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International Braz J Urol : Official... 2022This study aimed to explore the prevalence and clinical risk factors in patients diagnosed with incidental prostate cancer (IPC) during certain surgeries (transurethral... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This study aimed to explore the prevalence and clinical risk factors in patients diagnosed with incidental prostate cancer (IPC) during certain surgeries (transurethral resection of the prostate [TURP], open prostatectomy [OP], and holmium laser enucleation of the prostate [HoLEP]) after clinically suspected benign prostatic hyperplasia (BPH).
MATERIALS AND METHODS
Literature search of the MEDILINE, Web of Science, Embase, and Cochrane Library databases was performed to identify eligible studies published before June 2021. Multivariate adjusted odds ratios (ORs) and associated 95% confidence intervals (CIs) of the prevalence and clinical risk factors of IPC were calculated using random or fixed-effect models.
RESULTS
Twenty-three studies were included in the meta-analysis. Amongst the 94.783 patients, IPC was detected in 24.715 (26.1%). Results showed that the chance of IPC detection (10%, 95% CI: 0.07-4.00; P<0.001; I2=97%) in patients treated with TURP is similar to that of patients treated with HoLEP (9%, 95% CI: 0.07-0.11; P<0.001; I2=81.4%). However, the pooled prevalence estimate of patients treated with OP was 11% (95% CI: -0.03-0.25; P=0.113; I2=99.1%) with no statistical significance. We observed increased incidence of IPC diagnosis after BPH surgery amongst patients with higher prostate-specific antigen (PSA) level (OR: 1.13, 95% CI: 1.04-1.23; P=0.004; I2=89%), whereas no effect of age (OR: 1.02, 95% CI: 0.97-1.06; P=0.48; I2=78.8%) and prostate volume (OR: 0.99, 95% CI: 0.96-1.03; P=0.686; I2=80.5%) were observed.
CONCLUSIONS
The prevalence of IPC was similar amongst patients undergoing TURP, HoLEP, and OP for presumed BPH. Interestingly, increased PSA level was the only independent predictor of increasing risk of IPC after BPH surgery rather than age and prostate volume. Hence, future research should focus on predictors which accurately foretell the progression of prostate cancer to determine the optimal treatment for managing patients with IPC after BPH surgery.
Topics: Humans; Laser Therapy; Lasers, Solid-State; Male; Prevalence; Prostate-Specific Antigen; Prostatic Hyperplasia; Prostatic Neoplasms; Risk Factors; Transurethral Resection of Prostate; Treatment Outcome
PubMed: 35195386
DOI: 10.1590/S1677-5538.IBJU.2021.0653 -
American Journal of Men's Health 2021The objective of this study was to compare the efficacy and safety of 10 different surgical treatments for benign prostatic hyperplasia (BPH) with volume >60 mL. A... (Meta-Analysis)
Meta-Analysis
Comparison on the Efficacy and Safety of Different Surgical Treatments for Benign Prostatic Hyperplasia With Volume >60 mL: A Systematic Review and Bayesian Network Meta-Analysis of Randomized Controlled Trials.
The objective of this study was to compare the efficacy and safety of 10 different surgical treatments for benign prostatic hyperplasia (BPH) with volume >60 mL. A systematic literature review and network meta-analysis of randomized controlled trials (RCTs) within a Bayesian framework was performed. A total of 52 parallel-group RCTs included, reporting on 6,947 participants, comparing open prostatectomy (OP), monopolar/bipolar transurethral resection of prostate (monopolar/ bipolar TURP), thulium, holmium and diode laser enucleation of prostate (LEP), bipolar enucleation of prostate, potassium titanyl phosphate laser vaporization of prostate (KTP LVP), bipolar vaporization of prostate (bipolar VP), and laparoscopic simple prostatectomy (laparoscope SP). Compared with OP, laparoscope SP identified better maximal flow rate (Qmax; mean differences [MDs] = 2.89 mL/s) at the 24th month, but bipolar VP demonstrated worse Qmax (MD = -3.20 mL/s) and International Prostate Symptom Score (IPSS; MD = 2.60) at the 12th month. Holmium LEP (MD = 1.37) demonstrated better International Index of Erectile Function-5 at the 12th month compared with OP. However, compared with OP, KTP LVP demonstrated worse postvoid residual volume (PVR) at the sixth (MD = 10.42 mL) and 12th month (MD = 5.89 mL) and monopolar TURP (MD = 6.9 mL) demonstrated worse PVR at the 12th month. Eight new surgical methods for BPH with volume >60 mL appeared to be superior in safety compared with OP and monopolar TURP due to fewer complications. Bipolar VP and KTP LVP maybe not suitable for prostates more than 60 mL due to short- and middle-term worse Qmax, IPSS, and PVR than OP.
