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Background and objective: In 2019 and 2021, Europa Uomo initiated the Europa Uomo Patient Reported Outcome Study (EUPROMS) and the EUPROMS 2.0 survey, with the goal of collecting data on patients’ self-reported perspective on physical and mental well-being outside of a clinical trial setting, to be able to investigate the burden of prostate cancer (PCa) treatment from a patient-to-patient perspective. Acknowledging the importance of collecting quality of life (QoL) follow-up data, a 1-yr follow-up (1yrFU) study was conducted to assess the effect of additional PCa treatment on QoL. Methods: Men with PCa who participated in the EUPROMS 2.0 survey and indicated that they were open to collection of a follow-up measurement were reinvited to complete the 1yrFU survey. The EUPROMS 2.0 1yrFU survey included the validated European Quality of Life 5 Dimension 5 Level (EQ-5D-5L), European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30), Expanded Prostate Cancer Index Composite Short Form (EPIC-26), and International Index of Erectile Function (IIEF)-15 overall satisfaction domains. Descriptive statistics were used to assess demographic characteristics and to analyze the patient-reported outcome data. Key findings and limitations: A total of 1006 (54%) men completed the survey. The median age at the time of questionnaire completion was 72 yr (interquartile range 66–76 yr). Of them, 641 men (64%) underwent no new treatment, while 365 men (36%) underwent new treatment, including 247 (247/365, 68%) for PCa. In total, 114 patients (46%) underwent new androgen deprivation therapy (ADT) and 81 (33%) new external beam radiotherapy (EBRT). It is indicated that the impact of new ADT and EBRT on sexual function is immediate and detrimental, and continues to last over time. However, for men who underwent EBRT or radical prostatectomy earlier and did not undergo new treatment, slight improvements on various domains are reported. Conclusions and clinical implications: The EUPROMS 2.0 1yrFU study provides additional information on treatments that are already in common use and will help future PCa patients to make informed and shared decisions on PCa treatment. Patient summary: The follow-up data on quality of life collected by Europa Uomo can be used to inform future prostate cancer (PCa) patients about the impact of undergoing (multiple) PCa treatment(s).

Background and objective: Patient-reported outcome measures (PROMs) are increasingly being used to capture the patients’ perspective of their functional status and quality of life (QoL). Big data can help us better understand patient-reported outcomes (PROs). Using prospectively collected data from the Prostate Cancer Diagnosis and Treatment Enhancement Through the Power of Big Data in Europe (PIONEER) consortium, we aimed to describe the functional status and QoL in men with prostate cancer (PCa) treated with active surveillance (AS), radical prostatectomy (RP), and radiotherapy (RT), and to demonstrate the applicability of PROM data on a large scale and at a European level. Methods: We identified data sources that collected QoL data using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, EORTC QLQ-PR25, or Expanded Prostate Cancer Index Composite (EPIC)-26/50 questionnaires. Aggregated summary scores for urinary, bowel, and sexual dysfunction, global health status, and QoL were shared for each data source. Key findings and limitations: We identified eight data sources originating from various settings: routine hospital data, embedded research PRO collection, survey data collected by a patient organization, multi-institutional prospective cohort study, and registry data. PRO data were available for 709 men on AS, 20 508 on RP, and 3417 on RT, with a median time between diagnosis and PROM assessment ranging from 1 to 8.7 yr. Most men were diagnosed with Gleason ≤7 disease, and T1 or T2 PCa. We observed that sexual dysfunction was the most affected PRO and found large differences between data sources. Conclusions and clinical implications: Our results support the feasibility of PRO assessment using big data in Europe. Implementation of PROMs in clinical practice and the use of standardized methods could improve value-based health care provision. Patient summary: In this study, we combined several data sources that reported urinary, bowel, and sexual dysfunction, global health status, and quality of life. We identified eight data sources and show that sexual function is the most affected domain after treatment.

For men with prostate cancer (PCa) within the European Randomized Study of Screening for Prostate Cancer (ERSPC), the cause of death is determined by a Cause of Death Committee (CODC) that evaluates all medical records using a fixed algorithm. The aim of this study was to compare the classification of PCa-specific mortality (PCSM) between the CODC and Statistics Netherlands. We calculated the sensitivity (PCSM agreement divided by total PCSM deaths according to the CODC) and specificity (agreement for other-cause mortality [OCM] divided by total OCM deaths according to the CODC) using the last 21-yr follow-up data from ERSPC Rotterdam. For the core age group (age 55–69 yr at randomization; n = 1732), the sensitivity was 86% (95% CI 83-89) and specificity was 93% (95% CI 91-94), with no statistical difference between the youngest ages and the oldest ages. Extrapolation of our findings to 30 yr of follow-up would result in an expected risk reduction of PCSM of 30% using data from the CODC and 33% using official statistics in favor of screening. In conclusion, our results support the use of official statistics in determining the cause of death, without compromising the main outcome of ERSPC Rotterdam. Patient summary: We compared the classification of prostate cancer death between a dedicated trial committee and official statistics in the Netherlands. We found that official statistics are an accurate representation in determining the cause of death.

