Estimating the Effect of Radical Prostatectomy: Combining Data From the SPCG4 and PIVOT Randomized Trials With Contemporary Cohorts.

PURPOSE: Two randomized trials (SPCG4 and PIVOT) have compared surgery to conservative management for localized prostate cancer. The applicability of these trials to contemporary practice remains uncertain. We aimed to develop an individualized prediction model for prostate cancer mortality comparing immediate surgery at a high-volume center to active surveillance. MATERIALS AND METHODS: We determined whether the relative risk of prostate cancer mortality with surgery vs observation varied by baseline risk. We then used various estimates of relative risk to estimate 15-year mortality with and without surgery using, as a predictor, risk of biochemical recurrence calculated from a model. RESULTS: We saw no evidence that relative risk varied by baseline risk, supporting the use of a constant relative risk. Compared with observation, surgery was associated with negligible benefit for patients with Grade Group (GG) 1 disease (0.2% mortality reduction at 15 years) and small benefit for patients with GG2 with lower PSA and stage (≤5% mortality reduction). Benefit was greater (6%-9%) for patients with GG3 or GG4 though still modest, but effect estimates varied widely depending on choice of hazard ratio for surgery (6%-36% absolute risk reduction). CONCLUSIONS: Surgery should be avoided for men with low-risk (GG1) prostate cancer and for many men with GG2 disease. Surgical benefits are greater in men with higher-risk disease. Integration of findings with a life expectancy model will allow patients to make informed treatment decisions given their oncologic risk, risk of death from other causes, and estimated effects of surgery.

Management of Lower Urinary Tract Symptoms Attributed to Benign Prostatic Hyperplasia (BPH): AUA Guideline Amendment 2023.

PURPOSE: The purpose of this American Urological Association (AUA) Guideline amendment is to provide a useful reference on the effective evidence-based management of male lower urinary tract symptoms secondary/attributed to BPH (LUTS/BPH). MATERIALS AND METHODS: The Minnesota Evidence Review Team searched Ovid MEDLINE, the Cochrane Library, and the Agency for Healthcare Research and Quality (AHRQ) database to identify studies relevant to the management of BPH. The guideline was updated in 2023 to capture eligible literature published between September 2020 and October 2022. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions. RESULTS: The BPH amendment resulted in changes to statements/supporting text on combination therapy, photoselective vaporization of the prostate (PVP), water vapor thermal therapy (WVTT), laser enucleation, and prostate artery embolization (PAE). A new statement on temporary implanted prostatic devices (TIPD) was added. In addition, statements on transurethral needle ablation (TUNA) and transurethral microwave thermotherapy (TUMT) were removed and information regarding these legacy technologies was added to the background section. References and the accompanying treatment algorithms were updated to align with the updated text. CONCLUSION: This guideline seeks to improve clinicians' ability to evaluate and treat patients with BPH/LUTS based on currently available evidence. Future studies will be essential to further support these statements to improve patient care.

Percutaneous nephrolithotomy vs retrograde intrarenal surgery for renal stones: a Cochrane Review.

OBJECTIVES: To assess the effects of percutaneous nephrolithotomy (PCNL) vs retrograde intrarenal surgery (RIRS) for the treatment of renal stones in adults. 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 23 March 2023. We applied no restrictions on publication language or status. Screening, data extraction, risk-of-bias assessment, and certainty of evidence (CoE) rating using the Grading of Recommendations Assessment, Development and Evaluations (GRADE) approach were done in duplicate by two independent reviewers. This co-publication focuses on the primary outcomes of this review only. RESULTS: We included 42 trials that met the inclusion criteria. Stone-free rate (SFR): PCNL may improve SFRs (risk ratio [RR] 1.13, 95% confidence interval [CI] 1.08-1.18; I2 = 71%; 39 studies, 4088 participants; low CoE). Major complications: PCNL probably has little to no effect on major complications (RR 0.86, 95% CI 0.59-1.25; I2 = 15%; 34 studies, 3649; participants; moderate CoE) compared to RIRS. Need for secondary interventions: PCNL may reduce the need for secondary interventions (RR 0.31, 95% CI 0.17-0.55; I2 = 61%; 21 studies, 2005 participants; low CoE) compared to RIRS. CONCLUSION: Despite shortcomings in most studies that lowered our certainty in the estimates of effect to mostly very low or low, we found that PCNL may improve SFRs and reduce the need for secondary interventions while not impacting major complications. Ureteric stricture rates may be similar compared to RIRS. We expect the findings of this review to be helpful for shared decision-making about management choices for individuals with renal stones.

Tranexamic acid for percutaneous nephrolithotomy: an abridged Cochrane review.