Topics: Humans; Male; Network Meta-Analysis; Prostatic Hyperplasia; Quality of Life; Randomized Controlled Trials as Topic; Transurethral Resection of Prostate; Treatment Outcome
PubMed: 34939514
DOI: 10.1177/15579883211067086 -
Investigative and Clinical Urology Nov 2021To review safety and efficacy of robotic-assisted simple prostatectomy (RASP) compared to open simple prostatectomy (OP). (Meta-Analysis)
Meta-Analysis
PURPOSE
To review safety and efficacy of robotic-assisted simple prostatectomy (RASP) compared to open simple prostatectomy (OP).
MATERIALS AND METHODS
A comprehensive literature search was performed to assess the differences in perioperative course and functional outcomes in patients with benign prostatic hyperplasia and surgical indication. The incidences of complications were pooled using the Cochran-Mantel-Haenszel Method and expressed as odds ratio (OR), 95% confidence interval (CI), and p-values. Perioperative course and functional outcomes were pooled using the inverse variance of the mean difference (MD), 95% CI, and p-values. Analyses were two-tailed and the significance was set at p<0.05.
RESULTS
Eight studies were accepted. Meta-analysis showed significantly longer surgical time (MD, 43.72; 95% CI, 30.57-56.88; p<0.00001) with a significantly lower estimated blood loss (MD, -563.20; 95% CI, -739.95 to -386.46; p<0.00001) and shorter postoperative stay (MD, -2.85; 95% CI, -3.72 to -1.99; p<0.00001) in RASP. Catheterization time did not differ (MD, 0.65; 95% CI, -2.17 to 3.48; p=0.65). The risk of blood transfusion was significantly higher in OP (OR, 0.23; 95% CI, 0.17-0.33; p<0.00001). The risk of recatheterization (OR, 1.96; 95% CI, 0.32-11.93; p=0.47), postoperative urinary infections (OR, 0.89; 95% CI, 0.23-3.51; p=0.87) and 30-day readmission rate (OR, 0.96; 95% CI, 0.61-1.51; p=0.86) did not differ. At 3-month follow-up, functional outcomes were similar.
CONCLUSIONS
RASP demonstrated a better perioperative outcome and equal early functional outcomes as compared to OP. These findings should be balanced against the longer operative time and higher cost of robotic surgery.
Topics: Comparative Effectiveness Research; Cost-Benefit Analysis; Humans; Male; Operative Time; Postoperative Complications; Prostatectomy; Prostatic Hyperplasia; Recovery of Function; Robotic Surgical Procedures
PubMed: 34729963
DOI: 10.4111/icu.20210297 -
Frontiers in Surgery 2021To compare the efficacy and safety of robotic-assisted simple prostatectomy and open simple prostatectomy for large benign prostatic hyperplasia. We systematically...
