Evidence-Based Research In The Treatment Of Benign Prostatic Hyperplasia

Part I Comparative Effectiveness of Oral Drug Therapies for Lower Urinary Tract Symptoms due to Benign Prostatic Hyperplasia:A Systematic Review and Network Meta-AnalysisIntroduction Lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) are common in elder men and a number of drugs alone or combined are clinically used for this disorder. But available studies investigating the comparative effects of different drug therapies are limited. This study was aimed to compare the efficacy of different drug therapies for LUTS/BPH with network meta-analysis.Materials and Methods An electronic search of PubMed, Cochrane Library and Embase was performed to identify randomized controlled trials (RCTs) comparing different drug therapies for LUTS/BPH within 24 weeks. Comparative effects were calculated using Aggregate Data Drug Information System. Consistency models of network meta-analysis were created and cumulative probability was used to rank different therapies.Results A total 66 RCTs covering seven different therapies with 29384 participants were included. We found that a-blockers (ABs) plus phosphodiesterase 5 inhibitors (PDE5-Is) ranked highest in the test of IPSS total score, storage subscore and voiding subscore. The combination therapy of ABs plus 5u-reductase inhibitors was the best for increasing maximum urinary flow rate (Qmax) with a mean difference (MD) of 1.98 (95% CI,1.12 to 2.86) as compared to placebo. ABs plus muscarinic receptor antagonists (MRAs) ranked secondly on the reduction of IPSS storage subscore, although monotherapies including MRAs showed no effect on this aspect. Additionally, PDE5-Is alone showed great effectiveness for LUTS/BPH except Qmax.Conclusions Based on our novel findings, combination therapy, especially ABs plus PDE5-Is, is recommended for short-term treatment for LUTS/BPH. There was also evidence that PDE5-Is used alone was efficacious except on Qmax. Additionally, it should be cautious when using MRAs. However, further clinical studies are required for longer duration which considers more treatment outcomes such as disease progression, as well as basic research investigating mechanisms involving PDE5-Is and other pharmacologic agents alleviate the symptoms of LUTS/BPH.Part ? Holmium Laser Enucleation versus Transurethral Resection in Patients with BenignProstate Hyperplasia:An Updated Systematic Review with Meta-Analysis and Trial Sequential AnalysisBackground Holmium laser enucleation (HoLEP) in surgical treatment of benign prostate hyperplasia (BPH) potentially offers advantages over transurethral resection of the prostate (TURP).Objective To objectively evaluate the efficacy and safety of HoLEP vs TURP for treatment of BPH.Methods Published randomized controlled trials (RCTs) were identified from PubMed, EMBASE, Science Citation Index, and the Cochrane Library up to October 10,2013 (updated on February 5,2014). After methodological quality assessment and data extraction, meta-analysis was performed using STATA 12.0 and Trial Sequential Analysis (TSA) 0.9 software.Results Fifteen studies including 8 RCTs involving 855 patients met the criteria. The results of meta-analysis showed that:a) efficacy indicators:there was no significant difference in quality of life between the two groups (P>0.05), but compared with the TURP group, Qmax was better at 3 months and 12 months, PVR was less at 6,12 months, and IPSS was lower at 12 months in the HoLEP, b) safety indicators:compared with the TURP, HoLEP had less blood transfusion (RR 0.17,95% CI 0.06 to 0.47), but there was no significant difference in early and late postoperative complications (P>0.05), and c) perioperative indicators:HoLEP was associated with longer operation time (WMD 14.19 min,95% CI 6.30 to 22.08 min), shorter catheterization time (WMD -19.97 h,95% CI -24.24 to -15.70 h) and hospital stay (WMD -25.25 h,95%CI -29.81 to -20.68 h).Conclusion In conventional meta-analyses, there is no clinically relevant difference in early and late postoperative complications between the two techniques, but HoLEP is preferable due to advantage in the curative effect, less blood transfusion rate, shorter catheterization duration time and hospital stay. However, trial sequential analysis does not allow us to draw any solid conclusion in overall clinical benefit comparison