Minimally invasive treatments for lower urinary tract symptoms in men with benign prostatic hyperplasia: a network meta-analysis

Abstract

Background: A variety of minimally invasive treatments are available as an alternative to transurethral resection of the prostate (TURP) for management of lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH). However, it is unclear which treatments provide better results. Objectives: Our primary objective was to assess the comparative effectiveness of minimally invasive treatments for lower urinary tract symptoms in men with BPH through a network meta-analysis. Our secondary objective was to obtain an estimate of relative ranking of these minimally invasive treatments, according to their effects. Search methods: We performed a comprehensive search of multiple databases (CENTRAL, MEDLINE, Embase, Scopus, Web of Science and LILACS), trials registries, other sources of grey literature, and conference proceedings, up to 24 February 2021. We had no restrictions on language of publication or publication status. Selection criteria: We included parallel-group randomized controlled trials assessing the effects of the following minimally invasive treatments, compared to TURP or sham treatment, on men with moderate to severe LUTS due to BPH: convective radiofrequency water vapor therapy (CRFWVT); prostatic arterial embolization (PAE); prostatic urethral lift (PUL); temporary implantable nitinol device (TIND); and transurethral microwave thermotherapy (TUMT). Data collection and analysis: Two review authors independently screened the literature, extracted data, and assessed risk of bias. We performed statistical analyses using a random-effects model for pair-wise comparisons and a frequentist network meta-analysis for combined estimates. We interpreted them according to Cochrane methods. We planned subgroup analyses by age, prostate volume, and severity of baseline symptoms. We used risk ratios (RRs) with 95% confidence intervals (CIs) to express dichotomous data and mean differences (MDs) with 95% CIs to express continuous data. We used the GRADE approach to rate the certainty of evidence. Main results: We included 27 trials involving 3017 men, mostly over age 50, with severe LUTS due to BPH. The overall certainty of evidence was low to very low due to concerns regarding bias, imprecision, inconsistency (heterogeneity), and incoherence. Based on the network meta-analysis, results for our main outcomes were as follows. Urologic symptoms (19 studies, 1847 participants): PUL and PAE may result in little to no difference in urologic symptoms scores (MD of International Prostate Symptoms Score [IPSS]) compared to TURP (3 to 12 months; MD range 0 to 35; higher scores indicate worse symptoms; PUL: 1.47, 95% CI -4.00 to 6.93; PAE: 1.55, 95% CI -1.23 to 4.33; low-certainty evidence). CRFWVT, TUMT, and TIND may result in worse urologic symptoms scores compared to TURP at short-term follow-up, but the CIs include little to no difference (CRFWVT: 3.6, 95% CI -4.25 to 11.46; TUMT: 3.98, 95% CI 0.85 to 7.10; TIND: 7.5, 95% CI -0.68 to 15.69; low-certainty evidence). Quality of life (QoL) (13 studies, 1459 participants): All interventions may result in little to no difference in the QoL scores, compared to TURP (3 to 12 months; MD of IPSS-QoL score; MD range 0 to 6; higher scores indicate worse symptoms; PUL: 0.06, 95% CI -1.17 to 1.30; PAE: 0.09, 95% CI -0.57 to 0.75; CRFWVT: 0.37, 95% CI -1.45 to 2.20; TUMT: 0.65, 95% CI -0.48 to 1.78; TIND: 0.87, 95% CI -1.04 to 2.79; low-certainty evidence). Major adverse events (15 studies, 1573 participants): TUMT probably results in a large reduction of major adverse events compared to TURP (RR 0.20, 95% CI 0.09 to 0.43; moderate-certainty evidence). PUL, CRFWVT, TIND and PAE may also result in a large reduction in major adverse events, but CIs include substantial benefits and harms at three months to 36 months; PUL: RR 0.30, 95% CI 0.04 to 2.22; CRFWVT: RR 0.37, 95% CI 0.01 to 18.62; TIND: RR 0.52, 95% CI 0.01 to 24.46; PAE: RR 0.65, 95% CI 0.25 to 1.68; low-certainty evidence). Retreatment (10 studies, 799 participants): We are uncertain about the effects of PAE and PUL on retreatment compared to TURP (12 to 60 months; PUL: RR 2.39, 95% CI 0.51 to 11.1; PAE: RR 4.39, 95% CI 1.25 to 15.44; very low-certainty evidence). TUMT may result in higher retreatment rates (RR 9.71, 95% CI 2.35 to 40.13; low-certainty evidence). Erectile function (six studies, 640 participants): We are very uncertain of the effects of minimally invasive treatments on erectile function (MD of International Index of Erectile Function [IIEF-5]; range 5 to 25; higher scores indicates better function; CRFWVT: 6.49, 95% CI -8.13 to 21.12; TIND: 5.19, 95% CI -9.36 to 19.74; PUL: 3.00, 95% CI -5.45 to 11.44; PAE: -0.03, 95% CI -6.38, 6.32; very low-certainty evidence). Ejaculatory dysfunction (eight studies, 461 participants): We are uncertain of the effects of PUL, PAE and TUMT on ejaculatory dysfunction compared to TURP (3 to 12 months; PUL: RR 0.05, 95 % CI 0.00 to 1.06; PAE: RR 0.35, 95% CI 0.13 to 0.92; TUMT: RR 0.34, 95% CI 0.17 to 0.68; low-certainty evidence). TURP is the reference treatment with the highest likelihood of being the most efficacious for urinary symptoms, QoL and retreatment, but the least favorable in terms of major adverse events, erectile function and ejaculatory function. Among minimally invasive procedures, PUL and PAE have the highest likelihood of being the most efficacious for urinary symptoms and QoL, TUMT for major adverse events, PUL for retreatment, CRFWVT and TIND for erectile function and PUL for ejaculatory function. Authors' conclusions: Minimally invasive treatments may result in similar or worse effects concerning urinary symptoms and QoL compared to TURP at short-term follow-up. They may result in fewer major adverse events, especially in the case of PUL and PAE; resulting in better rankings for symptoms scores. PUL may result in fewer retreatments compared to other interventions, especially TUMT, which had the highest retreatment rates at long-term follow-up. We are very uncertain about the effects of these interventions on erectile function. There was limited long-term data, especially for CRFWVT and TIND. Future high-quality studies with more extended follow-up, comparing different, active treatment modalities, and adequately reporting critical outcomes relevant to patients, including those related to sexual function, could provide more information on the relative effectiveness of these interventions.