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BMJ (Clinical Research Ed.) Sep 2018To investigate the efficacy and safety of prostate-specific antigen (PSA) testing to screen for prostate cancer. (Meta-Analysis)
Meta-Analysis
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 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.
Topics: Aged; Biopsy; Early Detection of Cancer; Erectile Dysfunction; Humans; Magnetic Resonance Imaging; Male; Mass Screening; Medical Overuse; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Urinary Incontinence
PubMed: 30185521
DOI: 10.1136/bmj.k3519 -
European Urology Sep 2021Management of locally recurrent prostate cancer after definitive radiotherapy remains controversial due to the perceived high rates of severe genitourinary (GU) and... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Management of locally recurrent prostate cancer after definitive radiotherapy remains controversial due to the perceived high rates of severe genitourinary (GU) and gastrointestinal (GI) toxicity associated with any local salvage modality.
OBJECTIVE
To quantitatively compare the efficacy and toxicity of salvage radical prostatectomy (RP), high-intensity focused ultrasound (HIFU), cryotherapy, stereotactic body radiotherapy (SBRT), low-dose-rate (LDR) brachytherapy, and high-dose-rate (HDR) brachytherapy.
EVIDENCE ACQUISITION
We performed a systematic review of PubMed, EMBASE, and MEDLINE. Two- and 5-yr recurrence-free survival (RFS) rates and crude incidences of severe GU and GI toxicity were extracted as endpoints of interest. Random-effect meta-analyses were conducted to characterize summary effect sizes and quantify heterogeneity. Estimates for each modality were then compared with RP after adjusting for individual study-level covariates using mixed-effect regression models, while allowing for differences in between-study variance across treatment modalities.
EVIDENCE SYNTHESIS
A total of 150 studies were included for analysis. There was significant heterogeneity between studies within each modality, and covariates differed between modalities, necessitating adjustment. Adjusted 5-yr RFS ranged from 50% after cryotherapy to 60% after HDR brachytherapy and SBRT, with no significant differences between any modality and RP. Severe GU toxicity was significantly lower with all three forms of radiotherapeutic salvage than with RP (adjusted rates of 20% after RP vs 5.6%, 9.6%, and 9.1% after SBRT, HDR brachytherapy, and LDR brachytherapy, respectively; p ≤ 0.001 for all). Severe GI toxicity was significantly lower with HDR salvage than with RP (adjusted rates 1.8% vs 0.0%, p < 0.01), with no other differences identified.
CONCLUSIONS
Large differences in 5-yr outcomes were not uncovered when comparing all salvage treatment modalities against RP. Reirradiation with SBRT, HDR brachytherapy, or LDR brachytherapy appears to result in less severe GU toxicity than RP, and reirradiation with HDR brachytherapy yields less severe GI toxicity than RP. Prospective studies of local salvage for radiorecurrent disease are warranted.
PATIENT SUMMARY
In a large study-level meta-analysis, we looked at treatment outcomes and toxicity for men treated with a number of salvage treatments for radiorecurrent prostate cancer. We conclude that relapse-free survival at 5 years is equivalent among salvage modalities, but reirradiation may lead to lower toxicity.
Topics: Brachytherapy; Cryotherapy; High-Intensity Focused Ultrasound Ablation; Humans; Male; Neoplasm Recurrence, Local; Prospective Studies; Prostatectomy; Prostatic Neoplasms; Radiation Dosage; Radiosurgery; Salvage Therapy
PubMed: 33309278
DOI: 10.1016/j.eururo.2020.11.010 -
European Urology Oncology Dec 2022Multiple treatments for metastatic, hormone-sensitive prostate cancer (mHSPC) are available, but their effects on health-related quality of life (HRQoL) and benefit-harm... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Multiple treatments for metastatic, hormone-sensitive prostate cancer (mHSPC) are available, but their effects on health-related quality of life (HRQoL) and benefit-harm balance remain unclear.
OBJECTIVE
To assess clinical effectiveness regarding survival and HRQoL, safety, and benefit-harm balance of mHSPC treatments.
