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Prostate Cancer Early Detection in the European Union and UK
Abstract
Abstract
Background and objective
While prostate cancer (PCa) incidence and mortality rates continue to rise, early detection of PCa remains highly controversial, and the research landscape is rapidly evolving. Existing systematic reviews (SRs) and meta-analyses (MAs) provide valuable insights, but often focus on single aspects of early detection, hindering a comprehensive understanding of the topic. We aim to fill this gap by providing a comprehensive SR of contemporary SRs covering different aspects of early detection of PCa in the European Union (EU) and the UK.
Methods
On June 1, 2023, we searched four databases (Medline ALL via Ovid, Embase, Web of Science, and Cochrane Central Register of Controlled Trials) and Google Scholar. To avoid repetition of previous studies, only SRs (qualitative, quantitative, and/or MAs) were considered eligible. In the data, common themes were identified to present the evidence systematically.
Key findings and limitations
We identified 1358 citations, resulting in 26 SRs eligible for inclusion. Six themes were identified: (1) invitation: men at general risk should be invited at >50 yr of age, and testing should be discontinued at >70 yr or with <10 yr of life expectancy; (2) decision-making: most health authorities discourage population-based screening and instead recommend a shared decision-making (SDM) approach, but implementation of SDM in clinical practice varies widely; decision aids help men make more informed and value-consistent screening decisions and decrease men’s intention to attempt screening, but these do not affect screening uptake; (3) acceptance: facilitators for men considering screening include social prompting by partners and clinician recommendations, while barriers include a lack of knowledge, low-risk perception, and masculinity attributes; (4) screening test and algorithm: prostate-specific antigen–based screening reduces PCa-specific mortality and metastatic disease in men aged 55–69 yr at randomisation if screened at least twice; (5) harms and benefits: these benefits come at the cost of unnecessary biopsies, overdiagnosis, and subsequent overtreatment; and (6) future of screening: risk-adapted screening including (prebiopsy) risk calculators, magnetic resonance imaging, and blood- and urine-based biomarkers could reduce these harms. To enable a comprehensive overview, we focused on SRs. These do not include the most recent prospective studies, which were therefore incorporated in the discussion.
Conclusions and clinical implications
By identifying consistent and conflicting evidence, this review highlights the evidence-based foundations that can be built upon, as well as areas requiring further research and improvement to reduce the burden of PCa in the EU and UK.
Patient summary
This review of 26 reviews covers various aspects of prostate cancer screening such as invitation, decision-making, screening tests, harms, and benefits. This review provides insights into existing evidence, highlighting the areas of consensus and discrepancies, to guide future research and improve prostate cancer screening strategies in Europe.
... When researchers report an association without clarifying the conceptual framework they are working within, their findings may need more practical utility or remain at a purely descriptive level without practical application. This issue is particularly relevant in current biomedical literature, where associations are often reported without clarifying their nature or potential clinical utility [10]. For example, finding that a biomarker is "associated" with a disease reveals little about its real utility: Can it be used for early diagnosis? ...
... The first objective involves identifying and quantifying patterns in biomedical data. This includes estimating frequency measures (such as prevalence and incidence), central tendency and dispersion measures, and characterizing distributions [10]. For example, the Global Burden of Disease study represents one of the most comprehensive descriptive efforts, providing detailed estimates of the global distribution of diseases and risk factors [25]. ...
... Another reason this conceptual confusion manifests in practice is the selection of study design when determining relationships between variables. Researchers frequently resort to cross-sectional designs, which, while useful, have inherent limitations for causal inference, including the phenomenon known as "reverse causation" [10]. Faced with these methodological limitations, authors often take refuge in conservative terms like "association" or "risk," even when their true objective is to explore causal relationships (especially since, as noted initially, they use tools typically associated with an explanatory scientific task). ...
The traditional classification of studies as descriptive and analytical has proven insufficient to capture the complexity of modern biomedical research, including oncology. This article proposes classification based on scientific tasks that distinguish three main categories: descriptive, predictive, and explanatory. The descriptive scientific task seeks to characterize patterns, distributions, and trends in health, serving as a foundation for highlighting disparities and inequities. The predictive scientific task focuses on anticipating future outcomes or identifying conditions, distinguishing between diagnostic (current) and prognostic (future) predictions, and employing multivariable models beyond traditional metrics like sensitivity and specificity. The explanatory scientific task aims to establish causal relationships, whether in etiological studies or treatment effect studies, which can be exploration or confirmatory, depending on the maturity of the causal hypothesis. Differentiating these scientific tasks is crucial because it determines the appropriate analysis and result interpretation methods. While research with descriptive scientific tasks should avoid unnecessary adjustments that may mask disparities, research with predictive scientific tasks requires rigorous validation and calibration, and study with explanatory scientific tasks must explicitly address causal assumptions. Each scientific task uniquely contributes to knowledge generation: descriptive scientific tasks inform health planning, predictive scientific tasks guide clinical decisions, and explanatory scientific tasks underpin interventions. This classification provides a coherent framework for aligning research objectives with suitable methods, enhancing the quality and utility of biomedical research.
... It offers advantages including minimal invasiveness, low cost, operational simplicity, and reduced heterogeneity, and has been extensively researched and applied in recent years [10,11]. For PCa diagnosis, serum PSA testing remains the most established liquid biopsy approach, frequently employed even in routine health screenings [12,13]. However, the low specificity of PSA often leads to overdiagnosis and overtreatment when used in isolation [12,14]. ...
... For PCa diagnosis, serum PSA testing remains the most established liquid biopsy approach, frequently employed even in routine health screenings [12,13]. However, the low specificity of PSA often leads to overdiagnosis and overtreatment when used in isolation [12,14]. To address this limitation, researchers have explored various alternative biomarkers, though most remain in the validation phase. ...
Background
The global incidence of prostate cancer (PCa) has been rising annually, and early diagnosis and treatment remain pivotal for improving therapeutic outcomes and patient prognosis. Concurrently, advancements in liquid biopsy technology have facilitated disease diagnosis and monitoring, with its minimally invasive nature and low heterogeneity positioning it as a promising approach for predicting disease progression. However, current liquid biopsy strategies for PCa predominantly rely on prostate-specific antigen (PSA), which lacks specificity and compromises diagnostic accuracy. Thus, there is an urgent need to identify novel liquid biopsy biomarkers to enable early and precise PCa diagnosis.
Methods
We integrated 12 machine learning algorithms to construct 113 combinatorial models, screening and validating an optimal PCa diagnostic panel across five datasets from TCGA and GEO databases. Subsequently, the biological feasibility of the selected predictive model was verified in one prostate epithelial cell line and five PCa cell lines. Robust RNA diagnostic targets were further validated for their expression in plasma samples to establish an RNA-based liquid biopsy strategy for PCa. Finally, plasma samples from PCa and benign prostatic hyperplasia (BPH) patients at Wuhan Tongji Hospital were collected to evaluate the strategy’s clinical significance.
Results
Differential analysis identified 1,071 candidate mRNAs, which were input into the integrated machine learning framework. Among the 113 combinatorial models, the 9-gene diagnostic panel selected by the Stepglm[both] and Enet[alpha = 0.4] algorithms demonstrated the highest diagnostic efficacy (mean AUC = 0.91), including JPH4, RASL12, AOX1, SLC18A2, PDZRN4, P2RY2, B3GNT8, KCNQ5, and APOBEC3C. Cell line experiments further validated AOX1 and B3GNT8 as robust RNA biomarkers, both exhibiting consistent PCa-specific expression in human plasma samples. In liquid biopsy analyses, AOX1 and B3GNT8 outperformed PSA in diagnostic accuracy, achieving a combined AUC of 0.91. Notably, these biomarkers also demonstrated diagnostic utility in patients with ISUP ≤ 2.
Conclusions
Through an integrated machine learning approach and clinical validation, we developed an RNA-based diagnostic panel for PCa. Specifically, we identified AOX1 and B3GNT8 as novel liquid biopsy biomarkers with promising clinical diagnostic value. These findings provide new targets and insights for early and precise PCa diagnosis.
... Prostate cancer (PCa) is the second most frequently diagnosed cancer among men worldwide [1], representing a significant public health concern. Despite advances in PCa diagnostic algorithms, including the adoption of risk-adapted approaches using risk calculators [2] and Magnetic Resonance Imaging (MRI) [3], 36% of newly diagnosed tumors are still considered clinically insignificant (overdiagnosed) [4], meaning they would not have caused any clinical consequences during a man's lifetime if left untreated. To mitigate the overtreatment of these clinically insignificant tumors, patients are often recommended to participate in active surveillance (AS) programs [5,6]. ...
... Compared to an annual schedule, measured over 10 years on AS.2 Per 1000 men, measured over 4 years on AS, for the lowest risk decile.3 Compared to NICE guidelines, measured over 1 year on AS. ...
Background/Objectives: To summarize the current state of knowledge regarding personalized, risk-based approaches in active surveillance (AS) for prostate cancer (PCa) and to explore the lessons learned from AS practices in other types of cancer. Methods: This mixed methods review combined a systematic review and a narrative review. The systematic review was conducted according to the Preferred Reporting Items for Systematic rviews and Meta-Analyses (PRISMA) guidelines, with searches performed in the Medline, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and Google Scholar databases. Only studies evaluating personalized, risk-based AS programs for PCa were included. The narrative review focused on AS approaches in other solid tumors (thyroid, breast, kidney, and bladder cancer) to contextualize the findings and highlight lessons learned. Results: After screening 3137 articles, 9 were suitable for inclusion, describing the following four unique risk-based AS tools: PRIAS, Johns Hopkins, Canary PASS, and STRATCANS. These models were developed using data from men with low-risk (Grade Group 1) disease, with little to no magnetic resonance imaging (MRI) data. They used patient information such as (repeated) prostate-specific antigen (PSA) measurements and biopsy results to predict the risk of upgrading at the next biopsy or at radical prostatectomy, or to assign a patient to a pre-defined risk category with a corresponding pre-defined follow-up (FU) regimen. Performance was moderate across models, with the area under the curve/concordance index values ranging from 0.58 to 0.85 and calibration was generally good. The PRIAS, Canary PASS, and STRATCANS models demonstrated the benefits of less burdensome biopsies, clinic visits, and MRIs during FU when used, compared to current one-size-fits-all practices. Although little is known about risk-based AS in thyroid, breast, kidney, and bladder cancer, learning from their current practices could further refine patient selection, streamline monitoring protocols, and address adoption barriers, improving AS’s overall effectiveness in PCa management. Conclusions: Personalized, risk-based AS models allow for a reduction in the FU burden for men at low risk of progression while maintaining sensitive FU visits for those at higher risk. The comparatively limited evidence and practice of risk-based AS in other cancer types highlight the advanced state of AS in PCa.
