Testosterone replacement in men with sexual dysfunction.

BACKGROUND: Clinical practice guidelines recommend testosterone replacement therapy (TRT) for men with sexual dysfunction and testosterone deficiency. However, TRT is commonly promoted in men without testosterone deficiency and existing trials often do not clearly report participants' testosterone levels or testosterone-related symptoms. This review assesses the potential benefits and harms of TRT in men presenting with complaints of sexual dysfunction. OBJECTIVES: To assess the effects of testosterone replacement therapy compared to placebo or other medical treatments in men with sexual dysfunction. SEARCH METHODS: We performed a comprehensive search of CENTRAL (the Cochrane Library), MEDLINE, EMBASE, and the trials registries ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform, with no restrictions on language of publication or publication status, up to 29 August 2023. SELECTION CRITERIA: We included randomized controlled trials (RCTs) in men (40 years or over) with sexual dysfunction. We excluded men with primary or secondary hypogonadism. We compared testosterone or testosterone with phosphodiesterase-5 inhibitors (PDEI5I) to placebo or PDE5I alone. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the literature, assessed the risk of bias, extracted data, and rated the certainty of evidence (CoE) according to GRADE using a minimally contextualized approach. We performed statistical analyses using a random-effects model and interpreted them according to standard Cochrane methodology. Predefined primary outcomes were self-reported erectile dysfunction assessed by a validated instrument, sexual quality of life assessed by a validated instrument, and cardiovascular mortality. Secondary outcomes were treatment withdrawal due to adverse events, prostate-related events, and lower urinary tract symptoms (LUTS). We distinguished between short-term (up to 12 months) and long-term (> 12 months) outcomes. MAIN RESULTS: We identified 43 studies with 11,419 randomized participants across three comparisons: testosterone versus placebo, testosterone versus PDE5I, and testosterone with PDE5I versus PDE5I alone. This abstract focuses on the most relevant comparison of testosterone versus placebo. Testosterone versus placebo (up to 12 months) Based on a predefined sensitivity analysis of studies at low risk of bias, and an analysis combing data from the similar International Index of Erectile Function (IIEF-EF) and IIEF-5 instruments, TRT likely results in little to no difference in erectile function assessed with the IIEF-EF (mean difference (MD) 2.37, 95% confidence interval (CI) 1.67 to 3.08; I² = 0%; 6 RCTs, 2016 participants; moderate CoE) on a scale from 6 to 30 with larger values reflecting better erectile function. We assumed a minimal clinically important difference (MCID) of greater than or equal to 4. TRT likely results in little to no change in sexual quality of life assessed with the Aging Males' Symptoms scale (MD -2.31, 95% CI -3.63 to -1.00; I² = 0%; 5 RCTs, 1030 participants; moderate CoE) on a scale from 17 to 85 with larger values reflecting worse sexual quality of life. We assumed a MCID of greater than or equal to 10. TRT also likely results in little to no difference in cardiovascular mortality (risk ratio (RR) 0.83, 95% CI 0.21 to 3.26; I² = 0%; 10 RCTs, 3525 participants; moderate CoE). Based on two cardiovascular deaths in the placebo group and an assumed MCID of 3%, this would correspond to no additional deaths per 1000 men (95% CI 1 fewer to 4 more). TRT also likely results in little to no difference in treatment withdrawal due to adverse events, prostate-related events, or LUTS. Testosterone versus placebo (later than 12 months) We are very uncertain about the longer-term effects of TRT on erectile dysfunction assessed with the IIEF-EF (MD 4.20, 95% CI -2.03 to 10.43; 1 study, 42 participants; very low CoE). We did not find studies reporting on sexual quality of life or cardiovascular mortality. We are very uncertain about the effect of testosterone on treatment withdrawal due to adverse events. We found no studies reporting on prostate-related events or LUTS. AUTHORS' CONCLUSIONS: In the short term, TRT probably has little to no effect on erectile function, sexual quality of life, or cardiovascular mortality compared to a placebo. It likely results in little to no difference in treatment withdrawals due to adverse events, prostate-related events, or LUTS. In the long term, we are very uncertain about the effects of TRT on erectile function when compared to placebo; we did not find data on its effects on sexual quality of life or cardiovascular mortality. The certainty of evidence ranged from moderate (signaling that we are confident that the reported effect size is likely to be close to the true effect) to very low (indicating that the true effect is likely to be substantially different). The findings of this review should help to inform future guidelines and clinical decision-making at the point of care.

GRADE Reporting in Systematic Reviews Published in the Urological Literature (2009-2021).

PURPOSE: We evaluate the reporting of the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to rating the certainty of evidence in systematic reviews published in the urological literature. MATERIALS AND METHODS: Based on a predefined protocol, we identified all systematic reviews published in 5 major urological journals from 1998 to 2021 that reported the use of GRADE. Two authors performed study selection and data abstraction independently to assess reporting in accordance with established criteria for applying GRADE. RESULTS: We included 68 of 522 (13.0%) systematic reviews that reported the use of GRADE; the first was published in 2009. Approximately half were published between 2009-2018 (n=36) and the other half between 2019-2021 (n=32). Oncology (24; 35.3%) was the most common clinical topic, and the authors were mostly based in Europe (34; 50%). In their abstract, less than half of all systematic reviews (32; 47.1%) provided any certainty of evidence rating. Only 41 (60.3%) included a tabular result summary in the format of a summary of findings table (24; 35.3%) or evidence profile (17; 25.0%). Few (35.3%) addressed the GRADE certainty of evidence rating in the discussion section. Reporting did not improve over time when comparing the 2 time periods. CONCLUSIONS: Whereas GRADE is increasingly being applied for rating the certainty of evidence, systematic reviews published in the urological literature frequently have not followed established criteria for applying or using GRADE. There is a need for better training of authors and editors, as well as for a GRADE reporting checklist for systematic review authors.

Forsythia velutina Nakai extract: A promising therapeutic option for atopic dermatitis through multiple cell type modulation.

BACKGROUND: Atopic dermatitis (AD) is a complex condition characterized by impaired epithelial barriers and dysregulated immune cells. In this study, we demonstrated Forsythia velutina Nakai extract (FVE) simultaneously inhibits basophils, macrophages, keratinocytes, and T cells that are closely interrelated in AD development. METHODS: We analyzed the effect of FVE on nitric oxide and reactive oxygen species (ROS) production in macrophages, basophil degranulation, T cell activation, and tight junctions in damaged keratinocytes. Expression of cell-type-specific inflammatory mediators was analyzed, and the underlying signaling pathways for anti-inflammatory effects of FVE were investigated. The anti-inflammatory effects of FVE were validated using a DNCB-induced mouse model of AD. Anti-inflammatory activity of compounds isolated from FVE was validated in each immune cell type. RESULTS: FVE downregulated the expression of inflammatory mediators and ROS production in macrophages through TLR4 and NRF2 pathways modulation. It significantly reduced basophil degranulation and expression of type 2 (T2) and pro-inflammatory cytokines by perturbing FcεRI signaling. Forsythia velutina Nakai extract also robustly inhibited the expression of T2 cytokines in activated T cells. Furthermore, FVE upregulated the expression of tight junction molecules in damaged keratinocytes and downregulated leukocyte attractants, as well as IL-33, an inducer of T2 inflammation. In the AD mouse model, FVE showed superior improvement in inflammatory cell infiltration and skin structure integrity compared to dexamethasone. Dimatairesinol, a lignan dimer, was identified as the most potent anti-inflammatory FVE compound. CONCLUSION: Forsythia velutina Nakai extract and its constituent compounds demonstrate promising efficacy as a therapeutic option for prolonged AD treatment by independently inhibiting various cell types associated with AD and disrupting the deleterious link between them.

Prostatic arterial embolisation for men with benign prostatic hyperplasia: a Cochrane review.

