Systematic review of surgical treatments for benign prostatic hyperplasia and presentation of an approach to investigate therapeutic equivalence (non-inferiority)

Objective: • To assess the potential additional benefit of non-standard vs standard surgical treatments for benign prostatic hyperplasia (BPH) and to present a new methodological approach to investigate therapeutic equivalence (non-inferiority) regarding symptom reduction.

Patients and methods: • We conducted a systematic review and searched MEDLINE, Embase and the Cochrane Library (last search: 10/2009) for randomized controlled trials (RCTs) and non-randomized controlled clinical trials (CCTs). • Eligible studies were those that included patients with symptomatic BPH requiring surgical treatment and which compared non-standard procedures (e.g. minimally invasive technologies) with standard ones (e.g. transurethral resection of the prostate, TURP). In addition, only studies analysing patient-relevant outcomes were considered (e.g. irritative and obstructive symptoms, length of hospital stay, quality of life and adverse events). • The main outcome of interest for the present analysis was superiority or non-inferiority for symptom reduction. • As no trial investigated non-inferiority, we defined a non-inferiority threshold (0.25 standard deviation) on the basis of published literature. If a non-standard procedure showed non-inferiority for symptom reduction, additional outcomes were assessed. Meta-analyses were conducted if feasible and meaningful.

Results: • In all, 43 mainly low-quality trials (RCTs only) compared nine non-standard surgical treatments with standard ones. • Mean follow-up ranged from 6 to 84 months. • No non-standard procedure was superior for symptom reduction. Non-inferiority for symptom reduction was shown in patients who had undergone holmium laser resection of the prostate (HoLRP) or thulium laser resection of the prostate (TmLRP). • As procedural advantages (e.g. no occurrence of transurethral resection syndrome) and other advantages (e.g. shortened hospital stay) were found, an indication of an additional benefit of HoLRP and TmLRP was determined.

Conclusions: • No proof of superiority for symptom reduction has been shown for non-standard surgical treatments in patients with BPH. • There is a lack of high-quality RCTs and trials designed to investigate non-inferiority. • Future studies should define a non-inferiority threshold (ideally, uniform) a priori, so that results of individual studies are interpretable and comparable, and future systematic reviews should consider this issue.