To compare the efficacy and safety of robotic-assisted simple prostatectomy and open simple prostatectomy for large benign prostatic hyperplasia. We systematically searched the Cochrane Library, PubMed, Embase, and Science databases for studies published through December 2020. Controlled trials on RASP and OSP for large prostates were included. The meta-analysis was conducted with the Review Manager 5.4 software. A total of seven studies with 3,777 patients were included in the analysis. There were no significant differences in IPSS (WMD, 0.72; 95%CI: -0.31, 1.76; = 0.17), QoL (WMD, 0.00; 95%CI: -0.39, 0.39; > 0.99), Qmax (WMD, 1.88; 95% CI: -1.15, 4.91; = 0.22), or PVR (WMD, -10.48; 95%CI: -25.13, 4.17; = 0.16) among patients undergoing RASP and OSP. However, compared with patients who underwent OSP, patients who underwent RASP had a shorter LOS (WMD, -2.83; 95%CI: -3.68, -1.98; < 0.001), less EBL (WMD, -304.68; 95% CI: -432.91, -176.44; < 0.001), a shorter CT (WMD, -2.61; 95%CI: -3.94, -1.29; < 0.001), and fewer overall complications (OR, 0.30; 95% CI: 0.16, 0.57; < 0.001). Nevertheless, RASP was associated with a longer OT (WMD, 59.69, 95% CI: 49.40, 69.98; < 0.001). The results of the current study demonstrated that RASP provided similar efficacy to those of OSP in the treatment of large prostate, while maintaining better security. Our findings indicate that RASP is a feasible and effective alternative to OSP.
PubMed: 34355017
DOI: 10.3389/fsurg.2021.695318 -
Minerva Urology and Nephrology Dec 2021Robotic technologies are being increasingly implemented in healthcare, including urology, and holding promises for improving medicine worldwide. However, these new...
INTRODUCTION
Robotic technologies are being increasingly implemented in healthcare, including urology, and holding promises for improving medicine worldwide. However, these new approaches raise ethical concerns for professionals, patients, researchers and institutions that need to be addressed. The aim of this review was to investigate the existing literature related to bioethical issues associated with robotic surgery in urology, in order to identify current challenges and make preliminary suggestions to ensure an ethical implementation of these technologies.
EVIDENCE ACQUISITION
We performed a review of the pertaining literature through a systematic search of two databases (PubMed and Web of Science) in August 2020.
EVIDENCE SYNTHESIS
Our search yielded 76 articles for full-text evaluation and 48 articles were included in the narrative review. Several bioethical issues were identified and can be categorized into five main subjects: 1) robotic surgery accessibility (robotic surgery is expensive, and in some health systems may lead to inequality in healthcare access. In more affluent countries the national distribution of several robotic platforms may influence the centralization of robotic surgery, therefore potentially affecting oncological and functional outcomes in low-volume centers); 2) safety (there is a considerable gap between surgical skills and patients' perception of competence, leading to ethical consequences on modern healthcare. Published incidence of adverse events during robotic surgery in large series is between 2% and 15%, which does not significantly differ amongst open or laparoscopic approaches); 3) gender gap (no data about gap differences in accessibility to robotic platforms were retrieved from our search); 4) costs (robotic platforms are expensive but a key reason why hospitals are willing to absorb the high upfront costs is patient demand. It is possible to achieve cost-equivalence between open and robotic prostatectomy if the volume of centers is higher than 10 cases per week); and 5) learning curve (a validated, structured curriculum and accreditation has been created for robotic surgery. This allows acquisition and development of basic and complex robotic skills focusing on patient safety and short learning curve).
CONCLUSIONS
Tech-medicine is rapidly moving forward. Robotic approach to urology seems to be accessible in more affluent countries, safe, economically sustainable, and easy to learn with an appropriate learning curve for both sexes. It is mandatory to keep maintaining a critical rational approach with constant control of the available evidence regarding efficacy, efficiency and safety.
