Urologists regularly develop clinical risk prediction models to support clinical decisions. In contrast to traditional performance measures, decision curve analysis (DCA) can assess the utility of ...models for decision making. DCA plots net benefit (NB) at a range of clinically reasonable risk thresholds.
To provide recommendations on interpreting and reporting DCA when evaluating prediction models.
We informally reviewed the urological literature to determine investigators’ understanding of DCA. To illustrate, we use data from 3616 patients to develop risk models for high-grade prostate cancer (n=313, 9%) to decide who should undergo a biopsy. The baseline model includes prostate-specific antigen and digital rectal examination; the extended model adds two predictors based on transrectal ultrasound (TRUS).
We explain risk thresholds, NB, default strategies (treat all, treat no one), and test tradeoff. To use DCA, first determine whether a model is superior to all other strategies across the range of reasonable risk thresholds. If so, that model appears to improve decisions irrespective of threshold. Second, consider if there are important extra costs to using the model. If so, obtain the test tradeoff to check whether the increase in NB versus the best other strategy is worth the additional cost. In our case study, addition of TRUS improved NB by 0.0114, equivalent to 1.1 more detected high-grade prostate cancers per 100 patients. Hence, adding TRUS would be worthwhile if we accept subjecting 88 patients to TRUS to find one additional high-grade prostate cancer or, alternatively, subjecting 10 patients to TRUS to avoid one unnecessary biopsy.
The proposed guidelines can help researchers understand DCA and improve application and reporting.
Decision curve analysis can identify risk models that can help us make better clinical decisions. We illustrate appropriate reporting and interpretation of decision curve analysis.
Decision curve analysis (DCA) is a method to evaluate whether risk prediction models can have utility for supporting treatment decisions. This guide for researchers explains what DCA is, how to interpret it, and how to report its results.
Abstract Context Multiparametric magnetic resonance imaging (MRI) of the prostate may improve the diagnostic accuracy of prostate cancer detection in MRI-targeted biopsy (MRI-TBx) in comparison to ...transrectal ultrasound-guided biopsy (TRUS-Bx). Objective Systematic review and meta-analysis of evidence regarding the diagnostic benefits of MRI-TBx versus TRUS-Bx in detection of overall prostate cancer (primary objective) and significant/insignificant prostate cancer (secondary objective). Evidence acquisition A systematic review of Embase, Medline, Web of Science, Scopus, PubMed, Cinahl, and the Cochrane library was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Identified reports were critically appraised according to the Quality Assessment of Diagnostic Accuracy Studies criteria. Only men with a positive MRI were included. Evidence synthesis The reports we included (16 studies) used both MRI-TBx and TRUS-Bx for prostate cancer detection. A cumulative total of 1926 men with positive MRI were included, with prostate cancer prevalence of 59%. MRI-TBx and TRUS-Bx did not significantly differ in overall prostate cancer detection (sensitivity 0.85, 95% confidence interval CI 0.80–0.89, and 0.81, 95% CI 0.70–0.88, respectively). MRI-TBx had a higher rate of detection of significant prostate cancer compared to TRUS-Bx (sensitivity 0.91, 95% CI 0.87–0.94 vs 0.76, 95% CI 0.64–0.84) and a lower rate of detection of insignificant prostate cancer (sensitivity 0.44, 95% CI 0.26–0.64 vs 0.83, 95% confidence interval 0.77–0.87). Subgroup analysis revealed an improvement in significant prostate cancer detection by MRI-TBx in men with previous negative biopsy, rather than in men with initial biopsy (relative sensitivity 1.54, 95% CI 1.05–2.57 vs 1.10, 95% CI 1.00–1.22). Because of underlying methodological flaws of MRI-TBx, the comparison of MRI-TBx and TRUS-Bx needs to be regarded with caution. Conclusions In men with clinical suspicion of prostate cancer and a subsequent positive MRI, MRI-TBx and TRUS-Bx did not differ in overall prostate cancer detection. However, MRI-TBx had a higher rate of detection of significant prostate cancer and a lower rate of detection of insignificant prostate cancer compared with TRUS-Bx. Patient summary We reviewed recent advances in magnetic resonance imaging (MRI) for guidance and targeting of prostate biopsy for prostate cancer detection. We found evidence to suggest that MRI-guided targeted biopsy benefits the diagnosis of prostate cancer.
