Oncological outcomes after attempted nerve-sparing radical prostatectomy (NSRP) in patients with high-risk prostate cancer are comparable to standard non-NSRP: a longitudinal long-term propensity-matched single-centre study.

OBJECTIVE: To assess the long-term safety of nerve-sparing radical prostatectomy (NSRP) in men with high-risk prostate cancer (PCa) by comparing survival outcomes, disease recurrence, the need for additional therapy, and perioperative outcomes of patients undergoing NSRP to those having non-NSRP. PATIENTS AND METHODS: We included consecutive patients at a single, academic centre who underwent open RP for high-risk PCa, defined as preoperative prostate-specific antigen level of > 20 ng/mL and/or postoperative International Society of Urological Pathology Grade Group 4 or 5 (i.e., Gleason score ≥ 8) and/or ≥pT3 and/or pN1 assessing the RP and lymph node specimen. We calculated a propensity score and used inverse probability of treatment weighting to match baseline characteristics of patients with high-risk PCa who underwent NSRP vs non-NSRP. We analysed oncological outcome as time-to-event and calculated hazard ratios (HRs). RESULTS: A total of 726 patients were included in this analysis of which 84% (n = 609) underwent NSRP. There was no evidence for the positive surgical margin rate being different between the NSRP and non-NSRP groups (47% vs 49%, P = 0.64). Likewise, there was no evidence for the need for postoperative radiotherapy being different in men who underwent NSRP from those who underwent non-NSRP (HR 0.78, 95% confidence interval [CI] 0.53-1.15). NSRP did not impact the risk of any recurrence (HR 0.99, 95% CI 0.73-1.34, P = 0.09) and there was no evidence for survival being different in men who underwent NSRP to those who underwent non-NSRP (HR 0.65, 95% CI 0.39-1.08). There was also no evidence for the cancer-specific survival (HR 0.56, 95% CI 0.29-1.11) or progression-free survival (HR 0.99, 95% CI 0.73-1.34) being different between the groups. CONCLUSION: In patients with high-risk PCa, NSRP can be attempted without compromising long-term oncological outcomes provided a comprehensive assessment of objective (e.g., T Stage) and subjective (e.g., intraoperative appraisal of tissue planes) criteria are conducted.

Impact of Preoperative Immunonutrition on Perioperative Outcomes following Cystectomy.

PURPOSE: Radical cystectomy (RC) for the management of muscle-invasive bladder cancer remains a morbid procedure with high rates of perioperative complications. The role of preoperative immunonutritional supplementation (pre-INS) in improving post-RC outcomes is promising and needs further validation. MATERIALS AND METHODS: We performed a retrospective review of 204 patients who underwent RC for bladder cancer at a single institution, comparing patients who received oral L-arginine-based pre-INS, and those who did not. Preoperative features, postoperative complications, and readmission data were collected. Outcomes of interest included development of high-grade (Clavien-Dindo III-V) complications, readmission within 30 days, ileus, total parenteral nutrition (TPN) requirement, postoperative infection, and length of stay (LOS). Categorical and continuous outcomes were assessed using Fisher's exact test and Welch T-test, respectively. Multivariable logistic regression (MLoR) analysis was used to identify predictive factors for our outcomes. RESULTS: Patients who received pre-INS had significantly lower odds of requiring postoperative TPN (17.3% vs 35.6%; Fisher p=0.015, OR=0.38) and developing postoperative infection (25% vs 45%; Fisher p=0.003; OR=0.41) but no significant difference in the rates of other outcomes. On MLoR, when adjusting for age, gender, body mass index, Charlson comorbidity index, undergoing neoadjuvant chemotherapy and operative features, pre-INS was a significant predictor of postoperative infection (Fisher p=0.02; OR=0.35) but not for high-grade complications, readmission, ileus, needing TPN or LOS. CONCLUSIONS: Preoperative immunonutrition with an L-arginine-based supplement is associated with significant reduction in postoperative infection, one of the most common complications of RC.

Outcomes in robot-assisted partial nephrectomy for imperative vs elective indications.