Prostate cancer (PCa) is a major public health concern for men globally and the most commonly diagnosed cancer among men in the European Union (EU). Despite large trials suggesting benefits from early detection of PCa, risks of overdiagnosis and overtreatment are evident. In 2022, the EU Commission proposed introducing prostate-specific antigen (PSA) testing for men in an organised setting, in combination with magnetic resonance imaging (MRI) scanning as a follow-up test to minimise these risks. PRostate cancer Awareness and Initiative for Screening Europe (PRAISE-U) is a pilot study evaluating the implementation of a risk-stratified population-based approach to PCa screening in Ireland, Lithuania, Poland, and two areas in Spain (Galicia and Manresa) for feasibility, efficacy, and cost effectiveness. As per the protocol designed for the pilots, men aged 50–69 yr residing within the catchment area of the study sites will be invited to participate. Those consenting to participate will undergo PSA testing, and men with PSA >3 ng/ml will undergo risk stratification before MRI and, if necessary, after MRI before undergoing biopsy. A collaborative user board comprising health care professionals, patients, and decision-makers will be formed to provide stakeholder input throughout the study. PRAISE-U will be evaluated on three major pillars: analysis of clinical and programme outcomes, psychosocial impact, and cost effectiveness. A set of key performance indicators (KPIs) has been developed to be piloted in the PRAISE-U pilot sites. The KPIs will serve to assess the performance and outcomes of risk-stratified PCa screening at each site. A REDCap database will be used to collect and manage pseudoanonymised data from the pilot sites. Ethics approval was obtained from each pilot site. The PRAISE-U pilot implementation is expected to commence in the 3rd quarter of 2024 for 12 mo and provide valuable data on the implementation outcomes of a risk-stratified screening approach across Europe. The findings is expected to inform the development of an optimised screening strategy with an acceptable benefit to harm ratio.

Background and objective: Clinical practice guidelines for prostate cancer (PCa) are a valuable resource for everyday clinical practice. The clinical practice guidelines and recommendations produced by various societies should demonstrate a considerable level of consistency in terms of quality, regardless of the society that developed these given the common evidence base. However, to date, no study has assessed the quality of PCa clinical practice guidelines. As part of the Optimal Treatment for Patients with Solid Tumours in Europe Through Artificial intelligence (OPTIMA) project, we evaluated the quality of the most frequently used national and international clinical practice guidelines for PCa using the Appraisal of Guidelines for Research & Evaluation II (AGREE II) tool. Methods: The quality of the identified clinical practice guidelines was assessed independently by two assessors using the AGREE II tool. The AGREE II tool comprises 23 different items organised into six domains, rated on a 7-point scale (1: strongly disagree to 7: strongly agree). The total score of the appraisal was the mean value of the two assessments. The agreement between assessors’ scores was calculated using the interclass correlation coefficient (ICC). Four key recommendations were compared among the included clinical practice guidelines to assess consistency. Key findings and limitations: Sixteen clinical practice guidelines were assessed using their latest available version (cut-off April 2024). The European Association of Urology, S3LL PCa, Belgian Health Care Knowledge Centre, National Comprehensive Cancer Network, and Prostatacancer—Nationellt vårdprogram guidelines received the highest overall scores with a mean domain score of 82.4% (range: 75.5–88.3%). The de l’Association Française d’Urologie (AFU), American Urological Association, and National Institute for Health and Care Excellence received a mean domain score of 77.6% (range: 73.7–84.0%). Below average were the European Society for Medical Oncology, localised (L) and systemic (S) CPPC American Society of Clinical Oncology, and Nederlandse Vereniging voor Urologie (NVU) with a mean domain score of 58.4% (range: 43.5–76.3%). The reasons for scoring below average included the following: inadequate information about the methodology applied, limited scope of the guideline, and limited patient engagement. The highest inter-rater variability was observed in NVU (ICC: 0.58) and the lowest in AFU-L (ICC: 0.84). When examining the scores of each domain, “clarity of presentation” (domain 4) achieved the highest score with a mean of 86.9% ± 12.6%. The domain with the lowest score was applicability (domain 5), with a mean of 48.3% ± 24.8%. The ICC was calculated to be 0.72 (±0.08). Conclusions and clinical implications: This is the first study in which a comprehensive quality assessment of the majority of international and national clinical practice guidelines was undertaken, and the key recommendations were compared to assess consistency. Our study shows that the majority of international and national clinical practice guidelines demonstrate high-quality standards when assessed using the AGREE II evaluation tool. The clinical practice guidelines that did not meet the expected standards could be improved by adopting several key recommendations outlined by our study. Patient summary: The OPTIMA project used the Appraisal of Guidelines for Research & Evaluation II (AGREE II) tool to evaluate the quality of 16 commonly used national and international clinical practice guidelines for prostate cancer. While some of these international and national clinical practice guidelines received the highest score, few guidelines scored below average due to methodological deficiencies and limited patient engagement. These findings highlight the need for a standardised process to ensure high-quality, consistent guidelines across practices.