This review discusses evidence for population‐based screening with contemporary screening tools. In Europe, prostate‐specific antigen (PSA)‐based screening led to a relative reduction of prostate ...cancer (PCa) mortality, but also to a substantial amount of overdiagnosis and unnecessarily biopsies. Risk stratification based on a single variable (a clinical variable or based on the presence of a lesion on prostate imaging) or based on multivariable approaches can aid in reducing unnecessary prostate biopsies and overdiagnosis by selecting men who can benefit from further clinical assessment. Multivariable approaches include clinical variables, and biomarkers, often combined in risk calculators or nomograms. These risk calculators can also incorporate the result of MRI imaging. In general, as compared to a purely PSA based approach, the combination of relevant prebiopsy information results in superior selection of men at higher risk of harboring clinically significant prostate cancer. Currently, it is not possible to draw any conclusions on the superiority of these multivariable risk‐based approaches since head‐to‐head comparisons are virtually lacking. Recently initiated large population‐based screening studies in Finland, Germany and Sweden, incorporating various multivariable risk stratification approaches will hopefully give more insight in whether the harm‐benefit ratio can be improved, that is, maintain (or improving) the ability to reduce metastatic disease and prostate cancer mortality while reducing harm caused by unnecessary testing and overdiagnosis including related overtreatment.
Recommendations against prostate-specific antigen (PSA) testing in 2012 have increased advanced-stage diagnosis and prostate cancer–specific mortality rates.
To present the position of the European ...Association of Urology (EAU) in 2021 and provide recommendations for the use of PSA testing as part of a risk-adapted strategy for the early detection of prostate cancer.
The authors combined their review of relevant literature, including the EAU prostate cancer guidelines 2021 update, with their own knowledge to provide an expert opinion, representing the EAU’s position in 2021.
The EAU has developed a risk-adapted early prostate cancer detection strategy for well-informed men based on PSA testing, risk calculators, and multiparametric magnetic resonance imaging, which can differentiate significant from insignificant prostate cancer. This approach largely avoids the overdiagnosis/overtreatment of men unlikely to experience disease-related symptoms during their lifetime and facilitates an early diagnosis of men with significant cancer to receive active treatment. It also reduces advanced-stage diagnosis, thereby potentially reducing prostate cancer–specific mortality and improving quality of life. Education is required among urologists, general practitioners, radiologists, policy makers, and healthy men, including endorsement by the European Commission to adapt the European Council’s screening recommendations in its 2022 plan and requests to individual countries for its incorporation into national cancer plans.
This risk-adapted approach for the early detection of prostate cancer will reverse current unfavourable trends and ultimately save lives.
The European Association of Urology has developed a patient information leaflet and algorithm for the early diagnosis of prostate cancer. It can identify men who do not need magnetic resonance imaging or a biopsy and those who would not show any symptoms versus those with more aggressive disease who require further tests/treatment. We need to raise awareness of this algorithm to ensure that all well-informed men at risk of significant prostate cancer are offered a prostate-specific antigen test.
A risk-adapted early prostate cancer detection strategy, incorporating prostate-specific antigen testing, multiparametric magnetic resonance imaging, risk calculators, and biomarkers, will avoid overdiagnosis/overtreatment of insignificant cancers and ensure early detection and treatment of significant cancers, thereby improving quality of life and reducing prostate cancer–related deaths.
