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American Journal of Hematology Jun 2019Two specific reversal agents for direct oral anticoagulants (DOACs) have been approved in the United States: idarucizumab for dabigatran reversal and andexanet alfa for...
Two specific reversal agents for direct oral anticoagulants (DOACs) have been approved in the United States: idarucizumab for dabigatran reversal and andexanet alfa for apixaban and rivaroxaban reversal. Non-specific prohemostatic agents such as prothrombin complex concentrate (PCC) and activated PCC have also been used for DOAC reversal. The goal of this document is to provide comprehensive guidance from the Anticoagulation Forum, a North American organization of anticoagulation providers, regarding use of DOAC reversal agents. We discuss indications for reversal, provide guidance on how the individual reversal agents should be administered, and offer suggestions for stewardship at the health system level.
Topics: Antibodies, Monoclonal, Humanized; Anticoagulants; Factor Xa; Humans; Practice Guidelines as Topic; Recombinant Proteins
PubMed: 30916798
DOI: 10.1002/ajh.25475 -
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 -
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 -
BMJ (Clinical Research Ed.) May 2022To compare the impact of ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on cardiovascular outcomes in adults taking maximally tolerated... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To compare the impact of ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on cardiovascular outcomes in adults taking maximally tolerated statin therapy or who are statin intolerant.
DESIGN
Network meta-analysis.
DATA SOURCES
Medline, EMBASE, and Cochrane Library up to 31 December 2020.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Randomised controlled trials of ezetimibe and PCSK9 inhibitors with ≥500 patients and follow-up of ≥6 months.
MAIN OUTCOME MEASURES
We performed frequentist fixed-effects network meta-analysis and GRADE (grading of recommendations, assessment, development, and evaluation) to assess certainty of evidence. Results included relative risks (RR) and absolute risks per 1000 patients treated for five years for non-fatal myocardial infarction (MI), non-fatal stroke, all-cause mortality, and cardiovascular mortality. We estimated absolute risk differences assuming constant RR (estimated from network meta-analysis) across different baseline therapies and cardiovascular risk thresholds; the PREDICT risk calculator estimated cardiovascular risk in primary and secondary prevention. Patients were categorised at low to very high cardiovascular risk. A guideline panel and systematic review authors established the minimal important differences (MID) of 12 per 1000 for MI and 10 per 1000 for stroke.
RESULTS
We identified 14 trials assessing ezetimibe and PCSK9 inhibitors among 83 660 adults using statins. Adding ezetimibe to statins reduced MI (RR 0.87 (95% confidence interval 0.80 to 0.94)) and stroke (RR 0.82 (0.71 to 0.96)) but not all-cause mortality (RR 0.99 (0.92 to 1.06)) or cardiovascular mortality (RR 0.97 (0.87 to 1.09)). Similarly, adding PCSK9 inhibitor to statins reduced MI (0.81 (0.76 to 0.87)) and stroke (0.74 (0.64 to 0.85)) but not all-cause (0.95 (0.87 to 1.03)) or cardiovascular mortality (0.95 (0.87 to 1.03)). Among adults with very high cardiovascular risk, adding PCSK9 inhibitor was likely to reduce MI (16 per 1000) and stroke (21 per 1000) (moderate to high certainty); whereas adding ezetimibe was likely to reduce stroke (14 per 1000), but the reduction of MI (11 per 1000) (moderate certainty) did not reach MID. Adding ezetimibe to PCSK9 inhibitor and statin may reduce stroke (11 per 1000), but the reduction of MI (9 per 1000) (low certainty) did not reach MID. Adding PCSK9 inhibitors to statins and ezetimibe may reduce MI (14 per 1000) and stroke (17 per 1000) (low certainty). Among adults with high cardiovascular risk, adding PCSK9 inhibitor probably reduced MI (12 per 1000) and stroke (16 per 1000) (moderate certainty); adding ezetimibe probably reduced stroke (11 per 1000), but the reduction in MI did not achieve MID (8 per 1000) (moderate certainty). Adding ezetimibe to PCSK9 inhibitor and statins did not reduce outcomes beyond MID, while adding PCSK9 inhibitor to ezetimibe and statins may reduce stroke (13 per 1000). These effects were consistent in statin-intolerant patients. Among moderate and low cardiovascular risk groups, adding PCSK9 inhibitor or ezetimibe to statins yielded little or no benefit for MI and stroke.
