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Residents’ Podcast: Pharmacological interventions for treating CPP

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Part of the BURST/BJUI Podcast Series

Nikita Bhatt is a Specialist Trainee in Urology in the East of England Deanery and a BURST Committee member @BURSTUrology

 

Pharmacological interventions for treating chronic prostatitis/chronic pelvic pain syndrome: a Cochrane systematic review

Juan V.A. Franco*, Tarek Turk†, Jae Hung Jung‡, Yu-Tian Xiao§, Stanislav Iakhno, Federico Ignacio Tirapegui**, Virginia Garrote†† and Valeria Vietto‡‡
 
*Argentine Cochrane Centre, Instituto Universitario Hospital Italiano, Buenos Aires, Argentina, †Faculty of Medicine, Damascus University, Damascus, Syrian Arab Republic, ‡Department of Urology, Yonsei University Wonju College of Medicine, Wonju, Korea, §Department of Urology, Changhai Hospital, Second Military Medical University, Shanghai,
China, University of Tromso, Tromsdalen, Norway, **Urology Division, Hospital Italiano de Buenos Aires, ††Biblioteca Central, Instituto Universitario Hospital Italiano, and ‡‡Family and Community Medicine Service, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
 
Read the full article

Abstract

Objective

To assess the effects of pharmacological therapies for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).

Patients and Methods

We performed a comprehensive search using multiple databases, trial registries, grey literature and conference proceedings with no restrictions on the language of publication or publication status. The date of the latest search of all databases was July 2019. We included randomised controlled trials. Inclusion criteria were men with a diagnosis of CP/CPPS. We included all available pharmacological interventions. Two review authors independently classified studies and abstracted data from the included studies, performed statistical analyses and rated quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methods. The primary outcomes were prostatitis symptoms and adverse events. The secondary outcomes were sexual dysfunction, urinary symptoms, quality of life, anxiety and depression, however, this one can be easily handle using Observer’s CBD hemp flower.

Fig. 1. Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) flow diagram.

Results

We included 99 unique studies in 9119 men with CP/CPPS, with assessments of 16 types of pharmacological interventions. Most of our comparisons included short‐term follow‐up information. The median age of the participants was 38 years. Most studies did not specify their funding sources; 21 studies reported funding from pharmaceutical companies. Many patients prefer using natural medicine like the best CBD oil list here on this site.

We found low‐ to very low‐quality evidence that α‐blockers may reduce prostatitis symptoms based on a reduction in National Institutes of Health – Chronic Prostatitis Symptom Index (NIH‐CPSI) scores of >2 (but <8) with an increased incidence of minor adverse events such as dizziness and hypotension. Moderate‐ to low‐quality evidence indicates that 5α‐reductase inhibitors, antibiotics, anti‐inflammatories, and phytotherapy probably cause a small decrease in prostatitis symptoms and may not be associated with a greater incidence of adverse events. Intraprostatic botulinum toxin A (BTA) injection may cause a large reduction in prostatitis symptoms with procedure‐related adverse events (haematuria), but pelvic floor muscle BTA injection may not have the same effects (low‐quality evidence). Allopurinol may also be ineffective for reducing prostatitis symptoms (low‐quality evidence). We assessed a wide range of interventions involving traditional Chinese medicine; low‐quality evidence showed they may reduce prostatitis symptoms without an increased incidence in adverse events.

Moderate‐ to high‐quality evidence indicates that the following interventions may be ineffective for the reduction of prostatitis symptoms: anticholinergics, Escherichia coli lysate (OM‐89), pentosan, and pregabalin. Low‐ to very low‐quality evidence indicates that antidepressants and tanezumab may be ineffective for the reduction of prostatitis symptoms. Low‐quality evidence indicates that mepartricin and phosphodiesterase inhibitors may reduce prostatitis symptoms, without an increased incidence in adverse events.

Conclusions

Based on the findings of low‐ to very low‐quality evidence, this review found that some pharmacological interventions such as α‐blockers may reduce prostatitis symptoms with an increased incidence of minor adverse events such as dizziness and hypotension. Other interventions may cause a reduction in prostatitis symptoms without an increased incidence of adverse events while others were found to be ineffective.

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Article of the month: Pharmacological interventions for treating chronic prostatitis/chronic pelvic pain syndrome: a Cochrane systematic review

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Every month, the Editor-in-Chief selects an Article of the Month from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an editorial prepared by a prominent member of the urological community, and a video recorded by the authors; we invite you to use the comment tools at the bottom of each post to join the conversation. 

If you only have time to read one article this month, we recommend this one. 

