (HR) 1.3; 95% confidence interval (CI) 1.0–1.6; P = 0.04] and IC/IDC (log rank P < 0.001) were associated with shorter BCRFS, whereas TP5 (P = 0.12) and a dichotomised (<25%, ≥25%) GP4 percentage (P = 0.10) were not. In multivariable analysis, IC/IDC was an independent prognostic factor (HR 1.9; 95% CI 1.2–2.9; P = 0.005) for BCRFS, whereas a continuous or dichotomised GP4 percentage and TP5 were not independent prognostic factors. Conclusion: In conclusion, a higher GP4 percentage in RP specimens was associated with more frequent IC/IDC and TP5. IC/IDC was an independent predictor for BCRFS, whereas the GP4 percentage and TP5 were not. These findings underscore the importance of routinely including the presence of IC/IDC in RP pathology reports. [ABSTRACT FROM AUTHOR]

Background: Urinary incontinence is a prevalent form of pelvic floor dysfunction, with a non-negligible impact on a patient's quality of life. There are several treatment options, varying from conservative to invasive. The aim of this study is to predict treatment outcomes of pure or predominant urge urinary incontinence (UUI) in women to support shared decision-making and manage patient expectations. Methods: Data on patient characteristics, disease history, and investigations of 512 consecutive women treated for UUI in three hospitals in the Netherlands were retrospectively collected. The predicted outcome was the short-term subjective continence outcome, defined as patient-reported continence 3 months after treatment categorized as cure (no urinary leakage), improvement (any degree of improvement of urinary leakage), and failure (no improvement or worsening of urinary leakage). Multivariable ordinal regression with backward stepwise selection was performed to analyze association between outcome and patient's characteristics. Interactions between patient characteristics and treatment were added to estimate individual treatment benefit. Discriminative ability was assessed with the ordinal c-statistic. Results: Conservative treatment was applied in 12% of the patients, pharmacological in 62%, and invasive in 26%. Subjective continence outcome was cure, improvement, and failure in 20%, 49%, and 31%, respectively. Number of incontinence episodes per day, voiding frequency during the day, subjective quantity of UI, coexistence of stress urinary incontinence (SUI), night incontinence, and bladder capacity and the interactions between these variables were included in the model. After internal validation, the ordinal c-statistic was 0.699. Conclusions: Six variables were of value to predict pure or predominant UUI treatment outcome in women. Further development into a comprehensive set of models for the use in various pelvic floor disorders and treatments is recommended to optimize individualized care. This model requires external validation before implementation in clinical practice. [ABSTRACT FROM AUTHOR]

International guidelines recommend to inform men about the benefits and harms of prostate specific antigen (PSA) based early detection of prostate cancer. This study investigates the influence of a transactional decision aid (DA) or cost compensation (CC) for a PSA test on the decisional behaviour of men. Prospective, cluster-randomised trial to compare two interventions in a 2 × 2 factorial design: DA versus counselling as usual, and CC versus noCC for PSA-testing. 90 cluster-randomised physicians in the administrative district of Muenster, Germany recruited 962 participants aged 55–69 yrs. in 2018. Primary endpoint: the influence of the DA and CC on the decisional conflict. Secondary endpoints: factors which altered the involvement of the men regarding their decision to take a PSA-test. The primary endpoint was analysed by a multivariate regression model. The choice to take the PSA test was increased by CC and reduced by the DA, the latter also reduced PSA uptake in men who were offered CC. The DA led to an increase of the median knowledge about early detection, changed willingness to perform a PSA test without increasing the level of shared decision, giving participants a stronger feeling of having made the decision by themselves. The DA did not alter the decisional conflict, as it was very low in all study groups. DA reduced and CC increased the PSA uptake. The DA seemed to have a greater impact on the participants than CC, as it led to fewer PSA tests even if CC was granted. Trial registration: German Clinical Trial Register (Deutsches Register Klinischer Studien DRKS00007687). Registered: 06/05/2015. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00007687. [ABSTRACT FROM AUTHOR]