between the two approaches. Further large, welldesigned, multicentre/international RCTs with long-term data and the comparison between the two approaches remain open.Part ? Plasmakinetic resection technology for the treatment of benign prostatic hyperplasia:evidence from a systematic review with meta-analysis and trial sequential analysisObjective To compare the efficacy and safety of plasmakinetic resection of the prostate (PKRP) versus transurethral resection of the prostate (TURP) for benign prostatic hyperplasia (BPH).Materials and Methods Published RCTs were searched from PubMed, Embase, Science Citation Index, and Cochrane Library up to Sep 30,2013. After methodological quality assessment and data extraction, meta-analysis was performed using STATA 12.0 and Trial Sequential Analysis 0.9 software.Results 18 reports of 16 RCTs met the criteria, all trials with a low or moderate risk of bias. PKRP can significantly improve the Qmax at 12 months, but other efficacy outcomes had no significant difference. For safety outcomes, PKRP with less decrease in serum sodium (95% CI-3.35 to -0.69), lower TUR syndrome (95% CI 0.15 to 0.76), blood transfusion (95% CI 0.17 to 0.65) and clot retention (95% CI 0.11 to 0.41), shorter catheterization time (95% CI-26.56 to-12.77) and hospital stay (95% CI -1.44 to -0.27), but there was no significant difference in operative time, postoperative fever, and long-term postoperative complications.Conclusion Current evidence suggests PKRP and TURP are both effective for BPH. Moreover, PKRP has potential effective advantages and with more favorable safety. It seems PKRP possibly replace TURP and become the new surgical standard procedure in the future.Part ? Transurethral PlasmaKinetic Enucleation for Prostate versus Transurethral PlasmaKinetic Resection for Prostate in Treating Benign Prostate Hyperplasia:A Meta-analysisObjective To objectively evaluate the efficacy and safety of PKRP vs PK.EP for treatment of benign prostate hyperplasia (BPH).Methods We searched PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, the ISI Web of Knowledge databases, VIP, CNKI, CBM and WANFANG (the duration of search was from the data of the database set up to Mar,2011) for randomized controlled trials (RCTs) about PKRP vs PKEP for the treatment of BPH. After study selection, assessment, data collection, and analysis were undertaken by two reviewers independently, we performed meta-analyses by using the RevMan 5.1 software. The level of evidence was assessed by the GRADE system.Results Eight studies involing 991 patients met the inclusion criteia. The results of meta-analyses showed that: ? safety indicator:Compared with the PKRP, PKEP had shorter operation time[SMD=1.07,95% CI(0.19,1.94), P=0.02], less blood loss[SMD=2.06,95% CI(1.42,2.69),P<0.01], more weight of prostate resection [SMD=-0.91,95% CI(-1.33,-0.48), P<0.0001], less intraoperative perforation [RR=4.48,95% CI(1.43,14.02), P=0.01], shorter catheterization time[SMD=1.98,95% CI(0.39,3.57), P=0.01], shorter bladder wash-out time[SMD=3.49,95% CI(0.51,6.47), P=0.02], shorter hospital stay[SMD=0.89,95% CI(0.64,1.13),P<0.01], there was no statistical difference in postoperative complications[RR=0.82,95% CI(0.54,1.24), P=0.35]; ? efficacy indicator:Compared with the PKRP, the International Prostate Symptom Score (IPSS) was lower after 3 months, the Quality Of Life (QOL) was higher after 3 months, the improvement of residual urine volume (RUV) was better after 6 months, other efficacy indicators had no statistically significant difference between two groups (P>0.05). Based on GRADE system, all the evidences were level C and weak recommendation (2C)Conclusions The current evidence indicated that PKEP was similar to PKRP on the treatment effect, and was more safety than PKRP; for the poor quality of the original studies, a prudent choice was suggested; more high-quality, large sample studies were need.Part V Transurethral PlasmaKinetic Enucleation for Prostate versus Transurethral PlasmaKinetic Resection for Prostate in Treating Benign Prostate Hyperplasia:A Meta-analysisObjective To evaluate the recurrence rate of simultaneous transurethral resection bladder cancer and prostate (TURBT+TURP) in the treatment of non-muscle invasive bladder cancer (NMIBC) with benign prostatic hyperplasia (BPH).Methods We searched PubMed, the Cochrane Central Register of