OBJECTIVE: To assess the effects of tranexamic acid (TXA) in individuals with kidney stones undergoing percutaneous nephrolithotomy (PCNL). PATIENTS AND METHODS: We performed a literature search of Cochrane Library, PubMed (including MEDLINE), Embase, Scopus, Global Index Medicus, trials registries, grey literature, and conference proceedings. We included randomised controlled trials (RCTs) that compared treatment with PCNL with administration of TXA to placebo (or no TXA) for patients aged ≥18 years. Two review authors independently classified studies and abstracted data. Primary outcomes were blood transfusion, stone-free rate (SFR), thromboembolic events (TEE). We rated the certainty of evidence (CoE) according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach using a minimally contextualised approach with pre-defined thresholds for minimally clinically important differences (MCID). RESULTS: We included 10 RCTs assessing the effect of systemic TXA in PCNL vs placebo (or no TXA). Eight studies were published as full text. Based on an adjusted baseline risk of blood transfusion of 5.7%, systemic TXA may reduce blood transfusions (risk ratio [RR] 0.45, 95% confidence interval [CI] 0.27-0.76). Based on an adjusted baseline SFR of 75.7%, systemic TXA may increase SFR (RR 1.11, 95% CI 0.98-1.27). There is probably no difference in TEEs (risk difference 0.001, 95% CI -0.01 to 0.01). Systemic TXA may increase adverse events (AEs) (RR 5.22, 95% CI 0.52-52.72). Systemic TXA may have little to no effect on secondary interventions (RR 1.15, 95% CI 0.84-1.57). The CoE for most outcomes was assessed as low or very low. CONCLUSIONS: Based on a body of evidence of 10 RCTs, we found that systemic TXA in PCNL may reduce blood transfusions, major surgical complications, and hospital length of stay, as well as improve the SFR; however, it may increase AEs. These findings should inform urologists and their patients in making informed decisions about the use of TXA in the setting of PCNL.

Immunotherapy for advanced or metastatic urothelial carcinoma: an abridged Cochrane review.

OBJECTIVES: To assess the effects of immunotherapy compared to chemotherapy as first- and second-line treatment of advanced or metastatic urothelial carcinoma. METHODS: Based on a published protocol, we performed a systematic search of multiple databases. Two review authors independently performed the literature selection, identified relevant studies, assessed the eligibility of studies for inclusion, and extracted data. We performed statistical analyses using a random-effects model and assessed the quality of the evidence on a per-outcome basis according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: We included five randomised controlled trials and also identified seven single-arm studies. When used as first-line therapy, immunotherapy probably has little to no effect on the risk of death from any cause compared to chemotherapy (hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.87-1.07; moderate-certainty evidence). immunotherapy probably has little to no effect on health-related quality of life (mean difference [MD] 4.10, 95% CI 3.83-4.37; moderate). Immunotherapy probably reduces grade 3-5 adverse events (risk ratio [RR] 0.47, 95% CI 0.29-0.75; moderate). In the second-line setting immunotherapy may reduce the risk of death from any cause (HR 0.72, 95% CI 0.63-0.81; low). Immunotherapy may have little to no effect on health-related quality of life when compared to chemotherapy (MD 4.82, 95% CI -3.11 to 12.75; low). Immunotherapy may reduce grade 3-5 adverse events (RR 0.89, 95% CI 0.81-0.97; low). CONCLUSIONS: Compared to chemotherapy, immunotherapy has little to no effect on the risk of death from any cause in a first-line setting. Nevertheless, it may reduce the risk of death from any cause when used as second-line therapy. The health-related quality of life of participants receiving first- and second-line therapy does not appear to be affected by immunotherapy. Immunotherapy probably reduces or may reduce grade 3-5 adverse events when used as first- and second-line therapy, respectively.

Cytoreductive nephrectomy in metastatic renal cell carcinoma.

BACKGROUND: Nephrectomy is the surgical removal of all or part of a kidney. When the aim of nephrectomy is to reduce tumor burden in people with established metastatic disease, the procedure is called cytoreductive nephrectomy (CN). CN is typically combined with systemic anticancer therapy (SACT). SACT can be initiated before or immediately after the operation or deferred until radiological signs of disease progression. The benefits and harms of CN are controversial. OBJECTIVES: To assess the effects of cytoreductive nephrectomy combined with systemic anticancer therapy versus systemic anticancer therapy alone or watchful waiting in newly diagnosed metastatic renal cell carcinoma. SEARCH METHODS: We performed a comprehensive search in the Cochrane Library, MEDLINE, Embase, Scopus, two trial registries, and other gray literature sources up to 1 March 2024. We applied no restrictions on publication language or status. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that evaluated SACT and CN versus SACT alone or watchful waiting. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies and extracted data. Primary outcomes were time to death from any cause and quality of life. Secondary outcomes were time to disease progression, treatment response, treatment-related mortality, discontinuation due to adverse events, and serious adverse events. We performed statistical analyses using a random-effects model. We rated the certainty of evidence using the GRADE approach. MAIN RESULTS: Our search identified 10 records of four unique RCTs that informed two comparisons. In this abstract, we focus on the results for the two primary outcomes. Cytoreductive nephrectomy plus systemic anticancer therapy versus systemic anticancer therapy alone Three RCTs informed this comparison. Due to the considerable heterogeneity when pooling across these studies, we decided to present the results of the prespecified subgroup analysis by type of systemic agent. Cytoreductive nephrectomy plus interferon immunotherapy versus interferon immunotherapy alone CN plus interferon immunotherapy compared with interferon immunotherapy alone probably increases time to death from any cause (hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.51 to 0.89; I²= 0%; 2 studies, 326 participants; moderate-certainty evidence). Assuming 820 all-cause deaths at two years' follow-up per 1000 people who receive interferon immunotherapy alone, the effect estimate corresponds to 132 fewer all-cause deaths (237 fewer to 37 fewer) per 1000 people who receive CN plus interferon immunotherapy. We found no evidence to assess quality of life. Cytoreductive nephrectomy plus tyrosine kinase inhibitor therapy versus tyrosine kinase inhibitor therapy alone We are very uncertain about the effect of CN plus tyrosine kinase inhibitor (TKI) therapy compared with TKI therapy alone on time to death from any cause (HR 1.11, 95% CI 0.90 to 1.37; 1 study, 450 participants; very low-certainty evidence). Assuming 574 all-cause deaths at two years' follow-up per 1000 people who receive TKI therapy alone, the effect estimate corresponds to 38 more all-cause deaths (38 fewer to 115 more) per 1000 people who receive CN plus TKI therapy. We found no evidence to assess quality of life. Immediate cytoreductive nephrectomy versus deferred cytoreductive nephrectomy One study evaluated CN followed by TKI therapy (immediate CN) versus three cycles of TKI therapy followed by CN (deferred CN). Immediate CN compared with deferred CN may decrease time to death from any cause (HR 1.63, 95% CI 1.05 to 2.53; 1 study, 99 participants; low-certainty evidence). Assuming 620 all-cause deaths at two years' follow-up per 1000 people who receive deferred CN, the effect estimate corresponds to 173 more all-cause deaths (18 more to 294 more) per 1000 people who receive immediate CN. We found no evidence to assess quality of life. AUTHORS' CONCLUSIONS: CN plus SACT in the form of interferon immunotherapy versus SACT in the form of interferon immunotherapy alone probably increases time to death from any cause. However, we are very uncertain about the effect of CN plus SACT in the form of TKI therapy versus SACT in the form of TKI therapy alone on time to death from any cause. Immediate CN versus deferred CN may decrease time to death from any cause. We found no quality of life data for any of these three comparisons. We also found no evidence to inform any other comparisons, in particular those involving newer immunotherapy agents (programmed death receptor 1 [PD-1]/programmed death ligand 1 [PD-L1] immune checkpoint inhibitors), which have become the backbone of SACT for metastatic renal cell carcinoma. There is an urgent need for RCTs that explore the role of CN in the context of contemporary forms of systemic immunotherapy.