CONCLUSIONS
Ezetimibe or PCSK9 inhibitors may reduce non-fatal MI and stroke in adults at very high or high cardiovascular risk who are receiving maximally tolerated statin therapy or are statin-intolerant, but not in those with moderate and low cardiovascular risk.
Topics: Adult; Anticholesteremic Agents; Cardiovascular Diseases; Ezetimibe; Heart Disease Risk Factors; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Myocardial Infarction; Network Meta-Analysis; PCSK9 Inhibitors; Proprotein Convertase 9; Risk Factors; Stroke
PubMed: 35508321
DOI: 10.1136/bmj-2021-069116 -
The Cochrane Database of Systematic... Jul 2014Most strokes are due to blockage of an artery in the brain by a blood clot. Prompt treatment with thrombolytic drugs can restore blood flow before major brain damage has... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Most strokes are due to blockage of an artery in the brain by a blood clot. Prompt treatment with thrombolytic drugs can restore blood flow before major brain damage has occurred and improve recovery after stroke in some people. Thrombolytic drugs, however, can also cause serious bleeding in the brain, which can be fatal. One drug, recombinant tissue plasminogen activator (rt-PA), is licensed for use in selected patients within 4.5 hours of stroke in Europe and within three hours in the USA. There is an upper age limit of 80 years in some countries, and a limitation to mainly non-severe stroke in others. Forty per cent more data are available since this review was last updated in 2009.
OBJECTIVES
To determine whether, and in what circumstances, thrombolytic therapy might be an effective and safe treatment for acute ischaemic stroke.
SEARCH METHODS
We searched the Cochrane Stroke Group Trials Register (last searched November 2013), MEDLINE (1966 to November 2013) and EMBASE (1980 to November 2013). We also handsearched conference proceedings and journals, searched reference lists and contacted pharmaceutical companies and trialists.
SELECTION CRITERIA
Randomised trials of any thrombolytic agent compared with control in people with definite ischaemic stroke.
DATA COLLECTION AND ANALYSIS
Two review authors applied the inclusion criteria, extracted data and assessed trial quality. We verified the extracted data with investigators of all major trials, obtaining additional unpublished data if available.
MAIN RESULTS
We included 27 trials, involving 10,187 participants, testing urokinase, streptokinase, rt-PA, recombinant pro-urokinase or desmoteplase. Four trials used intra-arterial administration, while the rest used the intravenous route. Most data come from trials that started treatment up to six hours after stroke. About 44% of the trials (about 70% of the participants) were testing intravenous rt-PA. In earlier studies very few of the participants (0.5%) were aged over 80 years; in this update, 16% of participants are over 80 years of age due to the inclusion of IST-3 (53% of participants in this trial were aged over 80 years). Trials published more recently utilised computerised randomisation, so there are less likely to be baseline imbalances than in previous versions of the review. More than 50% of trials fulfilled criteria for high-grade concealment; there were few losses to follow-up for the main outcomes.Thrombolytic therapy, mostly administered up to six hours after ischaemic stroke, significantly reduced the proportion of participants who were dead or dependent (modified Rankin 3 to 6) at three to six months after stroke (odds ratio (OR) 0.85, 95% confidence interval (CI) 0.78 to 0.93). Thrombolytic therapy increased the risk of symptomatic intracranial haemorrhage (OR 3.75, 95% CI 3.11 to 4.51), early death (OR 1.69, 95% CI 1.44 to 1.98; 13 trials, 7458 participants) and death by three to six months after stroke (OR 1.18, 95% CI 1.06 to 1.30). Early death after thrombolysis was mostly attributable to intracranial haemorrhage. Treatment within three hours of stroke was more effective in reducing death or dependency (OR 0.66, 95% CI 0.56 to 0.79) without any increase in death (OR 0.99, 95% CI 0.82 to 1.21; 11 trials, 2187 participants). There was heterogeneity between the trials. Contemporaneous antithrombotic drugs increased the risk of death. Trials testing rt-PA showed a significant reduction in death or dependency with treatment up to six hours (OR 0.84, 95% CI 0.77 to 0.93, P = 0.0006; 8 trials, 6729 participants) with significant heterogeneity; treatment within three hours was more beneficial (OR 0.65, 95% CI 0.54 to 0.80, P < 0.0001; 6 trials, 1779 participants) without heterogeneity. Participants aged over 80 years benefited equally to those aged under 80 years, particularly if treated within three hours of stroke.