Abstract Background The Prostate Cancer Research International Active Surveillance (PRIAS) study was initiated a decade ago to study the most optimal selection and follow-up of men on active ...surveillance (AS). Objective We report on 10 yr of follow-up of men on AS in the PRIAS study and evaluate if criteria used to recommend a switch to active treatment truly predict unfavorable outcome on subsequent radical prostatectomy (RP). Design, setting, and participants Men with low-risk prostate cancer were included and followed prospectively on AS. Follow-up consisted of regular prostate-specific antigen (PSA) tests, digital rectal examinations, and biopsies. Men with Gleason >3 + 3, more than two positive biopsy cores, or stage higher than cT2 were advised to switch to active treatment (until 2014, a PSA doubling time PSA DT of 0–3 yr was also used). Outcome measurements and statistical analysis Reclassification rates, treatment after discontinuation, and outcome on RP after discontinuing AS were reported. Regression analysis on the outcome of RP was used to evaluate the predictive value of criteria currently used to recommend a switch to active treatment. Kaplan-Meier and competing risk analysis were used to report discontinuation rates over time and long-term oncologic end points. Results and limitations A total of 5302 men were included in PRIAS across 18 countries. Reclassification rates remained stable on all subsequent biopsies, with 22–33% of men having either Gleason >3 + 3 or more than two positive cores on any repeat biopsy. At 5 and 10 yr of follow-up, 52% and 73% of men, respectively, had discontinued AS, most of them because of protocol-based reclassification. A third of men undergoing subsequent RP had favorable pathologic tumor features (Gleason 3 + 3 and pT2). Of the criteria used to recommend a switch to active treatment, more than two positive cores and a PSA DT of 0–3 yr were not predictive of unfavorable pathologic outcome on RP. Conclusions A substantial group of men discontinued AS without subsequent unfavorable tumor features on RP; therefore, we propose Gleason upgrading and cT3 as the only indicators for an immediate switch to active treatment. Surrogate indicators (eg, more than two positive cores and a fast-rising PSA) should not trigger immediate active treatment but rather further investigation to confirm the suspicion of higher risk disease. Patient summary We confirmed the safety of active surveillance as a treatment option for men with low-risk prostate cancer; however, some changes could be made to the follow-up protocol to safely increase the number of men who remain on active surveillance.
Guidelines regarding recommendations for PSA screening for early detection of prostate cancer are conflicting. In 2012, the United States Preventive Services Task Force (USPSTF) assigned a grade of D ...(recommending against screening) for men aged ≥75 years in 2008 and for men of all ages in 2012. Understanding temporal trends in rates of screening before and after the 2012 recommendation in terms of usage patterns in PSA screening, changes in prostate cancer incidence and biopsy patterns, and how the recommendation has influenced physician's and men's attitudes about PSA screening and subsequent ordering of other screening tests is essential within the scope of prostate cancer screening policy. Since the 2012 recommendation, rates of PSA screening decreased by 3-10% in all age groups and across most geographical regions of the USA. Rates of prostate biopsy and prostate cancer incidence have declined in unison, with a shift towards tumours being of higher grade and stage upon detection. Despite the recommendation, some physicians report ongoing willingness to screen appropriately selected men, and many men report intending to continue to ask for the PSA test from their physician. In the coming years, we expect to have an improved understanding of whether these decreased rates of screening will affect prostate cancer metastasis and mortality.
Magnetic resonance imaging (MRI), with or without MRI-targeted biopsy (MRI pathway), is an alternative test to systematic transrectal ultrasonography-guided biopsy in men suspected of having prostate ...cancer. At present, evidence on which test to use is insufficient to inform detailed evidence-based decision making.
To determine the diagnostic accuracy of the index tests MRI only, MRI-targeted biopsy, MRI pathway, and systematic biopsy, as compared with template-guided biopsy (reference standard), in detecting clinically significant prostate cancer, defined as International Society of Urological Pathology grade 2 or higher, in biopsy-naive men or those with a prior-negative biopsy (or mix of both).
We systematically searched the literature and considered for inclusion any cross-sectional study if it investigated (1) one or more index tests verified by the reference standard, and (2) paired testing of the MRI pathway with systematic biopsy. Quality and certainty of evidence were assessed by the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) and Grading of Recommendations Assessment, Development and Evaluation, respectively.
Accuracy analyses: Using a baseline cancer prevalence of 30%, MRI pathway (sensitivity 0.72 95% confidence interval {CI}: 0.60–0.82; specificity 0.96 0.94–0.98; eight studies) may result in 216 (180–246) true positives, 28 (14–42) false positives, 672 (658–686) true negatives, and 84 (54–120) false negatives per 1000 men. Systematic biopsy (sensitivity 0.63 0.19–0.93; specificity 1.00 0.91–1.00; four studies) may result in 189 (57–279) true positives, 0 (0–63) false positives, 700 (637–700) true negatives, and 111 (21–243) false negatives per 1000 men. Agreement analyses: With a direct comparison of the MRI pathway with systematic biopsy concerning significant disease, we found pooled detection ratios of 1.05 (95% CI: 0.95–1.16; 20 studies) in biopsy-naive men and 1.44 (1.19–1.75; 10 studies) in men with a prior-negative biopsy. Concerning insignificant disease, we found detection ratios of 0.63 (95% CI: 0.54–0.74), and 0.62 (95% CI: 0.44–0.88), respectively.
