Prostatectomy 2020

An explanation of PROSPECT methodology and Working Group processes can be found at the following link: https://esraeurope.org/prospect-methodology

For the prostatectomy review, the Subgroup members were:

• Adrien Lemoine^1,2
• Annemijn Witdouck³
• Hélène Beloeil⁴
• Francis Bonnet^1,2

1. Anaesthesia – Intensive Care and Peri-Operative Medicine Department, Hopital Tenon, APHP, Paris, France.

2. Médecine-Sorbonne Université, Paris, France.

3. Department of Cardiovascular Sciences, KU Leuven and University Hospital Leuven, Leuven, Belgium.

4. Université de Rennes, CHU Rennes, Inserm, INRA, CIC 1414 NuMeCan, Anaesthesia and Intensive Care Department, Rennes, France.

Prostatectomy literature search

• This update was a systematic review of the literature associated with analgesia after robotic, laparoscopic and open prostatectomy between January 2015 and March 2020.
• The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2015 statement was used as a guide.
• The following databases were searched: EMBASE, MEDLINE, PubMed and Cochrane Databases (Cochrane Central Register of Controlled Trials, Cochrane Database of Abstracts or Reviews of Effects, and Cochrane Database of Systematic Reviews) (Search strategy).
• Reference lists of the relevant articles were screened to seek for any additional article that may have been missed in the initial literature search. This is how articles published before 2015 that were not assessed by the precedent review were also taken into consideration.
• Included studies were RCTs and systematic reviews of analgesic, anaesthetic and operative interventions, published in English, assessing pain management for patients undergoing open, laparoscopic or robot-assisted prostatectomy. Included studies were also required to measure pain intensity using NRS or VAS.
• Exclusions: studies that reported pooled data combining other perineal and/or abdominal surgical procedures together with radical prostatectomy, and studies concerning non-radical prostatectomy.
• From 2428 records retrieved, 394 full-text articles were reviewed in more detail.
• 356 studies were excluded after full-text screening. Reasons for exclusion are provided in the Summary of literature selection.
• 35 RCTs and 3 meta-analyses met the inclusion criteria (Summary of literature selection)
  • Included studies
  • Open surgery was performed in 15 studies, a laparoscopic approach was performed in one study, and a robot-assisted laparoscopic approach was performed in 17 studies.
  • Two studies considered the difference between robotic and open surgical procedures, and one study concerned fast track surgery.
• The previous PROSPECT review on radical prostatectomy included 38 studies (Joshi 2015). At that time there was insufficient procedure-specific evidence to support an optimal pain management protocol in patients undergoing radical prostatectomy. In the following folders, where relevant, evidence from the earlier review is detailed together with the updated procedure-specific evidence when there is a new recommendation.

Assessments of the quality of study methodology and reporting

All included studies were assessed for quality according to PROSPECT methodology (Joshi 2019, https://esraeurope.org/prospect-methodology). The study quality assessments for prostatectomy are summarised here: Quality assessments and level of evidence assigned to included trials.

• Data extraction and data analysis for prostatectomy adhered to the PROSPECT methodology (Joshi 2019, https://esraeurope.org/prospect-methodology).
• For each analysed study or meta-analysis, summary information was extracted and recorded in data tables. This information included the surgical technique, the timing of surgery, pain scores, whether pain was assessed at rest or during mobilisation, supplementary analgesics used, time to first analgesic administration, time intervals between pain measurements and complications, if any.
• The included studies were grouped together based upon the analgesic interventions. Within each group, the studies were further placed into subgroups of pre-operative, intra-operative, and postoperative interventions. The studies assessing the effects of surgical techniques on analgesic outcomes were grouped separately.
• Pain intensity scores were used as the primary outcome measure. A change of >10 mm on the VAS was defined as clinically relevant (Myles 2017). Unless specified, it was assumed that pain scores were assessed at rest.
• The effectiveness of each pain treatment for each outcome was evaluated qualitatively, by assessing the number of studies showing a significant difference between treatment arms (p<0.05 as reported in the study publication).

The methodology of the PROSPECT group is unique in that the available evidence is critically assessed for current clinical relevance, considering the analgesic benefit of interventions against the backdrop of basic analgesics (i.e. paracetamol and NSAIDs or COX-2-selective inhibitors), the degree of pain after surgery, and balancing the procedure-specific efficacy and benefits of an intervention against its general risks and invasiveness.

For recommending an analgesic, at least two RCTs have to show efficacy. Recommendations were made according to PROSPECT methodology (Joshi 2019, https://esraeurope.org/prospect-methodology). This involved a grading of A–D according to the overall level of evidence, as determined by the quality of studies included, consistency of evidence and study design: Relationship between quality of the study and levels of evidence and grades of recommendation.

Recommendations from the previous review (Joshi 2015) were kept as baseline. Based on the updated systematic review, a subgroup developed draft new recommendations, which were then circulated amongst all the Working Group members for review and comments. A modified Delphi approach was used as previously described (Joshi 2019), including several rounds of individual comments followed by a round-table discussion. Once consensus was achieved, the lead author drafted the final document, which was ultimately approved by the full PROSPECT group.

The included studies have some limitations:

• Study protocols vary in dosing regimens, route of administration, and standard of care in control groups.
• Some analgesic treatments were not evaluated against a control group that received an adequate analgesic regimen.
• Most studies included small sample groups, making the results inconclusive when they showed no difference between groups.
• Sample sizes were too limited to draw conclusions concerning the safety profile of the analgesic drugs or techniques in the specific setting of prostatectomy.
• Other outcomes such as deambulation, length of hospital stay, and patient satisfaction should be evaluated more systematically.

Other limiting factors include the possibility of selection bias by the primary reviewers, which could have developed because all studies fulfilling the search requirements were split between two reviewers. There was also a possibility of human error, in which an appropriate study could have been missed by a reviewer and excluded.

The AGREE II instrument (Brouwers 2010) is used internationally to assess the methodological rigour and transparency of practice guidelines. As far as possible, the methodology of the PROSPECT prostatectomy review meets the requirements of ‘Domain 3: Rigour of development’ of the AGREE II instrument:

• Systematic methods were used to search for evidence
• The criteria for selecting the evidence are clearly described
• The strengths and limitations of the body of evidence are clearly described
• The methods for formulating the recommendations are clearly described
• The health benefits, side effects, and risks have been considered in formulating the recommendations
• There is an explicit link between the recommendations and the supporting evidence
• The guideline has been externally reviewed by experts prior to its publication. (The evidence and recommendations are made available on the website after peer review and publication)
• A procedure for updating the guideline is provided. (Methodology is provided so that the systematic review can be updated as required)