Pharmacological interventions for treating chronic prostatitis/chronic pelvic pain syndrome: a Cochrane systematic review

Juan V.A. Franco*, Tarek Turk†, Jae Hung Jung‡, Yu-Tian Xiao§, Stanislav Iakhno, Federico Ignacio Tirapegui**, Virginia Garrote†† and Valeria Vietto‡‡
 
*Argentine Cochrane Centre, Instituto Universitario Hospital Italiano, Buenos Aires, Argentina, †Faculty of Medicine, Damascus University, Damascus, Syrian Arab Republic, ‡Department of Urology, Yonsei University Wonju College of Medicine, Wonju, Korea, §Department of Urology, Changhai Hospital, Second Military Medical University, Shanghai,
China, University of Tromso, Tromsdalen, Norway, **Urology Division, Hospital Italiano de Buenos Aires, ††Biblioteca Central, Instituto Universitario Hospital Italiano, and ‡‡Family and Community Medicine Service, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
 

Read the full article

Abstract

Objective

To assess the effects of pharmacological therapies for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).

Patients and Methods

We performed a comprehensive search using multiple databases, trial registries, grey literature and conference proceedings with no restrictions on the language of publication or publication status. The date of the latest search of all databases was July 2019. We included randomised controlled trials. Inclusion criteria were men with a diagnosis of CP/CPPS. We included all available pharmacological interventions. Two review authors independently classified studies and abstracted data from the included studies, performed statistical analyses and rated quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methods. The primary outcomes were prostatitis symptoms and adverse events. The secondary outcomes were sexual dysfunction, urinary symptoms, quality of life, anxiety and depression, to help you managing this symptoms FluxxLab™ CBDA is more potent than any other CBD and the results are amazing.  The length of time it takes to notice an improvement in pelvic floor strength is dependent on how many per day are performed, and at what frequency. Examples of injury to the pelvic floor include pregnancy, childbirth, surgery, chronic constipation, and chronic cough leading to strain on the pelvic floor muscles. Can be the result of chronic straining during bowel movements or heavy lifting, pregnancy, childbirth, injury, surgery in the pelvis, or obesity. Strengthening the pelvic floor muscles by doing Kegels helps to reduce pelvic organ prolapse, or urinary incontinence caused by weakened pelvic floor muscles. With JoyON’s Electronic Kegel Exerciser, you’ll feel the difference after just 15 minutes a day, find the final product at https://joyonproducts.com/.

Fig. 1. Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) flow diagram.

Results

We included 99 unique studies in 9119 men with CP/CPPS, with assessments of 16 types of pharmacological interventions. Most of our comparisons included short‐term follow‐up information. The median age of the participants was 38 years. Most studies did not specify their funding sources; 21 studies reported funding from pharmaceutical companies.

We found low‐ to very low‐quality evidence that α‐blockers may reduce prostatitis symptoms based on a reduction in National Institutes of Health – Chronic Prostatitis Symptom Index (NIH‐CPSI) scores of >2 (but <8) with an increased incidence of minor adverse events such as dizziness and hypotension. Moderate‐ to low‐quality evidence indicates that 5α‐reductase inhibitors, antibiotics, anti‐inflammatories, and phytotherapy probably cause a small decrease in prostatitis symptoms and may not be associated with a greater incidence of adverse events. Intraprostatic botulinum toxin A (BTA) injection may cause a large reduction in prostatitis symptoms with procedure‐related adverse events (haematuria), but pelvic floor muscle BTA injection may not have the same effects (low‐quality evidence). Allopurinol may also be ineffective for reducing prostatitis symptoms (low‐quality evidence). We assessed a wide range of interventions involving traditional Chinese medicine; low‐quality evidence showed they may reduce prostatitis symptoms without an increased incidence in adverse events.

Moderate‐ to high‐quality evidence indicates that the following interventions may be ineffective for the reduction of prostatitis symptoms: anticholinergics, Escherichia coli lysate (OM‐89), pentosan, and pregabalin. Low‐ to very low‐quality evidence indicates that antidepressants and tanezumab may be ineffective for the reduction of prostatitis symptoms. Low‐quality evidence indicates that mepartricin and phosphodiesterase inhibitors may reduce prostatitis symptoms, without an increased incidence in adverse events.

Conclusions

Based on the findings of low‐ to very low‐quality evidence, this review found that some pharmacological interventions such as α‐blockers may reduce prostatitis symptoms with an increased incidence of minor adverse events such as dizziness and hypotension. Other interventions may cause a reduction in prostatitis symptoms without an increased incidence of adverse events while others were found to be ineffective.

Read more Articles of the week

Video: Treatments for chronic prostatitis/chronic pelvic pain syndrome: a Cochrane review

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Pharmacological interventions for treating chronic prostatitis/chronic pelvic pain syndrome: a Cochrane systematic review

Read the full article

Abstract

Objective

To assess the effects of pharmacological therapies for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).