... The early diagnosis is of great significance for the prognosis and treatment of PCa patients. At present, risk screening indicators of PCa mainly include prostatespecific antigen (PSA) and digital rectal examination [6]. However, due to the gray area of PSA where non-cancer factors can also cause elevation, magnetic resonance imaging (MRI) is added as a supplement. ...
Prostate cancer (PCa) is a kind of malignant solid tumor commonly observed among males worldwide. The dilemma of increasing incidence with therapeutic resistance has become the leading issue in PCa clinical management. Ferroptosis is a new form of regulatory cell death caused by iron-dependent lipid peroxidation, which has a dual role in PCa evolution and treatment due to the multi-omics cascade of interactions among pathways and environmental stimuli. Hence deciphering the role of ferroptosis in carcinogenesis would provide novel insights and strategies for precision medicine and personalized healthcare against PCa. In this study, the mechanisms of ferroptosis during cancer development were summarized both at the molecular and tumor microenvironment level. Then literature-reported ferroptosis-related signatures in PCa, e.g., genes, non-coding RNAs, metabolites, natural products and drug components, were manually collected and functionally compared as drivers/inducers, suppressors/inhibitors, and biomarkers according to their regulatory patterns in PCa ferroptosis and pathogenesis. The state-of-the-art techniques for ferroptosis-related data integration, knowledge identification, and translational application to PCa theranostics were discussed from a combinative perspective of artificial intelligence-powered modelling and advanced material-oriented therapeutic scheme design. The prospects and challenges in ferroptosis-based PCa researches were finally highlighted to light up future wisdoms for the flourishing of current findings from bench to bedside.
... In addition, in contrast to the German guideline, the European Association of Urology recommends PSA as the primary screening test. 35 This recommendation is followed in several European countries with public health insurance (eg, Sweden). Until this divergence in clinical guidance can be solved, it remains relevant to provide preliminary evidence of the cost-effectiveness of different treatment options for patients with low-risk prostate cancer. ...
Background
Magnetic resonance-guided transurethral ultrasound ablation (MR-TULSA) is a new focal therapy for treating localised prostate cancer that is associated with fewer adverse effects (AEs) compared with established treatments. To support large-scale clinical implementation, information about cost-effectiveness is required.
Objective
To evaluate the cost–utility of MR-TULSA compared with robot-assisted radical prostatectomy (RARP), external beam radiation therapy (EBRT) and active surveillance (AS) for patients with low- to favourable intermediate-risk localised prostate cancer.
Design, setting and participants
A Markov model was developed targeting 60-year-old men diagnosed with low- to intermediate-risk localised prostate cancer over a time horizon of 40 years from the German Statutory Health Insurance (SHI) perspective. To assess the robustness of the results, deterministic and probabilistic sensitivity analyses were performed.
Intervention
Four different treatment strategies were compared: minimally invasive MR-TULSA, two definitive approaches (RARP and EBRT) and one observational strategy (AS).
Outcome measurements and statistical analysis
Outcomes were measured in overall costs, quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER).
Results
AS generated the highest number of QALYs (12.67), followed by MR-TULSA (12.35), EBRT (12.35) and RARP (12.20). RARP generated the lowest costs (€ 46 997) over one patient’s lifetime, while MR-TULSA was a slightly more expensive alternative (€48 826). The incremental cost-effectiveness ratio (ICER) of AS compared with RARP was €11 600 per QALY and of MR-TULSA compared with RARP was €12 193 per QALY, while EBRT was dominated. At a willingness-to-pay of €20 000 per QALY, the probability of being cost-effective is 44% for AS, 25% for RARP, 25% for MR-TULSA and 6% for EBRT.
Conclusions
All treatment options for 60-year-old men diagnosed with low- to intermediate-risk localised prostate cancer are affected by considerable uncertainty. Accepting high follow-up costs by applying a higher willingness-to-pay, AS is the most favourable treatment option.
Purpose of review
Men face distinctive health-related challenges as a result of biological, behavioral, and sociocultural factors. In addition, the modern healthcare system does not offer men equal opportunities and options to ensure sex-specific access and delivery to health services. Men's health concerns are, indeed, often not addressed or even forgotten. In this review, we wanted to assess the impact of biology and sociocultural effects on sex-specific life-expectancy.
Recent findings
Globally, men have a shorter life expectancy than women. With a 5.8 years gender gap in the USA and 5.4 in the EU-27 (both in 2022). Cardiovascular disease, cancer, and accidents continue to represent the primary causes of mortality for both genders with all having disproportional preponderance in men. In recent years, there has been a notable decline in age-adjusted mortality rates related to cancer, while there has been an increase in deaths from accidental and intentional self-harm. Moreover, in the United States, men are more likely than women to develop and die from nonsex-specific cancers. As a result, men's poor health affects productivity, absenteeism, and employment.
Summary
The status of men in healthcare is complex. It is rooted in history, culture, and institutions. To address disparities, we need a comprehensive approach that includes policy reforms, sociocultural changes, and a fair and equitable public discourse. Grassroots and top-down strategies are needed to ensure a value-based societal healthcare system acknowledging the unique health needs of men.
Background:
Patient decision aids are interventions designed to support people making health decisions. At a minimum, patient decision aids make the decision explicit, provide evidence-based information about the options and associated benefits/harms, and help clarify personal values for features of options. This is an update of a Cochrane review that was first published in 2003 and last updated in 2017.
Objectives:
To assess the effects of patient decision aids in adults considering treatment or screening decisions using an integrated knowledge translation approach.
Search methods:
We conducted the updated search for the period of 2015 (last search date) to March 2022 in CENTRAL, MEDLINE, Embase, PsycINFO, EBSCO, and grey literature. The cumulative search covers database origins to March 2022.
Selection criteria:
We included published randomized controlled trials comparing patient decision aids to usual care. Usual care was defined as general information, risk assessment, clinical practice guideline summaries for health consumers, placebo intervention (e.g. information on another topic), or no intervention.
Data collection and analysis:
Two authors independently screened citations for inclusion, extracted intervention and outcome data, and assessed risk of bias using the Cochrane risk of bias tool. Primary outcomes, based on the International Patient Decision Aid Standards (IPDAS), were attributes related to the choice made (informed values-based choice congruence) and the decision-making process, such as knowledge, accurate risk perceptions, feeling informed, clear values, participation in decision-making, and adverse events. Secondary outcomes were choice, confidence in decision-making, adherence to the chosen option, preference-linked health outcomes, and impact on the healthcare system (e.g. consultation length). We pooled results using mean differences (MDs) and risk ratios (RRs) with 95% confidence intervals (CIs), applying a random-effects model. We conducted a subgroup analysis of 105 studies that were included in the previous review version compared to those published since that update (n = 104 studies). We used Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to assess the certainty of the evidence.
Main results:
This update added 104 new studies for a total of 209 studies involving 107,698 participants. The patient decision aids focused on 71 different decisions. The most common decisions were about cardiovascular treatments (n = 22 studies), cancer screening (n = 17 studies colorectal, 15 prostate, 12 breast), cancer treatments (e.g. 15 breast, 11 prostate), mental health treatments (n = 10 studies), and joint replacement surgery (n = 9 studies). When assessing risk of bias in the included studies, we rated two items as mostly unclear (selective reporting: 100 studies; blinding of participants/personnel: 161 studies), due to inadequate reporting. Of the 209 included studies, 34 had at least one item rated as high risk of bias. There was moderate-certainty evidence that patient decision aids probably increase the congruence between informed values and care choices compared to usual care (RR 1.75, 95% CI 1.44 to 2.13; 21 studies, 9377 participants). Regarding attributes related to the decision-making process and compared to usual care, there was high-certainty evidence that patient decision aids result in improved participants' knowledge (MD 11.90/100, 95% CI 10.60 to 13.19; 107 studies, 25,492 participants), accuracy of risk perceptions (RR 1.94, 95% CI 1.61 to 2.34; 25 studies, 7796 participants), and decreased decisional conflict related to feeling uninformed (MD -10.02, 95% CI -12.31 to -7.74; 58 studies, 12,104 participants), indecision about personal values (MD -7.86, 95% CI -9.69 to -6.02; 55 studies, 11,880 participants), and proportion of people who were passive in decision-making (clinician-controlled) (RR 0.72, 95% CI 0.59 to 0.88; 21 studies, 4348 participants). For adverse outcomes, there was high-certainty evidence that there was no difference in decision regret between the patient decision aid and usual care groups (MD -1.23, 95% CI -3.05 to 0.59; 22 studies, 3707 participants). Of note, there was no difference in the length of consultation when patient decision aids were used in preparation for the consultation (MD -2.97 minutes, 95% CI -7.84 to 1.90; 5 studies, 420 participants). When patient decision aids were used during the consultation with the clinician, the length of consultation was 1.5 minutes longer (MD 1.50 minutes, 95% CI 0.79 to 2.20; 8 studies, 2702 participants). We found the same direction of effect when we compared results for patient decision aid studies reported in the previous update compared to studies conducted since 2015.