Objective: To externally validate and compare the performance of the European Randomized Study of Screening for Prostate Cancer risk calculator 3/4 (ERSPC‐RC3/4), the Prostate Biopsy Collaborative Group risk calculator (PBCG‐RC) and the van Leeuwen model to determine which prediction model would perform the best in a contemporary Australian cohort undergoing transperineal (TP) biopsy. Materials and Methods: A retrospective review identified all patients undergoing TP biopsy across two centres. Of the 797 patients identified, 373 had the data required to test all three risk calculators. The probability of high‐grade prostate cancer, defined as International Society of Urological Pathology Grade Group >1, was calculated for each patient. For each prediction model discrimination was assessed using area under the receiver‐operating characteristic curve (AUC), calibration using numerical and graphical summaries, and net benefit using decision curve analysis. Results: Assessment of model discrimination for detecting high‐grade prostate cancer showed AUCs of 0.79 (95% confidence interval [CI] 0.74–0.84) for the ERSPC‐RC3/4, 0.81 (95% CI 0.77–0.86) for the van Leeuwen model, and 0.68 (95% CI 0.63–0.74) for the PBCG‐RC, compared to 0.58 (95% CI 0.52–0.65) for prostate‐specific antigen alone. The ERSPC‐RC3/4 was the best calibrated in the moderate‐risk range of 10–40%, whilst the van Leeuwen model was the best calibrated in the low‐risk range of 0–10%. The van Leeuwen model demonstrated the greatest net benefit from 10% risk onwards, followed closely by the ERSPC‐RC3/4 and then the PBCG‐RC. Conclusion: The ERPSC‐RC3/4 demonstrated good performance and was comparable to the van Leeuwen model with regard to discrimination, calibration and net benefit for an Australian population undergoing TP prostate biopsy. It is one of the most accessible risk calculators with an easy‐to‐use online platform, therefore, we recommend that Australian urologists use the ERSPC‐RC3/4 to predict risk in the clinical setting. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the health-related quality of life (HRQoL) of Japanese men on active surveillance (AS) in the Prostate cancer Research International Active Surveillance study in Japan (PRIAS-JAPAN). Methods: Participants were included in the PRIAS-JAPAN HRQoL study between January 2010 and March 2016. Their general HRQoL was assessed using a validated Japanese version of the Short-Form 8 Health Survey (SF-8) at enrolment and annually thereafter until discontinuation of AS. The SF-8 mental component summary (MCS) and physical component summary (PCS) of men on AS were compared with scores of the general population (norm-based score [NBS]: 50) and MCS and PCS scores for men following AS were analysed over time. We tested whether MCS and PCS scores over time explained discontinuation of AS. Results: Five hundred and twenty-five patients enrolled, and the median age at baseline was 68 years. At enrolment and after 1-, 2-, and 3-year follow-ups, the PCS and MCS scores were significantly higher than the NBS of the general Japanese population except for the median PCS at 3 years. We found that age at diagnosis and time on AS negatively affected the PCS score of men on AS, while every additional year on AS led to a 0.27 point increase in MCS scores. Neither PCS nor MCS were predictors for discontinuation of AS. Conclusion: Japanese men following an AS strategy for 3 years reported better HRQoL compared with the general population, indicating that monitoring Japanese low-risk prostate cancer patients can be an effective treatment strategy. Study registration: Clinical trial registry—UMIN (University Hospital Medical Information Network); UMIN000002874 (2009/12/11) [ABSTRACT FROM AUTHOR]

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Purpose: To externally validate the clinical utility of Chinese Prostate Cancer Consortium Risk Calculator (CPCC-RC) and Asian adapted Rotterdam European Randomized Study of Screening for Prostate Cancer Risk Calculator 3 (A-ERSPC-RC3) for prediction prostate cancer (PCa) and high-grade prostate cancer (HGPCa, Gleason Score ≥ 3 + 4) in both Chinese and European populations. Materials and methods: The Chinese clinical cohort, the European population-based screening cohort, and the European clinical cohort included 2,508, 3,616 and 617 prostate biopsy-naive men, respectively. The area under the receiver operating characteristic curve (AUC), calibration plot and decision curve analyses were applied in the analysis. Results: The CPCC-RC's predictive ability for any PCa (AUC 0.77, 95% CI 0.75–0.79) was lower than the A-ERSPC-RC3 (AUC 0.79, 95% CI 0.77–0.81) in the European screening cohort (p < 0.001), but similar for HGPCa (p = 0.24). The CPCC-RC showed lower predictive accuracy for any PCa (AUC 0.65, 95% CI 0.61–0.70), but acceptable predictive accuracy for HGPCa (AUC 0.73, 95% CI 0.69–0.77) in the European clinical cohort. The A-ERSPC-RC3 showed an AUC of 0.74 (95% CI 0.72–0.76) in predicting any PCa, and a similar AUC of 0.74 (95% CI 0.72–0.76) in predicting HGPCa in Chinese cohort. In the Chinese population, decision curve analysis revealed a higher net benefit for CPCC-RC than A-ERSPC-RC3, while in the European screening and clinical cohorts, the net benefit was higher for A-ERSPC-RC3. Conclusions: The A-ERSPC-RC3 accurately predict the prostate biopsy in a contemporary Chinese multi-center clinical cohort. The CPCC-RC can predict accurately in a population-based screening cohort, but not in the European clinical cohort. [ABSTRACT FROM AUTHOR]