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.

The Quality of Literature Search Reporting in Systematic Reviews Published in the Urological Literature (1998-2021).

PURPOSE: We evaluate to what extent systematic reviews published in the urological literature follow best practices for the reporting of searches. MATERIALS AND METHODS: Systematic reviews addressing questions of therapy/prevention were sought out in 5 major urological journals from January 1998 to December 2021. Two members performed study selection and data abstraction independently and in duplicate. The methodological and reporting quality of these systematic reviews was assessed using operationalized criteria based on the PRISMA-S (Preferred Reporting Items for Systematic Reviews and Meta-analyses-literature search extension) and PRISMA 2020 checklists. Proportions of systematic reviews that satisfied each criterion were compared based on period (1998-2012, 2013-2016, and 2017-2021) and journal of publication. RESULTS: The search identified 483 systematic reviews that met inclusion criteria. Most systematic reviews searched 2 or more electronic databases (88.6%); few searched abstract proceedings (26.7%), clinical trial registries (15.1%), or dedicated databases of the "gray literature" (6.2%). Approximately 1 in 3 systematic reviews (32.3%) were explicit in not restricting searches by language. A few criteria demonstrated improved reporting over time including use of clinical trial registries (6.8% vs 14.4% vs 23.3%; P = .001), searches unrestricted by language (37.3% vs 49.3% vs 55.1%; P = .006), and flow diagram reporting (34.8% vs 82.9% vs 93.2%; P = .001) but not the search of abstract proceedings (28.6% vs 24.0% vs 27.3%; P = .647). Reporting characteristics across journals were similar. CONCLUSIONS: Systematic reviews published in the urological literature have considerable shortcomings regarding the reporting of their underlying search strategies. Efforts must be taken to improve search strategies in the form of better training in systematic review methods as well as the more stringent enforcement of reporting guidelines.

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.

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.

Percutaneous nephrolithotomy versus retrograde intrarenal surgery for treatment of renal stones in adults.