Authors' conclusions:
Compared to usual care, across a wide variety of decisions, patient decision aids probably helped more adults reach informed values-congruent choices. They led to large increases in knowledge, accurate risk perceptions, and an active role in decision-making. Our updated review also found that patient decision aids increased patients' feeling informed and clear about their personal values. There was no difference in decision regret between people using decision aids versus those receiving usual care. Further studies are needed to assess the impact of patient decision aids on adherence and downstream effects on cost and resource use.
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.
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.
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.
Introduction:
Prostate MRI is a well-established tool for the diagnostic work-up for men with suspected prostate cancer (PCa). Current recommendations advocate the use of multiparametric MRI (mpMRI), which is composed of three sequences: T2-weighted sequence (T2W), diffusion-weighted sequence (DWI) and dynamic contrast-enhanced sequence (DCE). Prior studies suggest that a biparametric MRI (bpMRI) approach, omitting the DCE sequences, may not compromise clinically significant cancer detection, though there are limitations to these studies, and it is not known how this may affect treatment eligibility. A bpMRI approach will reduce scanning time, may be more cost-effective and, at a population level, will allow more men to gain access to an MRI than an mpMRI approach.
Methods:
Prostate Imaging Using MRI±Contrast Enhancement (PRIME) is a prospective, international, multicentre, within-patient diagnostic yield trial assessing whether bpMRI is non-inferior to mpMRI in the diagnosis of clinically significant PCa. Patients will undergo the full mpMRI scan. Radiologists will be blinded to the DCE and will initially report the MRI using only the bpMRI (T2W and DWI) sequences. They will then be unblinded to the DCE sequence and will then re-report the MRI using the mpMRI sequences (T2W, DWI and DCE). Men with suspicious lesions on either bpMRI or mpMRI will undergo prostate biopsy. The main inclusion criteria are men with suspected PCa, with a serum PSA of ≤20 ng/mL and without prior prostate biopsy. The primary outcome is the proportion of men with clinically significant PCa detected (Gleason score ≥3+4 or Gleason grade group ≥2). A sample size of at least 500 patients is required. Key secondary outcomes include the proportion of clinically insignificant PCa detected and treatment decision.
Ethics and dissemination:
Ethical approval was obtained from the National Research Ethics Committee West Midlands, Nottingham (21/WM/0091). Results of this trial will be disseminated through peer-reviewed publications. Participants and relevant patient support groups will be informed about the results of the trial.
Trial registration number:
NCT04571840.
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.
In this article, Lazaros Belbasis and colleagues explain the rationale for umbrella reviews and the key steps involved in conducting an umbrella review, using a working example.
Purpose
Prostate cancer (PCa) screening, which relies on prostate-specific antigen (PSA) testing, is a contentious topic that received negative attention due to the low sensitivity and specificity of PSA to detect clinically significant PCa. In this context, due to the higher sensitivity and specificity of magnetic resonance imaging (MRI), several trials investigate the feasibility of “MRI-only” screening approaches, and question if PSA testing may be replaced within prostate cancer screening programs.
Methods
This narrative review discusses the current literature and the outlook on the potential of MRI-based PCa screening.
Results
Several prospective randomized population-based trials are ongoing. Preliminary study results appear to favor the “MRI-only” approach. However, MRI-based PCa screening programs face a variety of obstacles that have yet to be fully addressed. These include the increased cost of MRI, lack of broad availability, differences in MRI acquisition and interpretation protocols, and lack of long-term impact on cancer-specific mortality. Partly, these issues are being addressed by shorter and simpler MRI approaches (5–20 min bi-parametric MRI), novel quality indicators (PI-QUAL) and the implementation of radiomics (deep learning, machine learning).
Conclusion
Although promising preliminary results were reported, MRI-based PCa screening still lack long-term data on crucial endpoints such as the impact of MRI screening on mortality. Furthermore, the issues of availability, cost-effectiveness, and differences in MRI acquisition and interpretation still need to be addressed.
There is no generally accepted screening strategy for prostate cancer (PCa). From February 2014 to December 2019 a randomized trial (PROBASE) recruited 46 642 men at age 45 to determine the efficacy of risk‐adapted prostate‐specific antigen‐based (PSA) screening, starting at either 45 or 50 years. PSA tests are used to classify participants into a low (<1.5 ng/mL), intermediate (1.5‐2.99 ng/mL) or high (≥3 ng/mL) risk group. In cases of confirmed PSA values ≥3 ng/mL participants are recommended a prostate biopsy with multiparametric magnetic resonance imaging (mpMRI). Half of the participants (N = 23 341) were offered PSA screening immediately at age 45; the other half (N = 23 301) were offered digital rectal examination (DRE) with delayed PSA screening at age 50. Of 23 301 participants who accepted baseline PSA testing in the immediate screening arm, 89.2% fell into the low, 9.3% into intermediate, and 1.5% (N = 344) into the high risk group. Repeat PSA measurement confirmed high‐risk status for 186 men (0.8%), of whom 120 (64.5%) underwent a biopsy. A total of 48 PCas was detected (overall prevalence 0.2%), of which 15 had International Society of Uropathology (ISUP) grade 1, 29 had ISUP 2 and only 4 had ISUP ≥3 cancers. In the delayed screening arm, 23 194 participants were enrolled and 6537 underwent a DRE with 57 suspicious findings, two of which showed PCa (both ISUP 1; detection rate 0.03%). In conclusion, the prevalence of screen‐detected aggressive (ISUP ≥3) PCa in 45‐year‐old men is very low. DRE did not turn out effective for early detection of PCa.
Objectives
To evaluate the feasibility of a population‐based screening trial using prostate‐specific antigen (PSA), a kallikrein panel and multiparametric magnetic resonance imaging (MRI) aimed at minimizing overdiagnosis, while retaining mortality benefit.
Patients and Methods
Feasibility of the screening algorithm was evaluated in terms of participation, screening test results and cancer detection. A random sample of 400 men aged 65 years was identified from the population registry and invited for screening with three stepwise tests (PSA, kallikrein panel and MRI). Men with PSA levels ≥3 ng/mL were further tested with the kallikrein panel, and those with positive findings (risk >7.5%) were referred for prostate MRI. Men with positive MRI (Prostate Imaging Reporting and Data System [PI‐RADS] score 3–5) had targeted biopsies only. Men with negative MRI, but PSA density ≥0.15 underwent systematic biopsies.
Results
Of the 399 men invited, 158 (40%) participated and 27 had PSA levels ≥3 ng/mL (7% of the invited and 17% of the participants). Of these, 22 had a positive kallikrein panel (6% of the invited and 81% of the PSA‐positive men). Finally, 10 men (3% of the invited and 45% of 4Kscore [kallikrein panel]‐positive) had a suspicious MRI finding (PI‐RADS score ≥3) and five were diagnosed with a clinically significant prostate cancer (Gleason Grade Group [GG] ≥2) at fusion biopsy (3% of the participants), with two GG 1 cases (1%). Additional testing (kallikrein panel and MRI) after PSA reduced biopsies by 56%.
Conclusion
The findings constitute proof of principle for our screening protocol, as we achieved a substantial detection rate for clinically significant cancer with few clinically insignificant cases. Participation, however, was suboptimal.
Background:
Screening for prostate cancer has long been a debated, complex topic. The use of risk calculators for prostate cancer is recommended for determining patients' individual risk of cancer and the subsequent need for a prostate biopsy. These tools could lead to better discrimination of patients in need of invasive diagnostic procedures and optimized allocation of health care resources.
Objective:
The goal of the research was to systematically review available literature on the performance of current prostate cancer risk calculators in healthy populations by comparing the relative impact of individual items on different cohorts and on the models' overall performance.
Methods:
We performed a systematic review of available prostate cancer risk calculators targeted at healthy populations. We included studies published from January 2000 to March 2021 in English, Spanish, French, Portuguese, or German. Two reviewers independently decided for or against inclusion based on abstracts. A third reviewer intervened in case of disagreements. From the selected titles, we extracted information regarding the purpose of the manuscript, analyzed calculators, population for which it was calibrated, included risk factors, and the model's overall accuracy.
Results:
We included a total of 18 calculators from 53 different manuscripts. The most commonly analyzed ones were the Prostate Cancer Prevention Trial (PCPT) and European Randomized Study on Prostate Cancer (ERSPC) risk calculators developed from North American and European cohorts, respectively. Both calculators provided high diagnostic ability of aggressive prostate cancer (AUC as high as 0.798 for PCPT and 0.91 for ERSPC). We found 9 calculators developed from scratch for specific populations that reached a diagnostic ability as high as 0.938. The most commonly included risk factors in the calculators were age, prostate specific antigen levels, and digital rectal examination findings. Additional calculators included race and detailed personal and family history.
Conclusions:
Both the PCPR and ERSPC risk calculators have been successfully adapted for cohorts other than the ones they were originally created for with no loss of diagnostic ability. Furthermore, designing calculators from scratch considering each population's sociocultural differences has resulted in risk tools that can be well adapted to be valid in more patients. The best risk calculator for prostate cancer will be that which has been calibrated for its intended population and can be easily reproduced and implemented.
Trial registration:
PROSPERO CRD42021242110; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=242110.
Screening can reduce deaths if the people invited participate. However, good uptake is hard to achieve, and our current approaches are failing to engage the most vulnerable. A coherent model of screening behaviour to guide our understanding and intervention development is yet to be established. The present aim was to propose an Integrated Screening Action Model (I-SAM) to improve screening access.
The I-SAM synthesises existing models of health behaviour and empirical evidence. The I-SAM was developed following: i) an appraisal of the predominant models used within the screening literature; ii) the integration of the latest knowledge on behaviour change; with iii) the empirical literature, to inform the development of a theory-based approach to intervention development.
There are three key aspects to the I-SAM: i) a sequence of stages that people pass through in engaging in screening behaviour (based on the Precaution Adoption Process Model); ii) screening behaviour is shaped by the interaction between participant and environmental influences (drawing from the Access Framework); and iii) targets for intervention should focus on the sources of behaviour - ‘capability’, ‘opportunity’, and ‘motivation’ (based on the COM-B Model).