OBJECTIVES: To assess the effects of prostatic arterial embolisation (PAE) compared to other procedures for treatment of lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH). METHODS: We included randomised controlled trials (RCTs), as well as non-randomised studies (NRSs) enrolling men with BPH undergoing PAE vs other surgical interventions via a comprehensive search up until 8 November 2021. Two independent reviewers screened the literature, extracted data, assessed risk of bias, performed statistical analyses by using a random-effects model, and rated the certainty of evidence (CoE) of RCTs and NRSs. RESULTS: We found data to inform two comparisons: PAE vs transurethral resection of prostate (TURP; six RCTs and two NRSs), and PAE vs sham (one RCT). This abstract focuses on the primary outcomes in a comparison of PAE vs TURP. Short-term follow-up: based on RCT evidence, there may be little to no difference in urological symptom score improvement (mean difference [MD] 1.72, 95% confidence interval [CI] -0.37 to 3.81; low CoE) and quality of life (QoL; MD 0.28, 95% CI -0.28 to 0.84; low CoE) measured by International Prostatic Symptom Score. We are very uncertain about the effects of PAE on major adverse events (risk ratio [RR] 0.75, 95% CI 0.19-2.97; very low CoE). Long-term follow-up: based on RCT evidence, PAE may result in little to no difference in urological symptom scores (MD 2.58, 95% CI -1.54 to 6.71; low CoE) and QoL (MD 0.50, 95% CI -0.03 to 1.04; low CoE). We are very uncertain about major adverse events (RR 0.91, 95% CI 0.20-4.05; very low CoE). CONCLUSION: Compared to TURP, the impact on urological symptoms and QoL improvement as perceived by patients appears to be similar. This review did reveal major uncertainty as to how major adverse events compare.

Risk of uterine cervical cancer in inflammatory bowel disease: a systematic review and meta-analysis.

BACKGROUND AND AIMS: There are limited data on the association between uterine cervical cancer (UCC) and inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC). METHODS: This systematic review and meta-analysis assessed the risk of UCC in patients with IBD. We searched MEDLINE, Embase, Cochrane Library, Scopus, Web of Science, ClinicalTrials.gov, gray literature and conference proceedings for studies published before 21 January 2022. Two reviewers independently screened studies, extracted data and assessed quality using the Newcastle-Ottawa Scale. Subgroup analyses were based on IBD type, biologic era, immunosuppression status, study location and design, and publication status. Fifteen studies were included. RESULTS: The pooled relative risk (RR) of UCC in IBD was 1.34 (95% confidence interval [CI], 1.07-1.69; I2 = 53.4%). In subgroup analyses, the pooled RRs of UCC in CD and UC were 1.18 (95% CI, 0.97-1.42) and 1.50 (95% CI, 1.01-12.21), respectively. The pooled RRs of UCC in pre-biologic and biologic eras were 1.36 (95% CI, 0.83-2.23) and 1.99 (95% CI, 1.03-3.86), respectively. The pooled RR of UCC in immunomodulator users was 2.18 (95% CI, 0.81-5.87). The pooled RRs of UCC in Asia, Europe and North America were 5.65 (95% CI, 2.65-12.07), 1.13 (95% CI, 0.96-1.34) and 1.38 (95% CI, 1.10-1.73), respectively. CONCLUSIONS: The risk of UCC was significantly increased in IBD, particularly in UC but not in CD, suggesting that women with IBD should undergo regular UCC screening and consider vaccination.

Non-surgical therapies for Peyronie's disease.

BACKGROUND: Peyronie's disease is a condition that results in the development of penile plaques that can lead to penile curvature, pain, and erectile dysfunction, making sexual activity difficult. A number of non-surgical interventions exist to improve this condition, which include topical and injection agents as well as mechanical methods; however, their effectiveness remains uncertain. We performed this review to determine the effects of these non-surgical treatments. OBJECTIVES: To assess the effects of non-surgical therapies compared to placebo or no treatment in individuals with Peyronie's disease. SEARCH METHODS: We performed a comprehensive search using multiple databases (the Cochrane Library, MEDLINE, Embase, Scopus, Google Scholar, and Web of Science), trials registries, other sources of grey literature, and conference proceedings, up to 23 September 2022. We applied no restrictions on publication language or status. SELECTION CRITERIA: We included trials in which men with Peyronie's disease were randomized to undergo non-surgical therapies versus placebo or no treatment for penile curvature and sexual function. DATA COLLECTION AND ANALYSIS: Two of four review authors, working in pairs, independently classified studies and abstracted data from the included studies. Primary outcomes were: patient-reported ability to have intercourse, quality of life, and treatment-related adverse effects. Secondary outcomes were: degree of penile curvature, discontinuation from treatment (for any reason), subjective patient-reported change in penile curvature, and improvement in penile pain. We performed statistical analyses using a random-effects model. We rated the certainty of evidence (CoE) according to the GRADE approach. MAIN RESULTS: Our search identified 1288 relevant references of which we included 18 records corresponding to 14 unique randomized controlled trials (RCTs) with 1810 men. These informed 10 distinct comparisons with relevant outcome data that were mostly extracted from single trials. In this abstract, we focus only on the most clinically relevant comparisons for the three primary outcomes and also include the outcome of degree penile curvature. Injectional collagenase (short-term): We found no short-term evidence on injectional collagenase for patients' self-reported ability to have intercourse and treatment-related adverse effects compared to placebo injection. Injectional collagenase may result in little to no difference in quality of life (scale 0 to 20 with lower scores indicating better quality of life; mean difference (MD) 1.8 lower, 95% confidence interval (CI) -3.58 to -0.02; 1 study, 134 participants; low CoE) and there may be little to no effect on the degree of penile curvature (MD 10.90 degrees less, 95% CI -16.24 to -5.56; 1 study, 136 participants; low CoE). Injectional collagenase (long-term): We also found no long-term evidence on injectional collagenase for patients' self-reported ability to have intercourse compared to placebo injection. It likely results in little to no effect on quality of life (MD 1.00 lower, 95% CI -1.60 to -0.40; 1 study, 612 participants; moderate CoE). Treatment-related adverse effects are likely increased (risk ratio (RR) 2.32, 95% CI 1.98 to 2.72; 1 study, 832 participants; moderate CoE). Injectional collagenase likely results in little to no change in the degree of penile curvature (MD 6.90 degrees less, 95% CI -9.64 to -4.14; 1 study, 612 participants; moderate CoE). Injectional verapamil (short-term): We are very uncertain how injectional verapamil may affect patients' self-reported ability to have intercourse compared to placebo injection short-term (RR 7.00, 95% CI 0.43 to 114.70; 1 study, 14 participants; very low CoE). We found no evidence for the outcome of quality of life. We are very uncertain how injectional verapamil may affect treatment-related adverse effects (RR not estimable; 1 study, 14 participants; very low CoE). Similarly, we are very uncertain how injectional verapamil may affect degree of penile curvature (MD -1.86, 95% CI -10.39 to 6.67; 1 study, 14 participants; very low CoE). We found no long-term data for any outcome. Extracorporeal shock wave treatment (ESWT) (short-term): We are very uncertain how ESWT affects patients' self-reported ability to have intercourse short-term (RR 1.60, 95% CI 0.71 to 3.60; 1 study, 26 participants; very low CoE). ESWT may result in little to no difference in quality of life (MD 3.10, 95% CI 1.57 to 4.64; 2 studies, 130 participants; low CoE). We are very uncertain if ESWT has an effect on treatment-related adverse effects (RR 2.73, 95% CI 0.74 to 10.14; 3 studies, 166 participants; very low CoE). ESWT may result in little to no difference in the degree of penile curvature compared to placebo (RR -2.84, 95% -7.35 to 1.67; 3 studies, 166 participants; low CoE). We found no long-term data for any outcome. Penile traction therapy (short-term): We found no evidence for whether penile traction compared to no treatment affects patients' self-reported ability to have intercourse. We are very uncertain how traction therapy may affect quality of life (MD 1.50 lower, 95% CI -3.42 to 0.42; 1 study, 90 participants; very low CoE). We are also very uncertain how traction therapy may affect treatment-related adverse effects (RR not estimable; 1 study, 90 participants; very low CoE) and how it affects the degree of curvature (MD 7.40 degrees less, 95% CI -11.18 to -3.62; 1 study, 89 participants; very low CoE). We found no long-term data for any outcome. AUTHORS' CONCLUSIONS: There is little evidence supporting the effectiveness of most non-surgical treatments for Peyronie's disease. Existing trials are mostly of poor methodological quality and/or fail to address patient-centered outcomes. Injectional collagenase appears to have some effectiveness; however, many individuals may not experience the improvement as clinically relevant, and this comes with the risk of increased adverse events. There is a critical need for better non-surgical treatment options for men with Peyronie's disease.