Patients and Methods

We performed a comprehensive search using multiple databases, trial registries, grey literature and conference proceedings with no restrictions on the language of publication or publication status. The date of the latest search of all databases was July 2019. We included randomised controlled trials. Inclusion criteria were men with a diagnosis of CP/CPPS. We included all available pharmacological interventions. Two review authors independently classified studies and abstracted data from the included studies, performed statistical analyses and rated quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methods. The primary outcomes were prostatitis symptoms and adverse events. The secondary outcomes were sexual dysfunction, urinary symptoms, quality of life, anxiety and depression.

Results

We included 99 unique studies in 9119 men with CP/CPPS, with assessments of 16 types of pharmacological interventions. Most of our comparisons included short‐term follow‐up information. The median age of the participants was 38 years. Most studies did not specify their funding sources; 21 studies reported funding from pharmaceutical companies.

We found low‐ to very low‐quality evidence that α‐blockers may reduce prostatitis symptoms based on a reduction in National Institutes of Health – Chronic Prostatitis Symptom Index (NIH‐CPSI) scores of >2 (but <8) with an increased incidence of minor adverse events such as dizziness and hypotension. Moderate‐ to low‐quality evidence indicates that 5α‐reductase inhibitors, antibiotics, anti‐inflammatories, and phytotherapy probably cause a small decrease in prostatitis symptoms and may not be associated with a greater incidence of adverse events. Intraprostatic botulinum toxin A (BTA) injection may cause a large reduction in prostatitis symptoms with procedure‐related adverse events (haematuria), but pelvic floor muscle BTA injection may not have the same effects (low‐quality evidence). Allopurinol may also be ineffective for reducing prostatitis symptoms (low‐quality evidence). We assessed a wide range of interventions involving traditional Chinese medicine; low‐quality evidence showed they may reduce prostatitis symptoms without an increased incidence in adverse events.

Moderate‐ to high‐quality evidence indicates that the following interventions may be ineffective for the reduction of prostatitis symptoms: anticholinergics, Escherichia coli lysate (OM‐89), pentosan, and pregabalin. Low‐ to very low‐quality evidence indicates that antidepressants and tanezumab may be ineffective for the reduction of prostatitis symptoms. Low‐quality evidence indicates that mepartricin and phosphodiesterase inhibitors may reduce prostatitis symptoms, without an increased incidence in adverse events.

Conclusions

Based on the findings of low‐ to very low‐quality evidence, this review found that some pharmacological interventions such as α‐blockers may reduce prostatitis symptoms with an increased incidence of minor adverse events such as dizziness and hypotension. Other interventions may cause a reduction in prostatitis symptoms without an increased incidence of adverse events while others were found to be ineffective.

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Article of the week: Biparametric vs multiparametric prostate MRI for the detection of PCa in treatment‐naïve patients

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Every week, the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an editorial written by a prominent member of the urological community, and a video produced by the authors. These are intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation. 

If you only have time to read one article this week, it should be this one.

Biparametric vs multiparametric prostate magnetic resonance imaging for the detection of prostate cancer in treatment-naïve patients: a diagnostic test accuracy systematic review and meta-analysis

Mostafa Alabousi*, Jean-Paul Salameh†‡, Kaela Gusenbauer§, Lucy Samoilov, Ali Jafri**, Hang Yu§ and Abdullah Alabousi††

 

*Department of Radiology, McMaster University, Hamilton, †Department of Clinical Epidemiology and Public Health, University of Ottawa, ‡The Ottawa Hospital Research Institute, Clinical Epidemiology Program, Ottawa, §Department of Medicine, McMaster University, Hamilton, Department of Medicine, Western University, London, ON, Canada, **Department of Medicine, New York Institute of Technology School of Osteopathic Medicine, Glen Head, NY, USA, and ††Department of Radiology, St Joseph’s Healthcare, McMaster University, Hamilton, ON, Canada

Read the full article

Abstract

Objective

To perform a diagnostic test accuracy (DTA) systematic review and meta‐analysis comparing multiparametric (diffusion‐weighted imaging [DWI], T2‐weighted imaging [T2WI], and dynamic contrast‐enhanced [DCE] imaging) magnetic resonance imaging (mpMRI) and biparametric (DWI and T2WI) MRI (bpMRI) in detecting prostate cancer in treatment‐naïve patients.