The I-SAM proposes an integrated model to support our understanding of screening behaviour and to identify targets for intervention. It will be an iterative process to test and refine the I-SAM and establish its value in supporting effective interventions to improve screening for all.
Context
Prostate‐specific antigen (PSA) testing increases prostate cancer diagnoses and reduces long‐term disease‐specific mortality, but also results in overdiagnoses and treatment‐related harms.
Objective
To systematically assess the benefits and harms of population‐based PSA screening and the potential net benefit to inform health policy decision‐makers in Germany.
Evidence Acquisition
We performed a protocol‐guided comprehensive literature search according to the Preferred Reporting Items for Systematic Reviews and Meta‐analyses (PRISMA) statement. All steps were performed by one or two investigators; any discrepancies were resolved by consensus. To allow subgroup analyses for identifying the optimal screening parameters, the eight national trials conducted under the umbrella of the European Randomised study of Screening for Prostate Cancer (ERSPC) were included as individual trials.
Evidence Synthesis
We included a total 11 randomised controlled trials (RCTs) with a total of 416 000 study participants. For all‐cause mortality, we found neither benefit nor harm. PSA screening was associated with a reduced risk of both prostate cancer mortality and the development of metastases. For the outcomes of health‐related quality of life, adverse effects and the consequences of false‐negative screening results there was no difference; however, this was due to the lack of eligible RCT data. Finally, PSA screening was associated with large numbers of overdiagnoses with adverse downstream consequences of unnecessary treatment (e.g. incontinence, erectile dysfunction) and large numbers of false‐positive PSA tests leading to biopsies associated with a small but not negligible risk of complications. Limitations of this assessment include the clinical heterogeneity and methodological limitations of the underlying studies.
Conclusions
The benefits of PSA‐based prostate cancer screening do not outweigh its harms. We failed to identify eligible screening studies of newer biomarkers, PSA derivatives or modern imaging modalities, which may alter the balance of benefit to harm.
Patient Summary
In the present study, we reviewed the evidence on the PSA blood test to screen men without symptoms for prostate cancer. We found that the small benefits experienced by some men do not outweigh the harms to many more men.
Objective
To describe the study design of the GÖTEBORG prostate cancer screening (PC) 2 (Göteborg-2), a prospective, randomised, population-based trial of PC screening. This trial evaluates whether prostate-specific antigen (PSA) testing followed by 3 Tesla prostate magnetic resonance imaging (MRI) and targeted biopsy can reduce overdiagnosis, while maintaining the detection of clinically significant cancer, compared to PSA-screening and systematic biopsy.
Materials and methods
A random sample of men 50–60 years in the Göteborg area, Sweden, identified from the Total Population Register, were randomised to either a screening or control group (CG). Participants in the screening group (SG) were further randomised into one of three arms: (1) PSA-test; if PSA ≥ 3 ng/mL, then MRI and systematic biopsy, plus targeted biopsy to suspicious lesions as per Prostate Imaging – Reporting and Data System, version 2 (PI-RADSv2) 3–5; (2) PSA-test; if PSA ≥ 3 ng/mL, then MRI, and targeted biopsy only if PI-RADSv2 3–5; (3) identical to Arm 2, except lower PSA-cut-off ≥1.8 ng/mL. The primary outcome is the detection rate of clinically insignificant PC (defined as Gleason Score 3 + 3 [Grade Group 1]) comparing all men with PSA ≥ 3 ng/mL in Arm 1 vs. Arm 2 + 3.
Results
Randomisation and enrolment started in September 2015. Accrual has hitherto resulted in 38,770 men randomised to the SG. The participation rate is 50%. Invitation to the first screening round was completed in June 2020.
Conclusions
The Göteborg-2 trial will provide new knowledge about the performance of prostate MRI in a screening setting.
Background
Being diagnosed with cancer, irrespective of type initiates a serious psychological concern. The increasing rate of detection of indolent prostate cancers is a source of worry to public health. Digital rectal examination and prostate-specific antigen tests are the commonly used prostate cancer screening tests. Understanding the diagnostic accuracies of these tests may provide clearer pictures of their characteristics and values in prostate cancer diagnosis. This review compared the sensitivities and specificities of digital rectal examination and prostate-specific antigen test in detection of clinically important prostate cancers using studies from wider population.
Main body
We conducted literature search in PubMed, Medline, Science Direct, Wiley Online, CINAHL, Scopus, AJOL and Google Scholar, using key words and Boolean operators. Studies comparing the sensitivity and specificity of digital rectal examination and prostate-specific antigen tests in men 40 years and above, using biopsy as reference standard were retrieved. Data were extracted and analysed using Review manager (RevMan 5.3) statistical software. The overall quality of the studies was good, and heterogeneity was observed across the studies. The result comparatively shows that prostate-specific antigen test has higher sensitivity ( P < 0.00001, RR 0.74, CI 0.67–0.83) and specificity ( P < 0.00001, RR 1.81, CI 1.54–2.12) in the detection of prostate cancers than digital rectal examination.
Conclusion
Prostate-specific antigen test has higher sensitivity and specificity in detecting prostate cancers from men of multiple ethnic origins. However, combination of prostate-specific antigen test and standardized digital rectal examination procedure, along with patients history, may improve the accuracy and minimize over-diagnoses of indolent prostate cancers.
Importance:
Screening for prostate cancer using prostate-specific antigen (PSA) testing can lead to problems of underdiagnosis and overdiagnosis. Short, noncontrast magnetic resonance imaging (MRI) or transrectal ultrasonography might overcome these limitations.
Objective:
To compare the performance of PSA testing, MRI, and ultrasonography as screening tests for prostate cancer.
Design, setting, and participants:
This prospective, population-based, blinded cohort study was conducted at 7 primary care practices and 2 imaging centers in the United Kingdom. Men 50 to 69 years of age were invited for prostate cancer screening from October 10, 2018, to May 15, 2019.
Interventions:
All participants underwent screening with a PSA test, MRI (T2 weighted and diffusion), and ultrasonography (B-mode and shear wave elastography). The tests were independently interpreted without knowledge of other results. Both imaging tests were reported on a validated 5-point scale of suspicion. If any test result was positive, a systematic 12-core biopsy was performed. Additional image fusion-targeted biopsies were performed if the MRI or ultrasonography results were positive.
Main outcomes and measures:
The main outcome was the proportion of men with positive MRI or ultrasonography (defined as a score of 3-5 or 4-5) or PSA test (defined as PSA ≥3 μg/L) results. Key secondary outcomes were the number of clinically significant and clinically insignificant cancers detected if each test was used exclusively. Clinically significant cancer was defined as any Gleason score of 3+4 or higher.
Results:
A total of 2034 men were invited to participate; of 411 who attended screening, 408 consented to receive all screening tests. The proportion with positive MRI results (score, 3-5) was higher than the proportion with positive PSA test results (72 [17.7%; 95% CI, 14.3%-21.8%] vs 40 [9.9%; 95% CI, 7.3%-13.2%]; P < .001). The proportion with positive ultrasonography results (score, 3-5) was also higher than the proportion of those with positive PSA test results (96 [23.7%; 95% CI, 19.8%-28.1%]; P < .001). For an imaging threshold of score 4 to 5, the proportion with positive MRI results was similar to the proportion with positive PSA test results (43 [10.6%; 95% CI, 7.9%-14.0%]; P = .71), as was the proportion with positive ultrasonography results (52 [12.8%; 95% CI, 9.9%-16.5%]; P = .15). The PSA test (≥3 ng/mL) detected 7 clinically significant cancers, an MRI score of 3 to 5 detected 14 cancers, an MRI score of 4 to 5 detected 11 cancers, an ultrasonography score of 3 to 5 detected 9 cancer, and an ultrasonography score of 4 to 5 detected 4 cancers. Clinically insignificant cancers were diagnosed by PSA testing in 6 cases, by an MRI score of 3 to 5 in 7 cases, an MRI score of 4 to 5 in 5 cases, an ultrasonography score of 3 to 5 in 13 cases, and an ultrasonography score of 4 to 5 in 7 cases.
Conclusions and relevance:
In this cohort study, when screening the general population for prostate cancer, MRI using a score of 4 or 5 to define a positive test result compared with PSA alone at 3 ng/mL or higher was associated with more men diagnosed with clinically significant cancer, without an increase in the number of men advised to undergo biopsy or overdiagnosed with clinically insignificant cancer. There was no evidence that ultrasonography would have better performance compared with PSA testing alone.
Objective
To explore the barriers to and facilitators of healthcare professionals’ implementation of SDM regarding screening programmes.
Method
A systematic review was conducted in PubMed, Cochrane Library, CINHAL, and PsyscInfo. The barriers and facilitators identified were classified into three factors based on their origin: patients, healthcare system performance, and healthcare professionals themselves.
Results
Eight studies were selected: seven related to cancer screening. The most significant facilitators were literacy and interest in active participation, both of which have their origins in patients. The most significant barriers identified for the first time in a systematic review were legal conflict, lack of remuneration and lack of flexibility in clinical guidelines in screening programmes.
Conclusion
The results of this study show that there are differences between barriers and facilitators for SDM when it is applied in the context of healthy people who perform preventive activities, particularly screening, in contrast to general medical consultation contexts.
Practical implications
The authors suggest that to advance in the practice of SDM, we need to develop and disseminate training documents. Further, SDM should be incorporated into clinical guidelines. There should be more studies focusing on healthcare professionals’ behaviour within the context of the uncertainty of screening programmes.
Background
This study aimed to review studies on willingness to pay (WTP) for prostate cancer screening.
Methods
This systematic-review was conducted based on the Preferred Reporting Items for Systematic Reviews guidelines. By searching six-health-database, WTP studies on prostate cancer screening using contingent valuation method published in English until March 2020 were included and those with unavailable full-text and inadequate quality-assessment scores were excluded. Smith checklist was used for the quality assessment. Extracted WTPs were converted to US dollar in 2018 using exchange rate parity and net present value formula to make comparison. Factors’ effect was assessed by vote counting.