ANTECEDENTES: La enfermedad de Peyronie es una afección que da lugar al desarrollo de placas en el pene que pueden provocar curvatura peneana, dolor y disfunción eréctil, dificultando la actividad sexual. Existen varias intervenciones no quirúrgicas para mejorar esta afección, que incluyen agentes tópicos e inyectables, así como métodos mecánicos; sin embargo, su eficacia aún es incierta. Esta revisión se realizó para determinar los efectos de estos tratamientos no quirúrgicos. OBJETIVOS: Evaluar los efectos de los tratamientos no quirúrgicos en comparación con placebo o ningún tratamiento en individuos con enfermedad de Peyronie. MÉTODOS DE BÚSQUEDA: Se realizó una búsqueda exhaustiva en múltiples bases de datos (la Biblioteca Cochrane, MEDLINE, Embase, Scopus, Google Scholar y Web of Science), en registros de ensayos, otras fuentes de literatura gris y resúmenes de congresos, hasta el 23 de septiembre de 2022. No se impusieron restricciones respecto al idioma ni el estado de publicación. CRITERIOS DE SELECCIÓN: Se incluyeron ensayos en los que se asignó al azar a hombres con enfermedad de Peyronie a someterse a tratamientos no quirúrgicos versus placebo o ningún tratamiento para la curvatura del pene y la función sexual. OBTENCIÓN Y ANÁLISIS DE LOS DATOS: Dos de los cuatro autores de la revisión, trabajando en pareja, clasificaron de forma independiente los estudios y resumieron los datos de los estudios incluidos. Los desenlaces principales fueron: capacidad para mantener relaciones sexuales autoinformada por el paciente, calidad de vida y efectos adversos relacionados con el tratamiento. Los desenlaces secundarios fueron: grado de curvatura del pene, interrupción del tratamiento (por cualquier motivo), cambio subjetivo de la curvatura del pene autoinformado por el paciente y mejoría del dolor del pene. Se realizaron análisis estadísticos con un modelo de efectos aleatorios. La certeza de la evidencia se calificó según el método GRADE. RESULTADOS PRINCIPALES: La búsqueda identificó 1288 referencias pertinentes, de las cuales se incluyeron 18 registros correspondientes a 14 ensayos controlados aleatorizados (ECA) individuales con 1810 hombres. Éstos informaron 10 comparaciones distintas con datos de desenlaces relevantes que se extrajeron en su mayoría de ensayos individuales. Este resumen se centra solo en las comparaciones clínicamente más relevantes para los tres desenlaces principales y también se incluye el desenlace de grado de curvatura peneana. Colagenasa inyectable (a corto plazo): No se encontró evidencia a corto plazo de la colagenasa inyectable, en comparación con la inyección placebo, en la capacidad autoinformada por los pacientes de tener relaciones sexuales ni en los efectos adversos relacionados con el tratamiento. La colagenasa inyectable podría dar lugar a poca o ninguna diferencia en la calidad de vida (escala de 0 a 20 con puntuaciones más bajas que indican mejor calidad de vida; diferencia de medias [DM] 1,8 menor; intervalo de confianza [IC] del 95%: ­3,58 a ­0,02; un estudio, 134 participantes; evidencia de certeza baja) y podría haber poco o ningún efecto en el grado de curvatura del pene (DM 10,90 grados menos; IC del 95%: ­16,24 a ­5,56; un estudio, 136 participantes; evidencia de certeza baja). Colagenasa inyectable (a largo plazo): Tampoco se encontró evidencia a largo plazo sobre la colagenasa inyectable en la capacidad autoinformada por los pacientes de tener relaciones sexuales en comparación con la inyección placebo. Es probable que tenga un efecto escaso o nulo sobre la calidad de vida (DM 1,00 inferior; IC del 95%: ­1,60 a ­0,40; un estudio, 612 participantes; evidencia de certeza moderada). Es probable que aumenten los efectos adversos relacionados con el tratamiento (razón de riesgos [RR] 2,32; IC del 95%: 1,98 a 2,72; un estudio, 832 participantes; evidencia de certeza moderada). La colagenasa inyectable probablemente provoca poco o ningún cambio en el grado de curvatura del pene (DM 6,90 grados menos; IC del 95%: ­9,64 a ­4,14; un estudio, 612 participantes; evidencia de certeza moderada). Verapamilo inyectable (a corto plazo): No está muy claro cómo el verapamilo inyectable podría afectar la capacidad autoinformada por los pacientes de tener relaciones sexuales en comparación con la inyección placebo a corto plazo (RR 7,00; IC del 95%: 0,43 a 114,70; un estudio, 14 participantes; evidencia de certeza muy baja). No se encontró evidencia del desenlace de calidad de vida. No se sabe con certeza cómo podría afectar el verapamilo inyectable los efectos adversos relacionados con el tratamiento (RR no estimable; un estudio, 14 participantes; evidencia de certeza muy baja). Del mismo modo, es muy incierto cómo el verapamilo inyectable podría afectar el grado de curvatura peneana (DM ­1,86; IC del 95%: ­10,39 a 6,67; un estudio, 14 participantes; evidencia de certeza muy baja). No se encontraron datos a largo plazo para ningún desenlace. Tratamiento con ondas de choque extracorpóreas (OCE) (a corto plazo): No está muy claro cómo el tratamiento con OCE afecta la capacidad autoinformada por los pacientes de mantener relaciones sexuales a corto plazo (RR 1,60; IC del 95%: 0,71 a 3,60; un estudio, 26 participantes; evidencia de certeza muy baja). El tratamiento con OCE podría dar lugar a poca o ninguna diferencia en la calidad de vida (DM 3,10; IC del 95%: 1,57 a 4,64; dos estudios, 130 participantes; evidencia de certeza baja). No está muy claro si el tratamiento con OCE influye en los efectos adversos relacionados con el tratamiento (RR 2,73; IC del 95%: 0,74 a 10,14; tres estudios, 166 participantes; evidencia de certeza muy baja). El tratamiento con OCE podría dar lugar a poca o ninguna diferencia en el grado de curvatura peneana en comparación con el placebo (RR ­2,84; 95%: ­7,35 a 1,67; tres estudios, 166 participantes; evidencia de certeza baja). No se encontraron datos a largo plazo para ningún desenlace. Terapia de tracción peneana (a corto plazo): No se encontró evidencia de si la tracción peneana comparada con ningún tratamiento afecta la capacidad autoinformada por los pacientes de tener relaciones sexuales. No se sabe con certeza cómo podría afectar la terapia de tracción la calidad de vida (DM 1,50 inferior; IC del 95%: ­3,42 a 0,42; un estudio, 90 participantes; evidencia de certeza muy baja). Tampoco se sabe con certeza cómo podría afectar la terapia de tracción los efectos adversos relacionados con el tratamiento (RR no estimable; un estudio, 90 participantes; evidencia de certeza muy baja) ni cómo afecta el grado de curvatura (DM 7,40 grados menos; IC del 95%: ­11,18 a ­3,62; un estudio, 89 participantes; evidencia de certeza muy baja). No se encontraron datos a largo plazo para ningún desenlace. CONCLUSIONES DE LOS AUTORES: Existe poca evidencia que respalde la eficacia de la mayoría de los tratamientos no quirúrgicos para la enfermedad de Peyronie. Los ensayos existentes son en su mayoría de baja calidad metodológica y no abordan los desenlaces centrados en el paciente. La colagenasa inyectable parece tener cierta eficacia; sin embargo, es posible que muchas personas no experimenten una mejoría clínicamente relevante, lo que conlleva el riesgo de un aumento de los eventos adversos. Existe una necesidad imperiosa de mejores opciones terapéuticas no quirúrgicas para los hombres con enfermedad de Peyronie.