OBJECTIVES: To assess and compare peri-operative outcomes of patients undergoing robot-assisted partial nephrectomy (RAPN) for imperative vs elective indications. PATIENT AND METHODS: We retrospectively reviewed a multinational database of 3802 adults who underwent RAPN for elective and imperative indications. Laparoscopic or open partial nephrectomy (PN) were excluded. Baseline data for age, gender, body mass index, American Society of Anaesthesiologists score and PADUA score were examined. Patients undergoing RAPN for an imperative indication were matched to those having surgery for an elective indication using propensity scores in a 1:3 ratio. Primary outcomes included organ ischaemic time, operating time, estimated blood loss (EBL), rate of blood transfusions, Clavien-Dindo complications, conversion to radical nephrectomy (RN) and positive surgical margin (PSM) status. RESULTS: After propensity-score matching for baseline variables, a total of 304 patients (76 imperative vs 228 elective indications) were included in the final analysis. No significant differences were found between groups for ischaemia time (19.9 vs 19.8 min; P = 0.94), operating time (186 vs 180 min; P = 0.55), EBL (217 vs 190 mL; P = 0.43), rate of blood transfusions (2.7% vs 3.7%; P = 0.51), or Clavien-Dindo complications (P = 0.31). A 38.6% (SD 47.9) decrease in Day-1 postoperative estimated glomerular filtration rate was observed in the imperative indication group and an 11.3% (SD 45.1) decrease was observed in the elective indication group (P < 0.005). There were no recorded cases of permanent or temporary dialysis. There were no conversions to RN in the imperative group, and seven conversions (5.6%) in the elective group (P = 0.69). PSMs were seen in 1.4% (1/76) of the imperative group and in 3.3% of the elective group (7/228; P = 0.69). CONCLUSION: We conclude that RAPN is feasible and safe for imperative indications and demonstrates similar outcomes to those achieved for elective indications.

Delayed surgery for localised and metastatic renal cell carcinoma: a systematic review and meta-analysis for the COVID-19 pandemic.

PURPOSE: The COVID-19 pandemic has led to the cancellation or deferment of many elective cancer surgeries. We performed a systematic review on the oncological effects of delayed surgery for patients with localised or metastatic renal cell carcinoma (RCC) in the targeted therapy (TT) era. METHOD: The protocol of this review is registered on PROSPERO(CRD42020190882). A comprehensive literature search was performed on Medline, Embase and Cochrane CENTRAL using MeSH terms and keywords for randomised controlled trials and observational studies on the topic. Risks of biases were assessed using the Cochrane RoB tool and the Newcastle-Ottawa Scale. For localised RCC, immediate surgery [including partial nephrectomy (PN) and radical nephrectomy (RN)] and delayed surgery [including active surveillance (AS) and delayed intervention (DI)] were compared. For metastatic RCC, upfront versus deferred cytoreductive nephrectomy (CN) were compared. RESULTS: Eleven studies were included for quantitative analysis. Delayed surgery was significantly associated with worse cancer-specific survival (HR 1.67, 95% CI 1.23-2.27, p < 0.01) in T1a RCC, but no significant difference was noted for overall survival. For localised ≥ T1b RCC, there were insufficient data for meta-analysis and the results from the individual reports were contradictory. For metastatic RCC, upfront TT followed by deferred CN was associated with better overall survival when compared to upfront CN followed by deferred TT (HR 0.61, 95% CI 0.43-0.86, p < 0.001). CONCLUSION: Noting potential selection bias, there is insufficient evidence to support the notion that delayed surgery is safe in localised RCC. For metastatic RCC, upfront TT followed by deferred CN should be considered.

Selective serotonin re-uptake inhibitors for premature ejaculation in adult men.