Abstract Objectives To understand how best to further reduce the inappropriate use of pre‐surgical androgen deprivation therapy (ADT), we investigated the determinants (influences) of ADT prescribing in urologists in two European countries using an established behavioural science approach. Additionally, we sought to understand how resource limitations caused by COVID‐19 influenced this practice. Identification of key determinants, of undistributed and disrupted practice, will aid development of future strategies to reduce inappropriate ADT prescribing in current and future resource‐limited settings. Participants and Methods We conducted semi‐structured qualitative interviews with urologists practicing in Italy and the UK from February to July 2022. Interviews focussed on undisrupted (usual) practice and disrupted practice (changes made during COVID‐19 restrictions). Codes were generated inductively and were mapped to the 14 domains of the Theoretical Domains Framework. Relevant domains of influence were identified, and the similarities and differences between the UK and Italy were distinguished. Results We identified 10 domains that were influential to ADT prescribing in the UK and eight in Italy. The role of guidance and evidence, the cancer care setting, the patients and the urologist's beliefs and experiences were identified as areas that were influential to ADT prescribing before surgery. Twenty‐one similarities and 22 differences between the UK and Italy, for usual and COVID‐19 practice, were identified across these 10 domains. Conclusion Similarities and differences influencing ADT prescribing prior to surgery should be considered in behavioural strategy development and tailoring to reduce inappropriate ADT use. We gained an understanding of usual, undistributed care and resource‐limited or disrupted care due to COVID‐19 in two European countries. This gives an indication of how influences on ADT prescribing may change in future resource‐limited circumstances and where efforts can be focused now and in future.

Background and objective: The treatment landscape of metastatic prostate cancer (mPCa) has evolved significantly over the past two decades. Despite this, the optimal therapy for patients with mPCa has not been determined. This systematic review identifies available predictive models that assess mPCa patients’ response to treatment. Methods: We critically reviewed MEDLINE and CENTRAL in December 2022 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Only quantitative studies in English were included with no time restrictions. The quality of the included studies was assessed using the PROBAST tool. Data were extracted following the Checklist for Critical Appraisal and Data Extraction for Systematic Reviews criteria. Key findings and limitations: The search identified 616 citations, of which 15 studies were included in our review. Nine of the included studies were validated internally or externally. Only one study had a low risk of bias and a low risk concerning applicability. Many studies failed to detail model performance adequately, resulting in a high risk of bias. Where reported, the models indicated good or excellent performance. Conclusions and clinical implications: Most of the identified predictive models require additional evaluation and validation in properly designed studies before these can be implemented in clinical practice to assist with treatment decision-making for men with mPCa. Patient summary: In this review, we evaluate studies that predict which treatments will work best for which metastatic prostate cancer patients. We found that existing studies need further improvement before these can be used by health care professionals.

Background and objective: The ability of health care professionals to communicate with patients compassionately and effectively is crucial for shared decision-making, but little research has investigated patient-clinician communication. As part of PIONEER—an international Big Data Consortium led by the European Association of Urology to answer key questions for men with prostate cancer (PCa), funded through the IMI2 Joint Undertaking under grant agreement 777492— we investigated communication between men diagnosed with PCa and the health care professional(s) treating them across Europe. Methods: We used the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Communication 26, which was shared via the PIONEER and patient organisations on March 11, 2022. We sought men who spoke French, Italian, Spanish, German, Dutch, or English who were diagnosed with PCa and were undergoing or had already received treatment for their PCa. Results and limitations: A total of 372 men reported that they communicated with their clinician during either the diagnostic or the treatment period. Overall, the majority of participants reported positive experiences. However, important opportunities to enhance communication were identified, particularly with regard to correcting misunderstandings, understanding the patient’s preferred approach to information presentation, addressing challenging questions, supporting the patient’s comprehension of information, attending to the patient’s emotional needs, and assessing what information had already been given to patients about their disease and treatment, and how much of it was understood. Conclusions and clinical implications: These results help us to identify gaps and barriers to shared treatment decision making. This knowledge will help devise measures to improve patient-health care professional communication in the PCa setting. Patient summary: As part of the PIONEER initiative, we investigated the communication between men diagnosed with prostate cancer and their health care professionals across Europe. A total of 372 men from six different countries participated in the study. Most participants reported positive experiences, but areas where communication could be improved were identified. These included addressing misunderstandings, tailoring the presentation of information to the patient’s preferences, handling difficult questions, supporting emotional needs, and assessing the patient’s understanding of their diagnosis and treatment.