AUTHORS' CONCLUSIONS
Thrombolytic therapy given up to six hours after stroke reduces the proportion of dead or dependent people. Those treated within the first three hours derive substantially more benefit than with later treatment. This overall benefit was apparent despite an increase in symptomatic intracranial haemorrhage, deaths at seven to 10 days, and deaths at final follow-up (except for trials testing rt-PA, which had no effect on death at final follow-up). Further trials are needed to identify the latest time window, whether people with mild stroke benefit from thrombolysis, to find ways of reducing symptomatic intracranial haemorrhage and deaths, and to identify the environment in which thrombolysis may best be given in routine practice.
Topics: Brain Ischemia; Drug Administration Schedule; Fibrinolytic Agents; Humans; Intracranial Hemorrhages; Randomized Controlled Trials as Topic; Stroke; Thrombolytic Therapy; Time-to-Treatment; Tissue Plasminogen Activator
PubMed: 25072528
DOI: 10.1002/14651858.CD000213.pub3 -
Prostate Cancer and Prostatic Diseases Feb 2022The most recent overall survival (OS) and adverse event (AE) data have not been compared for the three guideline-recommended high-risk non-metastatic... (Meta-Analysis)
Meta-Analysis Review
Overall survival and adverse events after treatment with darolutamide vs. apalutamide vs. enzalutamide for high-risk non-metastatic castration-resistant prostate cancer: a systematic review and network meta-analysis.
BACKGROUND
The most recent overall survival (OS) and adverse event (AE) data have not been compared for the three guideline-recommended high-risk non-metastatic castration-resistant prostate cancer (nmCRPC) treatment alternatives.
METHODS
We performed a systematic review and network meta-analysis focusing on OS and AE according to the most recent apalutamide, enzalutamide, and darolutamide reports. We systematically examined and compared apalutamide vs. enzalutamide vs. darolutamide efficacy and toxicity, relative to ADT according to PRISMA. We relied on PubMed search for most recent reports addressing prospective randomized trials with proven predefined OS benefit, relative to ADT: SPARTAN, PROSPER, and ARAMIS. OS represented the primary outcome and AEs represented secondary outcomes.
RESULTS
Overall, data originated from 4117 observations made within the three trials that were analyzed. Regarding OS benefit relative to ADT, darolutamide ranked first, followed by enzalutamide and apalutamide, in that order. In the subgroup of PSA-doubling time (PSA-DT) ≤ 6 months patients, enzalutamide ranked first, followed by darolutamide and apalutamide in that order. Conversely, in the subgroup of PSA-DT 6-10 months patients, darolutamide ranked first, followed by apalutamide and enzalutamide, in that order. Regarding grade 3+ AEs, darolutamide was most favorable, followed by enzalutamide and apalutamide, in that order.