BACKGROUND: Premature ejaculation (PE) is a common problem among men that occurs when ejaculation happens sooner than a man or his partner would like during sex; it may cause unhappiness and relationship problems. Selective serotonin re-uptake inhibitors (SSRIs), which are most commonly used as antidepressants are being used to treat this condition. OBJECTIVES: To assess the effects of SSRIs in the treatment of PE in adult men. SEARCH METHODS: We performed a comprehensive search using multiple databases (the Cochrane Library, MEDLINE, Embase, Scopus, CINAHL), clinical trial registries, conference proceedings, and other sources of grey literature, up to 1 May 2020. We applied no restrictions on publication language or status. SELECTION CRITERIA: We included only randomized controlled clinical trials (parallel group and cross-over trials) in which men with PE  were administered SSRIs or placebo. We also considered 'no treatment' to be an eligible comparator but did not find any relevant studies. DATA COLLECTION AND ANALYSIS: Two review authors independently classified and abstracted data from the included studies. Primary outcomes were participant-perceived change with treatment, satisfaction with intercourse and study withdrawal due to adverse events. Secondary outcomes included self-perceived control over ejaculation, participant distress about PE, adverse events and intravaginal ejaculatory latency time (IELT). We performed statistical analyses using a random-effects model. We rated the certainty of evidence according to GRADE. MAIN RESULTS: We identified 31 studies in which 8254 participants were randomized to receiving either SSRIs or placebo. Primary outcomes: SSRI treatment probably improves self-perceived PE symptoms (defined as a rating of 'better' or 'much better') compared to placebo (risk ratio (RR) 1.92, 95% confidence interval (CI) 1.66 to 2.23; moderate-certainty evidence). Based on 220 participants per 1000 reporting improvement with placebo, this corresponds to 202 more men per 1000 (95% CI 145 more to 270 more) with improved symptoms with SSRIs.  SSRI treatment probably improves satisfaction with intercourse compared to placebo (defined as a rating of 'good' or 'very good'; RR 1.63, 95% CI 1.42 to 1.87; moderate-certainty evidence). Based on 278 participants per 1000 reporting improved satisfaction with placebo, this corresponds to 175 more (117 more to 242 more) per 1000 men with greater satisfaction with intercourse with SSRIs. SSRI treatment may increase treatment cessations due to adverse events compared to placebo (RR 3.80, 95% CI 2.61 to 5.51; low-certainty evidence). Based 11 study withdrawals per 1000 participants with placebo, this corresponds to 30 more men per 1000 (95% CI 17 more to 49 more) ceasing treatment due to adverse events with SSRIs.  Secondary outcomes: SSRI treatment likely improve participants' self-perceived control over ejaculation (defined as rating of 'good' or 'very good') compared to placebo (RR 2.29, 95% CI 1.72 to 3.05; moderate-certainty evidence). Assuming 132 per 1000 participants perceived at least good control, this corresponds to 170 more (95 more to 270 more) reporting at least good control with SSRIs.  SSRI probably lessens distress (defined as rating of 'a little bit' or 'not at all') about PE (RR 1.54, 95% CI 1.26 to 1.88; moderate-certainty evidence). Based on 353 per 1000 participants reporting low levels of distress, this corresponds to 191 more men (92 more to 311 more) per 1000 reporting low levels of distress with SSRIs.  SSRI treatment probably increases adverse events compared to placebo (RR 1.71, 95% CI 1.48 to 1.99; moderate-certainty evidence). Based on 243 adverse events per 1000 among men receiving placebo, this corresponds to 173 more (117 more to 241 more) men having an adverse event with SSRIs.  SSRI treatment may increase IELT compared to placebo (mean difference (MD) 3.09 minutes longer, 95% CI 1.94 longer to 4.25 longer; low-certainty evidence). AUTHORS' CONCLUSIONS: SSRI treatment for PE appears to substantially improve a number of outcomes of direct patient importance such as symptom improvement, satisfaction with intercourse and perceived control over ejaculation when compared to placebo. Undesirable effects are a small increase in treatment withdrawals due to adverse events as well as substantially increased adverse event rates. Issues affecting the certainty of evidence of outcomes were study limitations and imprecision.

Drain fluid creatinine-to-serum creatinine ratio as an initial test to detect urine leakage following cystectomy: A retrospective study.

INTRODUCTION: Urine leak following radical cystectomy is a known complication. Among the various methods to diagnose this, assessment of drain fluid creatinine is a relatively easy procedure. We aimed to ascertain the validity of the drain fluid creatinine-to-serum creatinine ratio (DCSCR) as an initial indicator of urinary leak in patients undergoing radical cystectomy. METHODS: We retrospectively identified consecutive patients with documentation of drain fluid creatinine in the postoperative period following cystectomy and urinary diversion at our institution between January 2009 and December 2018. All continent diversions and any patient with a DCSCR >1.5:1 underwent contrast study postoperatively. A diagnosis of urine leak was made following confirmatory imaging. Receiver operative characteristic curves were created, and Youden's index was used to determine the strength and clinical utility of DCSCR as a diagnostic test. RESULTS: Two hundred forty-four of the 340 patients included in the study underwent cystectomy with conduit and 81 underwent neobladder creation. Sixteen out of 340 (4.7%) patients had radiologically confirmed urinary leak. DCSCR was elevated in all ureteric anastomotic leaks and in 1 out of the 7 neobladder-urethral anastomotic (NUA) leaks. The sensitivity and specificity of DCSCR to predict all urinary leaks were 68.8% and 80.9% at 1.12 (area under the curve [AUC] = 0.838), whereas at a value of 1.18 (AUC = 0.876) and with the exclusion of NUA leaks, the sensitivity was 77.8% and specificity was 87.6%. CONCLUSIONS: DCSCR is a good preliminary test for identifying patients who need prompt confirmatory testing for localizing urinary leaks. A drain creatinine level just 18% higher than the serum creatinine level can signify a urine leak. This is different from general assumptions of a higher DCSCR.

Prostate-specific membrane antigen theranostics in advanced prostate cancer: an evolving option.