Objective: To develop a model and methodology for predicting the risk of Gleason upgrading in patients with prostate cancer on active surveillance (AS) and using the predicted risks to create risk‐based personalised biopsy schedules as an alternative to one‐size‐fits‐all schedules (e.g. annually). Furthermore, to assist patients and doctors in making shared decisions on biopsy schedules, by providing them quantitative estimates of the burden and benefit of opting for personalised vs any other schedule in AS. Lastly, to externally validate our model and implement it along with personalised schedules in a ready to use web‐application. Patients and Methods: Repeat prostate‐specific antigen (PSA) measurements, timing and results of previous biopsies, and age at baseline from the world's largest AS study, Prostate Cancer Research International Active Surveillance (PRIAS; 7813 patients, 1134 experienced upgrading). We fitted a Bayesian joint model for time‐to‐event and longitudinal data to this dataset. We then validated our model externally in the largest six AS cohorts of the Movember Foundation's third Global Action Plan (GAP3) database (>20 000 patients, 27 centres worldwide). Using the model predicted upgrading risks; we scheduled biopsies whenever a patient's upgrading risk was above a certain threshold. To assist patients/doctors in the choice of this threshold, and to compare the resulting personalised schedule with currently practiced schedules, along with the timing and the total number of biopsies (burden) planned, for each schedule we provided them with the time delay expected in detecting upgrading (shorter is better). Results: The cause‐specific cumulative upgrading risk at the 5‐year follow‐up was 35% in PRIAS, and at most 50% in the GAP3 cohorts. In the PRIAS‐based model, PSA velocity was a stronger predictor of upgrading (hazard ratio [HR] 2.47, 95% confidence interval [CI] 1.93–2.99) than the PSA level (HR 0.99, 95% CI 0.89–1.11). Our model had a moderate area under the receiver operating characteristic curve (0.6–0.7) in the validation cohorts. The prediction error was moderate (0.1–0.2) in theGAP3 cohorts where the impact of the PSA level and velocity on upgrading risk was similar to PRIAS, but large (0.2–0.3) otherwise. Our model required re‐calibration of baseline upgrading risk in the validation cohorts. We implemented the validated models and the methodology for personalised schedules in a web‐application (http://tiny.cc/biopsy). Conclusions: We successfully developed and validated a model for predicting upgrading risk, and providing risk‐based personalised biopsy decisions in AS of prostate cancer. Personalised prostate biopsies are a novel alternative to fixed one‐size‐fits‐all schedules, which may help to reduce unnecessary prostate biopsies, while maintaining cancer control. The model and schedules made available via a web‐application enable shared decision‐making on biopsy schedules by comparing fixed and personalised schedules on total biopsies and expected time delay in detecting upgrading. [ABSTRACT FROM AUTHOR]

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This study aimed to estimate the rates of biopsy undersampling and progression for four prostate cancer (PCa) active surveillance (AS) cohorts within the Movember Foundation's Global Action Plan Prostate Cancer Active Surveillance (GAP3) consortium. We used a hidden Markov model (HMM) to estimate factors that define PCa dynamics for men on AS including biopsy under‐sampling and progression that are implied by longitudinal data in four large cohorts included in the GAP3 database. The HMM was subsequently used as the basis for a simulation model to evaluate the biopsy strategies previously proposed for each of these cohorts. For the four AS cohorts, the estimated annual progression rate was between 6%–13%. The estimated probability of a biopsy successfully sampling undiagnosed non‐favorable risk cancer (biopsy sensitivity) was between 71% and 80%. In the simulation study of patients diagnosed with favorable risk cancer at age 50, the mean number of biopsies performed before age 75 was between 4.11 and 12.60, depending on the biopsy strategy. The mean delay time to detection of non‐favorable risk cancer was between 0.38 and 2.17 years. Biopsy undersampling and progression varied considerably across study cohorts. There was no single best biopsy protocol that is optimal for all cohorts, because of the variation in biopsy under‐sampling error and annual progression rates across cohorts. All strategies demonstrated diminishing benefits from additional biopsies. [ABSTRACT FROM AUTHOR]

This review discusses evidence for population‐based screening with contemporary screening tools. In Europe, prostate‐specific antigen (PSA)‐based screening led to a relative reduction of prostate cancer (PCa) mortality, but also to a substantial amount of overdiagnosis and unnecessarily biopsies. Risk stratification based on a single variable (a clinical variable or based on the presence of a lesion on prostate imaging) or based on multivariable approaches can aid in reducing unnecessary prostate biopsies and overdiagnosis by selecting men who can benefit from further clinical assessment. Multivariable approaches include clinical variables, and biomarkers, often combined in risk calculators or nomograms. These risk calculators can also incorporate the result of MRI imaging. In general, as compared to a purely PSA based approach, the combination of relevant prebiopsy information results in superior selection of men at higher risk of harboring clinically significant prostate cancer. Currently, it is not possible to draw any conclusions on the superiority of these multivariable risk‐based approaches since head‐to‐head comparisons are virtually lacking. Recently initiated large population‐based screening studies in Finland, Germany and Sweden, incorporating various multivariable risk stratification approaches will hopefully give more insight in whether the harm‐benefit ratio can be improved, that is, maintain (or improving) the ability to reduce metastatic disease and prostate cancer mortality while reducing harm caused by unnecessary testing and overdiagnosis including related overtreatment. [ABSTRACT FROM AUTHOR]