Controlled Trials, Embase, and the IS I Web of Knowledge Databases from their establishment to March 23, 2012, to collect all the original researches about TURBT+TURP versus TURBT alone in the treatment of NMIBC with BPH. After Screening literatures, methodological quality assessment and data extraction conducted by two reviewers independently, meta-analysis were performed by using the RevMan 5.1 software. The level of evidence was assessed by using the GRADE approach.Results Eight studies including seven Non-randomized concurrent controlled trials (NRCCTs) and one Randomized Controlled Trial (RCT) involving 1372 patients met the criteria. Meta-analyses of NRCCTs showed that in the TURBT+TURP group, overall recurrence rates were lower (OR=0.76,95%CI:0.60 to 0.96, p=0.02) and the difference was statistically significant; postoperative recurrence rate in the prostatic fossa/bladder neck (OR=0.96,95%CI:0.64 to 1.45, p=0.86) and bladder tumor progression rates (OR=0.96, 95%CI:0.49 to 1.87, p=0.91) were similar between TURBT+TURP group and TURBT group, the difference was not significant. According to the GRADE approach, the level of evidence was moderate or low. Only one RCT showed that overall postoperative tumor recurrence rates, recurrence rates at prostate fossa/bladder neck, bladder tumor progression rates between simultaneous groups and control groups were almost equal, there was no significant difference (P>0.05), and level of evidence was moderate.Conclusion For patients with non-muscle invasive bladder cancer and BPH, simultaneous resection did not increase the overall recurrence rate of bladder tumors, it also did not cause metastasis and tumor progression, but it might reduce recurrence rate. However, because of the low quality of researches included in the study, careful selection was necessary, more large-scale and high quality randomized controlled trials are also needed for further confirmation.Part ? A Evidence-based evaluation of recent clinical practice guidelines on the diagnosis and treatment of benign prostatic hyperplasia.Objective To systematically review the quality of evidence-based clinical practice guidelines on the diagnosis and treatment of benign prostatic hyperplasia (BPH), and compare the differences and similarities between recommendations in order to provide references for clinical application.Methods We searched databases such as the National Guideline Clearinghouse (NGC), Guidelines International Network (GIN), National Institute for Health and Clinical Excellence (NICE), Scottish Intercollegiate Guidelines Network (SIGN) and World Health Organization (WHO), PubMed, Embase, CNKI, VIP, WanFang Data, CBM, Medlive from their establishment until August 13,2015, to collect evidence-based guidelines and/or consensus on BPH. Methodological quality of included guidelines was assessed according to the AGREE ? instrument, and differences and similarities among recommendations were compared.Results A total of 15 guidelines were included. Two of them were from Chinese, other two were from Germany, and the rest of them were respective from Europe, America, England, Japan, Finland, Brazil, Italy, Malaysia, Canada, South Africa and WHO. According to theAGREE II instrument, only the "scope and purpose" and "clarity and presentation" were scored more than 50%, "stakeholder involvement", "rigor of development", "applicability" and "editorial independence" were scored less than 50%. The recommendations of different guidelines were basically similar, only with conflicts in some areas.Conclusion The quality of included guidelines remains to be unified. Especially in the field of application, because most of guidelines were lack of the advantages and disadvantages analysis and cost-benefit analysis, the score of AGREE II was the lowest. In addition, the results of analysis of the unithood of the included guidelines showed:(1) history and physical examination, urine routine test, IPSS, QoL, urine flow rate, residual urine volume, serum PSA and prostate ultrasound test should be evaluated as the initial diagnosis of BPH; (2) the watchful waiting, behavior, and diet therapy were important and necessary; (3) alpha blockers and 5 alpha reductase inhibitors were applied maturely in the treatment of BPH; (4) currently, the curative effect of open surgery, TURP, TUIP, B-TURP, holmium laser and green laser were certain.