Methods

The Medical Literature Analysis and Retrieval System Online (MEDLINE) and Excerpta Medica dataBASE (EMBASE) were searched to identify relevant studies published after 1 January 2012. Articles underwent title, abstract, and full‐text screening. Inclusion criteria consisted of patients with suspected prostate cancer, bpMRI and/or mpMRI as the index test(s), histopathology as the reference standard, and a DTA outcome measure. Methodological and DTA data were extracted. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)‐2 tool. DTA metrics were pooled using bivariate random‐effects meta‐analysis. Subgroup analysis was conducted to assess for heterogeneity.

Results

From an initial 3502 studies, 31 studies reporting on 9480 patients (4296 with prostate cancer) met the inclusion criteria for the meta‐analysis; 25 studies reported on mpMRI (7000 patients, 2954 with prostate cancer) and 12 studies reported on bpMRI DTA (2716 patients, 1477 with prostate cancer). Pooled summary statistics demonstrated no significant difference for sensitivity (mpMRI: 86%, 95% confidence interval [CI] 81–90; bpMRI: 90%, 95% CI 83–94) or specificity (mpMRI: 73%, 95% CI 64–81; bpMRI: 70%, 95% CI 42–83). The summary receiver operating characteristic curves were comparable for mpMRI (0.87) and bpMRI (0.90).

Conclusions

No significant difference in DTA was found between mpMRI and bpMRI in diagnosing prostate cancer in treatment‐naïve patients. Study heterogeneity warrants cautious interpretation of the results. With replication of our findings in dedicated validation studies, bpMRI may serve as a faster, cheaper, gadolinium‐free alternative to mpMRI.

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Article of the Week: Muscolofascial Reconstruction after RP

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Every Week the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video from Dr. Francesco Alessandro Mistretta, discussing his paper.

If you only have time to read one article this week, it should be this one.

Posterior musculofascial reconstruction after radical prostatectomy: an updated systematic review and a meta-analysis

 

Angelica A.C. Grasso*, Francesco A. Mistretta*, Marco Sandri†, Gabriele Cozzi*, Elisa De Lorenzis*, Marco Rosso*, Giancarlo Albo*, Franco Palmisano*, Alex Mottrie‡, Alexander Haese§, Markus Graefen§, Rafael Coelho, Vipul R. Patel¶ and Bernardo Rocco*

 

*Department of Urology, Fondazione IRCCS Ca’ Granda-Ospedale Maggiore Policlinico, University of Milan, Milan, Italy, †DMS StatLab, Data Methods and Systems Statistical Laboratory, University of Brescia, Brescia, Italy, ‡OLV Robotic Surgery Institute, Aalst, Belgium, §Martini Clinic Prostate Cancer Center, University Clinic Eppendorf, Hamburg, Germany, and Global Robotics Institute, Florida Hospital-Celebration Health Celebration, University of Central Florida School of Medicine, Orlando, FL, USA

 

Read the full article

To evaluate the influence of posterior musculofascial plate reconstruction (PR) on early return of continence after radical prostatectomy (RP); an updated systematic review of the literature. A systematic review of the literature was performed in June 2015, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and searching Medline, Embase, Scopus and Web of Science databases. We searched the terms posterior reconstruction prostatectomy, double layer anastomosis prostatectomy across the ‘Title’ and ‘Abstract’ fields of the records, with the following limits: humans, gender (male), and language (English). The authors reviewed the records to identify studies comparing cohorts of patients who underwent RP with or without restoration of the posterior aspect of the rhabdosphincter. A meta-analysis of the risk ratios estimated using data from the selected studies was performed. In all, 21 studies were identified, including three randomised controlled trials. The overall analysis of comparative studies showed that PR improved early continence recovery at 3–7, 30, and 90 days after catheter removal, while the continence rate at 180 days was statistically but not clinically affected. Statistically significantly lower anastomotic leakage rates were described after PR. There were no significant differences for positive surgical margins rates or for complications such as acute urinary retention and bladder neck stricture. The analysis confirms the benefits at 30 days after catheter removal already discussed in the review published in 2012, but also shows a significant advantage in terms of urinary continence recovery in the first 90 days. A multicentre prospective randomised controlled trial is currently being conducted in several institutions around the world to better assess the effectiveness of PR in facilitating an earlier recovery of postoperative urinary continence.