Results
Six final studies published after 2006 reported above 70% Smith checklist items needed to be considered in contingent valuation study reports. Seven factors have positive effects on WTP. The reported WTP value varied from 11 in Japan and Germany, respectively.
Conclusion
WTP for prostate cancer screening was positive among all studied men. The results of factors’ effect assessment showed that better understanding prostate cancer risks or screening tests and factors such as age, income, family history of cancer, hospitalization history, and educational level have positive effects. Moreover, prostate-specific antigen history, health insurance, employment, and subject’s health assessment received less attention.
The results’ generalization to all countries is not applicable because there are no studies for low- and middle-income countries.
Systematic review registration
PROSPERO 2020 CRD42020172789
INTRODUCTIONThe effectiveness of cancer screening programmes is highly dependent on screening uptake. Many interventions have been tested to increase screening uptake. AIMThe goal of this study was to evaluate the effectiveness of cancer screening pamphlets as a standalone intervention. The outcome of interest was uptake of cancer screening tests. METHODSA systematic review was performed on the effectiveness of pamphlets compared to usual care without pamphlets. We searched five databases for research papers in English from 2000 up to May 2019. Randomised controlled trials were included. This research group independently selected studies, extracted data, assessed risk of bias and then compared the information as a group. RESULTSA total of nine trials involving 4912 participants met our inclusion criteria, of which five were about colorectal cancer screening, three were about prostate cancer screening and one was about lung cancer screening. Five of the nine trials showed that pamphlets alone increased uptake significantly, while the remaining four trials did not show significant effects. DISCUSSIONThere is some evidence that pamphlets increase uptake for cancer screenings, especially for colorectal cancer. Due to the small number of studies in this area, generalisability could be limited.
Background:
All-cause mortality has been suggested as an end-point in cancer screening trials in order to avoid biases in attributing the cause of death. The aim of this study was to investigate which sample size and follow-up is needed to find a significant reduction in all-cause mortality.
Methods:
A literature review was conducted to identify previous studies that modeled the effect of screening on all-cause mortality. Microsimulation modeling was used to simulate breast cancer, lung cancer, and colorectal cancer screening trials. Model outputs were: cancer-specific deaths, all-cause deaths, and life-years gained per year of follow-up.
Results:
There were large differences between the evaluated cancers. For lung cancer, when 40 000 high-risk people are randomized to each arm, a significant reduction in all-cause mortality could be expected between 11 and 13 years of follow-up. For breast cancer, a significant reduction could be found between 16 and 26 years of follow-up for a sample size of over 300 000 women in each arm. For colorectal cancer, 600 000 persons in each arm were required to be followed for 15-20 years. Our systematic literature review identified seven papers, which showed highly similar results to our estimates.
Conclusion:
Cancer screening trials are able to demonstrate a significant reduction in all-cause mortality due to screening, but require very large sample sizes. Depending on the cancer, 40 000-600 000 participants per arm are needed to demonstrate a significant reduction. The reduction in all-cause mortality can only be detected between specific years of follow-up, more limited than the timeframe to detect a reduction in cancer-specific mortality.
Importance:
US guidelines recommend that physicians engage in shared decision-making with men considering prostate cancer screening.
Objective:
To estimate the association of decision aids with decisional outcomes in prostate cancer screening.
Data sources:
MEDLINE, Embase, PsycINFO, CINAHL, and Cochrane CENTRAL were searched from inception through June 19, 2018.
Study selection:
Randomized trials comparing decision aids for prostate cancer screening with usual care.
Data extraction and synthesis:
Independent duplicate assessment of eligibility and risk of bias, rating of quality of the decision aids, random-effects meta-analysis, and Grading of Recommendations, Assessment, Development and Evaluations rating of the quality of evidence.
Main outcomes and measures:
Knowledge, decisional conflict, screening discussion, and screening choice.
Results:
Of 19 eligible trials (12 781 men), 9 adequately concealed allocation and 8 blinded outcome assessment. Of 12 decision aids with available information, only 4 reported the likelihood of a true-negative test result, and 3 presented the likelihood of false-negative test results or the next step if the screening test result was negative. Decision aids are possibly associated with improvement in knowledge (risk ratio, 1.38; 95% CI, 1.09-1.73; I2 = 67%; risk difference, 12.1; low quality), are probably associated with a small decrease in decisional conflict (mean difference on a 100-point scale, -4.19; 95% CI, -7.06 to -1.33; I2 = 75%; moderate quality), and are possibly not associated with whether physicians and patients discuss prostate cancer screening (risk ratio, 1.12; 95% CI, 0.90-1.39; I2 = 60%; low quality) or with men's decision to undergo prostate cancer screening (risk ratio, 0.95; 95% CI, 0.88-1.03; I2 = 36%; low quality).
Conclusions and relevance:
The results of this study provide moderate-quality evidence that decision aids compared with usual care are associated with a small decrease in decisional conflict and low-quality evidence that they are associated with an increase in knowledge but not with whether physicians and patients discussed prostate cancer screening or with screening choice. Results suggest that further progress in facilitating effective shared decision-making may require decision aids that not only provide education to patients but are specifically targeted to promote shared decision-making in the patient-physician encounter.
Objectives
To summarise and evaluate evidence from men who had not been diagnosed with prostate cancer about their perspectives on prostate care and prostate cancer.
Design
A systematic review of qualitative research, on the perspectives of non-cancerous men regarding prostate cancer prevention and care.
Setting
A wide range of settings including primary and secondary care.
Participants
Men from varied demographic backgrounds ranging between 40 to 80 years of age.
Data sources
Three databases (Ovid MEDLINE, Informit, PsychInfo) and Google Scholar were searched for peer-reviewed papers in English reporting research using qualitative methods (in-depth or semistructured interviews and focus groups).
Review methods
Thematic analysis using inductive and deductive codes. Thematic synthesis was achieved through iterative open, axial and thematic coding.
Results
Eight papers (reporting seven studies conducted in Australia, UK and Germany) met inclusion criteria. Four major themes were identified: understanding prostate cancer, masculinity and prostate cancer, barriers to prostate healthcare and managing prostate health. It was reported that men often did not understand screening, prostate anatomy or their prostate cancer risk, and that concerns about masculinity could deter men from seeking health checks. There was evidence of a need to improve doctor–patient communication about case finding.
Conclusion
Further investigation is required to identify and understand any differences in the perspectives and experiences of men who have not been diagnosed with prostate cancer in metropolitan and regional areas, especially where there may be variations in access to healthcare
Context: Although screening recommendations for prostate cancer using prostate-specific antigen testing often include shared decision making, the effect of patient decision aids on patients’ intention and uptake is unclear. This study aimed to review the effect of decision aids on men's screening intention, screening utilization, and the congruence between intentions and uptake.
Evidence acquisition: Data sources were searched through April 6, 2018, and includedMEDLINE, Scopus, CENTRAL, CT.gov, Cochrane report, PsycARTICLES, PsycINFO, and reference lists. This study included RCTs and observational studies of decision aids that measured prostate screening intention or behavior. The analysis was completed in April 2018.
Evidence synthesis: Eighteen studies (13 RCTs, four before–after studies, and one non-RCT) reported data on screening intention for ≅8,400 men and screening uptake for 2,385 men. Compared with usual care, the use of decision aids in any format results in fewer men (aged ≥40 years) planning to undergo prostate-specific antigen testing (risk ratio=0.88, 95% CI=0.81, 0.95, p=0.006, I2=66%, p<0.001, n=8). Many men did not follow their screening intentions during the first year after using a decision aid; however, most men who were planning to undergo screening did so (probability that men who wanted to be screened would receive screening was 95%).
Conclusions: Integration of decision aids in clinical practice may result in a decrease in the number of men who elect prostate-specific antigen testing, which may in turn reduce screening uptake. To ensure high congruence between intention and screening utilization, providers should not delay the shared decision-making discussion after patients use a decision aid.
Objective:
To investigate the efficacy and safety of prostate-specific antigen (PSA) testing to screen for prostate cancer.
Design:
Systematic review and meta-analysis.
Data sources:
Electronic search of Cochrane Central Register of Controlled Trials, Web of Science, Embase, Scopus, OpenGrey, LILACS, and Medline, and search of scientific meeting abstracts and trial registers to April 2018.
Eligibility criteria for selecting studies:
Randomised controlled trials comparing PSA screening with usual care in men without a diagnosis of prostate cancer.
Data extraction:
At least two reviewers screened studies, extracted data, and assessed the quality of eligible studies. A parallel guideline committee (BMJ Rapid Recommendation) provided input on the design and interpretation of the systematic review, including selection of outcomes important to patients. We used a random effects model to obtain pooled incidence rate ratios (IRR) and, when feasible, conducted subgroup analyses (defined a priori) based on age, frequency of screening, family history, ethnicity, and socioeconomic level, as well as a sensitivity analysis based on the risk of bias. The quality of the evidence was assessed with the GRADE approach.
Results:
Five randomised controlled trials, enrolling 721 718 men, were included. Studies varied with respect to screening frequency and intervals, PSA thresholds for biopsy, and risk of bias. When considering the whole body of evidence, screening probably has no effect on all-cause mortality (IRR 0.99, 95% CI 0.98 to 1.01; moderate certainty) and may have no effect on prostate-specific mortality (IRR 0.96, 0.85 to 1.08; low certainty). Sensitivity analysis of studies at lower risk of bias (n=1) also demonstrates that screening seems to have no effect on all-cause mortality (IRR 1.0, 0.98 to 1.02; moderate certainty) but may have a small effect on prostate-specific mortality (IRR 0.79, 0.69 to 0.91; moderate certainty). This corresponds to one less death from prostate cancer per 1000 men screened over 10 years. Direct comparative data on biopsy and treatment related complications from the included trials were limited. Using modelling, we estimated that for every 1000 men screened, approximately 1, 3, and 25 more men would be hospitalised for sepsis, require pads for urinary incontinence, and report erectile dysfunction, respectively.