EVIDENCE ACQUISITION
We searched MEDLINE, EMBASE, CENTRAL, and ClinicalTrials.gov until March 1, 2022. Randomized controlled trials (RCTs) comparing docetaxel, abiraterone, enzalutamide, apalutamide, darolutamide, and radiotherapy combined with androgen deprivation therapy (ADT) mutually or with ADT alone were eligible. Three reviewers independently performed screening, data extraction, and risk of bias assessment in duplicate.
EVIDENCE SYNTHESIS
Across ten RCTs, we found relevant survival benefits for ADT + docetaxel (high certainty according to the Grading of Recommendations, Assessment, Development and Evaluation [GRADE]), ADT + abiraterone (moderate certainty), ADT + enzalutamide (low certainty), ADT + apalutamide (high certainty), and ADT + docetaxel + darolutamide (high certainty) compared with ADT alone. ADT + radiotherapy appeared effective only in low-volume de novo mHSPC. We found a short-term HRQoL decrease lasting 3-6 mo for ADT + docetaxel (moderate certainty) and a potential HRQoL benefit for ADT + abiraterone up to 24 mo of follow-up (moderate certainty) compared with ADT alone. There was no difference in HRQoL for ADT + enzalutamide, ADT + apalutamide, or ADT + radiotherapy over ADT alone (low-high certainty). Grade 3-5 adverse effect rates were increased with all systemic combination treatments. A benefit-harm assessment showed high probabilities (>60%) for a net clinical benefit with ADT + abiraterone, ADT + enzalutamide, and ADT + apalutamide, while ADT + docetaxel and ADT + docetaxel + darolutamide appeared unlikely (<40%) to be beneficial.
CONCLUSIONS
Despite substantial survival benefits, no systemic combination treatment showed a clear HRQoL improvement compared with ADT alone. We found evidence for a short-term HRQoL decline with ADT + docetaxel and a higher net clinical benefit with ADT + abiraterone, ADT + apalutamide and ADT + enzalutamide. While individualized decision-making remains important and economic factors need to be considered, the evidence may support a general preference for the combination of ADT with androgen receptor axis-targeted therapies over docetaxel-containing strategies.
PATIENT SUMMARY
We assessed different combination treatments for metastatic hormone-sensitive prostate cancer. While survival was better with all systemic combination treatments, there was no clear improvement in health-related quality of life compared with androgen deprivation therapy alone. Novel hormonal combination treatments had a more favorable benefit-harm balance than combination treatments that include chemotherapy.
Topics: Male; Humans; Docetaxel; Network Meta-Analysis; Androgens; Prostatic Neoplasms
PubMed: 35599144
DOI: 10.1016/j.euo.2022.04.007 -
European Journal of Nuclear Medicine... Mar 2021In recent years, the clinical availability of scanners for integrated positron emission tomography (PET) and magnetic resonance imaging (MRI) has enabled the practical... (Meta-Analysis)
Meta-Analysis Review
AIM
In recent years, the clinical availability of scanners for integrated positron emission tomography (PET) and magnetic resonance imaging (MRI) has enabled the practical potential of multimodal, combined metabolic-receptor, anatomical, and functional imaging to be explored. The present systematic review and meta-analysis summarize the diagnostic information provided by PET/MRI in patients with prostate cancer (PCa).
MATERIALS AND METHODS
A literature search was conducted in three different databases. The terms used were "choline" or "prostate-specific membrane antigen - PSMA" AND "prostate cancer" or "prostate" AND "PET/MRI" or "PET MRI" or "PET-MRI" or "positron emission tomography/magnetic resonance imaging." All relevant records identified were combined, and the full texts were retrieved. Reports were excluded if (1) they did not consider hybrid PET/MRI; or (2) the sample size was < 10 patients; or (3) the raw data were not enough to enable the completion of a 2 × 2 contingency table.
RESULTS
Fifty articles were eligible for systematic review, and 23 for meta-analysis. The pooled data concerned 2104 patients. Initial disease staging was the main indication for PET/MRI in 24 studies. Radiolabeled PSMA was the tracer most frequently used. In primary tumors, the pooled sensitivity for the patient-based analysis was 94.9%. At restaging, the pooled detection rate was 80.9% and was higher for radiolabeled PSMA than for choline (81.8% and 77.3%, respectively).