BackgroundThe optimal interval for repeat biopsy during active surveillance (AS) for prostate cancer is yet to be defined. This study examined whether risk of upgrading (to grade group ≥ 2) or risk of converting to treatment varied according to intensity of repeat biopsy using data from the GAP3 consortium's global AS database.Materials and methodsIntensity of surveillance biopsy schedules was categorized according to centers' protocols: (a) Prostate Cancer Research International Active Surveillance project (PRIAS) protocols with biopsies at years 1, 4, and 7 (10 centers; 7532 men); (b) biennial biopsies, that is, every other year (8 centers; 4365 men); and (c) annual biopsy schedules (4 centers; 1602 men). Multivariable Cox regression was used to compare outcomes according to biopsy intensity.ResultsOut of the 13,508 eligible participants, 56% were managed according to PRIAS protocols (biopsies at years 1, 4, and 7), 32% via biennial biopsy, and 12% via annual biopsy. After adjusting for baseline characteristics, risk of converting to treatment was greater for those on annual compared with PRIAS biopsy schedules (hazard ratio [HR] = 1.66; 95% confidence interval [CI] = 1.51-1.83; p

BackgroundActive surveillance (AS) is a management option for men diagnosed with low-risk prostate cancer. Opinions differ on whether it is safe to include young men (≤60 yr) or men with intermediate-risk disease.ObjectiveTo assess whether reasons for discontinuation, treatment choice after AS, and adverse pathology at radical prostatectomy (RP; N1, or ≥GG3, or ≥pT3) differ for men ≤60 yr or those with European Association of Urology (EAU) intermediate-risk disease from those for men >60 yr or those with EAU low-risk disease.Design setting and participantsWe analyzed data from 5411 men ≤60 yr and 14 959 men >60 yr, 14 064 men with low-risk cancer, and 2441 men with intermediate-risk cancer, originating from the GAP3 database (21 169 patients/27 cohorts worldwide).Outcome measurements and statistical analysisCumulative incidence curves were used to estimate the rates of AS discontinuation and treatment choice.Results and limitationsThe probability of discontinuation of AS due to disease progression at 5 yr was similar for men aged ≤60 yr (22%) and those >60 yr (25%), as well as those of any age with low-risk disease (24%) versus those with intermediate-risk disease (24%). Men with intermediate-risk disease are more prone to discontinue AS without evidence of progression than men with low-risk disease (at 1/5 yr: 5.9%/14.2% vs 2.0%/8.8%). Adverse pathology at RP was observed in 32% of men ≤60 yr compared with 36% of men >60 yr (p = 0.029), and in 34% with low-risk disease compared with 40% with intermediate-risk disease (p = 0.048).ConclusionsOur descriptive analysis of AS practices worldwide showed that the risk of progression during AS is similar across the age and risk groups studied. The proportion of adverse pathology was higher among men >60 yr than among men ≤60 yr. These results suggest that men ≤60 yr and those with EAU intermediate-risk disease should not be excluded from opting for AS as initial management.Patient summaryData from 27 international centers reflecting daily clinical practice suggest that younger men or men with intermediate-risk prostate cancer do not hold greater risk for disease progression during active surveillance.

BackgroundThe inclusion criterion for active surveillance (AS) is low- or intermediate-risk prostate cancer. The predictive value of the presence of a suspicious lesion at magnetic resonance imaging (MRI) at the time of inclusion is insufficiently known.ObjectiveTo evaluate the percentage of patients needing active treatment stratified by the presence or absence of a suspicious lesion at baseline MRI.Design setting and participantsA retrospective analysis of the data from the multicentric AS GAP3 Consortium database was conducted. The inclusion criteria were men with grade group (GG) 1 or GG 2 prostate cancer combined with prostate-specific antigen

Men diagnosed with low-risk prostate cancer (PC) are increasingly electing active surveillance (AS) as their initial management strategy. While this may reduce the side effects of treatment for prostate cancer, many men on AS eventually convert to active treatment. PC is one of the most heritable cancers, and genetic factors that predispose to aggressive tumors may help distinguish men who are more likely to discontinue AS. To investigate this, we undertook a multi-institutional genome-wide association study (GWAS) of 5,222 PC patients and 1,139 other patients from replication cohorts, all of whom initially elected AS and were followed over time for the potential outcome of conversion from AS to active treatment. In the GWAS we detected 18 variants associated with conversion, 15 of which were not previously associated with PC risk. With a transcriptome-wide association study (TWAS), we found two genes associated with conversion (MAST3, p = 6.9×10-7 and GAB2, p = 2.0×10-6). Moreover, increasing values of a previously validated 269-variant genetic risk score (GRS) for PC was positively associated with conversion (e.g., comparing the highest to the two middle deciles gave a hazard ratio [HR] = 1.13; 95% Confidence Interval [CI]= 0.94-1.36); whereas, decreasing values of a 36-variant GRS for prostate-specific antigen (PSA) levels were positively associated with conversion (e.g., comparing the lowest to the two middle deciles gave a HR = 1.25; 95% CI, 1.04-1.50). These results suggest that germline genetics may help inform and individualize the decision of AS-or the intensity of monitoring on AS-versus treatment for the initial management of patients with low-risk PC.