OBJECTIVES: To review current data for the role of prostate specific membrane antigen (PSMA) radioligand therapy (RLT) for patients with advanced prostate cancer. This review provides an update for multidisciplinary teams on the current and potential future applications of theranostics in prostate cancer. METHODS: Narrative review focussing on PSMA as a target for RLT, and data using RESULTS: RLT with PSMA is an exciting therapeutic alternative to the existing management options already in use for patients with metastatic castrate-resistant prostate cancer (mCRPC). To date, most evidence exists regarding small-molecule PSMA inhibitors bound to beta-emitting radioisotopes such as 177Lu (Lu-PSMA). Prospective phase II data supports the safety and efficacy of Lu-PSMA in men with heavily pre-treated progressive mCRPC, and several late-phase randomised trials of Lu-PSMA are underway, with many more in the pipeline. Early results are encouraging, indicating that the theranostic approach may play a vital role in management of advanced prostate cancer and perhaps even in much earlier disease states. CONCLUSIONS: PSMA RLT is a promising new treatment option for men with mCPRC, and may also have utility in less advanced prostate cancer.

Protocol for the PRIMARY clinical trial, a prospective, multicentre, cross-sectional study of the additive diagnostic value of gallium-68 prostate-specific membrane antigen positron-emission tomography/computed tomography to multiparametric magnetic resonance imaging in the diagnostic setting for men being investigated for prostate cancer.

OBJECTIVES: Primary objectives: To determine the additive value of gallium-68 prostate-specific membrane antigen (PSMA) positron emission topography (PET)/computed tomography (CT) when combined with multiparametric magnetic resonance imaging (mpMRI) detecting clinically significant prostate cancer (csPCa) in men undergoing initial biopsy for suspicion of PCa, and to determine the proportion of men who could have avoided prostate biopsy with positive mpMRI (PI-RADS ≥3) but negative PSMA-PET/CT. Secondary objectives: To determine the proportion of men who had csPCa detected only by PSMA-PET/CT or only by systematic prostate biopsy; to compare index lesions by template biopsies vs targeted lesions identified on mpMRI or PSMA-PET/CT; to assess whether there may be health economic benefit or harm if PSMA-PET/CT is incorporated into the diagnostic algorithm; and to develop a nomogram which combines clinical, imaging and biomarker data to predict the likelihood of csPCa. PATIENTS AND METHODS: The PRIMARY trial is a multicentre, prospective, cross-sectional study that meets the criteria for level 1 evidence in diagnostic test evaluation. PRIMARY will investigate if a limited (pelvic-only) PSMA-PET/CT in combination with routine mpMRI can reliably discriminate men with csPCa from those without csPCa. We conducted a power calculation based on pilot data and will recruit up to 600 men who will undergo PSMA-PET/CT (the index test), mpMRI (standard test) and transperineal template + targeted (PSMA-PET/CT and/or mpMRI) biopsies (reference test). The conduct and reporting of the mpMRI and PSMA-PET/CT will be blinded to each other. RESULTS: The PRIMARY trial will measure and compare sensitivity, specificity, positive predictive value and negative predictive value of both mpMRI and PSMA-PET/CT vs targeted prostrate biopsy. The results will be used to determine the proportion of men who could safely avoid biopsy without compromising detection of csPCa. Furthermore, we will assess whether there is a health economic benefit in incorporating PSMA-PET/CT into the diagnostic algorithm. CONCLUSIONS: This trial will provide robust prospective data to determine the diagnostic ability of PSMA-PET/CT used in addition to mpMRI. It will establish if certain patients can avoid biopsy in the investigation of PCa.

The fate of urological systematic reviews registered in PROSPERO.

PURPOSE: To identify urologic systematic reviews (SRs) registered to PROSPERO that resulted in a publication, and to evaluate their methodological quality and concordance with their stated a priori protocols. METHODS: We searched PubMed to identify urologic SR protocols registered in PROSPERO that resulted in a publication and assessed their methodological quality and protocols in relation to their stated a priori protocols in PROSPERO. RESULTS: Of the 576 urologic SR protocols registered in PROSPERO up to December 2017, 201 (34.9%) resulted in a full SR publication, but only 40 (17.7%) updated their registration record accordingly. Publications were spread over 100 different journals, with a median time-to-publication of 29 months (95% CI 25.0-33.0). The most common topic by far was prostate cancer (59.7%), followed by voiding issues (15.3%), and renal transplantation (15.3%). Only little over half the reviews (52.74%) explicitly stated primary outcome(s) that matched the primary outcome of their corresponding PROSPERO protocol. Notable methodologic deviations from registered protocols included planned restriction on study design (33%), heterogeneity analysis (42%) and planned risk of bias analysis (65.2%). CONCLUSION: SR authors in urology are increasingly using PROSPERO to register their titles, but our findings indicate that registration alone is not a guarantor of a high-quality SR product. There appears to be a critical need to raise the bar for review authors registering protocols in PROSPERO, with an emphasis on transparency in their publication status updates as well as deviations from their a priori protocols.

Abiraterone acetate in combination with androgen deprivation therapy compared to androgen deprivation therapy only for metastatic hormone-sensitive prostate cancer.