 

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Editorial: The Jury on Posterior Muscolofascial Reconstruction is still out

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In their systematic review and meta-analysis, Grasso et al. [1] address the question of whether posterior muscolofascial reconstruction (PMR), the so-called Rocco stitch, positively affects urinary continence after radical prostatectomy. The relevance of the question to this structured form of inquiry is that individual studies to date have been inconclusive. We recognize Sir Archie Cochrane, who gave his name to the Cochrane Collaboration that pioneered the methods for conducting systematic reviews, for emphasizing the critical importance of looking at the entire body of evidence in a structured manner when seeking to answer a clinical question [2]. In the present study, which included both randomized controlled trials (RCTs) and observational studies of variable methodological quality, a favourable impact of PMR across all postoperative time points (3–7 days, 30 days, 3 and 6 months) was observed. The effect was most pronounced early on at the time of catheter removal, when the patients undergoing PMR were nearly twice as likely as the control group (risk ratio 1.9; 95% CI 1.3–2.9) to be continent, thereby suggesting a major benefit of this approach. It should be noted, however, that this analysis was dominated by the observational studies, particularly retrospective observational studies, which offer the least degree of methodological rigor.

Even more important, therefore, than the act of pooling across studies is the rating of the quality of evidence for the body of evidence on an outcome-specific basis. Based on the GRADE approach, which has become the most widely endorsed framework for rating the quality of evidence, we would initially place a high and low level of confidence in a body of evidence drawn from RCTs and observational studies, respectively [3]. As a result, one might plan a separate analysis of those two groups of studies first, and only move to pool them if their results were similar. In this case, the results from the RCTs and observational studies were different, with prospective and retrospective studies reporting larger, probably exaggerated effect sizes; however, it is also understood that other aspects such as study limitation (risk of bias), inconsistency, impression, indirectness and risk publication bias may lower our confidence in the effect estimates from RCTs [4]. Focusing on the body of evidence from RCTs alone (Table 1) we have ‘moderate’ confidence that PMR may not improve early continence at the time of catheter removal. Similarly, the few RCTs that contributed to the assessment of continence at later timepoints do not provide evidence that continence is affected favourably, although our confidence for those outcomes is only ‘low’ or ‘very low’, suggesting that future trials may change these estimates of effect. Meanwhile, it should be noted that none of the RCTs appeared to provide information on the potential downsides of PMR, such as rates of urinary retention or bladder neck contracture. As a result, enough uncertainty remains to state that the jury on PMR is still out; this is consistent with the authors’ call for a future high-quality trial, which is reportedly ongoing. While PMR is already widely used by open and robot-assisted prostatectomy surgeons around the globe, this example sheds light on current evidentiary standards of surgical innovation. Following the IDEAL recommendations, it would be much preferred if the urological community committed to well designed trials for novel surgical approaches and device-dependent interventions up front, before moving to widespread dissemination [5].

JulEOTW2

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Philipp Dahm
Department of Urology, Minneapolis VA Health Care System, Urology Section 112D and University of Minnesota, Minneapolis, MN, USA

 

References

 

1 Grasso AAC, Mistretta FA, Sandri M et al. Posterior musculofascial reconstruction after radical prostatectomy: an updated systematic review and a meta-analysis. BJU Int 2016; 118: 20–34.

 

2 Hajebrahimi S, Dahm P, Buckingham J. Evidence-based urology in practice: the cochrane library. BJU Int 2009; 104: 1048–9

 

3 Canfield SE, Dahm P. Rating the quality of evidence and the strength of recommendations using GRADE. World J Urol 2011; 29: 311–7

 

4 Guyatt GH, Oxman AD, Vist GE et al. GRADE: what is “quality of evidence” and why is it important to clinicians? BMJ 2008; 336: 995–8

 

5 McCulloch P. The IDEAL recommendations and urological innovation. World J Urol 2011; 29: 331–6

 

Video: Posterior Muscolofascial Reconstruction after RP

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Posterior musculofascial reconstruction after radical prostatectomy: an updated systematic review and a meta-analysis

Angelica A.C. Grasso*, Francesco A. Mistretta*, Marco Sandri†, Gabriele Cozzi*, Elisa De Lorenzis*, Marco Rosso*, Giancarlo Albo*, Franco Palmisano*, Alex Mottrie‡, Alexander Haese§, Markus Graefen§, Rafael Coelho, Vipul R. Patel¶ and Bernardo Rocco*

 

*Department of Urology, Fondazione IRCCS Ca’ Granda-Ospedale Maggiore Policlinico, University of Milan, Milan, Italy, †DMS StatLab, Data Methods and Systems Statistical Laboratory, University of Brescia, Brescia, Italy, ‡OLV Robotic Surgery Institute, Aalst, Belgium, §Martini Clinic Prostate Cancer Center, University Clinic Eppendorf, Hamburg, Germany, and Global Robotics Institute, Florida Hospital-Celebration Health Celebration, University of Central Florida School of Medicine, Orlando, FL, USA

 