Serenoa repens for the treatment of lower urinary tract symptoms due to benign prostatic enlargement.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a non-malignant enlargement of the prostate, which can lead to obstructive and irritative lower urinary tract symptoms (LUTS). The pharmacologic use of plants and herbs (phytotherapy) for the treatment of LUTS associated with BPH is common. The extract of the berry of the American saw palmetto or dwarf palm plant, Serenoa repens (SR), which is also known by its botanical name of Sabal serrulatum, is one of several phytotherapeutic agents available for the treatment of BPH. OBJECTIVES: To assess the effects of Serenoa repens in the treatment of men with LUTS consistent with BPH. SEARCH METHODS: We performed a comprehensive search of multiple databases (the Cochrane Library, MEDLINE, Embase, Scopus, Web of Science, and LILACS), trials registries, other sources of grey literature, and conference proceedings published up to 16 September 2022, with no restrictions on language or publication status. SELECTION CRITERIA: We included randomized controlled trials of participants with BPH who were treated with Serenoa repens or placebo/no treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion at each stage and undertook data extraction and risk of bias assessment and GRADE assessment of the certainty of the evidence. We considered review outcomes measured up to 12 months after randomization as short term, and beyond 12 months as long term. Our main outcomes included urologic symptom scores, quality of life, and adverse events. MAIN RESULTS: For this update, we narrowed the review question to only comparisons with placebo. We included 27 studies (of which 9 were new) involving a total of 4656 participants, 19 studies comparing Serenoa repens with placebo, and 8 studies comparing Serenoa repens in combination with other phytotherapeutic agents versus placebo. Most studies included men aged > 50 (mean age range 52 to 68) with moderate urologic symptoms (International Prostate Symptom Score [IPSS] range 8 to 19). Ten studies were funded by the pharmaceutical industry; two studies were funded by government agencies; and the remaining studies did not specify funding sources. Serenoa repens versus placebo or no intervention Results for this comparison are based on predefined sensitivity analyses limited to studies at low risk of bias. Serenoa repens results in little to no difference in urologic symptoms at short-term follow-up (3 to 6 months; IPSS score range 0 to 35, higher scores indicate worse symptoms; mean difference (MD) -0.90, 95% confidence interval (CI) -1.74 to -0.07; I2 = 68%; 9 studies, 1681 participants; high-certainty evidence). Serenoa repens results in little to no difference in the quality of life at short-term follow-up (3 to 6 months; IPSS quality of life domain range 0 to 6, higher scores indicate worse quality of life; MD -0.20, 95% CI -0.40 to -0.00; I2 = 39%; 5 studies, 1001 participants; high-certainty evidence). Serenoa repens probably results in little to no difference in adverse events (1 to 17 months; risk ratio (RR) 1.01, 95% CI 0.77 to 1.31; I2 = 18%; 12 studies, 2399 participants; moderate-certainty evidence). Based on 164 cases per 1000 men in the placebo group, this corresponds to 2 more (38 fewer to 51 more) per 1000 men in the Serenoa repens group. Serenoa repens results in little to no difference in urologic symptoms at long-term follow-up (12 to 17 months, IPSS score, MD 0.07, 95% CI -0.75 to 0.88; I2 = 34%; 3 studies, 898 participants; high-certainty evidence). Serenoa repens results in little to no difference in quality of life at long-term follow-up (12 to 17 months, IPSS quality of life, MD -0.11, 95% CI -0.41 to 0.19; I2 = 65%; 3 studies, 882 participants; high-certainty evidence). There were no data on long-term adverse events for this comparison. Serenoa repens in combination with other phytotherapy versus placebo or no intervention Different phytotherapeutic agents that include Serenoa repens may result in little to no difference in urologic symptoms compared to placebo at short-term follow-up (12 to 24 weeks, IPSS score, MD -2.41, 95% CI -4.54 to -0.29; I2 = 67%; 4 studies, 460 participants; low-certainty evidence). We are very uncertain about the effects of these agents on quality of life (very low-certainty evidence). These agents may result in little to no difference in the occurrence of adverse events; however, the CIs included substantial benefits and harms (12 to 48 weeks, RR 0.91, 95% CI 0.58 to 1.41; I2 = 0%; 4 studies, 481 participants; low-certainty evidence). Based on 132 cases per 1000 men in the placebo group, this corresponds to 12 fewer (55 fewer to 54 more) per 1000 men in the combined phytotherapeutic agents with Serenoa repens group. AUTHORS' CONCLUSIONS: Serenoa repens alone provides little to no benefits for men with lower urinary tract symptoms due to benign prostatic enlargement. There is more uncertainty about the role of Serenoa repens in combination with other phytotherapeutic agents.

Fosfomycin for Antibiotic Prophylaxis in Men Undergoing a Transrectal Prostate Biopsy: A Systematic Review and Meta-Analysis.

Background and Objectives: To assess the effects of fosfomycin compared with other antibiotics as a prophylaxis for urinary tract infections (UTIs) in men undergoing transrectal prostate biopsies. Materials and Methods: We searched multiple databases and trial registries without publication language or status restrictions until 4 January 2022. Parallel-group randomized controlled trials (RCTs) and non-randomized studies (NRS) were included. The primary outcomes were febrile UTI, afebrile UTI, and overall UTI. We used GRADE guidance to rate the certainty of evidence of RCTs and NRSs. The protocol was registered with PROSPERO (CRD42022302743). Results: We found data on five comparisons; however, this abstract focuses on the primary outcomes of the two most clinically relevant comparisons. Regarding fosfomycin versus fluoroquinolone, five RCTs and four NRSs with a one-month follow-up were included. Based on the RCT evidence, fosfomycin likely resulted in little to no difference in febrile UTIs compared with fluoroquinolone. This difference corresponded to four fewer febrile UTIs per 1000 patients. Fosfomycin likely resulted in little to no difference in afebrile UTIs compared with fluoroquinolone. This difference corresponded to 29 fewer afebrile UTIs per 1000 patients. Fosfomycin likely resulted in little to no difference in overall UTIs compared with fluoroquinolone. This difference corresponded to 35 fewer overall UTIs per 1000 patients. Regarding fosfomycin and fluoroquinolone combined versus fluoroquinolone, two NRSs with a one- to three-month follow-up were included. Based on the NRS evidence, fosfomycin and fluoroquinolone combined may result in little to no difference in febrile UTIs compared with fluoroquinolone. This difference corresponded to 16 fewer febrile UTIs per 1000 patients. Conclusions: Compared with fluoroquinolone, fosfomycin or fosfomycin and fluoroquinolone combined may have a similar prophylactic effect on UTIs after a transrectal prostate biopsy. Given the increasing fluoroquinolone resistance and its ease to use, fosfomycin may be a good option for antibiotic prophylaxis.

Posterior musculofascial reconstruction in robot-assisted laparoscopic prostatectomy for the treatment of clinically localised prostate cancer: a Cochrane Review.

OBJECTIVES: To assess the effects of posterior musculofascial reconstruction robot-assisted laparoscopic prostatectomy (PR-RALP) compared to no PR during standard RALP (S-RALP) for the treatment of clinically localised prostate cancer. PATIENTS AND METHODS: We performed a systematic search with no restrictions including randomised controlled trials (RCTs) comparing variations of PR-RALP vs S-RALP for clinically localised prostate cancer. The quality of evidence was assessed on outcome basis according to Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. Our search identified 13 records of eight unique RCTs, of which six were published studies, and two were abstract proceedings. There were 1085 randomised patients, of whom 963 completed the trials. All patients had either cT1c or cT2 or cT3a disease. RESULTS: A PR-RALP may improve urinary continence 1 week after catheter removal compared to no PR (risk ratio [RR] 1.25, 95% confidence interval [CI] 0.90-1.73; I2 = 42%, five studies, 498 patients, low certainty of evidence [CoE]). A PR-RALP may have little to no effect on urinary continence 3 months after surgery compared to no PR (RR 0.98, 95% CI 0.84-1.14; I2 = 67%, six studies, 842 patients, low CoE). A PR-RALP probably results in little to no difference in serious adverse events compared to no PR (RR 0.75, 95% CI 0.29-1.92; I2 = 0%, six studies, 835 patients, moderate CoE). CONCLUSIONS: This review found evidence that PR-RALP may improve early continence 1 week after catheter removal but not thereafter. Meanwhile, adverse event rates are probably not impacted and positive surgical margin rates are likely similar. There was no difference in our subgroup analysis for all outcomes with anterior reconstruction technique when combined with PR vs only PR.