MRI pathway had the most favourable outcome in significant and insignificant prostate cancer detection compared with systematic biopsy. The certainty in our findings was reduced by study limitations.
We reviewed recent advances in prostate biopsy by magnetic resonance imaging (MRI) guidance and targeting for prostate cancer detection in comparison with standard diagnosis by systematic biopsies. The findings of this Cochrane review suggest that MRI pathway is better than systematic biopsies in making a correct diagnosis of clinically important prostate cancer and reducing redundant biopsies and the detection of unimportant cancers substantially. However, MRI pathway still misses some men with important prostate cancer. Therefore, further research in this area is important.
In all men suspected to have clinically significant prostate cancer, the magnetic resonance imaging (MRI) pathway, including prostate MRI and MRI-targeted biopsy, may represent a more favourable diagnostic test than systematic biopsy, which is the current standard practice. Therefore, performing prostate MRI before any biopsy should be structurally incorporated in the diagnostic work-up.
Multiparametric magnetic resonance imaging (MRI), with or without MRI-targeted biopsy, is an alternative test to systematic transrectal ultrasonography-guided biopsy in men suspected of having ...prostate cancer. At present, evidence on which test to use is insufficient to inform detailed evidence-based decision-making.
To determine the diagnostic accuracy of the index tests MRI only, MRI-targeted biopsy, the MRI pathway (MRI with or without MRI-targeted biopsy) and systematic biopsy as compared to template-guided biopsy as the reference standard in detecting clinically significant prostate cancer as the target condition, defined as International Society of Urological Pathology (ISUP) grade 2 or higher. Secondary target conditions were the detection of grade 1 and grade 3 or higher-grade prostate cancer, and a potential change in the number of biopsy procedures.
We performed a comprehensive systematic literature search up to 31 July 2018. We searched CENTRAL, MEDLINE, Embase, eight other databases and one trials register.
We considered for inclusion any cross-sectional study if it investigated one or more index tests verified by the reference standard, or if it investigated the agreement between the MRI pathway and systematic biopsy, both performed in the same men. We included only studies on men who were biopsy naïve or who previously had a negative biopsy (or a mix of both). Studies involving MRI had to report on both MRI-positive and MRI-negative men. All studies had to report on the primary target condition.
Two reviewers independently extracted data and assessed the risk of bias using the QUADAS-2 tool. To estimate test accuracy, we calculated sensitivity and specificity using the bivariate model. To estimate agreement between the MRI pathway and systematic biopsy, we synthesised detection ratios by performing random-effects meta-analyses. To estimate the proportions of participants with prostate cancer detected by only one of the index tests, we used random-effects multinomial or binary logistic regression models. For the main comparisions, we assessed the certainty of evidence using GRADE.