BACKGROUND: Kidney stones (also called renal stones) can be a source of pain, obstruction, and infection. Depending on size, location, composition, and other patient factors, the treatment of kidney stones can involve observation, shock wave lithotripsy, retrograde intrarenal surgery (RIRS; i.e. ureteroscopic approaches), percutaneous nephrolithotomy (PCNL), or a combination of these approaches. OBJECTIVES: To assess the effects of percutaneous nephrolithotomy (PCNL) versus retrograde intrarenal surgery (RIRS) for the treatment of renal stones in adults. SEARCH METHODS: We performed a comprehensive search of the Cochrane Library, MEDLINE, Embase, Scopus, and two trials registries up to 23 March 2023. We applied no restrictions on publication language or status. SELECTION CRITERIA: We included randomized controlled trials that evaluated PCNL (grouped by access size in French gauge [Fr] into three groups: ≥ 24 Fr [standard PCNL], 15-23 Fr [mini-PCNL and minimally invasive PCNL], and < 15 Fr [ultra-mini-, mini-micro-, super-mini-, and micro-PCNL]) versus RIRS. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies and extracted data from the included studies. Our primary outcomes were stone-free rate, major complications, and need for secondary interventions. Our main secondary outcomes were unplanned medical visits to emergency/urgent care or outpatient clinic, length of hospital stay, ureteral stricture or injury, and quality of life. We performed statistical analyses using a random-effects model. We rated the certainty of evidence using GRADE criteria. We adopted a minimally contextualized approach with predefined thresholds for minimal clinically important differences (MCIDs). MAIN RESULTS: We included 42 trials assessing the effects of PCNL versus RIRS in 4571 randomized participants. Twenty-two studies were published as full-text articles, and 20 were published as abstract proceedings. The average size of stones ranged from 10.1 mm to 39.1 mm. Most studies did not report sources of funding or conflicts of interest. The main results for the most important outcomes are summarized below. Stone-free rate PCNL compared with RIRS may improve stone-free rates (risk ratio [RR] 1.13, 95% confidence interval [CI] 1.08 to 1.18; I2 = 71%; 39 studies, 4088 participants; low-certainty evidence). Based on 770 participants per 1000 being stone-free with RIRS, this corresponds to 100 more (62 more to 139 more) stone-free participants per 1000 with PCNL (an absolute difference of 10%, where the predefined MCID was 5%). Major complications PCNL compared with RIRS probably has little or no effect on major complications (RR 0.86, 95% CI 0.59 to 1.25; I2 = 15%; 34 studies, 3649 participants; moderate-certainty evidence). Based on 31 complications in the RIRS group, this corresponds to six fewer (13 fewer to six more) major complications per 1000 with PCNL (an absolute difference of 0.6%, where the predefined MCID was 2%). Need for secondary interventions PCNL compared with RIRS may reduce the need for secondary interventions (RR 0.31, 95% CI 0.17 to 0.55; I2 = 61%; 21 studies, 2005 participants; low-certainty evidence). Based on 222 secondary interventions in the RIRS group, this corresponds to 153 fewer (185 fewer to 100 fewer) secondary interventions per 1000 with PCNL (an absolute difference of 15.3%, where the predefined MCID was 5%). Unplanned medical visits No studies reported unplanned medical visits. Length of hospital stay PCNL compared with RIRS may extend length of hospital stay (mean difference 1.04 days more, 95% CI 0.27 more to 1.81 more; I2 = 100%; 26 studies, 2804 participants; low-certainty evidence). This effect size is greater than the predefined MCID of one day. Ureteral stricture or injury PCNL compared with RIRS may have little or no effect on the occurrence of ureteral strictures (RR 0.93, 95% CI 0.39 to 2.21; I2 = 0%; 13 studies, 1574 participants; low-certainty evidence). Based on 14 ureteral strictures in the RIRS group, this corresponds to one fewer (nine fewer to 17 more) ureteral strictures per 1000 with PCNL (an absolute difference of 0.1%, where the predefined MCID was 2%). Quality of life No studies reported quality of life. AUTHORS' CONCLUSIONS: Based on a large body of evidence from 42 trials, we found that PCNL compared with RIRS may improve stone-free rates and may reduce the need for secondary interventions, but probably has little or no effect on major complications. PCNL compared with RIRS may have little or no effect on ureteral stricture rates and may increase length of hospital stay. We found no evidence on unplanned medical visits or participant quality of life. Because of the considerable shortcomings of the included trials, the evidence for most outcomes was of low certainty. Access size for PCNL was less than 24 Fr in most studies that provided this information. We expect the findings of this review to be helpful for shared decision-making about management choices for individuals with renal stones.

Immunotherapy for advanced or metastatic urothelial carcinoma.