Minimally invasive treatments for benign prostatic hyperplasia: a Cochrane network meta-analysis.

OBJECTIVE: To assess the comparative effectiveness and ranking of minimally invasive treatments (MITs) for lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: We searched multiple databases up to 24 February 2021. We included randomized controlled trials assessing the following treatments: convective radiofrequency water vapour thermal therapy (WVTT; or Rezum); prostatic arterial embolization (PAE); prostatic urethral lift (PUL; or Urolift); temporary implantable nitinol device (TIND); and transurethral microwave thermotherapy (TUMT) compared to transurethral resection of the prostate (TURP) or sham surgery. We performed a frequentist network meta-analysis. RESULTS: We included 27 trials involving 3017 men. The overall certainty of the evidence of most outcomes according to GRADE was low to very low. Compared to TURP, we found that PUL and PAE may result in little to no difference in urological symptoms, while WVTT, TUMT and TIND may result in worse urological symptoms. MITs may result in little to no difference in quality of life, compared to TURP. MITs may result in a large reduction in major adverse events compared to TURP. We were uncertain about the effects of PAE and PUL on retreatment compared to TURP, however, TUMT may result in higher retreatment rates. We were very uncertain of the effects of MITs on erectile function and ejaculatory function. Among MITs, PUL and PAE had the highest likelihood of being the most efficacious for urinary symptoms and quality of life, TUMT for major adverse events, WVTT and TIND for erectile function and PUL for ejaculatory function. Excluding WVTT and TIND, for which there were only studies with short-term (3-month) follow-up, PUL had the highest likelihood of being the most efficacious for retreatment. CONCLUSIONS: Minimally invasive treatments may result in similar or worse effects concerning urinary symptoms and quality of life compared to TURP at short-term follow-up.

Prostatic arterial embolization for the treatment of lower urinary tract symptoms in men with benign prostatic hyperplasia.

BACKGROUND: A variety of minimally invasive surgical approaches 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). Prostatic arterial embolization (PAE) is a relatively new, minimally invasive treatment approach. OBJECTIVES: To assess the effects of PAE compared to other procedures for treatment of LUTS in men with BPH. SEARCH METHODS: We performed a comprehensive search the Cochrane Library, MEDLINE, Embase, three other databases, trials registries, other sources of grey literature, and conference proceedings with no restrictions on language of publication or publication status, up to 8 November 2021. SELECTION CRITERIA: We included parallel-group randomized controlled trials (RCTs), as well as non-randomized studies (NRS, limited to prospective cohort studies with concurrent comparison groups) enrolling men over the age of 40 years with LUTS attributed to BPH undergoing PAE versus TURP or other surgical interventions.  DATA COLLECTION AND ANALYSIS: Two review authors independently classified studies for inclusion or exclusion and abstracted data from the included studies. We performed statistical analyses by using a random-effects model and interpreted them according to the Cochrane Handbook for Systematic Reviews of Interventions. We used GRADE guidance to rate the certainty of evidence of RCTs and NRSs.  MAIN RESULTS: We found data to inform two comparisons: PAE versus TURP (six RCTs and two NRSs), and PAE versus sham (one RCT). Mean age was 66 years, International Prostate Symptom Score (IPSS) was 22.8, and prostate volume of participants was 72.8 mL. This abstract focuses on the comparison of PAE versus TURP as the primary topic of interest. Prostatic arterial embolization versus transurethral resection of the prostate We included six RCTs and two NRSs with short-term (up to 12 months) follow-up, and two RCTs and one NRS with long-term follow-up (13 to 24 months).  Short-term follow-up: based on RCT evidence, there may be little to no difference in urologic symptom score improvement measured by the International Prostatic Symptom Score (IPSS) on a scale from 0 to 35, with higher scores indicating worse symptoms (mean difference [MD] 1.72, 95% confidence interval [CI] -0.37 to 3.81; 6 RCTs, 360 participants; I² = 78%; low-certainty evidence). There may be little to no difference in quality of life as measured by the IPSS-quality of life question on a scale from 0 to 6, with higher scores indicating worse quality of life between PAE and TURP, respectively (MD 0.28, 95% CI -0.28 to 0.84; 5 RCTs, 300 participants; I² = 63%; low-certainty evidence). While we are very uncertain about the effects of PAE on major adverse events (risk ratio [RR] 0.75, 95% CI 0.19 to 2.97; 4 RCTs, 250 participants; I² = 24%; very low-certainty evidence), PAE likely increases retreatments (RR 3.20, 95% CI 1.41 to 7.27; 4 RCTs, 303 participants; I² = 0%; moderate-certainty evidence). PAE may make little to no difference in erectile function measured by the International Index of Erectile Function-5 on a scale from 1 to 25, with higher scores indicating better function (MD -0.50 points, 95% CI -5.88 to 4.88; 2 RCTs, 120 participants; I² = 68%; low-certainty evidence). Based on NRS evidence, PAE may reduce the occurrence of ejaculatory disorders (RR 0.51, 95% CI 0.35 to 0.73; 1 NRS, 260 participants; low-certainty evidence). Long-term follow-up: based on RCT evidence, PAE may result in little to no difference in urologic symptom scores (MD 2.58 points, 95% CI -1.54 to 6.71; 2 RCTs, 176 participants; I² = 73%; low-certainty evidence) and quality of life (MD 0.50 points, 95% CI -0.03 to 1.04; 2 RCTs, 176 participants; I² = 29%; low-certainty evidence). We are very uncertain about major adverse events (RR 0.91, 95% CI 0.20 to 4.05; 2 RCTs, 206 participants; I² = 72%; very low-certainty evidence). PAE likely increases retreatments (RR 3.80, 95% CI 1.32 to 10.93; 1 RCT, 81 participants; moderate-certainty evidence). While PAE may result in little to no difference in erectile function (MD 3.09 points, 95% CI -0.76 to 6.94; 1 RCT, 81 participants; low-certainty evidence), PAE may reduce the occurrence of ejaculatory disorders (RR 0.67, 95% CI 0.45 to 0.98; 1 RCT, 50 participants; low-certainty evidence). AUTHORS' CONCLUSIONS: Compared to TURP, PAE may provide similar improvement in urologic symptom scores and quality of life. While we are very uncertain about major adverse events, PAE likely increases retreatment rates. While erectile function may be similar, PAE may reduce ejaculatory disorders. Certainty of evidence for the outcomes of this review was low or very low except for retreatment (moderate-certainty evidence), signaling that our confidence in the reported effect size is limited or very limited, and that this topic should be better informed by future research.

Perioperative Probiotics Application for Preventing Postoperative Complications in Patients with Colorectal Cancer: A Systematic Review and Meta-Analysis.