The test accuracy analyses included 18 studies overall.MRI compared to template-guided biopsy: Based on a pooled sensitivity of 0.91 (95% confidence interval (CI): 0.83 to 0.95; 12 studies; low certainty of evidence) and a pooled specificity of 0.37 (95% CI: 0.29 to 0.46; 12 studies; low certainty of evidence) using a baseline prevalence of 30%, MRI may result in 273 (95% CI: 249 to 285) true positives, 441 false positives (95% CI: 378 to 497), 259 true negatives (95% CI: 203 to 322) and 27 (95% CI: 15 to 51) false negatives per 1000 men. We downgraded the certainty of evidence for study limitations and inconsistency.MRI-targeted biopsy compared to template-guided biopsy: Based on a pooled sensitivity of 0.80 (95% CI: 0.69 to 0.87; 8 studies; low certainty of evidence) and a pooled specificity of 0.94 (95% CI: 0.90 to 0.97; 8 studies; low certainty of evidence) using a baseline prevalence of 30%, MRI-targeted biopsy may result in 240 (95% CI: 207 to 261) true positives, 42 (95% CI: 21 to 70) false positives, 658 (95% CI: 630 to 679) true negatives and 60 (95% CI: 39 to 93) false negatives per 1000 men. We downgraded the certainty of evidence for study limitations and inconsistency.The MRI pathway compared to template-guided biopsy: Based on a pooled sensitivity of 0.72 (95% CI: 0.60 to 0.82; 8 studies; low certainty of evidence) and a pooled specificity of 0.96 (95% CI: 0.94 to 0.98; 8 studies; low certainty of evidence) using a baseline prevalence of 30%, the MRI pathway may result in 216 (95% CI: 180 to 246) true positives, 28 (95% CI: 14 to 42) false positives, 672 (95% CI: 658 to 686) true negatives and 84 (95% CI: 54 to 120) false negatives per 1000 men. We downgraded the certainty of evidence for study limitations, inconsistency and imprecision.Systemic biopsy compared to template-guided biopsy: Based on a pooled sensitivity of 0.63 (95% CI: 0.19 to 0.93; 4 studies; low certainty of evidence) and a pooled specificity of 1.00 (95% CI: 0.91 to 1.00; 4 studies; low certainty of evidence) using a baseline prevalence of 30%, systematic biopsy may result in 189 (95% CI: 57 to 279) true positives, 0 (95% CI: 0 to 63) false positives, 700 (95% CI: 637 to 700) true negatives and 111 (95% CI: 21 to 243) false negatives per 1000 men. We downgraded the certainty of evidence for study limitations and inconsistency.Agreement analyses: In a mixed population of both biopsy-naïve and prior-negative biopsy men comparing the MRI pathway to systematic biopsy, we found a pooled detection ratio of 1.12 (95% CI: 1.02 to 1.23; 25 studies). We found pooled detection ratios of 1.44 (95% CI 1.19 to 1.75; 10 studies) in prior-negative biopsy men and 1.05 (95% CI: 0.95 to 1.16; 20 studies) in biopsy-naïve men.
Among the diagnostic strategies considered, the MRI pathway has the most favourable diagnostic accuracy in clinically significant prostate cancer detection. Compared to systematic biopsy, it increases the number of significant cancer detected while reducing the number of insignificant cancer diagnosed. The certainty in our findings was reduced by study limitations, specifically issues surrounding selection bias, as well as inconsistency. Based on these findings, further improvement of prostate cancer diagnostic pathways should be pursued.
The European Randomized study of Screening for Prostate Cancer (ERSPC) has previously demonstrated that prostate-specific antigen (PSA) screening decreases prostate cancer (PCa) mortality.
To ...determine whether PSA screening decreases PCa mortality for up to 16yr and to assess results following adjustment for nonparticipation and the number of screening rounds attended.
This multicentre population-based randomised screening trial was conducted in eight European countries. Report includes 182160 men, followed up until 2014 (maximum of 16yr), with a predefined core age group of 162389 men (55–69yr), selected from population registry.
The outcome was PCa mortality, also assessed with adjustment for nonparticipation and the number of screening rounds attended.
The rate ratio of PCa mortality was 0.80 (95% confidence interval CI 0.72–0.89, p<0.001) at 16yr. The difference in absolute PCa mortality increased from 0.14% at 13yr to 0.18% at 16yr. The number of men needed to be invited for screening to prevent one PCa death was 570 at 16yr compared with 742 at 13yr. The number needed to diagnose was reduced to 18 from 26 at 13yr. Men with PCa detected during the first round had a higher prevalence of PSA >20ng/ml (9.9% compared with 4.1% in the second round, p<0.001) and higher PCa mortality (hazard ratio=1.86, p<0.001) than those detected subsequently.
Findings corroborate earlier results that PSA screening significantly reduces PCa mortality, showing larger absolute benefit with longer follow-up and a reduction in excess incidence. Repeated screening may be important to reduce PCa mortality on a population level.
In this report, we looked at the outcomes from prostate cancer in a large European population. We found that repeated screening reduces the risk of dying from prostate cancer.
This European Randomized study of Screening for Prostate Cancer trial follow-up reports that repeated screening reduces the risk of dying from prostate cancer for up to 16yr.
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