Objectives: To develop an automatic method for identification and segmentation of clinically significant prostate cancer in low-risk patients and to evaluate the performance in a routine clinical setting. Methods: A consecutive cohort (n = 292) from a prospective database of low-risk patients eligible for the active surveillance was selected. A 3-T multi-parametric MRI at 3 months after inclusion was performed. Histopathology from biopsies was used as reference standard. MRI positivity was defined as PI-RADS score ≥ 3, histopathology positivity was defined as ISUP grade ≥ 2. The selected cohort contained four patient groups: (1) MRI-positive targeted biopsy-positive (n = 116), (2) MRI-negative systematic biopsy-negative (n = 55), (3) MRI-positive targeted biopsy-negative (n = 113), (4) MRI-negative systematic biopsy-positive (n = 8). Group 1 was further divided into three sets and a 3D convolutional neural network was trained using different combinations of these sets. Two MRI sequences (T2w, b = 800 DWI) and the ADC map were used as separate input channels for the model. After training, the model was evaluated on the remaining group 1 patients together with the patients of groups 2 and 3 to identify and segment clinically significant prostate cancer. Results: The average sensitivity achieved was 82–92% at an average specificity of 43–76% with an area under the curve (AUC) of 0.65 to 0.89 for different lesion volumes ranging from > 0.03 to > 0.5 cc. Conclusions: The proposed deep learning computer-aided method yields promising results in identification and segmentation of clinically significant prostate cancer and in confirming low-risk cancer (ISUP grade ≤ 1) in patients on active surveillance. Key Points: • Clinically significant prostate cancer identification and segmentation on multi-parametric MRI is feasible in low-risk patients using a deep neural network. • The deep neural network for significant prostate cancer localization performs better for lesions with larger volumes sizes (> 0.5 cc) as compared to small lesions (> 0.03 cc). • For the evaluation of automatic prostate cancer segmentation methods in the active surveillance cohort, the large discordance group (MRI positive, targeted biopsy negative) should be included. [ABSTRACT FROM AUTHOR]

Aims: Intraductal carcinoma (IDC) is an adverse histopathological parameter for prostate cancer outcome, but is not incorporated in current tumour grading. To account for its dismal prognosis and to omit basal cell immunohistochemistry, it has been proposed to grade IDC on the basis of its underlying architectural pattern. The aim of this study was to determine the impact of IDC grade assignment on prostate cancer biopsy and radical prostatectomy tumour grading. Methods and results: A cohort of 1031 prostate cancer biopsies and 835 radical prostatectomies were assigned a Grade Group according to the 2014 International Society of Urological Pathology guidelines, without incorporation of IDC in grading. Tumour grading was compared with a Grade Group in which IDC was graded on the basis of its underlying architecture. Of 1031 biopsies, 139 (13.5%) showed IDC. Grade assignment of IDC led to a Grade Group change in 17 (1.6%) cases: four of 486 (0.8%) Grade Group 1 cases were reclassified as Grade Group 2, nine of 375 (2.4%) Grade Group 2 cases were reclassified as Grade Group 3, and four of 58 (6.9%) Grade Group 4 cases were reclassified as Grade Group 5. IDC was observed in 213 of 835 (25.5%) radical prostatectomies, and its grading led to a change in tumour grade in five of 835 (0.6%) patients, with upgrading in two of 207 (1.0%) patients with Grade Group 1 cancer, in two of 420 (0.5%) patients with Grade Group 2 cancer, and in one of 50 (2%) patients with Grade Group 4 cancer. Conclusion: IDC grade assignment led to a Grade Group change in 1.6% of prostate biopsy specimens and in 0.6% of radical prostatectomy specimens. Although the inclusion of IDC in or the exclusion of IDC from the Grade Group might affect decision‐making in individual patients, it has a minimal impact on overall prostate cancer management. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer screening incurs a high risk of overdiagnosis and overtreatment. An organized and age‐targeted screening strategy may reduce the associated harms while retaining or enhancing the benefits. Methods: Using a micro‐simulation analysis (MISCAN) model, we assessed the harms, benefits, and cost‐effectiveness of 230 prostate‐specific antigen (PSA) screening strategies in a Dutch population. Screening strategies were varied by screening start age (50, 51, 52, 53, 54, and 55), stop age (51‐69), and intervals (1, 2, 3, 4, 8, and single test). Costs and effects of each screening strategy were compared with a no‐screening scenario. Results: The most optimum strategy would be screening with 3‐year intervals at ages 55–64 resulting in an incremental cost‐effectiveness ratio (ICER) of €19 733 per QALY. This strategy predicted a 27% prostate cancer mortality reduction and 28 life years gained (LYG) per 1000 men; 36% of screen‐detected men were overdiagnosed. Sensitivity analyses did not substantially alter the optimal screening strategy. Conclusions: PSA screening beyond age 64 is not cost‐effective and associated with a higher risk of overdiagnosis. Similarly, starting screening before age 55 is not a favored strategy based on our cost‐effectiveness analysis. [ABSTRACT FROM AUTHOR]

Aims: Radical prostatectomy for prostate cancer is frequently complicated by urinary incontinence and erectile dysfunction. Nerve‐sparing surgery reduces the risk of postoperative complications and can be optimised by the use of intraoperative frozen sections of the adjacent neurovascular structure (NeuroSAFE). The aims of this study were to evaluate the pathological outcomes of the NeuroSAFE technique and to develop a comprehensive algorithm for intraoperative clinical decision‐making. Methods and results: Between September 2018 and May 2019, 491 NeuroSAFE procedures were performed in 258 patients undergoing radical prostatectomy; 74 of 491 (15.1%) NeuroSAFE specimens had positive surgical margins. As compared with the corresponding paraffin sections, NeuroSAFE had a positive predictive value and negative predictive value of 85.1% and 95.4%, respectively. In 72.2% of secondary neurovascular bundle resections prompted by a NeuroSAFE positive surgical margin, no tumour was present. These cases more often had a positive surgical margin of ≤1 mm (48.7% versus 20.0%; P = 0.001) and only one positive slide (69.2% versus 33.3%; P = 0.008). None of the nine patients with Gleason pattern 3 at the surgical margin, a positive surgical margin length of ≤1 mm and one positive slide had tumour in the secondary resection. Conclusions: This study provides a systematic reporting template for pathological intraoperative NeuroSAFE evaluation, supporting intraoperative clinical decision‐making and comparison between prostate cancer operation centres. [ABSTRACT FROM AUTHOR]