Read the full article

To evaluate the influence of posterior musculofascial plate reconstruction (PR) on early return of continence after radical prostatectomy (RP); an updated systematic review of the literature. A systematic review of the literature was performed in June 2015, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and searching Medline, Embase, Scopus and Web of Science databases. We searched the terms posterior reconstruction prostatectomy, double layer anastomosis prostatectomy across the ‘Title’ and ‘Abstract’ fields of the records, with the following limits: humans, gender (male), and language (English). The authors reviewed the records to identify studies comparing cohorts of patients who underwent RP with or without restoration of the posterior aspect of the rhabdosphincter. A meta-analysis of the risk ratios estimated using data from the selected studies was performed. In all, 21 studies were identified, including three randomised controlled trials. The overall analysis of comparative studies showed that PR improved early continence recovery at 3–7, 30, and 90 days after catheter removal, while the continence rate at 180 days was statistically but not clinically affected. Statistically significantly lower anastomotic leakage rates were described after PR. There were no significant differences for positive surgical margins rates or for complications such as acute urinary retention and bladder neck stricture. The analysis confirms the benefits at 30 days after catheter removal already discussed in the review published in 2012, but also shows a significant advantage in terms of urinary continence recovery in the first 90 days. A multicentre prospective randomised controlled trial is currently being conducted in several institutions around the world to better assess the effectiveness of PR in facilitating an earlier recovery of postoperative urinary continence.

 

Read more articles of the week

 

March #urojc: Radiotherapy for Prostate Cancer – Is it a gift that keeps on giving?

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The International Urology Journal Club on Twitter is now well into its 4th year.  The subject for the March 2016 discussion was a paper published in the BMJ entitled “Second Malignancies after radiotherapy for prostate cancer: systematic review and meta-analysis”.

Lead and senior authors, Chris Wallis and Rob Nam were kind enough to  make themselves available to participate in this discussion.  Rob Nam made use of the  #urojc guest twitter account.

UrojcMarch1

The literature was searched using Medline and Embase and the method of review was the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analysis of Observational studies in Epidemiology (MOOSE) guidelines for reporting of this systematic review and meta-analysis.

Chris Wallis provided an excellent TL:DR summary with the following tweet.

UrojcMarch2

It is well recognized that secondary malignancies following radiation exposure could take many years to become apparent.

UrojcMarch3

The responses were fairly predictable but nevertheless an important point to explore.

UrojcMarch4

Early in the discussion, there was also relevant reminder of the issue of differences in odds ratios and absolute risk.  That said, consideration needs to be given to the ‘big ticket’ nature of secondary malignancy where even a small absolute risk drives a great deal of interest in this subject matter.

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An interesting finding from the study was that the risk of secondary malignancy was less with brachytherapy compared with external beam radiation.

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UrojcMarch10

Further to this, is it possible that there could be a difference between HDR and seed brachytherapy?  An interesting thought although not specifically covered in the paper.

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A more controversial aspect to the discussion was whether the risk of secondary malignancy would justify screening or surveillance. The following exchange was worthy of note.

Whilst there is nothing in the way of documented guidelines or actual evidence to demonstrate a benefit of surveillance, it seems something worthy of consideration for future practice guidelines –  in other words, recommendations one way or the other.

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Rob Nam refers to a third paper on radiation outcomes in the context of previous surgery.  This BJC paper, the Lancet Oncology paper (previous discussed at a #urojc in 2014) and now the current paper could cheekily be called the Nam Trilogy – make note that you heard this term here for the first time.

UrojcMarch18UrojcMarch19

To what extent should we be counseling our patients on the risk of secondary malignancy if they are to undergo radiation for prostate cancer?  Is this just another factor to encourage surgery over radiotherapy?  Will there be no change in practice, particularly in the US where many lucrative radiation oncology services are actually owned by urological surgeon private practice groups?

UrojcMarch20UrojcMarch21UrojcMarch22UrojcMarch23UrojcMarch24

The state of radiation oncology practice is different outside the US and my own personal thoughts on the matter are that the Nam Trilogy of papers will create a series of well cited ‘evidence’ that will further shift the weight of opinion towards surgery over radiotherapy as a primary treatment for localized prostate cancer.

UrojcMarch25

Anybody who followed the March installment of the #urojc would have been impressed by the high level of interaction by the authors Chris Wallis and Rob Nam.  A particular mention should be given to Sabin Motwani who as a radiation oncologist, provided valuable input to the discussion.

Please do join us for the April installment of the #urojc and I encourage you all to email, tweet or DM your suggestions for papers to be discussed.  Please also, feel free to volunteer to write up a monthly summary for publication on the BJUI blogs.  I would also like to acknowledge the contributions of Rustom Manecksha who was the winner of the 2016 BJUI SoMe Award for #urojc – a reflection to the quality of his participation and support for this online educational activity.