BACKGROUND: Systemic androgen deprivation therapy (ADT), also referred to as hormone therapy,àhas long been the primary treatment for metastatic prostate cancer. Additional agents have been reserved for the castrate-resistant disease stage when ADT start becoming less effective. Abiraterone is an agent with an established role in that disease stage, which has only recently been evaluated in the hormone-sensitive setting. OBJECTIVES: To assess the effects of early abiraterone acetate, in combination with systemic ADT, for newly diagnosed metastatic hormone-sensitive prostate cancer. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, six other databases, two trials registries, grey literature, and conference proceedings, up to 15 May 2020. We applied no restrictions on publication language or status. SELECTION CRITERIA: We included randomized trials, in which men diagnosed with hormone-sensitive prostate cancer were administered abiraterone acetate and prednisolone with ADT or ADTàalone. DATA COLLECTION AND ANALYSIS: Two review authors independently classified studies and abstracted data from the included studies. We performed statistical analyses using a random-effects model. We rated the quality of evidence according to the GRADE approach. MAIN RESULTS: The search identified two randomized controlled trials (RCT), with 2201 men, who were assigned to receive either abiraterone acetate 1000 mg once daily and low dose prednisone (5mg) in addition to ADT, or ADT alone. In the LATITUDE trial, the median age and range of men in the intervention group was 68 (38 to 89) years, and 67 (33 to 92) years in the control group. Nearly all of the men in thisàstudy (97.6%) had prostate cancer with a Gleason score of at least 8 (ISUP grade group 4). Primary outcomes The addition of abiraterone acetate to ADT reduces the probability of death from any cause compared to ADT alone (hazard ratio [HR] 0.64, 95% confidence interval [CI] 0.56 to 0.73; 2 RCTs, 2201 men; high certainty of evidence); this corresponds to 163 fewer deaths per 1000 men with hormone-sensitive metastaticàprostate cancerà(210 fewer to 115 fewer) at five years. Abiraterone acetate in addition to ADT probably results in little to no differenceàin quality of life compared to ADT alone, measured with the Functional Assessment of Cancer Therapy-prostate total score (FACT-P; range 0 to 156; higher values indicates better quality of life),àat 12 months (mean difference [MD] 2.90 points, 95% CI 0.11 to 5.60; 1 RCT, 838 men; moderate certainty of evidence). Secondary outcomes Abiraterone plus ADT increases the risk of grades III to V adverse events compared to ADT alone (risk ratio [RR] 1.34, 95% CI 1.22 to 1.47; 1 RCT, 1199 men; high certainty of evidence); this corresponds to 162 more grade III to Vàevents per 1000 men with hormone-sensitive metastaticàprostate cancerà(105 more to 224 more) at a median follow-up of 30àmonths. Abiraterone acetate in addition to ADT probably reduces the probability of death due to prostate cancer compared to ADT alone (HR 0.58, 95% CI 0.50 to 0.68; 2 RCTs, 2201 men; moderate certainty of evidence). This corresponds to 120 fewer death from prostate cancer per 1000 men with hormone-sensitive metastaticàprostate cancerà(95% CI 145 fewer to 90 fewer) afteràa median follow-up of 30 months. The addition of abiraterone acetate to ADT probably decreases the probability of disease progression compared to ADT alone (HR 0.35, 95%CI 0.26 to 0.49; 2 RCTs, 2097 men; moderate certainty of evidence). This corresponds to 369 fewer incidences of disease progression per 1000 men with hormone-sensitive metastaticàprostate cancerà(456 fewer to 256 fewer)àafter a median follow-up of 30 months. The addition of abiraterone acetate to ADT probably increases the risk of discontinuing treatment due to adverse events compared to ADT alone (RR 1.50, 95% CI 1.17 to 1.92; 1 RCT, 1199 men; moderate certainty of evidence). This corresponds to 51 more men (95% CI 17 more to 93 more) discontinuing treatment because of adverse events per 1000 men treated with abiraterone acetate and ADT compared to ADT alone afteràa median follow-up of 30 months. AUTHORS' CONCLUSIONS: The addition of abiraterone acetate to androgen deprivation therapy improves overall survival but probably not quality of life. Itàprobably also extends disease-specific survival, and delays disease progression compared to androgen deprivation therapy alone. However, the risk of grades III to V adverse events is increased, and probably, so is the risk of discontinuing treatment due to adverse events.

Alpha-blockers after shock wave lithotripsy for renal or ureteral stones in adults.