CONCLUSIONS
PET/MRI proved highly sensitive in detecting primary PCa, with a high detection rate for recurrent disease, particularly when radiolabeled PSMA was used.
Topics: Humans; Magnetic Resonance Imaging; Male; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Prostatic Neoplasms; Radiopharmaceuticals; Tomography, X-Ray Computed
PubMed: 32901351
DOI: 10.1007/s00259-020-05025-0 -
Archivos Espanoles de Urologia Mar 2018Prostate cancer is a disease that presents a wide spectrum from low aggressiveness localized to disseminated cancer. Locally advanced prostate cancer (LAPC) is a... (Review)
Review
UNLABELLED
Prostate cancer is a disease that presents a wide spectrum from low aggressiveness localized to disseminated cancer. Locally advanced prostate cancer (LAPC) is a particularly difficult to manage phase of this spectrum.
OBJECTIVES
We review the definition, diagnosis and treatment of this phase of the disease.
METHODS
We performed a non systematic literature review of the most relevant features of this pathology.
RESULTS
LAPC is more aggressive than organ confined disease. Its clinical diagnosis is not always easy. Local treatment, in spite of being aggressive with potential sequelae, seems to be advantageous in terms of patient survival.
CONCLUSIONS
Prostate cancer local staging is currently based on multiparametric magnetic resonance imaging (mpMRI). Local radical treatment with surgery or radiotherapy, with probable addition of systemic treatment, offers promising results for disease control and quality of life improvement.
Topics: Humans; Male; Neoplasm Staging; Prostatic Neoplasms
PubMed: 29633943
DOI: No ID Found -
European Urology Jul 2016To date, there is no Level 1 evidence comparing the efficacy of radical prostatectomy and radiotherapy for patients with clinically-localized prostate cancer. (Comparative Study)
Comparative Study Meta-Analysis Review
CONTEXT
To date, there is no Level 1 evidence comparing the efficacy of radical prostatectomy and radiotherapy for patients with clinically-localized prostate cancer.
OBJECTIVE
To conduct a meta-analysis assessing the overall and prostate cancer-specific mortality among patients treated with radical prostatectomy or radiotherapy for clinically-localized prostate cancer.
EVIDENCE ACQUISITION
We searched Medline, EMBASE, and the Cochrane Library through June 2015 without year or language restriction, supplemented with hand search, using Preferred Reporting Items for Systematic Reviews and Meta-Analysis and Meta-analysis of Observational Studies in Epidemiology guidelines. We used multivariable adjusted hazard ratios (aHRs) to assess each endpoint. Risk of bias was assessed using the Newcastle-Ottawa scale.
EVIDENCE SYNTHESIS
Nineteen studies of low to moderate risk of bias were selected and up to 118 830 patients were pooled. Inclusion criteria and follow-up length varied between studies. Most studies assessed patients treated with external beam radiotherapy, although some included those treated with brachytherapy separately or with the external beam radiation therapy group. The risk of overall (10 studies, aHR 1.63, 95% confidence interval 1.54-1.73, p<0.00001; I(2)=0%) and prostate cancer-specific (15 studies, aHR 2.08, 95% confidence interval 1.76-2.47, p < 0.00001; I(2)=48%) mortality were higher for patients treated with radiotherapy compared with those treated with surgery. Subgroup analyses by risk group, radiation regimen, time period, and follow-up length did not alter the direction of results.
CONCLUSIONS
Radiotherapy for prostate cancer is associated with an increased risk of overall and prostate cancer-specific mortality compared with surgery based on observational data with low to moderate risk of bias. These data, combined with the forthcoming randomized data, may aid clinical decision making.
PATIENT SUMMARY
We reviewed available studies assessing mortality after prostate cancer treatment with surgery or radiotherapy. While the studies used have a potential for bias due to their observational design, we demonstrated consistently higher mortality for patients treated with radiotherapy rather than surgery.