BACKGROUND: Immune checkpoint inhibitors are increasingly important in the treatment algorithm for locally advanced and metastatic bladder cancer. Numerous ongoing studies are investigating these agents as first- and second-line therapies, both alone and in combination with chemotherapy or in a maintenance therapy setting. OBJECTIVES: To assess the effects of immune checkpoint inhibitors compared to chemotherapy as first- and second-line treatment of advanced or metastatic urothelial carcinoma. SEARCH METHODS: We performed a comprehensive search including the Cochrane Library, MEDLINE, Embase, three other databases, several trial registers, other sources of gray literature, and conference proceedings, with no restrictions on language of publication. We limited the search period to run from 2000 until August 2022. SELECTION CRITERIA: We included randomized controlled trials (RCTs) using immunotherapy versus chemotherapy and would have considered non-randomized trials in the absence of randomized trial data. Participants had locally advanced inoperable (cT4b or N+, or both) or metastatic (M1) (or both) urothelial carcinoma of the bladder or upper urinary tract. We excluded studies of people in whom immunotherapy was used in combination with chemotherapy or in a surveillance setting. DATA COLLECTION AND ANALYSIS: Two review authors independently classified studies for inclusion and abstracted data from included studies. We performed statistical analyses 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 on a per-outcome basis. MAIN RESULTS: We included five RCTs and identified seven single-armed studies. The RCTs included 3572 participants comparing immunotherapy versus chemotherapy for the treatment of locally advanced and metastatic bladder cancer. First-line therapy Immunotherapy probably has little to no effect on the risk of death from any cause when used as first-line therapy compared to chemotherapy (hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.87 to 1.07; I2 = 0%; 3 studies, 2068 participants; moderate-certainty evidence). This corresponds to 750 deaths per 1000 participants with chemotherapy and 11 fewer (45 fewer to 26 more) deaths per 1000 participants with immunotherapy at 36 months. Immunotherapy probably has little to no effect on health-related quality of life (mean difference (MD) 4.10, 95% CI 3.83 to 4.37; 1 study, 393 participants; moderate-certainty evidence), when assuming a minimal clinically important difference (MCID) of at least 6 points (using the Functional Assessment of Cancer Therapy - Bladder [FACT-BL] tool; scale 0 to 156 with higher scores representing better quality of life). Immunotherapy probably reduces adverse events grade 3 to 5 (RR 0.47, 95% CI 0.29 to 0.75; I2 = 97%; 3 studies, 2046 participants; moderate-certainty evidence). This corresponds to 908 grade 3 to 5 adverse events per 1000 participants with chemotherapy, with 481 fewer (644 fewer to 227 fewer) grade 3 to 5 adverse events per 1000 participants with immunotherapy. We found no evidence for the outcome time to death from bladder cancer. Immunotherapy probably increases the risk of time to disease progression (HR 1.33, 95% CI 1.17 to 1.50; I2 = 0%; 2 studies, 1349 participants; moderate-certainty evidence). This corresponds to 660 events per 1000 participants with chemotherapy and 102 more (57 more to 152 more) events per 1000 participants with immunotherapy at 36 months. Immunotherapy may reduce discontinuations due to adverse effects (RR 0.47, 95% CI 0.20 to 1.10; I2 = 94%; 3 studies, 2046 participants; low-certainty evidence). This corresponds to 338 discontinuations per 1000 participants with chemotherapy and 179 fewer (271 fewer to 34 more) discontinuations per 1000 participants with immunotherapy. Second-line therapy Immunotherapy may reduce the risk of death from any cause when used as second-line therapy (HR 0.72, 95% CI 0.63 to 0.81; I2 = 0%; 2 studies, 1473 participants; low-certainty evidence). This corresponds to 920 deaths per 1000 participants with chemotherapy (vinflunine, paclitaxel, docetaxel) and 59 fewer (95 fewer to 28 fewer) deaths per 1000 participants with immunotherapy at 36 months. Immunotherapy may have little to no effect on health-related quality of life when compared to chemotherapy (MD 4.82, 95% CI -3.11 to 12.75; I2 = 85%; 2 studies, 727 participants; low-certainty evidence), assuming an MCID of at least 10 points (using the EORTC QLQ tool; scale 0 to 100 with higher scores representing better quality of life). Immunotherapy may reduce adverse events grade 3 to 5 in participants undergoing second-line therapy (RR 0.89, 95% CI 0.81 to 0.97; I2 = 9%; 2 studies, 1423 participants; low-certainty evidence). This corresponds to 630 grade 3 to 5 adverse events per 1000 participants with chemotherapy and 76 fewer (126 fewer to 25 fewer) grade 3 to 5 adverse events per 1000 participants with immunotherapy. We found no evidence for the outcome of time to death from bladder cancer. We are very uncertain if immunotherapy reduces the risk of disease progression (HR 0.99, 95% CI 0.84 to 1.16; I2 = 0%; 2 studies, 1473 participants; very low-certainty evidence). Immunotherapy may reduce discontinuations due to adverse events in participants undergoing second-line therapy (RR 0.35, 95% CI 0.17 to 0.72; I2 = 69%; 2 studies, 1473 participants; low-certainty evidence). This corresponds to 110 discontinuations per 1000 participants with chemotherapy and 72 fewer (91 fewer to 31 fewer) discontinuations per 1000 participants with immunotherapy. AUTHORS' CONCLUSIONS: Compared to chemotherapy, immunotherapy for treating advanced or metastatic urothelial carcinoma probably has little to no effect on the risk of death from any cause when used as first-line therapy. Still, it may reduce the risk of death from any cause when used as second-line therapy. Health-related quality of life for participants receiving first- and second-line therapy does not appear to be affected by immunotherapy. Immunotherapy probably reduces or may reduce adverse events grade 3 to 5 when used as first- and second-line therapy, respectively.