It remains elusive whether some of the associations identified in genome-wide association studies of prostate cancer (PrCa) may be due to regulatory effects of genetic variants on CpG sites, which may further influence expression of PrCa target genes. To search for CpG sites associated with PrCa risk, here we establish genetic models to predict methylation (N = 1,595) and conduct association analyses with PrCa risk (79,194 cases and 61,112 controls). We identify 759 CpG sites showing an association, including 15 located at novel loci. Among those 759 CpG sites, methylation of 42 is associated with expression of 28 adjacent genes. Among 22 genes, 18 show an association with PrCa risk. Overall, 25 CpG sites show consistent association directions for the methylation-gene expression-PrCa pathway. We identify DNA methylation biomarkers associated with PrCa, and our findings suggest that specific CpG sites may influence PrCa via regulating expression of candidate PrCa target genes. Genome wide association studies have identified multiple loci associated with risk of developing prostate cancer but the functional significance of many of these are unknown. Here, after generating models to predict methylation, the authors identify CpG methylation sites associated with prostate cancer. [ABSTRACT FROM AUTHOR]

Objectives: To investigate whether serial prostate magnetic resonance imaging (MRI) may guide the utility of repeat targeted (TBx) and systematic biopsy (SBx) when monitoring men with low‐risk prostate cancer (PCa) at 1‐year of active surveillance (AS). Patients and Methods: We retrospectively included 111 consecutive men with low‐risk (International Society of Urological Pathology [ISUP] Grade 1) PCa, who received protocolled repeat MRI with or without TBx and repeat SBx at 1‐year of AS. TBx was performed in Prostate Imaging‐Reporting and Data System (PI‐RADS) score ≥3 lesions (MRI‐positive men). Upgrading defined as ISUP Grade ≥2 PCa (I), Grade ≥2 with cribriform growth/intraductal carcinoma PCa (II), and Grade ≥3 PCa (III) was investigated. Upgrading detected by TBx only (not by SBx) and SBx only (not by TBx) was investigated in MRI‐positive and ‐negative men, and related to radiological progression on MRI (Prostate Cancer Radiological Estimation of Change in Sequential Evaluation [PRECISE] score). Results: Overall upgrading (I) was 32% (35/111). Upgrading in MRI‐positive and ‐negative men was 48% (30/63) and 10% (5/48) (P < 0.001), respectively. In MRI‐positive men, there was upgrading in 23% (seven of 30) by TBx only and in 33% (10/30) by SBx only. Radiological progression (PRECISE score 4–5) in MRI‐positive men was seen in 27% (17/63). Upgrading (I) occurred in 41% (seven of 17) of these MRI‐positive men, while this was 50% (23/46) in MRI‐positive men without radiological progression (PRECISE score 1–3) (P = 0.534). Overall upgrading (II) was 15% (17/111). Upgrading in MRI‐positive and ‐negative men was 22% (14/63) and 6% (three of 48) (P = 0.021), respectively. In MRI‐positive men, there was upgrading in three of 14 by TBx only and in seven of 14 by SBx only. Overall upgrading (III) occurred in 5% (five of 111). Upgrading in MRI‐positive and ‐negative men was 6% (four of 63) and 2% (one of 48) (P = 0.283), respectively. In MRI‐positive men, there was upgrading in one of four by TBx only and in two of four by SBx only. Conclusion: Upgrading is significantly lower in MRI‐negative compared to MRI‐positive men with low‐risk PCa at 1‐year of AS. In serial MRI‐negative men, the added value of repeat SBx at 1‐year surveillance is limited and should be balanced individually against the harms. In serial MRI‐positive men, the added value of repeat SBx is substantial. Based on this cohort, SBx is recommended to be performed in combination with TBx in all MRI‐positive men at 1‐year of AS, also when there is no radiological progression. [ABSTRACT FROM AUTHOR]