Conclusions:
At best, screening for prostate cancer leads to a small reduction in disease-specific mortality over 10 years but has does not affect overall mortality. Clinicians and patients considering PSA based screening need to weigh these benefits against the potential short and long term harms of screening, including complications from biopsies and subsequent treatment, as well as the risk of overdiagnosis and overtreatment.
Systematic review registration:
PROSPERO registration number CRD42016042347.
Objectives
To investigate men’s values and preferences regarding prostate-specific antigen (PSA)-based screening for prostate cancer.
Design
Systematic review.
Data sources
We searched MEDLINE, EMBASE, PsycINFO and grey literature up to 2 September 2017.
Eligibility criteria
Primary studies of men’s values and preferences regarding the benefits and harms of PSA screening.
Data extraction and synthesis
Two independent reviewers extracted data and assessed risk of bias with a modified version of a risk of bias tool for values and preferences studies, the International Patient Decision Aid Standards instrument V.3 and the Cochrane Collaboration risk of bias tool.
Results
We identified 4172 unique citations, of which 11 studies proved eligible. Five studies investigated PSA screening using a direct choice study design, whereas six used decisions aids displaying patient-important outcomes. The direct choice studies used different methodologies and varied considerably in the reporting of outcomes. Two studies suggested that men were willing to forego screening with a small benefit in prostate cancer mortality if it would decrease the likelihood of unnecessary treatment or biopsies. In contrast, one study reported that men were willing to accept a substantial overdiagnosis to reduce their risk of prostate cancer mortality. Among the six studies involving decision aids, willingness to undergo screening varied substantially from 37% when displaying a hypothetical reduction in mortality of 10 per 1000 men, to 44% when displaying a reduction in mortality of 7 per 1000. We found no studies that specifically investigated whether values and preferences differed among men with family history, of African descent or with lower socioeconomic levels.
Conclusion
The variability of men’s values and preferences reflect that the decision to screen is highly preference sensitive. Our review highlights the need for shared decision making in men considering prostate cancer screening.
Trial registration number
CRD42018095585.
Background: Prostate cancer is a leading cause of cancer among men. Because screening for prostate cancer is a controversial issue, many experts in the field have defended the use of shared decision making using validated decision aids, which can be presented in different formats (eg, written, multimedia, Web). Recent studies have concluded that decision aids improve knowledge and reduce decisional conflict.
Objective: This meta-analysis aimed to investigate the impact of using Web-based decision aids to support men’s prostate cancer screening decisions in comparison with usual care and other formats of decision aids.
Methods: We searched PubMed, CINAHL, PsycINFO, and Cochrane CENTRAL databases up to November 2016. This search identified randomized controlled trials, which assessed Web-based decision aids for men making a prostate cancer screening decision and reported quality of decision-making outcomes. Two reviewers independently screened citations for inclusion criteria, extracted data, and assessed risk of bias. Using a random-effects model, meta-analyses were conducted pooling results using mean differences (MD), standardized mean differences (SMD), and relative risks (RR).
Results: Of 2406 unique citations, 7 randomized controlled trials met the inclusion criteria. For risk of bias, selective outcome reporting and participant/personnel blinding were mostly rated as unclear due to inadequate reporting. Based on seven items, two studies had high risk of bias for one item. Compared to usual care, Web-based decision aids increased knowledge (SMD 0.46; 95% CI 0.18-0.75), reduced decisional conflict (MD –7.07%; 95% CI –9.44 to –4.71), and reduced the practitioner control role in the decision-making process (RR 0.50; 95% CI 0.31-0.81). Web-based decision aids compared to printed decision aids yielded no differences in knowledge, decisional conflict, and participation in decision or screening behaviors. Compared to video decision aids, Web-based decision aids showed lower average knowledge scores (SMD –0.50; 95% CI –0.88 to –0.12) and a slight decrease in prostate-specific antigen screening (RR 1.12; 95% CI 1.01-1.25).
Conclusions: According to this analysis, Web-based decision aids performed similarly to alternative formats (ie, printed, video) for the assessed decision-quality outcomes. The low cost, readiness, availability, and anonymity of the Web can be an advantage for increasing access to decision aids that support prostate cancer screening decisions among men.
Objective:
Considering the importance of screening for prostate cancer, the possibility of damage resulting from indiscriminate screening and the difficulty of disclosure and adherence to the main guidelines on the subject, we aimed to identify current guidelines, look for common approaches and establish a core of conducts.
Method:
Systematic review of the literature on screening practice guidelines for prostate cancer searching the databases PubMed, Lilacs and Google Scholar and active search in the sites of several national health entities.
Results:
Twelve (12) guidelines were selected, whose analysis resulted in the identification of six common points of conduct, with the following minimum core of recommendations: (1) screening indication or not: must be individualized, and preceded by an informed decision; (2) tests used: PSA with or without rectal digital examination; (3) age at which initiate testing in men in general risk: 50-55 years; (4) age at which to initiate testing in men at increased risk: 40-45 years; (5) the interval between screening: annual or biennial; and (6) age at which to discontinue testing: 70 years-old or life expectancy less than 10 years.
Conclusion:
Although there are differences between them, it was possible to establish a minimum core of conducts that may be useful in the daily practice of the physician.
Purpose:
Although the digital rectal examination (DRE) is commonly performed to screen for prostate cancer, there is limited data to support its use in primary care. This review and meta-analysis aims to evaluate the diagnostic accuracy of DRE in screening for prostate cancer in primary care settings.
Methods:
We searched MEDLINE, Embase, DARE (Database of Abstracts of Reviews of Effects), Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) from their inception to June 2016. Six reviewers, in pairs, independently screened citations for eligibility and extracted data. Pooled estimates were calculated for sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of DRE in primary care settings using an inverse-variance meta-analysis. We used QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) and GRADE (Grades of Recommendation Assessment, Development, and Evaluation) guidelines to assess study risk of bias and quality.
Results:
Our search yielded 8,217 studies, of which 7 studies with 9,241 patients were included after the screening process. All patients analyzed underwent both DRE and biopsy. Pooled sensitivity of DRE performed by primary care clinicians was 0.51 (95% CI, 0.36-0.67; I2= 98.4%) and pooled specificity was 0.59 (95% CI, 0.41-0.76; I2= 99.4%). Pooled PPV was 0.41 (95% CI, 0.31-0.52; I2= 97.2%), and pooled NPV was 0.64 (95% CI, 0.58-0.70; I2= 95.0%). The quality of evidence as assessed with GRADE was very low.
Conclusion:
Given the considerable lack of evidence supporting its efficacy, we recommend against routine performance of DRE to screen for prostate cancer in the primary care setting.
Executive summary
Prostate cancer is the most common cancer in men in 112 countries, and accounts for 15% of cancers. In this Commission, we report projections of prostate cancer cases in 2040 on the basis of data for demographic changes worldwide and rising life expectancy. Our findings suggest that the number of new cases annually will rise from 1·4 million in 2020 to 2·9 million by 2040. This surge in cases cannot be prevented by lifestyle changes or public health interventions alone, and governments need to prepare strategies to deal with it. We have projected trends in the incidence of prostate cancer and related mortality (assuming no changes in treatment) in the next 10–15 years, and make recommendations on how to deal with these issues.
For the Commission, we established four working groups, each of which examined a different aspect of prostate cancer: epidemiology and future projected trends in cases, the diagnostic pathway, treatment, and management of advanced disease, the main problem for most men diagnosed with prostate cancer worldwide. Throughout we have separated problems in high-income countries (HICs) from those in low-income and middle-income countries (LMICs), although we acknowledge that this distinction can be an oversimplification (some rich patients in LMICs can access high-quality care, whereas many patients in HICs, especially the USA, cannot because of inadequate insurance coverage). The burden of disease globally is already substantial, but options to improve care are already available at moderate cost. We found that late diagnosis is widespread worldwide, but especially in LMICs, where it is the norm. Early diagnosis improves prognosis and outcomes, and reduces societal and individual costs, and we recommend changes to the diagnostic pathway that can be immediately implemented. For men diagnosed with advanced disease, optimal use of available technologies, adjusted to the resource levels available, could produce improved outcomes. We also found that demographic changes (ie, changing age structures and increasing life expectancy) in LMICs will drive big increases in prostate cancer, and cases are also projected to rise in high-income countries. This projected rise in cases has driven the main thrust of our recommendations throughout. Dealing with this rise in cases will require urgent and radical interventions, particularly in LMICs, including an emphasis on education (both of health professionals and the general population) linked to outreach programmes to increase awareness. If implemented, these interventions would shift the case mix from advanced to earlier-stage disease, which in turn would necessitate different treatment approaches: earlier diagnosis would prompt a shift from palliative to curative therapies based around surgery and radiotherapy. Although age-adjusted mortality from prostate cancer is falling in HICs, it is rising in LMICs. And, despite large, well known differences in disease incidence and mortality by ethnicity (eg, incidence in men of African heritage is roughly double that in men of European heritage), most prostate cancer research has disproportionally focused on men of European heritage. Without urgent action, these trends will cause global deaths from prostate cancer to rise rapidly.
Decisions around prostate-specific antigen screening require a patient-centred approach, considering the benefits and risks of potential harm. Using shared decision-making (SDM) can improve men's knowledge and reduce decisional conflict. SDM is supported by evidence, but can be difficult to implement in clinical settings. An inclusive definition of SDM was used in order to determine the prevalence of SDM in prostate cancer screening decisions. Despite consensus among guidelines endorsing SDM practice, the prevalence of SDM occurring before the decision to undergo or forgo prostate-specific antigen testing varied between 11% and 98%, and was higher in studies in which SDM was self-reported by physicians than in patient-reported recollections and observed practices. The influence of trust and continuity in physician-patient relationships were identified as facilitators of SDM, whereas common barriers included limited appointment times and poor health literacy. Decision aids, which can help physicians to convey health information within a limited time frame and give patients increased autonomy over decisions, are underused and were not shown to clearly influence whether SDM occurs. Future studies should focus on methods to facilitate the use of SDM in clinical settings.