Tranexamic acid for percutaneous nephrolithotomy.

BACKGROUND: Percutaneous nephrolithotomy (PCNL) is the gold standard for the treatment of large kidney stones but comes with an increased risk of bleeding compared to other treatments, such as ureteroscopy and shock wave lithotripsy. Tranexamic acid (TXA) is an antifibrinolytic agent that has been used to reduce bleeding complications in other settings. OBJECTIVES: To assess the effects of TXA in individuals with kidney stones undergoing PCNL. SEARCH METHODS: We performed a comprehensive literature search of the Cochrane Library, PubMed (including MEDLINE), Embase, Scopus, Global Index Medicus, trials registries, other sources of the grey literature, and conference proceedings. We applied no restrictions on the language of publication nor publication status. The latest search date was 11 May 2023. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that compared treatment with PCNL with administration of TXA to placebo (or no TXA) for patients ≥ 18 years old. DATA COLLECTION AND ANALYSIS: Two review authors independently classified studies and abstracted data. Primary outcomes were: blood transfusion, stone-free rate (SFR), and thromboembolic events (TEEs). Secondary outcomes were: adverse events (AEs), secondary interventions, major surgical complications, minor surgical complications, unplanned hospitalizations or readmissions, and hospital length of stay (LOS). We performed statistical analyzes using a random-effects model. We rated the certainty of evidence (CoE) according to the GRADE approach using a minimally contextualized approach with predefined thresholds for minimally clinically important differences (MCIDs). MAIN RESULTS: We analyzed 10 RCTs assessing the effect of systemic TXA in PCNL versus placebo (or no TXA) with 1883 randomized participants. Eight studies were published as full text. One was published in abstract proceedings, but it was separated into two separate studies for the purpose of our analyzes. Average stone surface area ranged 3.45 to 6.62 cm2. We also found a single RCT published in full text assessing the effects of topical TXA in PCNL versus placebo (or no TXA) with 400 randomized participants, the results of which are further described in the review. Here we focus only on the results of TXA used systemically. Blood transfusion - Based on a representative baseline risk of 5.7% for blood transfusions taken from a large presentative observational studies, systemic TXA may reduce blood transfusions (risk ratio (RR) 0.45, 95% confidence interval (CI) 0.27 to 0.76; I2 = 28%; 9 studies, 1353 participants; low CoE). We assumed an MCID of ≥ 2%. Based on 57 participants per 1000 with placebo (or no TXA) being transfused, this corresponds to 31 fewer (from 42 fewer to 14 fewer) participants being transfused per 1000. Stone-free rate - Based on a representative baseline risk of 75.7% for SFR, systemic TXA may increase SFRs (RR 1.11, 95% CI 0.98 to 1.27; I2 = 62%; 4 studies, 603 participants; low CoE). We assumed an MCID of ≥ 5%. Based on 757 participants per 1000 being stone free with placebo (or no TXA), this corresponds to 83 more (from 15 fewer to 204 more) stone-free participants per 1000. Thromboembolic events - There is probably no difference in TEEs (risk difference (RD) 0.00, 95% CI -0.01 to 0.01; I2 = 0%; 6 studies, 841 participants; moderate CoE). We assumed an MCID of ≥ 2%. Since there were no thromboembolic events in intervention and/or control groups in 5 out of6 studies, we opted to assess a risk difference with systemic TXA for this outcome. Adverse events - Systemic TXA may increase AEs (RR 5.22, 95% CI 0.52 to 52.72; I2 = 75%; 4 studies, 602 participants; low CoE). We assumed an MCID of ≥ 5%. Based on 23 participants per 1000 with placebo (or no TXA) having an adverse event, this corresponds to 98 more (from 11 fewer to 1000 more) participants with adverse events per 1000. Secondary interventions - Systemic TXA may have little to no effect on secondary interventions (RR 1.15, 95% CI 0.84 to 1.57; I2 = 0%; 2 studies, 319 participants; low CoE). We assumed an MCID of ≥ 5%. Based on 278 participants per 1000 with placebo (or no TXA) having a secondary intervention, this corresponds to 42 more (from 44 fewer to 158 more) participants with secondary interventions per 1000. Major surgical complications - Based on a representative baseline risk for major surgical complications of 4.1%, systemic TXA may reduce major surgical complications (RR 0.36, 95% CI 0.21 to 0.62; I2 = 0%; 5 studies, 733 participants; moderate CoE). We assumed an MCID of ≥ 2%. Based on 41 participants per 1000 with placebo (or no TXA) having a major surgical complication, this corresponds to 26 fewer (from 32 fewer to 16 fewer) participants with major surgical complications per 1000. Minor surgical complications - Systemic TXA may reduce minor surgical complications (RR 0.71, 95% CI 0.45 to 1.10; I2 = 76%; 5 studies, 733 participants; low CoE). We assumed an MCID of ≥ 5%. Based on 396 participants per 1000 with placebo (or no TXA) having a minor surgical complication, this corresponds to 115 fewer (from 218 fewer to 40 more) participants with minor surgical complications per 1000. Unplanned hospitalizations or readmissions - We are very uncertain how unplanned hospitalizations or readmissions are affected (RR 1.55, 95% CI 0.45 to 5.31; I2 = not applicable; 1 study, 189 participants; very low CoE). We assumed an MCID of ≥ 2%. Hospital length of stay - Systemic TXA may reduce hospital LOS (mean difference 0.52 days lower, 95% CI 0.93 lower to 0.11 lower; I2 = 98%; 7 studies, 1151 participants; low CoE). We assumed an MCID of ≥ 0.5 days. AUTHORS' CONCLUSIONS: Based on 10 RCTs with substantial methodological limitations that lowered all CoE of effect, we found that systemic TXA in PCNL may reduce blood transfusions, major and minor surgical complications, and hospital LOS, as well as improve SFRs; however, it may increase AEs. We are uncertain about the effects of systemic TXA on other outcomes. Findings of this review should assist urologists and their patients in making informed decisions about the use of TXA in the setting of PCNL.

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.

First-line therapy for adults with advanced renal cell carcinoma: a systematic review and network meta-analysis.