Cancer survivorship was recently identified as a prostate cancer (PCa) research priority by PIONEER, a European network of excellence for big data in PCa. Despite being a research priority, cancer survivorship lacks a clear and agreed definition, and there is a distinct paucity of patient-reported outcome (PRO) data available on the subject. Data collection on cancer survivorship depends on the availability and implementation of (validated) routinely collected patient-reported outcome measures (PROMs). There have been recent advances in the availability of such PROMs. For instance, the European Organisation for Research and Treatment of Cancer Quality of Life Group (EORTC QLG) is developing survivorship questionnaires. This provides an excellent first step in improving the data available on cancer survivorship. However, we propose that an agreed, standardised definition of (prostate) cancer survivorship must first be established. Only then can real-world data on survivorship be collected to strengthen our knowledge base. With more men than ever surviving PCa, this type of research is imperative to ensure that the quality of life of these men is considered as much as their quantity of life. Patient summary: As there are more prostate cancer survivors than ever before, research into cancer survivorship is crucial. We highlight the importance of such research and provide recommendations on how to carry it out. The first step should be establishing agreement on a standardised definition of survivorship. From this, patient-reported outcome measures can then be used to collect important survivorship data.

BackgroundPolygenic hazard scores (PHS) can identify individuals with increased risk of prostate cancer. We estimated the benefit of additional SNPs on performance of a previously validated PHS (PHS46).Materials and method180 SNPs, shown to be previously associated with prostate cancer, were used to develop a PHS model in men with European ancestry. A machine-learning approach, LASSO-regularized Cox regression, was used to select SNPs and to estimate their coefficients in the training set (75,596 men). Performance of the resulting model was evaluated in the testing/validation set (6,411 men) with two metrics: (1) hazard ratios (HRs) and (2) positive predictive value (PPV) of prostate-specific antigen (PSA) testing. HRs were estimated between individuals with PHS in the top 5% to those in the middle 40% (HR95/50), top 20% to bottom 20% (HR80/20), and bottom 20% to middle 40% (HR20/50). PPV was calculated for the top 20% (PPV80) and top 5% (PPV95) of PHS as the fraction of individuals with elevated PSA that were diagnosed with clinically significant prostate cancer on biopsy.Results166 SNPs had non-zero coefficients in the Cox model (PHS166). All HR metrics showed significant improvements for PHS166 compared to PHS46: HR95/50 increased from 3.72 to 5.09, HR80/20 increased from 6.12 to 9.45, and HR20/50 decreased from 0.41 to 0.34. By contrast, no significant differences were observed in PPV of PSA testing for clinically significant prostate cancer.ConclusionsIncorporating 120 additional SNPs (PHS166 vs PHS46) significantly improved HRs for prostate cancer, while PPV of PSA testing remained the same.

BackgroundCareful assessment of the reasons for discontinuation of active surveillance (AS) is required for men with prostate cancer (PCa).ObjectiveUsing Movember's Global Action Plan Prostate Cancer Active Surveillance initiative (GAP3) database, we report on reasons for AS discontinuation.Design, setting, and participantsWe compared data from 10296 men on AS from 21 centres across 12 countries.Outcome measurements and statistical analysisCumulative incidence methods were used to estimate the cumulative incidence rates of AS discontinuation.Results and limitationsDuring 5-yr follow-up, 27.5% (95% confidence interval [CI]: 26.4-28.6%) men showed signs of disease progression, 12.8% (95% CI: 12.0-13.6%) converted to active treatment without evidence of progression, 1.7% (95% CI: 1.5-2.0%) continued to watchful waiting, and 1.7% (95% CI: 1.4-2.1%) died from other causes. Of the 7049 men who remained on AS, 2339 had follow-up for >5yr, 4561 had follow-up for

Genetic models for cancer have been evaluated using almost exclusively European data, which could exacerbate health disparities. A polygenic hazard score (PHS1) is associated with age at prostate cancer diagnosis and improves screening accuracy in Europeans. Here, we evaluate performance of PHS2 (PHS1, adapted for OncoArray) in a multi-ethnic dataset of 80,491 men (49,916 cases, 30,575 controls). PHS2 is associated with age at diagnosis of any and aggressive (Gleason score ≥ 7, stage T3-T4, PSA ≥ 10 ng/mL, or nodal/distant metastasis) cancer and prostate-cancer-specific death. Associations with cancer are significant within European (n = 71,856), Asian (n = 2,382), and African (n = 6,253) genetic ancestries (p

ObjectiveTo 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 methodsRepeat 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).ResultsThe 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).ConclusionsWe 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.

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.