Topics: Female; Humans; Learning Curve; Male; Prostatectomy; Robotic Surgical Procedures; Robotics; Urology
PubMed: 34308607
DOI: 10.23736/S2724-6051.21.04240-3 -
Anaesthesia, Critical Care & Pain... Aug 2021The aim of this review was to update the recommendations for optimal pain management after open and laparoscopic or robotic prostatectomy. Optimal pain management is... (Review)
Review
The aim of this review was to update the recommendations for optimal pain management after open and laparoscopic or robotic prostatectomy. Optimal pain management is known to influence postoperative recovery, but patients undergoing open radical prostatectomy typically experience moderate dynamic pain in the immediate postoperative day. Robot-assisted and laparoscopic surgery may be associated with decreased pain levels as opposed to open surgery. We performed a systematic review using Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) with PROcedure SPECific Postoperative Pain ManagemenT (PROSPECT) methodology. Randomised controlled trials (RCTs) published in English language, from January 2015 until March 2020, assessing postoperative pain, using analgesic, anaesthetic and surgical interventions, were identified from MEDLINE, EMBASE and Cochrane Databases. Of the 1797 studies identified, 35 RCTs and 3 meta-analyses met our inclusion criteria. NSAIDs and COX-2 selective inhibitors proved to lower postoperative pain scores. Continuous intravenous lidocaine reduced postoperative pain scores during open surgery. Local wound infiltration showed positive results in open surgery. Bilateral transversus abdominis plane (TAP) block was performed at the end of surgery and lowered pain scores in robot-assisted procedures, but results were conflicting for open procedures. Basic analgesia for prostatic surgery should include paracetamol and NSAIDs or COX-2 selective inhibitors. TAP block should be recommended as the first-choice regional analgesic technique for laparoscopic/robotic radical prostatectomy. Intravenous lidocaine should be considered for open surgeries.
Topics: Abdominal Muscles; Humans; Male; Neoplasms; Nerve Block; Pain Management; Pain, Postoperative; Practice Guidelines as Topic; Prostatectomy
PubMed: 34197976
DOI: 10.1016/j.accpm.2021.100922 -
Ontario Health Technology Assessment... 2021Benign prostatic hyperplasia (BPH) is a noncancerous enlargement of the prostate that commonly affects older people with prostates and may lead to obstructive urinary...
BACKGROUND
Benign prostatic hyperplasia (BPH) is a noncancerous enlargement of the prostate that commonly affects older people with prostates and may lead to obstructive urinary symptoms. Symptoms may initially be mild but tend to worsen over time. Prostatic artery embolization (PAE) is an endovascular procedure to treat BPH, wherein an interventional radiologist inserts a catheter into the patient to inject tiny particles intended to reduce blood flow to the enlarged prostate, causing it to shrink in size. We conducted a health technology assessment on PAE for people with BPH, which included an evaluation of effectiveness, safety, cost-effectiveness, the budget impact of publicly funding PAE, and patient preferences and values.
METHODS
We performed a systematic literature search of the clinical evidence. We assessed the risk of bias of each included study using the Cochrane Risk of Bias tool for randomized controlled trials (RCTs) and the Risk of Bias in Nonrandomized Studies-of Interventions (ROBINS-I) tool for observational studies. We assessed the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We performed a systematic review of the economic literature. We then assessed the cost-effectiveness of PAE compared with alternative treatments (i.e., transurethral resection of the prostate [TURP] or open simple prostatectomy [OSP]) using a Markov microsimulation model. The analysis was conducted from the Ontario Ministry of Health perspective over a time horizon of 6.5 years. We also analyzed the budget impact of publicly funding PAE in people with moderate to severe BPH in Ontario.
RESULTS
We included six studies in our systematic review. Four RCTs and one observational study compared PAE with TURP, and one observational study compared PAE with OSP. All studies had considerable risk-of-bias concerns. PAE may improve BPH symptoms and urodynamic measures, but we are uncertain whether PAE achieves better results than TURP (GRADE: Very low to Low). Compared with TURP, PAE may result in higher patient satisfaction and fewer adverse events (GRADE: Not assessed). Compared with OSP, PAE may result in smaller improvements in BPH symptoms and urodynamic measures and may lead to fewer adverse events, but the evidence is very uncertain (GRADE: Very low).We did not find any published cost-effectiveness studies in the economic literature review. Our primary economic evaluation showed that, compared with TURP, PAE has an incremental cost of $328 (95% CrI: -$686 to $1,423) and a very small incremental quality-adjusted life-year (QALY) of 0.007 (95% CrI: -0.004 to 0.018). The resulting incremental cost-effectiveness ratio (ICER) of PAE versus TURP is $44,930 per QALY gained. At the commonly used willingness-to-pay values of $50,000 and $100,000 per QALY, the cost-effectiveness of PAE is uncertain (52% and 68% probability, respectively, of being cost-effective compared with TURP). In a scenario analysis, we compared PAE with OSP for individuals with large prostates (who may be ineligible for TURP). We found that PAE is less costly (-$1,231; 95% CrI: -$2,457 to $69) and less effective (-0.12 QALYs; 95% CrI: -0.18 to -0.04). The resulting ICER of PAE versus OSP is $10,241 saved per QALY lost. At the commonly used willingness-to-pay value of $50,000 per QALY, PAE is unlikely to be cost-effective (2% probability of being cost-effective compared with OSP). Assuming a low uptake (i.e., an additional 10 to 50 procedures per year in years 1 to 5), we estimated that publicly funding PAE in Ontario would lead to an additional cost of about $11,400 over the next 5 years.People we spoke with who have lived experience with BPH reported on the negative impact it can have on their quality of life. Those who had received PAE reported a positive experience with the procedure and meaningful improvement in their symptoms.