BACKGROUND: Since the approval of tyrosine kinase inhibitors, angiogenesis inhibitors and immune checkpoint inhibitors, the treatment landscape for advanced renal cell carcinoma (RCC) has changed fundamentally. Today, combined therapies from different drug categories have a firm place in a complex first-line therapy. Due to the large number of drugs available, it is necessary to identify the most effective therapies, whilst considering their side effects and impact on quality of life (QoL). OBJECTIVES: To evaluate and compare the benefits and harms of first-line therapies for adults with advanced RCC, and to produce a clinically relevant ranking of therapies. Secondary objectives were to maintain the currency of the evidence by conducting continuous update searches, using a living systematic review approach, and to incorporate data from clinical study reports (CSRs). SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, conference proceedings and relevant trial registries up until 9 February 2022. We searched several data platforms to identify CSRs. SELECTION CRITERIA: We included randomised controlled trials (RCTs) evaluating at least one targeted therapy or immunotherapy for first-line treatment of adults with advanced RCC. We excluded trials evaluating only interleukin-2 versus interferon-alpha as well as trials with an adjuvant treatment setting. We also excluded trials with adults who received prior systemic anticancer therapy if more than 10% of participants were previously treated, or if data for untreated participants were not separately extractable. DATA COLLECTION AND ANALYSIS: All necessary review steps (i.e. screening and study selection, data extraction, risk of bias and certainty assessments) were conducted independently by at least two review authors. Our outcomes were overall survival (OS), QoL, serious adverse events (SAEs), progression-free survival (PFS), adverse events (AEs), the number of participants who discontinued study treatment due to an AE, and the time to initiation of first subsequent therapy. Where possible, analyses were conducted for the different risk groups (favourable, intermediate, poor) according to the International Metastatic Renal-Cell Carcinoma Database Consortium Score (IMDC) or the Memorial Sloan Kettering Cancer Center (MSKCC) criteria. Our main comparator was sunitinib (SUN). A hazard ratio (HR) or risk ratio (RR) lower than 1.0 is in favour of the experimental arm. MAIN RESULTS: We included 36 RCTs and 15,177 participants (11,061 males and 4116 females). Risk of bias was predominantly judged as being 'high' or 'some concerns' across most trials and outcomes. This was mainly due to a lack of information about the randomisation process, the blinding of outcome assessors, and methods for outcome measurements and analyses. Additionally, study protocols and statistical analysis plans were rarely available. Here we present the results for our primary outcomes OS, QoL, and SAEs, and for all risk groups combined for contemporary treatments: pembrolizumab + axitinib (PEM+AXI), avelumab + axitinib (AVE+AXI), nivolumab + cabozantinib (NIV+CAB), lenvatinib + pembrolizumab (LEN+PEM), nivolumab + ipilimumab (NIV+IPI), CAB, and pazopanib (PAZ). Results per risk group and results for our secondary outcomes are reported in the summary of findings tables and in the full text of this review. The evidence on other treatments and comparisons can also be found in the full text. Overall survival (OS) Across risk groups, PEM+AXI (HR 0.73, 95% confidence interval (CI) 0.50 to 1.07, moderate certainty) and NIV+IPI (HR 0.69, 95% CI 0.69 to 1.00, moderate certainty) probably improve OS, compared to SUN, respectively. LEN+PEM may improve OS (HR 0.66, 95% CI 0.42 to 1.03, low certainty), compared to SUN. There is probably little or no difference in OS between PAZ and SUN (HR 0.91, 95% CI 0.64 to 1.32, moderate certainty), and we are uncertain whether CAB improves OS when compared to SUN (HR 0.84, 95% CI 0.43 to 1.64, very low certainty). The median survival is 28 months when treated with SUN. Survival may improve to 43 months with LEN+PEM, and probably improves to: 41 months with NIV+IPI, 39 months with PEM+AXI, and 31 months with PAZ. We are uncertain whether survival improves to 34 months with CAB. Comparison data were not available for AVE+AXI and NIV+CAB. Quality of life (QoL) One RCT measured QoL using FACIT-F (score range 0 to 52; higher scores mean better QoL) and reported that the mean post-score was 9.00 points higher (9.86 lower to 27.86 higher, very low certainty) with PAZ than with SUN. Comparison data were not available for PEM+AXI, AVE+AXI, NIV+CAB, LEN+PEM, NIV+IPI, and CAB. Serious adverse events (SAEs) Across risk groups, PEM+AXI probably increases slightly the risk for SAEs (RR 1.29, 95% CI 0.90 to 1.85, moderate certainty) compared to SUN. LEN+PEM (RR 1.52, 95% CI 1.06 to 2.19, moderate certainty) and NIV+IPI (RR 1.40, 95% CI 1.00 to 1.97, moderate certainty) probably increase the risk for SAEs, compared to SUN, respectively. There is probably little or no difference in the risk for SAEs between PAZ and SUN (RR 0.99, 95% CI 0.75 to 1.31, moderate certainty). We are uncertain whether CAB reduces or increases the risk for SAEs (RR 0.92, 95% CI 0.60 to 1.43, very low certainty) when compared to SUN. People have a mean risk of 40% for experiencing SAEs when treated with SUN. The risk increases probably to: 61% with LEN+PEM, 57% with NIV+IPI, and 52% with PEM+AXI. It probably remains at 40% with PAZ. We are uncertain whether the risk reduces to 37% with CAB. Comparison data were not available for AVE+AXI and NIV+CAB. AUTHORS' CONCLUSIONS: Findings concerning the main treatments of interest comes from direct evidence of one trial only, thus results should be interpreted with caution. More trials are needed where these interventions and combinations are compared head-to-head, rather than just to SUN. Moreover, assessing the effect of immunotherapies and targeted therapies on different subgroups is essential and studies should focus on assessing and reporting relevant subgroup data. The evidence in this review mostly applies to advanced clear cell RCC.

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.

Lack of Gender Diversity Among Systematic Reviews Authors in the Urological Literature (1998-2021).

PURPOSE: Gender equity is a key performance metric in research, including systematic reviews, and is increasingly noted in publications. We performed this study to assess gender parity in scientific authorship of systematic reviews published in the urological literature. MATERIALS AND METHODS: We identified all published systematic reviews addressing questions of therapy/prevention in 5 major urological journals (The Journal of Urology®, European Urology, Urology, BJU International, and World Journal of Urology) from 1998 to 2021. We determined gender of first, second, corresponding, and any author as a binary variable (woman or man) using a predefined algorithm. RESULTS: We included 523 systematic reviews. The main journal contributors were European Urology (32.6%), BJU International (22.0%), and The Journal of Urology (19.5%). Slightly more than half (51.8%) of reviews included at least 1 woman coauthor, 37.5% did not, and in 10.7% it was unclear. First, second, and corresponding authors were women in 13.7%, 12.4%, and 4.7%, respectively, and the median number of women contributors was 1 (interquartile range 0-2). Women-first authorship for the time period 1998-2012 was 13.0% (P = .139), and senior authorship was 5.0% (P = .270). In 2013-2016 it was 11.0% and 4.1%, and in 2017-2021 it increased somewhat to 16.5% and 5.1% (P = .270), respectively. CONCLUSIONS: The number of women involved in systematic reviews is low and has not improved over time. Since scientific authorship is important for academic advancement, this finding may contribute to the underrepresentation of women in academic leadership positions. Efforts to improve gender diversity in urology should include more collaboration across genders.

An International Needs Assessment Survey of Guideline Developers Demonstrates Variability in Resources and Challenges to Collaboration between Organizations.