Objectives: To examine the anatomical distribution of prostate cancer (PCa) recurrence on gallium‐68 prostate‐specific membrane antigen (68Ga‐PSMA) positron‐emission tomography (PET)/computed tomography (CT) in patients with biochemical recurrence (BCR) after undergoing radical prostatectomy (RP) with pathological lymph node metastasis (pN1) in their extended pelvic lymph node dissection (ePLND), and to compare the location of PCa recurrence with the location of the initial lymph node metastasis at ePLND. Materials and Methods: We retrospectively reviewed 100 patients with BCR (PSA 0.05–5.00 ng/mL) after RP with pN1 ePLND who underwent 68Ga‐PSMA PET/CT to guide salvage therapy. Clinical and pathological features and anatomical locations of PCa recurrence on 68Ga‐PSMA PET/CT were obtained, and management impact was recorded. Results: In all, 68 patients (68%) had a positive and 32 patients (32%) had a negative 68Ga‐PSMA PET/CT result. Of the 68 patients with a positive 68Ga‐PSMA PET/CT, 44 (65%) showed abnormal uptake only in the pelvic area, seven (10%) only outside the pelvic area, and 17 (25%) both within and outside the pelvic area. 68Ga‐PSMA PET/CT‐positive pelvic lymph nodes were often (84%) detected on the same side as the lymph node metastasis diagnosed at ePLND. Based on the outcomes of the 68Ga‐PSMA PET/CT, change of management was noted in 68% of the patients. Conclusion: Recurrence of PCa on 68Ga‐PSMA PET/CT was limited to the pelvis in the majority of patients with BCR after RP with pN1 ePLND. Moreover, recurrence was often detected on the same side as the lymph node metastasis at ePLND. The results confirm the diagnostic value of 68Ga‐PSMA PET/CT in patients with BCR after RP with pN1 ePLND. Prospective studies are needed to support the long‐term benefit of 68Ga‐PSMA PET/CT‐dictated management changes. [ABSTRACT FROM AUTHOR]

Aims: Invasive cribriform and intraductal carcinoma are associated with aggressive disease in Grade Group 2 (GG2) prostate cancer patients. However, the characteristics and clinical outcome of patients with GG2 prostate cancer without cribriform architecture (GG2−) as compared with those with Grade Group 1 (GG1) prostate cancer are unknown. The aim of this study was to investigate the clinical and pathological characteristics of GG1 and GG2− prostate cancer in radical prostatectomy specimens. Methods and results: We reviewed 835 radical prostatectomy specimens for Grade Group, pT stage, surgical margin status, and the presence of cribriform architecture. Biochemical recurrence‐free survival and metastasis were used as clinical outcomes. GG1 prostate cancer was seen in 207 patients, and GG2 prostate cancer was seen in 420 patients, of whom 228 (54%) showed cribriform architecture (GG2+) and 192 (46%) did not. GG2− patients had higher prostate‐specific antigen levels (9.4 ng/ml versus 7.0 ng/ml; P < 0.001), more often had extraprostatic extension (36% versus 11%; P < 0.001) and had more positive surgical margins (27% versus 17%; P = 0.01) than GG1 patients. GG2− patients had shorter biochemical recurrence‐free survival (hazard ratio 2.7, 95% confidence interval 1.4–4.9; P = 0.002) than GG1 patients. Lymph node and distant metastasis were observed neither in GG2− nor in GG1 patients, but occurred in 22 of 228 (10%) GG2+ patients. Conclusion: In conclusion, patients with GG2− prostate cancer at radical prostatectomy have more advanced disease and shorter biochemical recurrence‐free survival than those with GG1 prostate cancer, but both groups have a very low risk of developing metastasis. [ABSTRACT FROM AUTHOR]

Background and purpose: Individualized risk-adapted algorithms in prostate cancer (PCa) diagnosis using predictive prebiopsy variables in addition to prostate-specific antigen value may result in a considerable reduction of unnecessary systematic biopsies. Multi-parametric magnetic resonance imaging (mpMRI) has emerged as a secondary prediction tool that can further improve the detection of clinically significant prostate cancer (csPCa). This review explores the performance of new MRI risk models for indicating a biopsy for prostate cancer diagnosis. Results and considerations: The area under the receiver-operating characteristic curve for detecting csPCa varies between 0.64 and 0.91 in biopsy-naïve men, and between 0.78 and 0.93 in men with a previous negative biopsy. The utility of multivariate risk prediction tools including MRI suspicion scores as an extra input parameter has the potential to avoid a notable number of biopsies and detection of clinically insignificant PCa at a low price of missing some csPCa. The trade-off depends on the risk threshold that is chosen. In biopsy-naïve men a net benefit was obtained at a risk threshold of above 10% for csPCa in most MRI risk prediction models. All constructed MRI risk models used (referral) patient cohorts with high prevalence of csPCa. Using more representative cohorts from daily clinical screening, net benefit may attenuate at lower risk thresholds. Strengths and limitations of these models are discussed. Future directions: To assess their wider applicability, in-depth analysis of mpMRI predictive qualities should be further investigated, in combination with required external validation of these models in a multicenter setting with large prospective datasets. [ABSTRACT FROM AUTHOR]