CONCLUSIONS
Prostatic artery embolization may improve BPH symptoms and urodynamic measures, but we are uncertain if the procedure results in similar outcomes to those of TURP. Based on one observational study, PAE may result in smaller improvements compared with OSP, but we are very uncertain of the evidence. Compared with TURP and OSP, PAE may result in fewer adverse events. Longer-term comparative studies are needed to assess the durability and long-term adverse events of PAE, the potential need for reintervention after PAE, and how PAE compares with other available BPH treatment options.We found the cost-effectiveness of PAE compared with TURP to be uncertain. Also, PAE is unlikely to be cost-effective compared with OSP. If PAE is publicly funded in Ontario, the budget impact is estimated to be small over the next 5 years.People who have lived experience with BPH reported that PAE improves quality of life and reduces negative symptoms of BPH.
Topics: Aged; Humans; Male; Arteries; Cost-Benefit Analysis; Observational Studies as Topic; Prostatic Hyperplasia; Quality-Adjusted Life Years; Technology Assessment, Biomedical; Embolization, Therapeutic
PubMed: 34188733
DOI: No ID Found -
Arab Journal of Urology Nov 2020: To assess the prevalence of frailty, a status of vulnerability to stressors leading to adverse health events, in bladder cancer patients undergoing radical cystectomy... (Review)
Review
: To assess the prevalence of frailty, a status of vulnerability to stressors leading to adverse health events, in bladder cancer patients undergoing radical cystectomy (RC), and test the impact of frailty measurements on postoperative adverse outcomes. : A systematic review of English-language articles published up to April 2020 was performed. Electronic databases were searched to quantify the frailty prevalence in RC patients and assess the predictive ability of frailty indexes on RC-related outcomes as postoperative complications, early mortality, hospitalization length (LOS), costs, discharge dispositions, readmission rate. : Eleven studies were selected. Patients' frailty was identified by Johns Hopkins indicator (JHI) in two studies, 11-item modified Frailty Index (mFI) in four, 5-item simplified FI (sFI) in three, 15-point mFI in one, Fried Frailty Criteria in one. Considering all the frailty measurements applied, 8% and 31% of patients were frail or pre-frail, respectively. Frail (43%) and pre-frail patients (35%) were more at risk of major complications compared to non-frail (27%) using sFI; with JHI the percentages of frail and non-frail were 53% versus 19%. According to JHI and mFI frailty was related to longer LOS and higher costs. JHI identified that 3% of frail patients experience in-hospital mortality versus 1.5% of non-frail. Finally, using sFI, frail (28%), and pre-frail (19%) were more likely to be discharged non-home compared to non-frail patients (8%) and had a higher risk of 30-day mortality (4% and 2% versus 1%). : Almost half of RC patients were frail or pre-frail, conditions significantly related to an increased risk of postoperative adverse events with higher rates of major complications and early mortality. The most-used frailty index was mFI, while JHI and sFI resulted the most reliable to predict early postoperative RC-related adverse outcomes and should be routinely included in clinical practice after better standardization throughout prospective comparative studies. : ACG: Adjusted Clinical Groups; ACS: American College Surgeons; AUC: area under the curve; BCa: bladder cancer; CCI: Charlson Comorbidity Index; CSHA-FI: Canadian Study of Health and Aging Frailty Index; CCS: Clavien-Dindo Classification Score; ERAS: Enhanced Recovery After Surgery; FFC: Fried Frailty Criteria; (e)(m)(s)FI: (extended) (modified) (simplified) Frailty Index; ICU: intensive care unit; IQR: interquartile range; (p)LOS: (prolonged) length of hospital stay; NSQIP: National Surgical Quality Improvement Program; OR: odds ratio; (O)PN: (open) partial nephrectomy; PRISMA: Preferred Reporting Items for Systematic reviews and Meta-Analyses; (O)(RA)RC: (open)(robot-assisted) radical cystectomy; (O)RN: (open) radical nephrectomy; ROC: receiver operating characteristic; RNU: radical nephroureterectomy; (R)RP: (retropubic) radical prostatectomy; RR: relative risk; THCs: total hospital charges; nephrectomy; UD: urinary diversion.