Background and Objectives: Perioperative probiotic administration in patients who undergo gastrointestinal surgery can reduce postoperative infectious complications. This systematic review and meta-analysis aimed to evaluate the effect of probiotics on postoperative outcomes in patients who underwent colorectal cancer surgery. Materials and Methods: For this study, we followed the protocol published by PROSPERO (registration number: CRD42021247277). We included studies on patients undergoing open, laparoscopic, or robotic colorectal cancer surgery for curative intent. We conducted a comprehensive search with online databases (trial registries and ClinicalTrials.gov), other literature sources, and conference proceedings, with no language restriction, up until 12 August 2022. We assessed risk of bias, extracted data, and conducted statistical analyses by using a random-effects model and interpreted the results based on the Cochrane Handbook for Systematic Reviews of Interventions. We rated the certainty of evidence (CoR) according to the GRADE approach. Results: We identified 20 published full-text studies. The use of probiotics probably results in little to no difference in perioperative mortality (risk ratio (RR): 0.17, 95% CI: 0.02 to 1.38; I2 = 0%; moderate CoE) and may result in reducing the overall postoperative infectious complications (RR: 0.45, 95% CI: 0.27 to 0.76; I2 = 38%; low CoE) after colorectal cancer surgery. Probiotics may result in little to no difference in probiotics-related adverse events (RR: 0.73, 95% CI: 0.45 to 1.19; I2 = 0%; low CoE). While probiotics may result in reducing the overall postoperative complications (RR: 0.47, 95% CI: 0.30 to 0.74; I2 = 8%; low CoE), it may result in little to no difference in hospital length of stay (LOS) (MD: -1.06, 95% CI: -1.64 to -0.47; I2 = 8%; low CoE) and postoperative quality of life (QOL) (MD: +5.64, 95% CI: 0.98 to 10.3; low CoE). Conclusions: Perioperative probiotic administration may reduce complications, including overall infectious complications, in patients undergoing colorectal cancer surgery without any additional adverse effects. In addition, probiotics may have similar effects on perioperative mortality; procedure-related complications such as anastomotic leakage, and hospital LOS; or improve the QOL. Thus, probiotics may be considered a beneficial supplement to routine perioperative care for colorectal cancer surgery.

High Versus Low Ligation of the Inferior Mesenteric Artery in Colorectal Cancer Surgery: A Systematic Review and Meta-Analysis.

Background and Objectives: This study aimed to compare the effects of high ligation (HL) versus low ligation (LL) in colorectal cancer surgery. Materials and Methods: We performed a comprehensive search using multiple databases (trial registries and ClinicalTrials.gov), other sources of grey literature, and conference proceedings, with no restrictions on the language or publication status, up until 10 March 2021. We included all parallel-group randomized controlled trials (RCTs) and considered cluster RCTs for inclusion. The risk of bias domains were "low risk," "high risk," or "unclear risk." We performed statistical analyses using a random-effects model and interpreted the results according to the Cochrane Handbook for Systematic Reviews of Interventions. We used the GRADE guidelines to rate the certainty of evidence (CoE) of the randomized controlled trials. Results: We found 12 studies (24 articles) from our search. We were very uncertain about the effects of HL on overall mortality, disease recurrence, cancer-specific mortality, postoperative mortality, and anastomotic leakage (very low CoE). There may be little to no difference between HL and LL in postoperative complications (low CoE). For short-term follow-up (within 6 months), HL may reduce defecatory function (constipation; low CoE). While HL and LL may have similar effects on sexual function in men, HL may reduce female sexual function compared with LL (low CoE). For long-term follow-up (beyond 6 months), HL may reduce defecatory function (constipation; low CoE). There were discrepancies in the effects regarding urinary dysfunction according to which questionnaire was used in the studies. HL may reduce male and female sexual function (low CoE). Conclusions: We are very uncertain about the effects of HL on survival outcomes, and there is no difference in the incidence of postoperative complications between HL and LL. More rigorous RCTs are necessary to evaluate the effect of HL and LL on functional outcomes.

Retzius-sparing versus standard robot-assisted laparoscopic prostatectomy for the treatment of clinically localized prostate cancer.

OBJECTIVES: To assess the effects of Retzius-sparing (RS) robotic-assisted laparoscopic prostatectomy (RALP) compared to standard RALP for the treatment of clinically localized prostate cancer. METHODS: We performed a systematic search of multiple databases and the grey literature with no restrictions on the language of publication or publication status, up until June 2020. We included randomized controlled trials (RCTs) comparing RS-RALP with standard RALP. We performed a meta-analysis using a random-effect model. The quality of evidence was assessed on an outcome basis according to the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. RESULTS: Our search identified six records of five unique RCTs, of which two were published studies, one was in press, and two were abstract proceedings. There were 571 randomized participants, of whom 502 completed the trials. The mean age of participants was 64.6 years and the mean prostate-specific antigen level was 6.9 ng/mL. Approximately 54.2% of participants had cT1c disease, 38.6% had cT2a-b disease, and 7.1% had cT2c disease. RS-RALP probably improves continence within 1 week after catheter removal (risk ratio [RR] 1.74, 95% confidence interval [CI] 1.41-2.14; I2 = 0%; studies = 4; participants = 410; moderate-certainty evidence). Assuming 335 per 1000 men undergoing standard RALP are continent at this time point, this corresponds to 248 more men per 1000 (137 more to 382 more) reporting continence recovery. RS-RALP may increase continence at 3 months after surgery compared to standard RALP (RR 1.33, 95% CI 1.06-1.68; I2 = 86%; studies = 5; participants = 526; low-certainty evidence). Assuming 750 per 1000 men undergoing standard RALP are continent at this time point, this corresponds to 224 more men per 1000 (41 more to 462 more) reporting continence recovery. We are very uncertain about the effects of RS-RALP on serious adverse events compared to standard RALP (RR 1.40, 95% CI 0.47-4.17; studies = 2; participants = 230; very low-certainty evidence). CONCLUSIONS: The findings of this review indicate that RS-RALP may result in better continence outcomes than standard RALP up to 6 months after surgery. Continence outcomes at 12 months may be similar. The disadvantages of RS-RALP may be higher positive surgical margin rates. We are very uncertain about the effect on biochemical recurrence-free survival and potency outcomes. Longer-term oncological and functional outcomes are lacking, and no preplanned subgroup analyses could be performed to explore the observed heterogeneity. Surgeons should discuss these trade-offs and the limitations of the evidence with their patients when considering this approach.

Posterior musculofascial reconstruction in robotic-assisted laparoscopic prostatectomy for the treatment of clinically localized prostate cancer.