CONCLUSION
The current network meta-analysis suggests the highest OS efficacy and lowest grade 3+ toxicity for darolutamide. However, in the PSA-DT ≤ 6 months subgroup, the highest efficacy was recorded for enzalutamide. It is noteworthy that study design, study population, and follow-up duration represent some of the potentially critical differences that distinguish between the three studies and remained statistically unaccounted for using the network meta-analysis methodology. Those differences should be strongly considered in the interpretation of the current and any network meta-analyses.
Topics: Benzamides; Humans; Male; Network Meta-Analysis; Nitriles; Phenylthiohydantoin; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Pyrazoles; Thiohydantoins; Treatment Outcome
PubMed: 34054128
DOI: 10.1038/s41391-021-00395-4 -
Lancet (London, England) Nov 2020Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers.
METHODS
We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0-1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0-2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4-6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903.
FINDINGS
Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10-2·03]; p=0·011), with low heterogeneity across studies (I=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05-1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06-2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4-6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52-1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03-4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [<1%], adjusted OR 5·58 [1·22-25·50]; p=0·024).
INTERPRETATION
In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death.
FUNDING
None.
Topics: Diffusion Magnetic Resonance Imaging; Fibrinolytic Agents; Humans; Infusions, Intravenous; Ischemic Stroke; Recovery of Function; Time-to-Treatment; Tissue Plasminogen Activator; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 33176180
DOI: 10.1016/S0140-6736(20)32163-2 -
Journal of Thrombosis and Thrombolysis Feb 2023Tenecteplase (TNK) is a promising candidate to replace alteplase as the standard of care for acute ischemic stroke (AIS); however, the optimal dosage is still to be... (Meta-Analysis)
Meta-Analysis Review
The efficacy and safety of tenecteplase versus alteplase for acute ischemic stroke: an updated systematic review, pairwise, and network meta-analysis of randomized controlled trials.
Tenecteplase (TNK) is a promising candidate to replace alteplase as the standard of care for acute ischemic stroke (AIS); however, the optimal dosage is still to be investigated. Therefore, we aim to evaluate the safety and efficacy of TNK versus alteplase and to investigate the optimal TNK dosage. A systematic review, pairwise, and network meta-analysis synthesizing randomized controlled trials (RCTs) from WOS, SCOPUS, EMBASE, and PubMed until July 26, 2022. We used the risk ratio (RR) for dichotomous outcomes presented with the corresponding 95% confidence interval (CI). We registered our protocol in PROSPERO with ID: CRD42022352038. Nine RCTs with a total of 3,707 patients were included. TNK significantly led to complete recanalization (RR: 1.27 with 95% CI [1.02, 1.57], P = 0.03); however, we found no difference regarding early neurological improvement (RR: 1.07 with 95% CI [0.94, 1.21], P = 0.33) and excellent neurological recovery (RR: 1.03 with 95% CI [0.96, 1.10], P = 0.42). Also, TNK was similar to alteplase regarding mortality (RR: 0.99 with 95% CI [0.82, 1.18], P = 0.88), intracranial haemorrhage (RR: 1.00 with 95% CI [0.85, 1.18], P = 0.99), and parenchymal hematoma (RR: 1.13 with 95% CI [0.83, 1.54], P = 0.44). TNK in the dose of 0.25 mg is a viable candidate to displace alteplase as the standard of care in patients with an AIS within 4.5 h of presentation due to its better rate of early neurological recovery and non-inferiority in terms of safety outcomes. However, the evidence regarding TNK's role in AIS presenting after 4.5 h from symptoms onset, wake-up stroke, and minor stroke/TIA is still lacking, necessitating further double-blinded pragmatic RCTs in this regard.