Background: The ERSPC study has demonstrated that prostate-specific antigen (PSA)-based screening results in a relative increase in diagnosis of (low-risk) prostate cancer (PCa) and a reduction in metastatic disease and PCa mortality. Objective: To evaluate the burden of PCa among men randomized to active screening compared to those in the control arm in ERSPC Rotterdam. Design, setting, and participants: We analyzed data for participants in the Dutch section of the ERSPC, including 21 169 men randomized to the screening arm and 21 136 randomized to the control arm. Men in the screening arm were invited for PSA-based screening every 4 yr, and transrectal ultrasound–guided prostate biopsy was recommended for those with PSA ≥3.0 ng/ml. Outcome measurements and statistical analysis: We analyzed detailed follow-up and mortality data up to January 1, 2019, to a maximum of 21 yr, using multistate models. Results and limitations: At 21 yr, 3046 men (14%) had been diagnosed with nonmetastatic PCa and 161 (0.76%) with metastatic PCa in the screening arm. In the control arm, 1698 men (8.0%) had been diagnosed with nonmetastatic PCa and 346 (1.6%) with metastatic PCa. In comparison to the control arm, men in the screening arm were diagnosed with PCa almost 1 yr earlier and if diagnosed with nonmetastatic PCa lived on average for almost 1 yr longer without disease progression. Among those who experienced biochemical recurrence (18–19% after nonmetastatic PCa), progression to metastatic disease or death was quicker in the control arm: men in the screening arm lived for 7.17 yr without progression, while the progression-free interval was only 1.59 yr for men in the control arm over a 10-yr time period. Among those who experienced metastatic disease, men in both study arms lived for 5 yr over a 10-yr time period. Conclusions: PCa diagnosis was earlier after study entry for men in the PSA-based screening arm. However, disease progression was not as fast in the screening arm as in the control arm: once men in the control arm experienced biochemical recurrence, progression to metastatic disease or death was 5.6 yr faster than in the screening arm. Our results confirm the ability of early disease detection to reduce suffering and death from PCa at the cost of earlier (and more frequent) treatment-induced reductions in quality of life. Patient summary: Our study shows that early detection of prostate cancer can reduce suffering and death from this disease. However, screening based on measurement of prostate-specific antigen (PSA) can also result in an earlier treatment-induced reduction in quality of life.

An updated Council of the EU recommendation on cancer screening was adopted in December 2022 during the Czech EU presidency. The recommendation included prostate cancer as a suitable target disease for organised screening, and invited countries to proceed with piloting and further research. To support further discussions and actions to promote early detection of prostate cancer, an international conference in November 2022 (Prostaforum 2022) resulted in a joint declaration. Here we describe the EU policy background, summarise the preparation of the declaration and the key underlying evidence and expert recommendations, and report the text of the declaration. The declaration summarises the striking inequalities in prostate cancer burden in Europe and calls on all stakeholders to consider and support concrete steps for advancement of organised early detection of prostate cancer. Our aim is to request endorsement of the text and potential initiation of practical actions by all stakeholders to support the aims of the declaration. Patient summary: Prostate cancer is among the most frequent cancers and is one of the most common causes of cancer death among men. The European Union has recommended new pilot programmes for prostate cancer screening. The Prostaforum 2022 declaration invites all stakeholders to support this new recommendation with specific steps.

Using prostate-specific antigen (PSA) for prostate cancer (PCa) screening led to overinvestigation and overdiagnosis of indolent PCa. We aimed to investigate the value of prostate health index (PHI) and magnetic resonance imaging (MRI) prostate in an Asian PCa screening program. Men aged 50–75 years were prospectively recruited from a community-based PSA screening program. Men with PSA 4.0–10.0 ng ml−1 had PHI result analyzed. MRI prostate was offered to men with PSA 4.0–50.0 ng ml−1. A systematic prostate biopsy was offered to men with PSA 4.0–9.9 ng ml−1 and PHI ≥35, or PSA 10.0–50.0 ng ml−1. Additional targeted prostate biopsy was offered if they had PI-RADS score ≥3. Clinically significant PCa (csPCa) was defined as the International Society of Urological Pathology (ISUP) grade group (GG) ≥2 or ISUP GG 1 with involvement of ≥30% of total systematic cores. In total, 12.8% (196/1536) men had PSA ≥4.0 ng ml−1. Among 194 men with PSA 4.0–50.0 ng ml−1, 187 (96.4%) received MRI prostate. Among them, 28.3% (53/187) had PI-RADS ≥3 lesions. Moreover, 7.0% (107/1536) men were indicated for biopsy and 94.4% (101/107) men received biopsy. Among the men received biopsy, PCa, ISUP GG ≥2 PCa, and csPCa was diagnosed in 42 (41.6%), 24 (23.8%), and 34 (33.7%) men, respectively. Compared with PSA/PHI pathway in men with PSA 4.0–50.0 ng ml−1, additional MRI increased diagnoses of PCa, ISUP GG ≥2 PCa, and csPCa by 21.2% (from 33 to 40), 22.2% (from 18 to 22), and 18.5% (from 27 to 32), respectively. The benefit of additional MRI was only observed in PSA 4.0–10.0 ng ml−1, and the number of MRI needed to diagnose one additional ISUP GG ≥2 PCa was 20 in PHI ≥35 and 94 in PHI