BACKGROUND: Delayed recovery of urinary continence is a major adverse effect of robotic-assisted laparoscopic prostatectomy (RALP) in men undergoing prostate cancer treatment. To address this issue, a number of surgical techniques have been designed to reconstruct the posterior aspect of the rhabdosphincter, which is responsible for urinary continence after removal of the prostate; however, it is unclear how well they work.  OBJECTIVES: To assess the effects of posterior musculofascial reconstruction RALP compared to no posterior reconstruction during RALP for the treatment of clinically localized prostate cancer. SEARCH METHODS: We performed a comprehensive search of the Cochrane Library, MEDLINE, Embase, three other databases, trials registries, other sources of the grey literature, and conference proceedings, up to 12 March 2021. We applied no restrictions on publication language or status. SELECTION CRITERIA: We included randomized controlled trials (RCTs) in which participants were randomized to undergo variations of posterior musculofascial reconstruction RALP versus no posterior reconstruction during RALP for clinically localized prostate cancer. DATA COLLECTION AND ANALYSIS: Two review authors independently classified studies and abstracted data from the included studies. Primary outcomes were: urinary continence recovery within one week after catheter removal, at three months after surgery, and serious adverse events. Secondary outcomes were: urinary continence recovery at six and twelve months after surgery, potency recovery twelve months after surgery, positive surgical margins (PSM), and biochemical recurrence-free survival (BCRFS). We performed statistical analyses using a random-effects model. We rated the certainty of evidence (CoE) according to the GRADE approach. MAIN RESULTS: Our search identified 13 records of eight unique RCTs, of which six were published studies and two were abstract proceedings. We included 1085 randomized participants, of whom 963 completed the trials (88.8%). All participants had either cT1c or cT2 or cT3a disease, with a mean prostate-specific antigen level of 8.15 ng/mL. Primary outcomes Posterior reconstruction RALP (PR-RALP) may improve urinary continence one week after catheter removal compared to no posterior reconstruction during RALP (risk ratio (RR) 1.25, 95% confidence interval (CI) 0.90 to 1.73; I2 = 42%; studies = 5, participants = 498; low CoE) although the CI also includes the possibility of no effect. Assuming 335 per 1000 men undergoing standard RALP are continent at this time point, this corresponds to 84 more men per 1000 (33 fewer to 244 more) reporting urinary continence recovery.  Posterior reconstruction may have little to no effect on urinary continence three months after surgery compared to no posterior reconstruction during RALP (RR 0.98, 95% CI 0.84 to 1.14; I2 = 67%; studies = 6, participants = 842; low CoE). Assuming 701 per 1000 men undergoing standard RALP are continent at this time point, this corresponds to 14 fewer men per 1000 (112 fewer to 98 more) reporting urinary continence after three months. PR-RALP probably results in little to no difference in serious adverse events compared to no posterior reconstruction during RALP (RR 0.75, 95% CI 0.29 to 1.92; I2 = 0%; studies = 6, participants = 835; moderate CoE). Assuming 25 per 1000 men undergoing standard RALP experience a serious adverse event at this time point, this corresponds to six fewer men per 1000 (17 fewer to 23 more) reporting serious adverse events.  Secondary outcomes PR-RALP may result in little to no difference in recovery of continence 12 months after surgery compared to no posterior reconstruction during RALP (RR 1.02, 95% CI 0.98 to 1.07; I2 = 25%; studies = 3, participants = 602; low CoE). Assuming 918 per 1000 men undergoing standard RALP are continent at this time point, this corresponds to 18 more men per 1000 (18 fewer to 64 more) reporting urinary continence recovery.  We are very uncertain about the effects of PR-RALP on recovery of potency 12 months after surgery compared to no posterior reconstruction during RALP (RR 1.02, 95% CI 0.82 to 1.26; I2 = 3%; studies = 2, participants = 308; very low CoE). Assuming 433 per 1000 men undergoing standard RALP are potent at this time point, this corresponds to nine more men per 1000 (78 fewer to 113 more) reporting potency recovery.  PR-RALP may result in little to no difference in positive surgical margins compared to no posterior reconstruction during RALP (RR 1.24, 95% CI 0.65 to 2.33; I2 = 50%; studies = 3, participants = 517; low CoE). Assuming 130 per 1000 men undergoing standard RALP have a positive surgical margin, this corresponds to 31 more men per 1000 (46 fewer to 173 more) reporting positive surgical margins.  PR-RALP may result in little to no difference in biochemical recurrence compared to no posterior reconstruction during RALP (RR 1.36, 95% CI 0.74 to 2.52; I2 = 0%; studies = 2, participants = 468; low CoE). Assuming 70 per 1000 men undergoing standard RALP have experienced biochemical recurrence at this time point, this corresponds to 25 more men per 1000 (18 fewer to 107 more) reporting biochemical recurrence.  AUTHORS' CONCLUSIONS: This review found evidence that PR-RALP may improve early continence one week after catheter removal but not thereafter. Meanwhile, adverse event rates are probably not impacted and surgical margins rates are likely similar. This review was unable to determine if or how these findings may be impacted by the person's age, nerve-sparing status, or clinical stage. Study limitations, imprecision, and inconsistency lowered the certainty of evidence for the outcomes assessed.

Intravesical gemcitabine for non-muscle invasive bladder cancer.

BACKGROUND: It remains unclear whether people with non-muscle invasive bladder cancer (NMIBC) benefit from intravesical gemcitabine compared to other agents in the primary or recurrent setting following transurethral resection of a bladder tumor. This is an update of a Cochrane Review first published in 2012. Since that time, several randomized controlled trials (RCTs) have been reported, making this update relevant.  OBJECTIVES: To assess the comparative effectiveness and toxicity of intravesical gemcitabine instillation for NMIBC. SEARCH METHODS: We performed a comprehensive literature search of the Cochrane Library, MEDLINE, Embase, four other databases, trial registries, and conference proceedings to 11 September 2020, with no restrictions on the language or status of publication. SELECTION CRITERIA: We included RCTs in which participants received intravesical gemcitabine for primary or recurrent NMIBC. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the included studies and extracted data for the primary outcomes: time to recurrence, time to progression, grade III to V adverse events determined by the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0), and the secondary outcomes: time to death from bladder cancer, time to death from any cause, grade I or II adverse events determined by the CTCAE v5.0 and disease-specific quality of life. We performed statistical analyses using a random-effects model and rated the certainty of the evidence using GRADE. MAIN RESULTS: We included seven studies with 1222 participants with NMIBC across five comparisons. This abstract focuses on the primary outcomes of the three most clinically relevant comparisons. 1. Gemcitabine versus saline: based on two years' to four years' follow-up, gemcitabine may reduce the risk of recurrence over time compared to saline (39% versus 47% recurrence rate, hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.54 to 1.09; studies = 2, participants = 734; I2 = 49%; low-certainty evidence), but the CI included the possibility of no effect.  Gemcitabine may result in little to no difference in the risk of progression over time compared to saline (4.6% versus 4.8% progression rate, HR 0.96, 95% CI 0.19 to 4.71; studies = 2, participants = 654; I2 = 53%; low-certainty evidence).  Gemcitabine may result in little to no difference in the CTCAE grade III to V adverse events compared to saline (5.9% versus 4.7% adverse events rate, risk ratio [RR] 1.26, 95% CI 0.58 to 2.75; studies = 2, participants = 668; I2 = 24%; low-certainty evidence).  2. Gemcitabine versus mitomycin: based on three years' follow-up (studies = 1, participants = 109), gemcitabine may reduce the risk of recurrence over time compared to mitomycin (17% versus 40% recurrence rate, HR 0.36, 95% CI 0.19 to 0.69; low-certainty evidence). Gemcitabine may reduce the risk of progression over time compared to mitomycin (11% versus  18% progression rate, HR 0.57, 95% CI 0.32 to 1.01; low-certainty evidence), but the CI included the possibility of no effect.  We are very uncertain about the effect of gemcitabine on the CTCAE grade III to V adverse events compared to mitomycin (RR 0.51, 95% CI 0.13 to 1.93; very low-certainty evidence). The analysis was only based on recurrent NMIBC. 3. Gemcitabine versus Bacillus Calmette-Guérin (BCG) for recurrent (one-course BCG failure) high-risk NMIBC: based on 6 months' to 22 months' follow-up (studies = 1, participants = 80), gemcitabine may reduce the risk of recurrence compared to BCG (41% versus 97% recurrence rate, HR 0.15, 95% CI 0.09 to 0.26; low-certainty evidence) and progression over time (16% versus 33% progression rate, HR 0.45, 95% CI 0.27 to 0.76; low-certainty evidence). We are very uncertain about the effect of gemcitabine on the CTCAE grade III to V adverse events compared to BCG (RR 1.00, 95% CI 0.21 to 4.66; very low-certainty evidence).  In addition, the review provides information on  the comparison of gemcitabine versus BCG and gemcitabine versus one-third dose BCG.  AUTHORS' CONCLUSIONS: Based on findings of this review, gemcitabine may have a more favorable impact on recurrence and progression-free survival than mitomycin but we are very uncertain as to how major adverse events compare. The same is true when comparing gemcitabine to BCG in individuals with high risk disease who have previously failed BCG. The underlying low- to very low-certainty evidence indicates that our confidence in these results is limited; the true effects may be substantially different from these findings; therefore, better quality studies are needed.

Anticholinergics combined with alpha-blockers for treating lower urinary tract symptoms related to benign prostatic obstruction.