Topics: Humans; Tissue Plasminogen Activator; Tenecteplase; Fibrinolytic Agents; Network Meta-Analysis; Randomized Controlled Trials as Topic; Stroke; Ischemic Stroke; Treatment Outcome; Brain Ischemia
PubMed: 36449231
DOI: 10.1007/s11239-022-02730-5 -
The Cochrane Database of Systematic... Sep 2017Prostate cancer is commonly diagnosed in men worldwide. Surgery, in the form of radical prostatectomy, is one of the main forms of treatment for men with localised... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Prostate cancer is commonly diagnosed in men worldwide. Surgery, in the form of radical prostatectomy, is one of the main forms of treatment for men with localised prostate cancer. Prostatectomy has traditionally been performed as open surgery, typically via a retropubic approach. The advent of laparoscopic approaches, including robotic-assisted, provides a minimally invasive alternative to open radical prostatectomy (ORP).
OBJECTIVES
To assess the effects of laparoscopic radical prostatectomy or robotic-assisted radical prostatectomy compared to open radical prostatectomy in men with localised prostate cancer.
SEARCH METHODS
We performed a comprehensive search using multiple databases (CENTRAL, MEDLINE, EMBASE) and abstract proceedings with no restrictions on the language of publication or publication status, up until 9 June 2017. We also searched bibliographies of included studies and conference proceedings.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) with a direct comparison of laparoscopic radical prostatectomy (LRP) and robotic-assisted radical prostatectomy (RARP) to ORP, including pseudo-RCTs.
DATA COLLECTION AND ANALYSIS
Two review authors independently classified studies and abstracted data. The primary outcomes were prostate cancer-specific survival, urinary quality of life and sexual quality of life. Secondary outcomes were biochemical recurrence-free survival, overall survival, overall surgical complications, serious postoperative surgical complications, postoperative pain, hospital stay and blood transfusions. We performed statistical analyses using a random-effects model and assessed the quality of the evidence according to GRADE.
MAIN RESULTS
We included two unique studies with 446 randomised participants with clinically localised prostate cancer. The mean age, prostate volume, and prostate-specific antigen (PSA) of the participants were 61.3 years, 49.78 mL, and 7.09 ng/mL, respectively. Primary outcomes We found no study that addressed the outcome of prostate cancer-specific survival. Based on data from one trial, RARP likely results in little to no difference in urinary quality of life (MD -1.30, 95% CI -4.65 to 2.05) and sexual quality of life (MD 3.90, 95% CI -1.84 to 9.64). We rated the quality of evidence as moderate for both quality of life outcomes, downgrading for study limitations. Secondary outcomes We found no study that addressed the outcomes of biochemical recurrence-free survival or overall survival.Based on one trial, RARP may result in little to no difference in overall surgical complications (RR 0.41, 95% CI 0.16 to 1.04) or serious postoperative complications (RR 0.16, 95% CI 0.02 to 1.32). We rated the quality of evidence as low for both surgical complications, downgrading for study limitations and imprecision.Based on two studies, LRP or RARP may result in a small, possibly unimportant improvement in postoperative pain at one day (MD -1.05, 95% CI -1.42 to -0.68 ) and up to one week (MD -0.78, 95% CI -1.40 to -0.17). We rated the quality of evidence for both time-points as low, downgrading for study limitations and imprecision. Based on one study, RARP likely results in little to no difference in postoperative pain at 12 weeks (MD 0.01, 95% CI -0.32 to 0.34). We rated the quality of evidence as moderate, downgrading for study limitations.Based on one study, RARP likely reduces the length of hospital stay (MD -1.72, 95% CI -2.19 to -1.25). We rated the quality of evidence as moderate, downgrading for study limitations.Based on two study, LRP or RARP may reduce the frequency of blood transfusions (RR 0.24, 95% CI 0.12 to 0.46). Assuming a baseline risk for a blood transfusion to be 8.9%, LRP or RARP would result in 68 fewer blood transfusions per 1000 men (95% CI 78 fewer to 48 fewer). We rated the quality of evidence as low, downgrading for study limitations and indirectness.We were unable to perform any of the prespecified secondary analyses based on the available evidence. All available outcome data were short-term and we were unable to account for surgeon volume or experience.