BACKGROUND: Shock wave lithotripsy (SWL) is a widely used method to treat renal and ureteral stone. It fragments stones into smaller pieces that are then able to pass spontaneously down the ureter and into the bladder. Alpha-blockers may assist in promoting the passage of stone fragments, but their effectiveness remains uncertain.  OBJECTIVES: To assess the effects of alpha-blockers as adjuvant medical expulsive therapy plus usual care compared to placebo and usual care or usual care alone in adults undergoing shock wave lithotripsy for renal or ureteral stones. SEARCH METHODS: We performed a comprehensive literature search of the Cochrane Library, the Cochrane Database of Systematic Reviews, MEDLINE, Embase, several clinical trial registries and grey literature for published and unpublished studies irrespective of language. The date of the most recent search was 27 February 2020. SELECTION CRITERIA: We included randomized controlled trials of adults undergoing SWL. Participants in the intervention group had to have received an alpha-blocker as adjuvant medical expulsive therapy plus usual care. For the comparator group, we considered studies in which participants received placebo. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies for inclusion/exclusion, and performed data abstraction and risk of bias assessment. We conducted meta-analysis for the identified dichotomous and continuous outcomes using RevManWeb according to Cochrane methods using a random-effects model. We judged the certainty of evidence on a per outcome basis using GRADE. MAIN RESULTS: We included 40 studies with 4793 participants randomized to usual care and an alpha-blocker versus usual care alone. Only four studies were placebo controlled. The mean age of participants was 28.6 to 56.8 years and the mean stone size prior to SWL was 7.1 mm to 13.2 mm. The most widely used alpha-blocker was tamsulosin; others were silodosin, doxazosin, terazosin and alfuzosin.  Alpha-blockers may improve clearance of stone fragments after SWL (risk ratio (RR) 1.16, 95% confidence interval (CI) 1.09 to 1.23; I² = 78%; studies = 36; participants = 4084; low certainty evidence). Based on the stone clearance rate of 69.3% observed in the control arm, an alpha-blocker may increase stone clearance to 80.4%. This corresponds to 111 more (62 more to 159 more) participants per 1000 clearing their stone fragments. Alpha-blockers may reduce the need for auxiliary treatments after SWL (RR 0.67, 95% CI 0.45 to 1.00; I² = 16%; studies = 12; participants = 1251; low certainty evidence), but also includes the possibility of no effect. Based on a rate of auxiliary treatments in the usual care arm of 9.7%, alpha-blockers may reduce the rate to 6.5%. This corresponds 32 fewer (53 fewer to 0 fewer) participants per 1000 undergoing auxiliary treatments. Alpha-blockers may reduce major adverse events (RR 0.60, 95% CI 0.46 to 0.80; I² = 0%; studies = 7; participants = 747; low certainty evidence). Major adverse events occurred in 25.8% of participants in the usual care group; alpha-blockers would reduce this to 15.5%. This corresponds to 103 fewer (139 fewer to 52 fewer) major adverse events per 1000 with alpha-blocker treatment. None of the reported major adverse events appeared drug-related; most were emergency room visits or rehospitalizations. Alpha-blockers may reduce stone clearance time in days (mean difference (MD) -3.74, 95% CI -5.25 to -2.23; I² = 86%; studies = 14; participants = 1790; low certainty evidence). We found no evidence for the outcome of quality of life. For those outcomes for which we were able to perform subgroup analyses, we found no evidence of interaction with stone location, stone size or type of alpha-blocker. We were unable to conduct an analysis by lithotripter type. The results were also largely unchanged when the analyses were limited to placebo controlled studies and those in which participants explicitly only received a single SWL session. AUTHORS' CONCLUSIONS: Based on low certainty evidence, adjuvant alpha-blocker therapy following SWL in addition to usual care may result in improved stone clearance, less need for auxiliary treatments, fewer major adverse events and a reduced stone clearance time compared to usual care alone. We did not find evidence for quality of life. The low certainty of evidence means that our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.

Social Media Coverage of Scientific Articles Immediately After Publication Predicts Subsequent Citations - #SoME_Impact Score: Observational Analysis.

BACKGROUND: Social media coverage is increasingly used to spread the message of scientific publications. Traditionally, the scientific impact of an article is measured by the number of citations. At a journal level, this conventionally matures over a 2-year period, and it is challenging to gauge impact around the time of publication. OBJECTIVE: We, therefore, aimed to assess whether Web-based attention is associated with citations and to develop a predictive model that assigns relative importance to different elements of social media coverage: the #SoME_Impact score. METHODS: We included all original articles published in 2015 in a selection of the highest impact journals: The New England Journal of Medicine, The Lancet, the Journal of the American Medical Association, Nature, Cell, and Science. We first characterized the change in Altmetric score over time by taking a single month's sample of recently published articles from the same journals and gathered Altmetric data daily from the time of publication to create a mixed effects spline model. We then obtained the overall weighted Altmetric score for all articles from 2015, the unweighted data for each Altmetric component, and the 2-year citation count from Scopus for each of these articles from 2016 to 2017. We created a stepwise multivariable linear regression model to develop a #SoME_Score that was predictive of 2-year citations. The score was validated using a dataset of articles from the same journals published in 2016. RESULTS: In our unselected sample of 145 recently published articles, social media coverage appeared to plateau approximately 14 days after publication. A total of 3150 articles with a median citation count of 16 (IQR 5-33) and Altmetric score of 72 (IQR 28-169) were included for analysis. On multivariable regression, compared with articles in the lowest quantile of #SoME_Score, articles in the second, third, and upper quantiles had 0.81, 15.20, and 87.67 more citations, respectively. On the validation dataset, #SoME_Score model outperformed the Altmetric score (adjusted R2 0.19 vs 0.09; P<.001). Articles in the upper quantile of #SoME_Score were more than 5 times more likely to be among the upper quantile of those cites (odds ratio 5.61, 95% CI 4.70-6.73). CONCLUSIONS: Social media attention predicts citations and could be used as an early surrogate measure of scientific impact. Owing to the cross-sectional study design, we cannot determine whether correlation relates to causation.