Topics: Brachytherapy; Humans; Male; Prostatectomy; Prostatic Neoplasms; Radiotherapy, Intensity-Modulated; Survival Rate
PubMed: 26700655
DOI: 10.1016/j.eururo.2015.11.010 -
Annals of Family Medicine Mar 2018Although 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... (Meta-Analysis)
Meta-Analysis Review
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; I = 98.4%) and pooled specificity was 0.59 (95% CI, 0.41-0.76; I = 99.4%). Pooled PPV was 0.41 (95% CI, 0.31-0.52; I = 97.2%), and pooled NPV was 0.64 (95% CI, 0.58-0.70; I = 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.
Topics: Digital Rectal Examination; Early Detection of Cancer; Humans; Male; Primary Health Care; Prostatic Neoplasms
PubMed: 29531107
DOI: 10.1370/afm.2205 -
European Urology Jul 2019Many trials are evaluating therapies for men with metastatic hormone-sensitive prostate cancer (mHSPC). (Meta-Analysis)
Meta-Analysis
BACKGROUND
Many trials are evaluating therapies for men with metastatic hormone-sensitive prostate cancer (mHSPC).
OBJECTIVE
To systematically review trials of prostate radiotherapy.
DESIGN, SETTING, AND PARTICIPANTS
Using a prospective framework (framework for adaptive meta-analysis [FAME]), we prespecified methods before any trial results were known. We searched extensively for eligible trials and asked investigators when results would be available. We could then anticipate that a definitive meta-analysis of the effects of prostate radiotherapy was possible. We obtained prepublication, unpublished, and harmonised results from investigators.
INTERVENTION
We included trials that randomised men to prostate radiotherapy and androgen deprivation therapy (ADT) or ADT only.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
Hazard ratios (HRs) for the effects of prostate radiotherapy on survival, progression-free survival (PFS), failure-free survival (FFS), biochemical progression, and subgroup interactions were combined using fixed-effect meta-analysis.
RESULTS AND LIMITATIONS
We identified one ongoing (PEACE-1) and two completed (HORRAD and STAMPEDE) eligible trials. Pooled results of the latter (2126 men; 90% of those eligible) showed no overall improvement in survival (HR=0.92, 95% confidence interval [CI] 0.81-1.04, p=0.195) or PFS (HR=0.94, 95% CI 0.84-1.05, p=0.238) with prostate radiotherapy. There was an overall improvement in biochemical progression (HR=0.74, 95% CI 0.67-0.82, p=0.94×10) and FFS (HR=0.76, 95% CI 0.69-0.84, p=0.64×10), equivalent to ∼10% benefit at 3yr. The effect of prostate radiotherapy varied by metastatic burden-a pattern consistent across trials and outcome measures, including survival (<5, ≥5; interaction HR=1.47, 95% CI 1.11-1.94, p=0.007). There was 7% improvement in 3-yr survival in men with fewer than five bone metastases.
CONCLUSIONS
Prostate radiotherapy should be considered for men with mHSPC with a low metastatic burden.
PATIENT SUMMARY
Prostate cancer that has spread to other parts of the body (metastases) is usually treated with hormone therapy. In men with fewer than five bone metastases, addition of prostate radiotherapy helped them live longer and should be considered.
Topics: Bone Neoplasms; Disease-Free Survival; Gonadotropin-Releasing Hormone; Humans; Male; Orchiectomy; Progression-Free Survival; Prostate-Specific Antigen; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Survival Rate; Tumor Burden
PubMed: 30826218
DOI: 10.1016/j.eururo.2019.02.003 -
Lancet (London, England) Oct 2020It is unclear whether adjuvant or early salvage radiotherapy following radical prostatectomy is more appropriate for men who present with localised or locally advanced... (Comparative Study)
Comparative Study Meta-Analysis
Adjuvant or early salvage radiotherapy for the treatment of localised and locally advanced prostate cancer: a prospectively planned systematic review and meta-analysis of aggregate data.