BACKGROUND: The development of rigorous, high-quality clinical guidelines increases the need for resources and skilled personnel within guideline-producing organizations. While collaboration between organizations provides a unique opportunity to pool resources and save time and effort, the collaboration presents its own unique challenges. OBJECTIVE: To assess the perceived needs and current challenges of guideline producers worldwide related to guideline development and collaboration efforts. DESIGN: Survey questions were developed by the Guidelines International Network and the US GRADE Network, pilot-tested among attendees of a guideline development workshop, and disseminated electronically using convenience and snowball sampling methods. PARTICIPANTS: A total of 171 respondents representing 30 countries and more than 112 unique organizations were included in this analysis. MAIN MEASURES: The survey included free-response, multiple-choice, and seven-point Likert-scale questions. Questions assessed respondents' perceived value of guidelines, resource availability and needs, guideline development processes, and collaboration efforts of their organization. KEY RESULTS: Time required to develop high-quality systematic reviews and guidelines was the most relevant need (median=7; IQR=5.5-7). In-house resources to conduct literature searches (median=4; IQR=3-6) and the resources to develop rigorous guidelines rapidly (median=4; IQR=2-5) were perceived as the least available resources. Difficulties reconciling differences in guideline methodology (median=6; IQR=4-7) and the time required to establish collaborative agreements (median=6; IQR=5-6) were the most relevant barriers to collaboration between organizations. Results also indicated a general need for improvement in conflict of interest (COI) disclosure policies. CONCLUSION: The survey identified organizational challenges in supporting rigorous guideline development, including the time, resources, and personnel required. Connecting guideline developers to existing databases of high-quality systematic reviews and the use of freely available online platforms may facilitate guideline development. Guideline-producing organizations may also consider allocating resources to hiring or training personnel with expertise in systematic review methodologies or utilizing resources more effectively by establishing collaborations with other organizations.

Blue vs white light for transurethral resection of non-muscle-invasive bladder cancer: an abridged Cochrane Review.

OBJECTIVES: To assess the effects of blue-light (BL)-enhanced transurethral resection of bladder tumour (TURBT) compared to white-light (WL)-based TURBT in the treatment of non-muscle-invasive bladder cancer (NMIBC). METHODS: Based on a published protocol, we performed a systematic search of multiple databases from their inception to March 2021. We included randomized controlled trials (RCTs) comparing blue-light (BL) TURBT to white-light (WL) TURBT. Our meta-analysis was based on a random-effects model. We assessed the quality of evidence on a per-outcome basis according to the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. RESULTS: We included 16 RCTs involving a total of 4325 participants in this review. BL TURBT may reduce the risk of disease recurrence over time (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.54-0.81; low-certainty evidence) depending on baseline risk. For participants with low-, intermediate- and high-risk NMIBC, this corresponded to 48 (66 fewer to 27 fewer), 109 (152 fewer to 59 fewer) and 147 (211 fewer to 76 fewer) fewer recurrences per 1000 participants when compared to WL TURBT, respectively. BL TURBT may also reduce the risk of disease progression over time (HR 0.65, 95% CI 0.50-0.84; low-certainty evidence) depending on baseline risk. For participants with low-, intermediate- and high-risk NMIBC, this corresponded to 1 (1 fewer to 0 fewer), 17 (25 fewer to 8 fewer), and 56 (81 fewer to 25 fewer) fewer progressions per 1000 participants when compared to WL TURBT, respectively. CONCLUSIONS: Our findings suggest a favourable impact of BL TURBT on the risk of disease recurrence and progression; however, whether this risk reduction is clinically relevant greatly depends on the baseline risk of patients. We did not find an increase in severe surgical complications with BL cystoscopy, and we did not find any trial evidence on other, non-surgical adverse events.

Assessment of prostate-specific antigen screening: an evidence-based report by the German Institute for Quality and Efficiency in Health Care.

CONTEXT: Prostate-specific antigen (PSA) testing increases prostate cancer diagnoses and reduces long-term disease-specific mortality, but also results in overdiagnoses and treatment-related harms. OBJECTIVE: To systematically assess the benefits and harms of population-based PSA screening and the potential net benefit to inform health policy decision-makers in Germany. EVIDENCE ACQUISITION: We performed a protocol-guided comprehensive literature search according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. All steps were performed by one or two investigators; any discrepancies were resolved by consensus. To allow subgroup analyses for identifying the optimal screening parameters, the eight national trials conducted under the umbrella of the European Randomised study of Screening for Prostate Cancer (ERSPC) were included as individual trials. EVIDENCE SYNTHESIS: We included a total 11 randomised controlled trials (RCTs) with a total of 416 000 study participants. For all-cause mortality, we found neither benefit nor harm. PSA screening was associated with a reduced risk of both prostate cancer mortality and the development of metastases. For the outcomes of health-related quality of life, adverse effects and the consequences of false-negative screening results there was no difference; however, this was due to the lack of eligible RCT data. Finally, PSA screening was associated with large numbers of overdiagnoses with adverse downstream consequences of unnecessary treatment (e.g. incontinence, erectile dysfunction) and large numbers of false-positive PSA tests leading to biopsies associated with a small but not negligible risk of complications. Limitations of this assessment include the clinical heterogeneity and methodological limitations of the underlying studies. CONCLUSIONS: The benefits of PSA-based prostate cancer screening do not outweigh its harms. We failed to identify eligible screening studies of newer biomarkers, PSA derivatives or modern imaging modalities, which may alter the balance of benefit to harm. PATIENT SUMMARY: In the present study, we reviewed the evidence on the PSA blood test to screen men without symptoms for prostate cancer. We found that the small benefits experienced by some men do not outweigh the harms to many more men.