PubMed: 33763244
DOI: 10.1080/2090598X.2020.1841538 -
Canadian Urological Association Journal... Oct 2021Unplanned visits (UPV) - re-admissions and emergency room (ER) visits - are markers of healthcare system quality. Radical prostatectomy (RP) is a commonly performed...
INTRODUCTION
Unplanned visits (UPV) - re-admissions and emergency room (ER) visits - are markers of healthcare system quality. Radical prostatectomy (RP) is a commonly performed cancer procedure, where variation in UPV represents a gap in care for prostate cancer patients. Here, we systematically synthesize the rates, reasons, predictors, and interventions for UPV after RP to inform evidence-based quality improvement (QI) initiatives.
METHODS
A systematic review was performed for studies from 2000-2020 using keywords: "re-admission," "emergency room/department," "unplanned visit," and "prostatectomy." Studies that focused on UPV following RP and that reported rates, reasons, predictors, or interventions, were included. Data was extracted via a standardized form. Meta-analysis was completed.
RESULTS
Sixty studies, with 406 107 RP patients, were eligible; 16 028 UPV events (approximately 5%) were analyzed from 317 050 RP patients. UPV rates after RP varied between studies (ER visit range 6-24%; re-admissions range 0-56%). The 30-day and 90-day ER visit rates were 12% and 14%, respectively; the 30-day and 90-day re-admission rates were 4% and 9%, respectively. A total of 55% of all re-admissions after RP are directly due to postoperative genitourinary (GU)-related complications, such as strictures, obstructions, fistula, bladder-related, incontinence, urine leak, renal problems, and other unspecified urinary complications. The next most common re-admission reasons were anastomosis-related, infection-related, cardiovascular/pulmonary events, and wound-related issues. Thirty-four percent of all ER visits after RP are directly due to urine-related issues, such as retention, urinoma, obstruction, leak, and catheter problems. The next most common ER visit reasons were abdominal/gastrointestinal issues, infection-related, venous thromboembolic events, and wound-related issues. Predictors for increased re-admission included: open RP, lymph node dissection, Charlson comorbidity index ≥2, low surgeon/hospital case volume, and socioeconomic determinants of health. Of the 10 interventions evaluated, a 3.4% average reduction in UPV rate was observed, highlighting an approximate two-fold decrease. Meta-analysis demonstrated a significant benefit of interventions over controls, with odds ratio 0.62 (95% confidence interval 0.46-0.84). Interventions that used multidisciplinary, nurse-centered, programs, with patient self-care/empowerment were more beneficial than algorithmic patient care pathways and preoperative patient education.
CONCLUSIONS
Twenty years of international, retrospective experience suggests UPV after RP are often related to GU complications and infection- or wound-related factors. QI interventions to reduce UPV should target these factors. While many re-admissions after RP appear to be unavoidable, ER visits have more opportunity for volume reduction by QI. The interventions evaluated herein have the potential to reduce UPV after RP.
PubMed: 33750517
DOI: 10.5489/cuaj.6931 -
JAMA Network Open Feb 2021Combining 2 first-line treatments for erectile dysfunction (ED) or initiating other modalities in addition to a first-line therapy may produce beneficial outcomes. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Combining 2 first-line treatments for erectile dysfunction (ED) or initiating other modalities in addition to a first-line therapy may produce beneficial outcomes.
