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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’.

Objectives: To prospectively evaluate how the Prostate Health Index (PHI) impacts on clinical decision in a real‐life setting for men with a prostate‐specific antigen (PSA) level between 4 and 10 ng/mL and normal digital rectal examination. Patients and Methods: Since 2016, the PHI has been available at no cost to eligible men in all Hong Kong public hospitals. All eligible patients who received PHI testing in all public Urology units (n = 16) in Hong Kong between May 2016 and August 2017 were prospectively included and followed up. All included men had a PHI test, with its result and implications explained; the subsequent follow‐up plan was then decided via shared decision‐making with urologists. Patients were followed up for 2 years, with outcomes including prostate biopsy rates and biopsy findings analysed in relation to the initial PHI measurements. Results: A total of 2828 patients were followed up for 2 years. The majority (82%) had PHI results in the lower risk range (score <35). Knowing the PHI findings, 83% of the patients with elevated PSA decided not to undergo biopsy. In all, 11% and 45% opted for biopsy in the PHI score <35 and ≥35 groups, respectively. The initial detection rate of International Society of Urological Pathology (ISUP) Grade Group (GG) ≥2 cancer was higher in the PHI score ≥35 group (23%) than in the PHI score <35 group (7.9%). Amongst patients with no initial positive biopsy findings, the subsequent positive biopsy rate for ISUP GG ≥2 cancer was higher in the PHI score ≥35 group (34%) than the PHI score <35 group (13%) with a median follow‐up of 2.4 years. Conclusion: In a real‐life setting, with the PHI incorporated into the routine clinical pathway, 83% of the patients with elevated PSA level decided not to undergo prostate biopsy. The PHI pathway also improved the high‐grade prostate cancer detection rate when compared to PSA‐driven strategies. Higher baseline PHI predicted subsequent biopsy outcome at 2 years. The PHI can serve as a tool to individualise biopsy decisions and frequency of follow‐up visits. [ABSTRACT FROM AUTHOR]

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.

Aims: To investigate the surgical margin status in patients with prostate cancer who underwent robot‐assisted radical prostatectomy (RARP) with intraoperative neurovascular structure‐adjacent frozen‐section analysis (NeuroSAFE) and evaluate differences compared to patients who underwent radical prostatectomy without NeuroSAFE. Patients and Methods: Between September 2018 and January 2021, 962 patients underwent centralized RARP with NeuroSAFE. A secondary resection was performed in case of a positive surgical margin (PSM) on intraoperative frozen section (IFS) analysis to convert a PSM into a negative surgical margin (NSM). A retrospective cohort consisted of 835 patients who had undergone radical prostatectomy in a tertiary centre without NeuroSAFE between January 2000 and December 2017. We performed multivariable logistic regression to evaluate differences in risk of PSM between cohorts after controlling for clinicopathological variables. Results: Patients operated with NeuroSAFE in the centralized clinic had 29% PSM at a definitive pathological RP examination. The median cumulative length of definitive PSM was 1.1 mm (interquartile range: 0.4–3.8). Among 275 men with PSM, 136 (49%) had a cumulative length ≤1 mm and 198 (72%) ≤3 mm. After controlling for PSA, Grade group, cribriform pattern, pT‐stage, and pN‐stage, patients treated in the centralized clinic with NeuroSAFE had significantly lower odds on PSM (odds ratio [OR]: 0.70, 95% confidence interval [CI]: 0.56–0.88; P = 0.002), PSM length >1 mm (OR: 0.14, 95% CI: 0.09–0.22; P < 0.001), and >3 mm (OR: 0.21, 95% CI: 0.14–0.30; P < 0.001). Conclusion: This study provides a detailed overview of surgical margin status in a centralized RP NeuroSAFE cohort. Centralization with NeuroSAFE was associated with lower PSM rates and significantly shorter PSM cumulative lengths, indicating improved control of surgical margin status. [ABSTRACT FROM AUTHOR]

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.