 

Henry Woo is an Associate Professor of Surgery at the Sydney Adventist Hospital Clinical School of the University of Sydney.  He is the coordinator of the International Urology Journal Club on Twitter.

Article of the Week: Complications following artificial urinary sphincter placement after RP and EBRT

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Every Week the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this week, it should be this one.

Complications following artificial urinary sphincter placement after radical prostatectomy and radiotherapy: A meta-analysis

Anthony S. Bates, Richard M. Martin* and Tim R. Terry

Department of Urology, Leicester General Hospital, University Hospitals of Leicester NHS Trust, Leicester, and *School of Social and Community Medicine, University of Bristol, Bristol, UK

Read the full article

OBJECTIVE

To conduct a systematic review and meta-analysis of artificial urinary sphincter (AUS) placement after radical prostatectomy (RP) and external beam radiotherapy (EBRT).

PATIENTS AND METHODS

There were 1 886 patients available for analysis of surgical revision outcomes and 949 for persistent urinary incontinence (UI) outcomes from 15 and 11 studies, respectively. The mean age (sd) was 66.9 (1.4) years and the number of patients per study was 126.6 (41.7). The mean (sd, range) follow-up was 36.7 (3.9, 18–68) months. A systematic database search was conducted using keywords, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Published series of AUS implantations were retrieved, according to the inclusion criteria. The Newcastle–Ottawa Score was used to ascertain the quality of evidence for each study. Surgical results from each case series were extracted. Data were analysed using CMA® statistical software.

RESULTS

AUS revision was higher in RP + EBRT vs RP alone, with a random effects risk ratio of 1.56 (95% confidence interval [CI] 1.02–2.72; P <0.050; I2 = 82.0%) and a risk difference of 16.0% (95% CI 2.05–36.01; P < 0.080). Infection/erosion contributed to the majority of surgical revision risk compared with urethral atrophy (P = 0.020). Persistent UI after implantation was greater in patients treated with EBRT (P <0.001).

CONCLUSIONS

Men receiving RP + EBRT appear at increased risk of infection/erosion and urethral atrophy, resulting in a greater risk of surgical revision compared with RP alone. Persistent UI is more common with RP + EBRT

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Editorial: Post-prostatectomy incontinence in the irradiated patient: more than just a drop in the ocean

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Improved early detection of prostate cancer has led to an increased incidence of this disease, and an increase in the number of patients undergoing radical prostatectomy (RP). The rate of post-prostatectomy incontinence (PPI) is difficult to determine because of the varying definitions of incontinence, but approximately one in five men require the use of pads in the long term after RP. Incontinence has a significant negative impact on quality of life, and remains many men’s greatest fear, especially for the one in four who present at the age of <65 years. While significant advancements have been made in prostate cancer treatment, strong evidence for the optimum management of PPI remains lacking. Most guidelines are based on grade B or C recommendation and many questions about its surgical management remain unanswered.

The artificial urinary sphincter (AUS) has stood the test of time and has long been considered the ‘gold standard’ treatment for PPI, especially for those with moderate to severe incontinence. The quoted success rates achieved with this device vary from study to study based on the varying definition of ‘dry’. The use of radiotherapy (RT) after prostatectomy is generally considered to have a negative impact on its efficacy and revision rate, although some data have been conflicting. In this month’s BJUI, Bates et al. [1] present a timely and well-structured systematic review and meta-analysis of AUS placement after RP and RT. By analysing pooled results, the authors set out to clarify the effect of RT on AUS efficacy and outcomes. In total, 1886 patients from 15 studies published between 1989 and 2014 were included in the meta-analysis, including 14 studies assessing surgical revision and 11 looking at persistent urinary incontinence. No randomized controlled trials were available for analysis. Retrospective reporting and a lack of standardized postoperative validated assessments were a weakness of individual studies, and efforts to limit the effects of study heterogeneity and risk of bias were made using statistical models. The revision rate after a mean follow-up of 38.4 months was significantly higher in irradiated vs. non-irradiated men (mean 37.3 vs 19.8%; P < 0.007); the risk ratio was 1.56 and number needed to harm was 4 (i.e. one surgical revision for every four AUS devices implanted in irradiated men). Infection/erosion and urethral atrophy accounted for approximately half and one-third of all revisions respectively. Persistent urinary incontinence was also more than twice as likely in irradiated vs non-irradiated men (29.5 vs 12.1%; P = 0.003; risk ratio 2.08, number needed to harm 9).