OBJECTIVE
To assess whether different ED combination therapies were associated with improved outcomes compared with first-line ED monotherapy in various subgroups of patients with ED.
DATA SOURCES
Studies were identified through a systematic search in MEDLINE, Cochrane Library, and Scopus from inception of these databases to October 10, 2020.
STUDY SELECTION
Randomized clinical trials or prospective interventional studies of the outcomes of combination therapy vs recommended monotherapy in men with ED were identified. Only comparative human studies, which evaluated the change from baseline of self-reported erectile function using validated questionnaires, that were published in any language were included.
DATA EXTRACTION AND SYNTHESIS
Data extraction and synthesis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline.
MAIN OUTCOMES AND MEASURES
A meta-analysis was conducted that included randomized clinical trials that compared outcomes of combination therapy with phosphodiesterase type 5 (PDE5) inhibitors plus another agent vs PDE5 inhibitor monotherapy. Separate analyses were performed for the mean International Index of Erectile Function (IIEF) score change from baseline and the number of adverse events (AEs) by different treatment modalities and subgroups of patients.
RESULTS
A total of 44 studies included 3853 men with a mean (SD) age of 55.8 (11.9) years. Combination therapy compared with monotherapy was associated with a mean IIEF score improvement of 1.76 points (95% CI, 1.27-2.24; I2 = 77%; 95% PI, -0.56 to 4.08). Adding daily tadalafil, low-intensity shockwave therapy, vacuum erectile device, folic acid, metformin hydrochloride, or angiotensin-converting enzyme inhibitors was associated with a significant IIEF score improvement, but each measure was based on only 1 study. Specifically, the weighted mean difference (WMD) in IIEF score was 1.70 (95% CI, 0.79-2.61) for the addition of daily tadalafil, 3.50 (95% CI, 0.22-6.78) for the addition of low-intensity shockwave therapy, 8.40 (95% CI, 4.90-11.90) for the addition of a vacuum erectile device, 3.46 (95% CI, 2.16-4.76) for the addition of folic acid, 4.90 (95% CI, 2.82-6.98) for the addition of metformin hydrochloride and 2.07 (95% CI, 1.37-2.77) for the addition of angiotensin-converting enzyme inhibitors. The addition of α-blockers to PDE5 inhibitors was not associated with improvement in IIEF score (WMD, 0.80; 95% CI, -0.06 to 1.65; I2 = 72%). Compared with monotherapy, combination therapy was associated with improved IIEF score in patients with hypogonadism (WMD, 1.61; 95% CI, 0.99-2.23; I2 = 0%), monotherapy-resistant ED (WMD, 4.38; 95% CI, 2.37-6.40; I2 = 52%), or prostatectomy-induced ED (WMD, 5.47; 95% CI, 3.11-7.83; I2 = 53%). The treatment-related AEs did not differ between combination therapy and monotherapy (odds ratio, 1.10; 95% CI, 0.66-1.85; I2 = 78%). Despite multiple subgroup and sensitivity analyses, the levels of heterogeneity remained high.
CONCLUSIONS AND RELEVANCE
This study found that combination therapy of PDE5 inhibitors and antioxidants was associated with improved ED without increasing the AEs. Treatment with PDE5 inhibitors and daily tadalafil, shockwaves, or a vacuum device was associated with additional improvement, but this result was based on limited data. These findings suggest that combination therapy is safe, associated with improved outcomes, and should be considered as a first-line therapy for refractory, complex, or difficult-to-treat cases of ED.
Topics: Adrenergic alpha-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antioxidants; Combined Modality Therapy; Drug Therapy, Combination; Equipment and Supplies; Erectile Dysfunction; Extracorporeal Shockwave Therapy; Folic Acid; Humans; Hypoglycemic Agents; Male; Metformin; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate; Tadalafil; Treatment Outcome; Vitamin B Complex
PubMed: 33599772
DOI: 10.1001/jamanetworkopen.2020.36337