Background:
Previous research quantified the effect of prostate-specific antigen (PSA)-based prostate cancer (PCa) screening on quality-adjusted life years using 11-yr follow-up data from the European Randomized Study of Screening for Prostate Cancer (ERSPC) extrapolated by the Microsimulation Screening Analysis (MISCAN). ERSPC data now matured to 21 yr of follow-up.
Objective:
To provide an overview of the effect of PSA-based screening on tumour characteristics and PCa treatment using long-term, detailed, empirical ERSPC data.
Design, setting, and participants:
Men were included from the ERSPC Rotterdam who were randomised to a PSA-based screening (S) or control (C) arm.
Outcome measurements and statistical analysis:
We assessed the effects of PSA-based screening on the number of PCa diagnoses, tumour characteristics, treatments, and cumulative incidence of disease progression. We also evaluated the changes in tumour characteristics and treatments over time for both study arms.
Results and limitations:
Among PCa patients in the S-arm, fewer patients were diagnosed with advanced tumour stages (T3/T4: 12% vs 23%; relative risk [RR] = 0.50; 95% confidence interval [CI] 0.44-0.57), less disease progression was observed, and less secondary treatment (30% vs 48%; RR = 0.61; 95% CI 0.57-0.66; p < 0.001) and less palliative treatment were needed (21% vs 55%; RR = 0.38; 95% CI 0.35-0.42) than among those in the C-arm. This was at the cost of overdiagnosis and increased local treatments (eg, radical prostatectomy: 32% vs 14%; RR = 2.18; 95% CI 1.92-2.48). Over time, the number of local treatments decreased, whereas expectant management strategies increased. The RRs of treatments were slightly different from those of the MISCAN.
Conclusions:
After 21 yr of follow-up, empirical data of the ERSPC showed that PSA-based screening reduces advanced PCa stages, disease progression, and extensive treatments at the cost of more overdiagnosis and probably more overtreatment. Our data showed reduced local treatments and increased expectant management strategies over time.
Patient summary:
Prostate-specific antigen-based screening reduces the number of invasive prostate cancer treatments needed, however, at the cost of more overdiagnosis and probably more overtreatment. Limiting these costs remains crucial to benefit optimally from prostate cancer screening.
Unlabelled:
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.
Context:
Prostate cancer (PCa) is one of the most common cancers worldwide. Understanding the epidemiology and risk factors of the disease is paramount to improve primary and secondary prevention strategies.
Objective:
To systematically review and summarize the current evidence on the descriptive epidemiology, large screening studies, diagnostic techniques, and risk factors of PCa.
Evidence acquisition:
PCa incidence and mortality rates for 2020 were obtained from the GLOBOCAN database of the International Agency for Research on Cancer. A systematic search was performed in July 2022 using PubMed/MEDLINE and EMBASE biomedical databases. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines and was registered in PROSPERO (CRD42022359728).
Evidence synthesis:
Globally, PCa is the second most common cancer, with the highest incidence in North and South America, Europe, Australia, and the Caribbean. Risk factors include age, family history, and genetic predisposition. Additional factors may include smoking, diet, physical activity, specific medications, and occupational factors. As PCa screening has become more accepted, newer approaches such as magnetic resonance imaging (MRI) and biomarkers have been implemented to identify patients who are likely to harbor significant tumors. Limitations of this review include the evidence being derived from meta-analyses of mostly retrospective studies.
Conclusions:
PCa remains the second most common cancer among men worldwide. PCa screening is gaining acceptance and will likely reduce PCa mortality at the cost of overdiagnosis and overtreatment. Increasing use of MRI and biomarkers for the detection of PCa may mitigate some of the negative consequences of screening.
Patient summary:
Prostate cancer (PCa) remains the second most common cancer among men, and screening for PCa is likely to increase in the future. Improved diagnostic techniques can help reduce the number of men who need to be diagnosed and treated to save one life. Avoidable risk factors for PCa may include factors such as smoking, diet, physical activity, specific medications, and certain occupations.
In the pre-PSA-detection era, a large proportion of men were diagnosed with metastatic prostate cancer and died of the disease; after the introduction of the serum PSA test, randomized controlled prostate cancer screening trials in the USA and Europe were conducted to assess the effect of PSA screening on prostate cancer mortality. Contradictory outcomes of the trials and the accompanying overdiagnosis resulted in recommendations against prostate cancer screening by organizations such as the United States Preventive Services Task Force. These recommendations were followed by a decline in PSA testing and a rise in late-stage diagnosis and prostate cancer mortality. Re-evaluation of the randomized trials, which accounted for contamination, showed that PSA-based screening does indeed reduce prostate cancer mortality; however, the debate about whether to screen or not to screen continues because of the considerable overdiagnosis that occurs using PSA-based screening. Meanwhile, awareness among the population of prostate cancer as a potentially lethal disease stimulates opportunistic screening practices that further increase overdiagnosis without the benefit of mortality reduction. However, in the past decade, new screening tools have been developed that make the classic PSA-only-based screening an outdated strategy. With improved use of PSA, in combination with age, prostate volume and with the application of prostate cancer risk calculators, a risk-adapted strategy enables improved stratification of men with prostate cancer and avoidance of unnecessary diagnostic procedures. This combination used with advanced detection techniques (such as MRI and targeted biopsy), can reduce overdiagnosis. Moreover, new biomarkers are becoming available and will enable further improvements in risk stratification.
Objectives
To systematically evaluates the evidence on ethnic differences in age-adjusted reference values of PSA.
Materials and Methods
In concordance with the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement, a review of English articles using Medline, Embase and Cochrane databases, from inception to December 2019 was conducted. Studies that reported the PSA upper reference value as 95th percentile of the cohort distribution, in healthy men aged 40 – 79, were included. Methodological quality was assessed with a modified version of the Agency for Healthcare Research and Quality checklist for cross-sectional studies.
Results
Forty-three studies examining 325,514 participants were included in the analysis. These were published between 1993 - 2018. Majority were prospective observational studies and reported the reference values in ten-year age intervals. Only five reports directly compared ethnic differences in PSA values. Due to missing data, six studies were not considered in the quantitative synthesis. For the remainder (37/43), heterogeneity in PSA reference values was considerable (Higgin's index = 99.2%), with age and ethnicity being the sole identified significant contributors. Accordingly, the pooled upper limits for PSA reference values were 2.1, 3.2, 4.9 and 6.5 ng/ml for men in their 40s, 50s, 60s, and 70s, respectively.
Conclusions
Moderate quality evidence suggest that upper PSA reference limits increased with age and significant ethnic differences were present.
ReIMAGINE Screening is a single-centre study assessing the feasibility of biparametric magnetic resonance imaging as a screening tool for prostate cancer. The study outcomes will take us a step towards more accurate and less harmful prostate cancer screening.
The burden of prostate cancer is increasing. Therefore, we need to implement a contemporary, organized, risk-stratified program for early detection to reduce both the harm from the disease and potential overdiagnosis and overtreatment, while avoiding underdiagnosis to considerably improve the harm-to-benefit ratio.
Multiparametric magnetic resonance imaging (mpMRI), the use of three multiple imaging sequences, typically T2-weighted, diffusion weighted (DWI) and dynamic contrast enhanced (DCE) images, has a high sensitivity and specificity for detecting significant cancer. Current guidance now recommends its use prior to biopsy. However, the impact of DCE is currently under debate regarding test accuracy. Biparametric MRI (bpMRI), using only T2 and DWI has been proposed as a viable alternative. We conducted a contemporary systematic review and meta-analysis to further examine the diagnostic performance of bpMRI in the diagnosis of any and clinically significant prostate cancer.
A systematic review of the literature from 01/01/2017 to 06/07/2019 was performed by two independent reviewers using predefined search criteria. The index test was biparametric MRI and the reference standard whole-mount prostatectomy or prostate biopsy. Quality of included studies was assessed by the QUADAS-2 tool. Statistical analysis included pooled diagnostic performance (sensitivity; specificity; AUC), meta-regression of possible covariates and head-to-head comparisons of bpMRI and mpMRI where both were performed in the same study.
Forty-four articles were included in the analysis. The pooled sensitivity for any cancer detection was 0.84 (95% CI, 0.80–0.88), specificity 0.75 (95% CI, 0.68–0.81) for bpMRI. The summary ROC curve yielded a high AUC value (AUC = 0.86). The pooled sensitivity for clinically significant prostate cancer was 0.87 (95% CI, 0.78–0.93), specificity 0.72 (95% CI, 0.56–0.84) and the AUC value was 0.87. Meta-regression analysis revealed no difference in the pooled diagnostic estimates between bpMRI and mpMRI.
This meta-analysis on contemporary studies shows that bpMRI offers comparable test accuracies to mpMRI in detecting prostate cancer. These data are broadly supportive of the bpMRI approach but heterogeneity does not allow definitive recommendations to be made. There is a need for prospective multicentre studies of bpMRI in biopsy naïve men.
In 2009, routine prostate cancer screening using a prostate-specific antigen (PSA) test was described as “the controversy that refuses to die.”¹(p1351) Unfortunately, 10 years later, the controversy is still alive and thriving.² Clinical trials have failed to resolve whether or to what degree screening using PSA tests help reduce prostate cancer–specific mortality, and it has long been clear that PSA screening tests increase the diagnosis of low-risk cancers and can lead to patient harm from potentially unnecessary biopsies and cancer treatment. As a result, many expert groups recommend shared decision-making (SDM) and informed patient choice for routine prostate cancer screening.³,4
Importance
Prostate cancer is the second leading cause of cancer death among US men.
Objective
To systematically review evidence on prostate-specific antigen (PSA)–based prostate cancer screening, treatments for localized prostate cancer, and prebiopsy risk calculators to inform the US Preventive Services Task Force.
Data Sources
Searches of PubMed, EMBASE, Web of Science, and Cochrane Registries and Databases from July 1, 2011, through July 15, 2017, with a surveillance search on February 1, 2018.