Variation in Accrual and Race/Ethnicity Reporting in Urological and Nonurological Related Cancer Trials.

PURPOSE: We performed a multiregistry analysis to assess relative differences in accrual sufficiency and race/ethnicity reporting in trials of common urological cancers and other nonurological solid organ tumors. MATERIALS AND METHODS: We queried ClinicalTrials.gov and the ISRCTN (International Standard Randomised Controlled Trial Number) Registry for closed phase III and IV trials focused on prostate, colorectal, kidney, bladder, testicular, breast and lung cancer. Identified trials were cross-verified with appropriate published data sources. Comparative accrual sufficiency and rates of race/ethnicity reporting were calculated. Multivariable logistic regression analysis was performed to determine factors associated with accrual status and race/ethnicity reporting. RESULTS: A total of 326 trials were identified based on our prespecified criteria, of which 63% reported sufficient accrual by time of closure and 58% reported data by race/ethnicity. Nonurological trials were significantly more likely to mention race data than urological trials (OR 3.25, 95% CI 1.24-8.55, p = 0.02). Industry sponsored trials were more likely to meet accrual targets than government funded projects (OR 5.44, 95% CI 1.64-18.20, p = 0.001). Although funding source did not influence race reporting, the reported recruitment of participants of African ethnicity was lower in industry sponsored trials (11.49% vs 3.18%, p <0.01). Two-thirds of the studies did not report baseline characteristics by African American race/ethnicity. CONCLUSIONS: Insufficient accrual and inadequate race/ethnicity reporting are prevalent issues, limiting interpretation of the results of clinical trials of major solid organ malignancies. Addressing these shortcomings would enhance result validity by raising statistical power and improving the transparency of reporting to better evaluate the generalizability of results.

Robotic Assisted Radical Cystectomy vs Open Radical Cystectomy: Systematic Review and Meta-Analysis.

PURPOSE: We performed an updated systematic review and meta-analysis of outcomes important to patients in those undergoing robot-assisted and open radical cystectomy. MATERIALS AND METHODS: Multiple scientific databases were searched up to July 2018 for randomized, controlled trials comparing robot-assisted and open radical cystectomy. The primary outcomes of interest were disease progression, major (Clavien III-V) complications and 90-day quality of life. The quality of evidence was evaluated according to the framework in the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: Five studies with a total of 540 participants were included in this review. There was no difference between robot-assisted and open radical cystectomy in disease progression (RR 0.94, 95% CI 0.69-1.29), major complications (RR 1.06, 95% CI 0.75-1.49) or quality of life (standardized mean difference -0.03, 95% CI -0.27-0.21). However, robot-assisted radical cystectomy demonstrated a reduced risk of perioperative blood transfusion (RR 0.58, 95% CI 0.43-0.80) and a marginally shorter hospital stay (RR -0.63 days, 95% CI -1.21-0.05). Operative time was longer in the robot-assisted group (mean difference 68.51 minutes, 95% CI 30.55-105.48). There was no statistically significant difference in local recurrence rates between the procedures (RR 2.08, 95% CI 0.96-4.50) but this difference may be clinically significant and it favored open radical cystectomy. The overall quality of evidence was judged to be moderate. CONCLUSIONS: Surgical approach does not have a considerable impact on oncologic, safety and quality of life outcomes in patients who undergo radical cystectomy. The benefits conferred by robot-assisted radical cystectomy are a decreased need for blood transfusion and earlier hospital discharge.

Skeletal Muscle and Fat Mass Indexes Predict Discharge Disposition after Radical Cystectomy.