AUTHORS' CONCLUSIONS
There is no high-quality evidence to inform the comparative effectiveness of LRP or RARP compared to ORP for oncological outcomes. Urinary and sexual quality of life-related outcomes appear similar.Overall and serious postoperative complication rates appear similar. The difference in postoperative pain may be minimal. Men undergoing LRP or RARP may have a shorter hospital stay and receive fewer blood transfusions. All available outcome data were short-term, and this study was unable to account for surgeon volume or experience.
Topics: Humans; Laparoscopy; Male; Middle Aged; Organ Size; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Quality of Life; Randomized Controlled Trials as Topic; Robotic Surgical Procedures; Sexual Behavior; Urination
PubMed: 28895658
DOI: 10.1002/14651858.CD009625.pub2 -
European Urology Jun 2019In men with prostate cancer (PCa) treated with curative intent, controversy exists regarding the impact of biochemical recurrence (BCR) on oncological outcomes. (Review)
Review
CONTEXT
In men with prostate cancer (PCa) treated with curative intent, controversy exists regarding the impact of biochemical recurrence (BCR) on oncological outcomes.
OBJECTIVE
To perform a systematic review of the existing literature on BCR after treatment with curative intent for nonmetastatic PCa. Objective 1 is to investigate whether oncological outcomes differ between patients with or without BCR. Objective 2 is to study which clinical factors and tumor features in patients with BCR have an independent prognostic impact on oncological outcomes.
EVIDENCE ACQUISITION
Medline, Medline In-Process, Embase, and the Cochrane Central Register of Controlled Trials were searched. For objective 1, prospective and retrospective studies comparing survival outcomes of patients with or without BCR following radical prostatectomy (RP) or radical radiotherapy (RT) were included. For objective 2, all studies with at least 100 participants and reporting on prognostic patient and tumor characteristics in patients with BCR were included. Risk-of-bias and confounding assessments were performed according to the Quality in Prognosis Studies tool. Both a narrative synthesis and a meta-analysis were undertaken.
EVIDENCE SYNTHESIS
Overall, 77 studies were included for analysis, of which 14 addressed objective 1, recruiting 20 406 patients. Objective 2 was addressed by 71 studies with 29 057, 11 301, and 4272 patients undergoing RP, RT, and a mixed population (mix of patients undergoing RP or RT as primary treatment), respectively. There was a low risk of bias for study participation, confounders, and statistical analysis. For most studies, attrition bias, and prognostic and outcome measurements were not clearly reported. BCR was associated with worse survival rates, mainly in patients with short prostate-specific antigen doubling time (PSA-DT) and a high final Gleason score after RP, or a short interval to biochemical failure (IBF) after RT and a high biopsy Gleason score.
CONCLUSIONS
BCR has an impact on survival, but this effect appears to be limited to a subgroup of patients with specific clinical risk factors. Short PSA-DT and a high final Gleason score after RP, and a short IBF after RT and a high biopsy Gleason score are the main factors that have a negative impact on survival. These factors may form the basis of new BCR risk stratification (European Association of Urology BCR Risk Groups), which needs to be validated formally.
PATIENT SUMMARY
This review looks at the risk of death in men who shows rising prostate-specific antigen (PSA) in the blood test performed after curative surgery or radiotherapy. For many men, rising PSA does not mean that they are at a high risk of death from prostate cancer in the longer term. Men with PSA that rises shortly after they were treated with radiotherapy or rapidly rising PSA after surgery and a high tumor grade for both treatment modalities are at the highest risk of death. These factors may form the basis of new risk stratification (European Association of Urology biochemical recurrence Risk Groups), which needs to be validated formally.
Topics: Humans; Kallikreins; Male; Neoplasm Recurrence, Local; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Survival Rate
PubMed: 30342843
DOI: 10.1016/j.eururo.2018.10.011