Study Selection
English-language reports of randomized clinical trials (RCTs) of screening; cohort studies reporting harms; RCTs and cohort studies of active localized cancer treatments vs conservative approaches (eg, active surveillance, watchful waiting); external validations of prebiopsy risk calculators to identify aggressive cancers.
Data Extraction and Synthesis
One investigator abstracted data; a second checked accuracy. Two investigators independently rated study quality.
Main Outcomes and Measures
Prostate cancer and all-cause mortality; false-positive screening results, biopsy complications, overdiagnosis; adverse effects of active treatments. Random-effects meta-analyses were conducted for treatment harms.
Results
Sixty-three studies in 104 publications were included (N = 1 904 950). Randomization to PSA screening was not associated with reduced risk of prostate cancer mortality in either a US trial with substantial control group contamination (n = 76 683) or a UK trial with low adherence to a single PSA screen (n = 408 825) but was associated with significantly reduced prostate cancer mortality in a European trial (n = 162 243; relative risk [RR], 0.79 [95% CI, 0.69-0.91]; absolute risk reduction, 1.1 deaths per 10 000 person-years [95% CI, 0.5-1.8]). Of 61 604 men screened in the European trial, 17.8% received false-positive results. In 3 cohorts (n = 15 136), complications requiring hospitalization occurred in 0.5% to 1.6% of men undergoing biopsy after abnormal screening findings. Overdiagnosis was estimated to occur in 20.7% to 50.4% of screen-detected cancers. In an RCT of men with screen-detected prostate cancer (n = 1643), neither radical prostatectomy (hazard ratio [HR], 0.63 [95% CI, 0.21-1.93]) nor radiation therapy (HR, 0.51 [95% CI, 0.15-1.69]) were associated with significantly reduced prostate cancer mortality vs active monitoring, although each was associated with significantly lower risk of metastatic disease. Relative to conservative management, radical prostatectomy was associated with increased risk of urinary incontinence (pooled RR, 2.27 [95% CI, 1.82-2.84]; 3 trials; n = 1796) and erectile dysfunction (pooled RR, 1.82 [95% CI, 1.62-2.04]; 2 trials; n = 883). Relative to conservative management (8 cohort studies; n = 3066), radiation therapy was associated with increased risk of erectile dysfunction (pooled RR, 1.31 [95% CI, 1.20-1.42]).
Conclusions and Relevance
PSA screening may reduce prostate cancer mortality risk but is associated with false-positive results, biopsy complications, and overdiagnosis. Compared with conservative approaches, active treatments for screen-detected prostate cancer have unclear effects on long-term survival but are associated with sexual and urinary difficulties.
INTRODUCTION: Men facing prostate cancer screening and treatment need to make critical and highly preferencesensitive decisions that involve a variety of potential benefits and risks. Shared decision-making (SDM) is considered fundamental for "preference-sensitive" medical decisions and it is guideline-recommended. There is no single definition of SDM however. We systematically reviewed the extent of SDM implementation in interventions to facilitate SDM for prostate cancer screening and treatment. METHODS: We searched Medline Ovid, Embase (Elsevier), CINHAL (EBSCOHost), The Cochrane Library (Wiley), PsychINFO (EBSCOHost), Scopus, clinicaltrials.gov, ISRCTN registry, the WHO search portal, ohri.ca, opengrey. eu, Google Scholar, and the reference lists of included studies, clinical guidelines and relevant reviews. We also contacted the authors of relevant abstracts without available full text. We included primary peer-reviewed and grey literature of randomised controlled trials (RCTs) reported in English, conducted in primary and specialised care, addressing interventions aiming to facilitate SDM for prostate cancer screening and treatment. Two reviewers independently selected studies, appraised interventions and assessed the extent of SDM implementation based on the key features of SDM, namely information exchange, deliberation and implementation. We considered bi-directional deliberation as a central and mandatory component of SDM. We performed a narrative synthesis. RESULTS: Thirty-six RCTs including 19 196 randomised patients met the eligibility criteria; they were mainly conducted in North America (n = 28). The median year of publication was 2008 (1997-2015). Twenty-three RCTs addressed decision-making for screening, twelve for treatment and one for both screening and treatment for prostate cancer. Bi-directional interactions between healthcare providers and patients were verified in 31 RCTs, but only 14 fulfilled the three key SDM features, 14 had at least "deliberation", one had "unclear deliberation" and two had no signs of deliberation. CONCLUSIONS: There is significant variation in the extent of SDM implementation among studies addressing SDM for prostate cancer screening and treatment. Further evaluation of these results on patient outcomes, a standardised SDM definition and guidance for an effective implementation in several clinical settings are needed.
Importance
Prostate cancer screening remains controversial because potential mortality or quality-of-life benefits may be outweighed by harms from overdetection and overtreatment.
Objective
To evaluate the effect of a single prostate-specific antigen (PSA) screening intervention and standardized diagnostic pathway on prostate cancer–specific mortality.
Design, Setting, and Participants
The Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP) included 419 582 men aged 50 to 69 years and was conducted at 573 primary care practices across the United Kingdom. Randomization and recruitment of the practices occurred between 2001 and 2009; patient follow-up ended on March 31, 2016.
Intervention
An invitation to attend a PSA testing clinic and receive a single PSA test vs standard (unscreened) practice.
Main Outcomes and Measures
Primary outcome: prostate cancer–specific mortality at a median follow-up of 10 years. Prespecified secondary outcomes: diagnostic cancer stage and Gleason grade (range, 2-10; higher scores indicate a poorer prognosis) of prostate cancers identified, all-cause mortality, and an instrumental variable analysis estimating the causal effect of attending the PSA screening clinic.
Results
Among 415 357 randomized men (mean [SD] age, 59.0 [5.6] years), 189 386 in the intervention group and 219 439 in the control group were included in the analysis (n = 408 825; 98%). In the intervention group, 75 707 (40%) attended the PSA testing clinic and 67 313 (36%) underwent PSA testing. Of 64 436 with a valid PSA test result, 6857 (11%) had a PSA level between 3 ng/mL and 19.9 ng/mL, of whom 5850 (85%) had a prostate biopsy. After a median follow-up of 10 years, 549 (0.30 per 1000 person-years) died of prostate cancer in the intervention group vs 647 (0.31 per 1000 person-years) in the control group (rate difference, −0.013 per 1000 person-years [95% CI, −0.047 to 0.022]; rate ratio [RR], 0.96 [95% CI, 0.85 to 1.08]; P = .50). The number diagnosed with prostate cancer was higher in the intervention group (n = 8054; 4.3%) than in the control group (n = 7853; 3.6%) (RR, 1.19 [95% CI, 1.14 to 1.25]; P < .001). More prostate cancer tumors with a Gleason grade of 6 or lower were identified in the intervention group (n = 3263/189 386 [1.7%]) than in the control group (n = 2440/219 439 [1.1%]) (difference per 1000 men, 6.11 [95% CI, 5.38 to 6.84]; P < .001). In the analysis of all-cause mortality, there were 25 459 deaths in the intervention group vs 28 306 deaths in the control group (RR, 0.99 [95% CI, 0.94 to 1.03]; P = .49). In the instrumental variable analysis for prostate cancer mortality, the adherence-adjusted causal RR was 0.93 (95% CI, 0.67 to 1.29; P = .66).
Conclusions and Relevance
Among practices randomized to a single PSA screening intervention vs standard practice without screening, there was no significant difference in prostate cancer mortality after a median follow-up of 10 years but the detection of low-risk prostate cancer cases increased. Although longer-term follow-up is under way, the findings do not support single PSA testing for population-based screening.
Trial Registration
ISRCTN Identifier: ISRCTN92187251
Already in 1991 when the prostate-specific antigen (PSA) test was proposed as a diagnostic test, screening for prostate cancer (PCa) was considered controversial due to the considerable risk of detecting latent PCa. Randomised controlled trials were initiated to assess the potential of PSA-based screening in reducing disease-specific mortality. Harms and benefit were closely monitored and both were confirmed. A reduction in mortality was seen and at the same time the initial fear of unnecessary testing and over diagnosis became reality. This triggered professional organizations to adapt their guidelines and to focus on shared decision making (SDM) and selective screening for those men considered at high risk. Unfortunately implementation of guidelines into daily clinical practice is bothersome. As a result many men are being (re) tested while not being at risk and the potential benefit being unclear. This raises the question on whether PSA screening should be organized in controlled programs. While the PSA test will remain the mainstay of PCa early detection many other additional tests (biomarkers/imaging) are currently being tested in large population-based initiatives as a first step to organized programs in selective groups of men.
Context:
Globally, uptake of health screening in men remains low and the effectiveness of interventions to promote screening uptake in men is not well established. This review aimed to determine the effectiveness of interventions in improving men's uptake of and intention to undergo screening, including interventions using information and communication technology and a male-sensitive approach.
Evidence acquisition:
Studies were sourced from five electronic databases (October 2015), experts, and references of included studies. This study included RCTs or cluster RCTs that recruited men and reported uptake of or intention to undergo screening. Two researchers independently performed study selection, appraisal, and data extraction. The interventions were grouped into those that increase uptake and those that promote informed decision making. They were further sub-analyzed according to types of intervention, male-sensitive, and web- and video-based interventions. The analysis was completed in December 2016.
Evidence synthesis:
This review included 58 studies. Most studies were on prostate cancer (k=31) and HIV (k=11) screening. Most of the studies had low methodologic quality (79.3%) and after excluding them from the analysis, one study found that educational intervention (which was also male-sensitive) was effective in improving men's intention to screen (risk ratio=1.36, 95% CI=1.23, 1.50, k=1) and partner educational intervention increased men's screening uptake (risk ratio=1.77, 95% CI=1.48, 2.12, k=1). Video-based educational interventions reduced prostate cancer screening uptake (risk ratio=0.89, 95%CI=0.80, 0.99, k=1) but web-based interventions did not change men's screening intention or uptake.
Conclusions:
This review highlights the need to conduct more robust studies to provide conclusive evidence on the effectiveness of different interventions to improve men's screening behavior.