BACKGROUND: Lower urinary tract symptoms (LUTS) due to benign prostatic obstruction (BPO) represent one of the most common clinical complaints in men. Alpha-blockers are widely used as first-line therapy for men with LUTS secondary to BPO, but up to one third of men report no improvement in their LUTS after taking alpha-blockers. Anticholinergics used in addition to alpha-blockers may help improve symptoms but it is uncertain how effective they are.  OBJECTIVES: To assess the effects of combination therapy with anticholinergics and alpha-blockers in men with LUTS related to BPO. SEARCH METHODS: We performed a comprehensive search of medical literature, including the Cochrane Library, MEDLINE, Embase, and trials registries, with no restrictions on the language of publication or publication status. The date of the latest search was 7 August 2020. SELECTION CRITERIA: We included randomized controlled trials. Inclusion criteria were men with LUTS secondary to BPO, ages 40 years or older, and a total International Prostate Symptom Score of 8 or greater. We excluded trials of men with a known neurogenic bladder due to spinal cord injury, multiple sclerosis, or central nervous system disease, and those examining medical therapy for men who were treated with surgery for BPO. We performed three comparisons: combination therapy versus placebo, combination therapy versus alpha-blockers monotherapy, and combination therapy versus anticholinergics monotherapy. 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 and interpreted data according to the Cochrane Handbook for Systematic Reviews of Interventions. We used the GRADE approach to rate the certainty of evidence. MAIN RESULTS: We included 23 studies with 6285 randomized men across three comparisons. The mean age of participants ranged from 54.4 years to 73.9 years (overall mean age 65.7 years). Of the included studies, 12 were conducted with a single-center setting, while 11 used a multi-center setting. We only found short-term effect (12 weeks to 12 months) of combination therapy based on available evidence. Combination therapy versus placebo: based on five studies with 2369 randomized participants, combination therapy may result in little or no difference in urologic symptom scores (mean difference (MD) -2.73, 95% confidence interval (CI) -5.55 to 0.08; low-certainty evidence). We are very uncertain about the effect of combination therapy on quality of life (QoL) (MD -0.97, 95% CI -2.11 to 0.16; very low-certainty evidence). Combination therapy likely increases adverse events (risk ratio (RR) 1.24, 95% CI 1.04 to 1.47; moderate-certainty evidence); based on 252 adverse events per 1000 participants in the placebo group, this corresponds to 61 more adverse events (95% CI 10 more  to 119 more) per 1000 participants treated with combination therapy. Combination therapy versus alpha-blockers alone: based on 22 studies with 4904 randomized participants, we are very uncertain about the effect of combination therapy on urologic symptom scores (MD -2.04, 95% CI -3.56 to -0.52; very low-certainty evidence) and QoL (MD -0.71, 95% CI -1.03 to -0.38; very low-certainty evidence). Combination therapy may result in little or no difference in adverse events rate (RR 1.10, 95% CI 0.90 to 1.34; low-certainty evidence); based on 228 adverse events per 1000 participants in the alpha-blocker group, this corresponds to 23 more adverse events (95% CI 23 fewer to 78 more) per 1000 participants treated with combination therapy. Combination therapy compared to anticholinergics alone: based on three studies with 1218 randomized participants, we are very uncertain about the effect of combination therapy on urologic symptom scores (MD -3.71, 95% CI -9.41 to 1.98; very low-certainty evidence). Combination therapy may result in an improvement in QoL (MD -1.49, 95% CI -1.88 to -1.11; low-certainty evidence). Combination therapy likely results in little to no difference in adverse events (RR 1.26, 95% CI 0.81 to 1.95; moderate-certainty evidence); based on 115 adverse events per 1000 participants in the anticholinergic alone group, this corresponds to 4 fewer adverse events (95% CI 7 fewer to 13 more) per 1000 participants treated with combination therapy. AUTHORS' CONCLUSIONS: Based on the findings of the review, combination therapy with anticholinergics and alpha-blockers are associated with little or uncertain effects on urologic symptom scores compared to placebo, alpha-blockers, or anticholinergics monotherapy. However, combination therapy may result in an improvement in quality of life compared to anticholinergics monotherapy, but an uncertain effect compared to placebo, or alpha-blockers. Combination therapy likely increases adverse events compared to placebo, but not compared to alpha-blockers or anticholinergics monotherapy. The findings of this review were limited by study limitations, inconsistency, and imprecision. We were unable to conduct any of the predefined subgroup analyses.

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

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.

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

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.

Convective radiofrequency water vapour thermal therapy for lower urinary tract symptoms in men with benign prostatic hyperplasia.

BACKGROUND: New minimal invasive surgeries have been suggested as alternative options to transurethral resection of the prostate (TURP) for the management of lower urinary tract symptoms (LUTS) in men with benign prostatic hyperplasia (BPH). Convective radiofrequency water vapour thermal therapy is a new technology that uses targeted, controlled water vapour energy (steam) to create necrotic tissue in the prostate. OBJECTIVES: To assess the effects of convective radiofrequency water vapour thermal therapy for the treatment of lower urinary tract symptoms in men with benign prostatic hyperplasia. SEARCH METHODS: We performed a comprehensive search of multiple databases (the Cochrane Library, MEDLINE, Embase, Latin American and the Caribbean Health Sciences Literature, Scopus, Web of Science), trials registries, other sources of grey literature, and conference proceedings published up to 18 February 2020, with no restriction on the language or status of publication. SELECTION CRITERIA: We included parallel-group randomised controlled trials (RCTs), cluster-RCTs, and non-randomised observational prospective studies with concurrent comparison groups, in which men with BPH underwent convective radiofrequency water vapour thermal therapy, another active therapy, or a sham procedure. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the literature, extracted data, and assessed risk of bias. We had planned to perform statistical analyses using a random-effects model, and interpret them according to the Cochrane Handbook for Systematic Reviews of Interventions. We rated the certainty of the evidence according to the GRADE approach. MAIN RESULTS: We included a single, industry-sponsored RCT, with 197 randomised men, that compared convective radiofrequency water vapour thermal therapy to a sham procedure. The mean age 62.9 years, the International Prostate Symptom Score (IPSS) was 21.97, and the mean prostate volume was 45.4 mL. We only found short-term data, measured up to three months. Primary outcomes Convective radiofrequency water vapour thermal therapy may improve urologic symptom scores more than a sham procedure, measured on a IPSS scale (0 to 35; higher score represents worse urological symptoms) by a mean difference (MD) of -6.9 (95% confidence interval (CI) -9.06 to -4.74; 195 men; low-certainty evidence), and likely improves quality of life (QoL), measured on a IPSS-QoL scale (0 to 6; higher score represents worse QoL), by a MD of -1.2 (95% CI -1.66 to -0.74; 195 men; moderate-certainty evidence). We are very uncertain about the effects of convective radiofrequency water vapour thermal therapy on major adverse events (risk ratio (RR) 6.79, 95% CI 0.39 to 117.00; 197 men; very low-certainty evidence) assessed by the Clavien-Dindo classification system of III, IV, and V complications. Secondary outcomes We are very uncertain about the effects of convective radiofrequency water vapour thermal therapy on retreatment (RR 1.36, 95% CI 0.06 to 32.86; 197 men; very low-certainty evidence). Convective radiofrequency water vapour thermal therapy may have little to no effect on erectile function (MD 0.4, 95% CI -1.91 to 2.71; 130 men; low-certainty evidence) and ejaculatory function (MD 0.5, 95% CI -0.83 to 1.83; 130 men; low-certainty evidence). Convective radiofrequency water vapour thermal therapy may increase minor adverse events assessed by the Clavien-Dindo classification system of Grade I and II complications (RR 1.89, 95% CI 1.15 to 3.11; 197 men; low-certainty evidence). This would correspond to 434 minor adverse events per 1000 men (95% CI 264 more to 714 more). We are very uncertain about the effects of convective radiofrequency water vapour thermal therapy on acute urinary retention (RR 4.98, 95% CI 0.28 to 86.63; 197 men; very low-certainty evidence). It likely greatly increases the rate of men requiring indwelling urinary catheters (RR 35.58, 95% CI 15.37 to 82.36; 197 men; moderate-certainty evidence). We were unable to perform any of the predefined secondary analyses. We found no evidence for other comparisons, such as convective radiofrequency water vapour thermal therapy versus TURP or other minimal invasive procedures. AUTHORS' CONCLUSIONS: Compared to a sham procedure, urologic symptom scores and quality of life appear to improve with convective radiofrequency water vapour thermal therapy, but we are very uncertain about major adverse events. The certainty of evidence ranged from moderate to very low, with study limitations and imprecision being the most common reasons for rating down. These findings are based on a single industry-sponsored study, with three-month short-term follow-up. We did not find any studies comparing convective radiofrequency water vapour thermal therapy to any other active treatment form, such as TURP.