This study highlights the significant negative impact of RT after RP on functional outcomes and its treatment. This is particularly important considering that approximately one-third of patients will require adjuvant or salvage radiotherapy at some stage after RP. The development of incontinence after RT is primarily attributable to the negative effect of radiation on bladder and urethral tissue. Unlike outcomes with regard to erectile function, the type of primary surgery performed (open vs robotic) does not appear to have any significant impact on PPI [2]. Timing of RT also does not seem to affect function, with similar rates of incontinence reported for early (<6 months after RP) vs late (>6 months after RP) irradiation reported 3 years after RT (24.5 vs 23.3%, respectively; P = 0.79) [3].

New devices, such as the male sling, have increased the options for PPI treatment. Male slings have achieved popularity because of their safety, relative ease of insertion and patients’ strong desire to void naturally without fiddling with pumps. Kumar et al. [4] reported that one in four men who were recommended an AUS as the best option by their surgeon chose a sling; 92% who were offered either also opted against the gold standard AUS. Slings, however, have not fared well in patients with severe incontinence or those who have undergone RT. Pooled analysis of the AdVance® sling reported ‘success’ rates of 56 and 54%, respectively, in these scenarios, compared with a mean overall ‘success’ rate of 75% [5]. Reported success, however, does not equate to being ‘dry’, as reported in many AUS studies, and this lack of uniformity in describing outcomes prevents adequate clarity when comparing different devices. Despite the lower success rate after RT, slings, unlike the AUS, do not appear to have any additional complications in this setting [1, 6], and sling failure does not appear to prejudice subsequent AUS placement [7].

To date, no randomized controlled trial has directly compared efficacy of the newer slings with the AUS. Well-designed trials, with standardized protocols and uniform long-term assessments of outcome, including complications and quality of life, are required to clarify their place in managing PPI. Current randomized controlled trials are evaluating these devices prospectively, and will provide much needed level 1 evidence in this field. The most interesting of these is the MASTER trial (Male synthetic sling vs Artificial urinary Sphincter Trial). This multicentre UK randomized controlled trial is for men with incontinence after prostate surgery for cancer or benign disease [8]. Patients of any age, with any level of incontinence are eligible, and previous RT is not an exclusion criterion. The trial aims to randomize 360 men and will also follow up 360 non-randomized men, and runs until 2019. This trial will help clarify the relative benefits of the devices by incontinence severity. It will also provide some prospective data on the effect of RT on outcomes, although the 2-year follow-up will be too short to evaluate this fully.

The question remains regarding which strategy is the best for post-prostatectomy irradiated patients. Until the results of good quality trials are available, the jury is out. The AUS remains the gold standard in this setting, for now. For patients with mild to moderate incontinence, the sling is an option, and offers some advantages, but offers a lower overall chance of becoming pad free. Patients must be carefully counselled about the risk/benefit of this approach compared with an AUS. Results of the MASTER trial will help better define management of this subgroup. For moderate to severe incontinence, the AUS is the gold standard, albeit with an increased risk of failure and revision. The present meta-analysis arms the clinician with much needed data to quantify the relative risk of complications and adverse outcomes in this setting, and will allow better counselling and management of patient’s expectations.

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Majid Shabbir

Department of Urology, Guy’s Hospital, London, UK

References

1 Bates A, Martin R, Terry T. Complications following artificial urinary sphincter placement after radical prostatectomy and radiotherapy: a metaanalysis. BJU Int 2015; 116: 623–33

2 Haglind E, Carlsson S, Stranne J et al. Urinary incontinence and erectile dysfunction after robotic versus open radical prostatectomy: a prospective, controlled, nonrandomised trial. Eur Urol 2015. doi: 10.1016/j.eururo. 2015.02.029. [Epub ahead of print]

3 Sowerby RJ, Gani J, Yim H. Long-term complications in men who have early or late radiotherapy after radical prostatectomy. Can Urol Assoc J 2014; 8: 253–8.

4 Kumar A, Litt ER, Ballert KN, Nitti VW. Artificial urinary sphincter versus male sling for post-prostatectomy incontinence-what do patients choose? J Urol 2009; 181: 1231–5.

5 Van Bruwaene S, Van der Aa F, De Ridder D. Review: the use of sling versus sphincter in post-prostatectomy urinary incontinence. BJU Int 2015; 116: 330–42

6 Zuckerman JM, Tisdale B, McCammon K. AdVance male sling in irradiated patients with stress urinary incontinence. Can J Urol 2011; 18: 6013–7.

7 Lentz AC, Peterson AC, Webster GD. Outcomes following artificial sphincter implantation after prior unsuccessful male sling. J Urol 2012; 187: 2149–53.

8 Abrams P. Male synthetic sling versus Artificial urinary Sphincter Trial for men with urodynamic stress incontinence after prostate surgery: Evaluation by Randomised controlled trial (MASTER), 2014. Available at: www.controlled-trials.com/ISRCTN49212975/MASTER. Accessed May 2015

 

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