BACKGROUND
It is unclear whether adjuvant or early salvage radiotherapy following radical prostatectomy is more appropriate for men who present with localised or locally advanced prostate cancer. We aimed to prospectively plan a systematic review of randomised controlled trials (RCTs) comparing these radiotherapy approaches.
METHODS
We used a prospective framework for adaptive meta-analysis (FAME), starting the review process while eligible trials were ongoing. RCTs were eligible if they aimed to compare immediate adjuvant radiotherapy versus early salvage radiotherapy, following radical prostatectomy in men (age ≥18 years) with intermediate-risk or high-risk, localised or locally advanced prostate cancer. We searched trial registers and conference proceedings until July 8, 2020, to identify eligible RCTs. By establishing the ARTISTIC collaboration with relevant trialists, we were able to anticipate when eligible trial results would emerge, and we developed and registered a protocol with PROSPERO before knowledge of the trial results (CRD42019132669). We used a harmonised definition of event-free survival, as the time from randomisation until the first evidence of either biochemical progression (prostate-specific antigen [PSA] ≥0·4 ng/mL and rising after completion of any postoperative radiotherapy), clinical or radiological progression, initiation of a non-trial treatment, death from prostate cancer, or a PSA level of at least 2·0 ng/mL at any time after randomisation. We predicted when we would have sufficient power to assess whether adjuvant radiotherapy was superior to early salvage radiotherapy. Investigators supplied results for event-free survival, both overall and within predefined patient subgroups. Hazard ratios (HRs) for the effects of radiotherapy timing on event-free survival and subgroup interactions were combined using fixed-effect meta-analysis.
FINDINGS
We identified three eligible trials and were able to obtain updated results for event-free survival for 2153 patients recruited between November, 2007, and December, 2016. Median follow-up ranged from 60 months to 78 months, with a maximum follow-up of 132 months. 1075 patients were randomly assigned to receive adjuvant radiotherapy and 1078 to a policy of early salvage radiotherapy, of whom 421 (39·1%) had commenced treatment at the time of analysis. Patient characteristics were balanced within trials and overall. Median age was similar between trials at 64 or 65 years (with IQRs ranging from 59 to 68 years) across the three trials and most patients (1671 [77·6%]) had a Gleason score of 7. All trials were assessed as having low risk of bias. Based on 270 events, the meta-analysis showed no evidence that event-free survival was improved with adjuvant radiotherapy compared with early salvage radiotherapy (HR 0·95, 95% CI 0·75-1·21; p=0·70), with only a 1 percentage point (95% CI -2 to 3) change in 5-year event-free survival (89% vs 88%). Results were consistent across trials (heterogeneity p=0·18; I=42%).
INTERPRETATION
This collaborative and prospectively designed systematic review and meta-analysis suggests that adjuvant radiotherapy does not improve event-free survival in men with localised or locally advanced prostate cancer. Until data on long-term outcomes are available, early salvage treatment would seem the preferable treatment policy as it offers the opportunity to spare many men radiotherapy and its associated side-effects.
FUNDING
UK Medical Research Council.
Topics: Biomarkers, Tumor; Disease-Free Survival; Humans; Male; Neoplasm Grading; Prospective Studies; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Radiotherapy, Adjuvant; Randomized Controlled Trials as Topic; Salvage Therapy
PubMed: 33002431
DOI: 10.1016/S0140-6736(20)31952-8 -
The Cochrane Database of Systematic... Apr 2019Multiparametric magnetic resonance imaging (MRI), with or without MRI-targeted biopsy, is an alternative test to systematic transrectal ultrasonography-guided biopsy in...
BACKGROUND
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.
OBJECTIVES
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.
SEARCH METHODS
We performed a comprehensive systematic literature search up to 31 July 2018. We searched CENTRAL, MEDLINE, Embase, eight other databases and one trials register.
SELECTION CRITERIA
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.
DATA COLLECTION AND ANALYSIS
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.
MAIN RESULTS
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.
AUTHORS' CONCLUSIONS
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.
Topics: Biopsy; Humans; Magnetic Resonance Imaging; Male; Prostate; Prostatic Neoplasms
PubMed: 31022301
DOI: 10.1002/14651858.CD012663.pub2