Abstract Objectives To recalibrate and validate the European Randomized Study of Screening for Prostate Cancer risk calculators (ERSPC RCs) 3/4 and the magnetic resonance imaging (MRI)‐ERSPC‐RCs to a contemporary Norwegian setting to reduce upfront prostate multiparametric MRI (mpMRI) and prostate biopsies. Patients and Methods We retrospectively identified and entered all men who underwent prostate mpMRI and subsequent prostate biopsy between January 2016 and March 2017 in a Norwegian centre into a database. mpMRI was reported using PI‐RADS v2.0 and clinically significant prostate cancer (csPCa) defined as Gleason ≥ 3 + 4. Probabilities of csPCa and any prostate cancer (PCa) on biopsy were calculated by the ERSPC RCs 3/4 and the MRI‐ERSPC‐RC and compared with biopsy results. RCs were then recalibrated to account for differences in prevalence between the development and current cohorts (if indicated), and calibration, discrimination and clinical usefulness assessed. Results Three hundred and three patients were included. The MRI‐ERSPC‐RCs were perfectly calibrated to our cohort, although the ERSPC RCs 3/4 needed recalibration. Area under the receiver operating curve (AUC) for the ERSPC RCs 3/4 was 0.82 for the discrimination of csPCa and 0.77 for any PCa. The AUC for the MRI‐ERSPC‐RCs was 0.89 for csPCa and 0.85 for any PCa. Decision curve analysis showed clear net benefit for both the ERSPC RCs 3/4 (>2% risk of csPCa threshold to biopsy) and for the MRI‐ERSPC‐RCs (>1% risk of csPCa threshold), with a greater net benefit for the MRI‐RCs. Using a >10% risk of csPCa or 20% risk of any PCa threshold for the ERSPC RCs 3/4, 15.5% of mpMRIs could be omitted, missing 0.8% of csPCa. Using the MRI‐ERSPC‐RCs, 23.4% of biopsies could be omitted with the same threshold, missing 0.8% of csPCa. Conclusion The ERSPC RCs 3/4 and MRI‐ERSPC‐RCs can considerably reduce both upfront mpMRI and prostate biopsies with little risk of missing csPCa.

Long-term screening with serum prostate-specific antigen (PSA) and systematic prostate biopsies can reduce prostate cancer mortality but leads to unacceptable overdiagnosis. Over the past decade, diagnostic methods have improved and the indolent nature of low-grade prostate cancer has been established. These advances now enable more selective detection of potentially lethal prostate cancer. This non-systematic review summarises relevant diagnostic advances, previous and ongoing screening trials, healthcare policies and important remaining knowledge gaps.Evidence synthesis and conclusions: The strong association between low serum PSA values and minimal long-term risk of prostate cancer death allows for adjusting screening intervals. Use of risk calculators, biomarkers and MRI to select men with a raised PSA value for biopsy and lesion-targeting rather than systematic prostate biopsies reduce the detection of low-grade cancer and thereby overdiagnosis. These improvements recently led the European Union to recommend its member states to evaluate the feasibility and effectiveness of organised screening programmes for prostate cancer. Nonetheless, important knowledge gaps remain such as the performance of modern diagnostic methods in long-term screening programmes and their impact on mortality. The knowledge gaps are currently being addressed in three large randomised screening trials. Population-based pilot programmes will contribute critical practical experience.

Background: Guidelines 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. Objective: To 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 participants: Men 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

Abstract 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’.

The original version of this Article contained an error in the spelling of the author Manuela Gago-Dominguez, which was incorrectly given as Manuela G. Dominguez. This has now been corrected in both the PDF and HTML versions of the Article.

The Rotterdam Prostate Cancer Risk Calculator (RPCRC) is a well-validated tool for upfront risk stratification to reduce the number of prostate biopsies and magnetic resonance imaging scans among both biopsy-naïve and previously biopsied men. The presence of invasive cribriform and/or intraductal carcinoma (CR/IDC) identifies men with aggressive grade group (GG) 2 tumors. This finding was recently incorporated in the RPCRC for biopsy-naïve men to predict the probability of no PCa, indolent PCa (GG 1 disease and GG 2 disease without CR/IDC), and clinically significant PCa (csPCa: GG 2 disease with CR/IDC and higher). The aim of the current study was to update the RPCRC for men with a previous negative biopsy with the presence of CR/IDC. A total of 2215 men were eligible for analyses, of whom 1776 (80%) were not diagnosed with PCa, 358 (16%) were diagnosed with indolent PCa, and 81 (4%) were diagnosed with csPCa according to the original 2014 Gleason grading. The optimism-corrected area under the curve was 0.69 for any PCa and 0.77 for csPCa. With a threshold of 10% for indolent PCa or 1% for csPCa, 20% of all prostate biopsies could be avoided and 2% of all csPCa cases would be missed. Our results support upfront risk stratification with the updated RPCRC. Patient summary: Risk stratification for men without a prior diagnosis of prostate cancer can reduce the number of prostate biopsies and magnetic resonance imaging scans carried out in this patient population. Our study shows that it is possible to update the Rotterdam Prostate Cancer Risk Calculator for men with a previous negative biopsy with the presence of invasive cribriform and/or intraductal carcinoma.