Objectives: To validate, in an external cohort, three novel risk models, including the recently updated European Randomized Study of Screening for Prostate Cancer (ERSPC) risk calculator, that combine multiparametric magnetic resonance imaging (mpMRI) and clinical variables to predict clinically significant prostate cancer (PCa). Patients and Methods: We retrospectively analysed 307 men who underwent mpMRI prior to transperineal ultrasound fusion biopsy between October 2015 and July 2018 at two German centres. mpMRI was rated by Prostate Imaging Reporting and Data System (PI‐RADS) v2.0 and clinically significant PCa was defined as International Society of Urological Pathology Gleason grade group ≥2. The prediction performance of the three models (MRI‐ERSPC‐3/4, and two risk models published by Radtke et al. and Distler et al., ModRad and ModDis) were compared using receiver‐operating characteristic (ROC) curve analyses, with area under the ROC curve (AUC), calibration curve analyses and decision curves used to assess net benefit. Results: The AUCs of the three novel models (MRI‐ERSPC‐3/4, ModRad and ModDis) were 0.82, 0.85 and 0.83, respectively. Calibration curve analyses showed the best intercept for MRI‐ERSPC‐3 and ‐4 of 0.35 and 0.76. Net benefit analyses indicated clear benefit of the MRI‐ERSPC‐3/4 risk models compared with the other two validated models. The MRI‐ERSPC‐3/4 risk models demonstrated a discrimination benefit for a risk threshold of up to 15% for clinically significant PCa as compared to the other risk models. Conclusion: In our external validation of three novel prostate cancer risk models, which incorporate mpMRI findings, a head‐to‐head comparison indicated that the MRI‐ERSPC‐3/4 risk model in particular could help to reduce unnecessary biopsies. [ABSTRACT FROM AUTHOR]

Objectives: To review the literature to determine the sensitivity and specificity of gallium‐68 prostate‐specific membrane antigen (68Ga‐PSMA) positron‐emission tomography (PET) for detecting pelvic lymph node metastases in patients with primary prostate cancer (PCa), and the positive predictive value in patients with biochemical recurrence (BCR) after initial curative treatment, and, in addition, to determine the detection rate and management impact of 68Ga‐PSMA PET in patients with BCR after radical prostatectomy (RP). Materials and Methods: We performed a comprehensive literature search. Search terms used in MEDLINE, EMBASE and Science Direct were '(PSMA, 68Ga‐PSMA, 68Gallium‐PSMA, Ga‐68‐PSMA or prostate‐specific membrane antigen)' and '(histology, lymph node, staging, sensitivity, specificity, positive predictive value, recurrence, recurrent or detection)'. Relevant abstracts were reviewed and full‐text articles obtained where possible. References to and from obtained articles were searched to identify further relevant articles. Results: Nine retrospective and two prospective studies described the sensitivity and specificity of 68Ga‐PSMA PET for detecting pelvic lymph node metastases before initial treatment, which ranged from 33.3% to 100% and 80% to 100%, respectively. In eight retrospective studies, the positive predictive value of 68Ga‐PSMA PET in patients with BCR before salvage lymph node dissection ranged from 70% to 100%. The detection rate of 68Ga‐PSMA PET in patients with BCR after RP in the PSA subgroups <0.2 ng/mL, 0.2–0.49 ng/mL and 0.5 to <1.0 ng/mL ranged from 11.3% to 50.0%, 20.0% to 72.7% and 25.0% to 87.5%, respectively. Conclusion: The review results showed that 68Ga‐PSMA PET had a high specificity for the detection of pelvic lymph node metastases in primary PCa. Furthermore, 68Ga‐PSMA PET had a very high positive predictive value in detecting lymph node metastases in patients with BCR. By contrast, sensitivity was only moderate; therefore, based on the currently available literature, 68Ga‐PSMA PET cannot yet replace pelvic lymph node dissection to exclude lymph node metastases. In the salvage phase, 68Ga‐PSMA PET had both a high detection rate and impact on radiotherapy planning in early BCR after RP. [ABSTRACT FROM AUTHOR]

Objectives: To perform a comparison and external validation of three models predicting biochemical recurrence (BCR) and three models predicting prostate cancer (PCa)‐specific mortality (PCSM) in a screening setting, i.e. patients with screening‐detected PCa (S‐PCa) and in those with clinically detected PCa (C‐PCa). Subjects and Methods: We retrospectively evaluated 795 men with S‐PCa, from the European Randomized Study of Screening for Prostate Cancer, Rotterdam, and 1123 men with C‐PCa initially treated with RP. The discriminative ability of the models was assessed according to the area under the curve (AUC) of the receiver‐operating characteristic, and calibration was assessed graphically using calibration plots. Results: The median (interquartile range [IQR]) follow‐up for the S‐PCa group was 10.4 (6.8–14.3) years and for the C‐PCa group it was 8.8 (4.8–12.9) years. A total of 123 men with S‐PCa (15%) and 389 men with C‐PCa (35%) experienced BCR. Of the men with S‐PCa and BCR, 24 (20%) died from PCa and 29 (23%) died from other causes. Of the men with C‐PCa and BCR, 68 (17%) died from PCa and 105 (27%) died from other causes. The discrimination of the models predicting BCR or PCSM was higher for men with S‐PCa (AUC: BCR 0.77–0.84, PCSM 0.60–0.77) than for the men with C‐PCa (AUC: BCR 0.75–0.79, PCSM 0.51–0.68) as a result of the similar patient characteristics of the men with S‐PCa in the present study and those of the cohorts used to develop these models. The risk of BCR was typically overestimated, while the risk of PCSM was typically underestimated. Conclusion: Prediction models for BCR showed good discrimination and reasonable calibration for both men with S‐PCa and men with C‐PCa, and even better discrimination for men with S‐PCa. For PCSM, the evaluated models are not applicable in both settings of this Dutch cohort as a result of substantial miscalibration. This warrants caution when using these models to communicate future risks in other clinical settings. [ABSTRACT FROM AUTHOR]

Aims: Invasive cribriform and/or intraductal carcinoma have been identified as independent adverse parameters for prostate cancer outcome. Little is known on biopsy undersampling of cribriform architecture. Our aim was to determine the extent of cribriform architecture undersampling and to find predictive factors for identifying false cribriform‐negative cases. Methods and results: We reviewed 186 matched prostate biopsies and radical prostatectomy specimens. Of 97 biopsy grade group 2 (Gleason score 3 + 4 = 7) patients, 22 (23%) had true cribriform‐negative (TN), 39 (40%) false‐negative (FN) and 36 (37%) true‐positive (TP) biopsies. Patients with FN biopsies had higher, although not statistically significant (P = 0.06), median PSA levels than patients with TP biopsies (12 versus 8 ng/ml). A PI‐RADS 5 lesion was present in nine of 16 (54%) FN and three of 11 (27%) TN biopsies (P = 0.05). Positive biopsy rate (P = 0.47), percentage Gleason pattern 4 (P = 0.55) and glomeruloid architecture (P = 1.0) were not different. Logistic regression identified PSA as an independent predictor (odds ratio = 3.5; 95% confidence interval = 1.2–9.4, P = 0.02) for cribriform architecture on radical prostatectomy, but not PI‐RADS score. The FN rate for large cribriform architecture at radical prostatectomy was 27%, which was lower than for any cribriform architecture (P = 0.01). During follow‐up (median 27 months), biochemical recurrence‐free survival of patients with TP biopsies was significantly shorter than that of those with FN biopsies (P = 0.03). Conclusion: In conclusion, 40% of grade group 2 prostate cancer biopsies were FN for cribriform architecture. These patients had higher PSA levels and more frequent PI‐RADS score 5 lesions than men with TN biopsies. [ABSTRACT FROM AUTHOR]

Background. Low-risk prostate cancer patients enrolled in active surveillance programs commonly undergo biopsies for examination of cancer progression. Biopsies are conducted as per a fixed and frequent schedule (e.g., annual biopsies). Since biopsies are burdensome, patients do not always comply with the schedule, which increases the risk of delayed detection of cancer progression. Objective. Our aim is to better balance the number of biopsies (burden) and the delay in detection of cancer progression (less is beneficial) by personalizing the decision of conducting biopsies. Data Sources. We used patient data of the world's largest active surveillance program (Prostate Cancer Research International Active Surveillance; PRIAS). It enrolled 5270 patients, had 866 cancer progressions, and an average of 9 prostate-specific antigen (PSA) and 5 digital rectal examination (DRE) measurements per patient. Methods. Using joint models for time-to-event and longitudinal data, we model the historical DRE and PSA measurements and biopsy results of a patient at each follow-up visit. This results in a visit and patient-specific cumulative risk of cancer progression. If this risk is above a certain threshold, we schedule a biopsy. We compare this personalized approach with the currently practiced biopsy schedules via an extensive and realistic simulation study, based on a replica of the patients from the PRIAS program. Results. The personalized approach saved a median of 6 biopsies (median: 4, interquartile range [IQR]: 2–5) compared with the annual schedule (median: 10, IQR: 3–10). However, the delay in detection of progression (years) is similar for the personalized (median: 0.7, IQR: 0.3–1.0) and the annual schedule (median: 0.5, IQR: 0.3–0.8). Conclusions. We conclude that personalized schedules provide substantially better balance in the number of biopsies per detected progression for men with low-risk prostate cancer. [ABSTRACT FROM AUTHOR]

Objectives: To develop a consensus statement on current best practice of active surveillance (AS) in the UK, informed by patients and clinical experts. Subjects and Methods: A consensus statement was drafted on the basis of three sources of data: systematic literature search of national and international guidelines; data arising from a Freedom of Information Act request to UK urology departments regarding their current practice of AS; and survey and interview responses from men with localized prostate cancer regarding their experiences and views of AS. The Prostate Cancer UK Expert Reference Group (ERG) on AS was then convened to discuss and refine the statement. Results: Guidelines and protocols for AS varied significantly in terms of risk stratification, criteria for offering AS, and protocols for AS between and within countries. Patients and healthcare professionals identified clinical, emotional and process needs for AS to be effective. Men with prostate cancer wanted more information and psychological support at the time of discussing AS with the treating team and in the first 2 years of AS, and a named healthcare professional to discuss any questions or concerns they had. The ERG agreed 30 consensus statements regarding best practice for AS. Statements were grouped under headings: 'Inclusion/Exclusion Criteria'; 'AS follow‐up protocol' and 'When to stop AS'. Conclusion: Significant variation currently exists in the practice of AS in the UK and internationally. Men have clear views on the level of involvement in treatment decisions and support from their treating professionals when receiving AS. The Prostate Cancer UK AS ERG has developed a set of consensus statements for best practice in AS. Evidence for best practice in AS, and the use of multiparametric magnetic resonance imaging in AS, is still evolving, and further studies are needed to determine how to optimize AS outcomes. [ABSTRACT FROM AUTHOR]