Background: Identification of intervention-related deaths is important for an accurate assessment of the ratio of benefit to harm in screening trials. Objective: To investigate intervention-related deaths by study arm in the European Randomized Study of Prostate Cancer Screening (ERSPC). Design, setting, and participants: ERSPC is a multicenter trial initiated in the 1990s to investigate whether screening on the basis of prostate-specific antigen (PSA) can decrease prostate cancer mortality. The present study included men in the core age group (55–69 yr: screening group n = 112 553, control group n = 128 681) with 16-yr follow-up. Outcome measurements and statistical analysis: Causes of death among men with prostate cancer in ERSPC were predominantly evaluated by independent national committees via review of medical records according to a predefined algorithm. Intervention-related deaths were defined as deaths caused by complications during the screening procedure, treatment, or follow-up. Descriptive statistics were used for the results. Results and limitations: In total, 34 deaths were determined to be intervention-related, of which 21 were in the screening arm and 13 in the control arm. The overall risk of intervention-related death was 1.41 (95% confidence interval 0.99–1.99) per 10 000 randomized men for both arms combined and varied among centers from 0 to 7.0 per 10 000 randomized men. A limitation of this study is that differences in procedures among centers decreased the comparability of the results. Conclusions: Intervention-related deaths were rare in ERSPC. Monitoring of intervention-related deaths in screening trials is important for assessment of harms. Patient summary: We investigated deaths due to screening or treatment to assess harm in a trial of prostate cancer screening. Few such deaths were identified.

Abstract 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 .

Two nomograms have been developed to predict the outcome of positron emission tomography (PET)/computed tomography (CT) imaging with68Ga-labeled ligands for prostate-specific membrane antigen (68Ga-PSMA) for patients with rising prostate-specific antigen after radical prostatectomy (RP). These nomograms quantify the ability of PSMA PET/CT to detect prostate cancer recurrences, and therefore provide critical information in determining the optimal timing for PSMA PET/CT in guiding salvage therapies. We validated the ability of these nomograms to accurately predict PET/CT outcome using another ligand tracer, 18F-DCFPyL. The external validation cohort consisted of 157 men from the Prostate Cancer Network Netherlands who underwent 18F-DCFPyL PET/CT to guide salvage therapies after RP. The nomogram of Rauscher et al (predicting a positive scan) showed accurate prediction of 50–80% (discrimination 0.68, 95% confidence interval [CI] 0.59–0.76). The nomogram of Luiting et al (predicting recurrence outside the prostatic fossa) showed accurate prediction for predicted probability values between 15% and 65%, with a small degree of overestimation for predicted probability values between 30% and 50% (discrimination 0.74, 95% CI 0.28–1.24). According to calibration curves, discrimination results, and decision curve analysis, we conclude that clinicians can use these 68Ga-PSMA–based nomograms to predict 18F-DCFPyL PET/CT outcome. These nomograms improve shared decision-making in determining the optimal time to initiate PSMA PET/CT–guided salvage therapies. Patient summary: Prediction tools developed for prostate scans (positron emission tomography, PET) using one type of radioactive tracer (chemicals labeled with gallium-68) are also accurate in predicting scan findings with another tracer (a chemical labeled with fluorine-18). Our study confirms that these tools can be used to guide decisions on the timing of treatments for prostate cancer recurrence.

This four-year longitudinal study examines how two facets of employability-professional ability and developmental proactivity-are linked to career events among workers ages 45 years and older. We construe employability as a personal resource that predicts a higher likelihood of experiencing positive career events and a lower likelihood of experiencing negative ones. Results reveal that developmental proactivity leads to a higher probability of internal promotion, while professional ability leads to a lower probability of salary loss, demotion, and unemployment. The findings indicate that these two facets of employability can offer critical insights for understanding the career events of older workers.

The role of insulin-like growth factors (IGF) in prostate cancer development is not fully understood. To investigate the association between circulating concentrations of IGFs (IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3) and prostate cancer risk, we pooled individual participant data from 17 prospective and two cross-sectional studies, including up to 10,554 prostate cancer cases and 13,618 control participants. Conditional logistic regression was used to estimate the ORs for prostate cancer based on the study-specific fifth of each analyte. Overall, IGF-I, IGF-II, IGFBP-2, and IGFBP-3 concentrations were positively associated with prostate cancer risk (Ptrend all ≤ 0.005), and IGFBP-1 was inversely associated weakly with risk (Ptrend = 0.05). However, heterogeneity between the prospective and cross-sectional studies was evident (Pheterogeneity = 0.03), unless the analyses were restricted to prospective studies (with the exception of IGF-II, Pheterogeneity = 0.02). For prospective studies, the OR for men in the highest versus the lowest fifth of each analyte was 1.29 (95% confidence interval, 1.16-1.43) for IGF-I, 0.81 (0.68-0.96) for IGFBP-1, and 1.25 (1.12-1.40) for IGFBP-3. These associations did not differ significantly by time-to-diagnosis or tumor stage or grade. After mutual adjustment for each of the other analytes, only IGF-I remained associated with risk. Our collaborative study represents the largest pooled analysis of the relationship between prostate cancer risk and circulating concentrations of IGF-I, providing strong evidence that IGF-I is highly likely to be involved in prostate cancer development. Cancer Res; 76(8); 2288-300. ©2016 AACR.

A polygenic hazard score (PHS1) improves prostate cancer screening accuracy in European patients. Here, the authors test the performance of a version compatible with OncoArray genotypes (PHS2) in a multi-ethnic dataset and find that it risk-stratifies men for any, aggressive, and fatal prostate cancer.