PURPOSE: Skeletal muscle and fat mass indexes have emerged as easily obtained, objective and useful tools to assess susceptibility to unfavorable postoperative outcomes. We examined the association between skeletal muscle and fat mass indexes, and the discharge disposition after radical cystectomy. MATERIALS AND METHODS: In a retrospectively collected, single institution cohort we studied patients who underwent radical cystectomy with pelvic lymphadenectomy of primary, nonmetastatic muscle invasive bladder cancer between 2009 and 2015. Included patients had undergone adequate axial computerized tomography at the L3 level within 90 days prior to surgery. Skeletal muscle and fat mass indexes were measured on preoperative computerized tomography and relationships to the outcomes of interest were analyzed. Multivariable logistic regression analysis was performed to assess the effect of the skeletal muscle and fat mass indexes on the discharge disposition while controlling for age, comorbidities, complications and previous neoadjuvant chemotherapy. RESULTS: A total of 136 patients met study inclusion criteria. The median skeletal muscle index among women and men in our study cohort was 36.4 and 47.6 cm2/m2, respectively. On multivariable logistic regression analysis a decreased skeletal muscle index (OR 0.94, 95% CI 0.90-0.98) and an increased fat mass index (OR 1.24, 95% CI 1.04-1.48) were associated with greater odds of discharge to a facility. Higher fat mass-to-skeletal muscle [corrected] index ratios were also associated with greater odds of discharge to a facility (OR 1.69, 95% CI 1.22-2.44). Study limitations include the retrospective design and unknown confounders. CONCLUSIONS: Low skeletal muscle and high fat compositions are independent predictors of discharge to a facility after radical cystectomy of nonmetastatic muscle invasive bladder cancer.

Potential patient harms from misinterpretation of publically reported surgical outcomes.

OBJECTIVE: To determine how the general public interprets surgical complication rates presented from a publicly available online surgical-rating website. SUBJECTS AND METHODS: An in-person electronic survey was administered at the local State Fair to a convenience sample. Participants were presented with a representative output from an online surgeon-rating website and were asked to choose from three statistically equivalent surgeons for a hypothetical medical decision. We then suggested that their insurance company would only cover one surgeon and probed their willingness to pay to switch surgeons for a small chance of lowering the risk of a complication (0.7%, 95% confidence interval [CI] -8.1% to 9.5%, P = 0.9). We quantified the characteristics of those willing to switch, the degree of misinterpretation, and the subsequent potential patient harms. RESULTS: There were 343 completed responses. When presented with a hypothetical healthcare decision, most participants (n = 209, 61%) said they were willing to pay out-of-pocket expenses to switch to a statistically equivalent surgeon. Those who were willing to pay to switch surgeons were more likely to be older (odds ratio [OR] 1.02, 95% CI 1.01-1.03), poorer (OR 1.81, 95% CI 1.07-3.11), previously had cancer (OR 5.9, 95% CI 1.9-25), and misinterpreted the data (OR 3.03, 95% CI 1.87-4.96). Those who were willing to pay out-of-pocket expenses were more inaccurate in their estimation of surgeon complication rates (mean estimate 34.0% vs 8.9%, P < 0.001, correct rate = 3.6%), and on average were willing to pay $6 494 (95% CI 4 108-8 880). CONCLUSION: Understanding of a publicly reported surgical-complication website is often prone to misinterpretation by the general population and may lead to patient harm from a financial aspect.

Taxane-based chemohormonal therapy for metastatic hormone-sensitive prostate cancer: a Cochrane Review.

To provide a precis of the Cochrane Collaboration Review of taxane-based chemohormonal therapy for metastatic hormone-sensitive prostate cancer by Sathianathen NJ, Philippou YA, Kuntz GM et al. Cochrane Database of Systematic Reviews 2018, Issue 10. Art. No.: CD012816. https://doi.org/10.1002/14651858.cd012816.pub2.

A clinical prediction tool to determine the need for concurrent systematic sampling at the time of magnetic resonance imaging-guided biopsy.

OBJECTIVE: To develop a clinical prediction tool that characterises the risk of missing significant prostate cancer by omitting systematic biopsy in men undergoing transrectal ultrasonography/magnetic resonance imaging (TRUS/MRI)-fusion-guided biopsy. PATIENTS AND METHODS: A consecutive sample of men undergoing TRUS/MRI-fusion-guided biopsy with the UroNav® system (Invivo International, Best, The Netherlands) who also underwent concurrent systematic biopsy was included. By comparing the grade of cancer diagnosed on targeted and systematic biopsy cores, we identified cases where clinically significant disease (Gleason score ≥3+4) was only found on systematic and not targeted cores. Multivariable logistic regression analyses were used to identify predictive factors for finding significant cancer on systematic cores only. We then used these data to develop a nomogram and evaluated its utility using decision curve analysis. RESULTS: Of the 398 men undergoing TRUS/MRI-fusion-guided biopsy in our study, there were 46 (11.6%) cases in which clinically significant cancer was missed on targeted biopsy and detected on systematic biopsy. The clinical setting, number of MRI lesions identified, and the highest Prostate Imaging-Reporting and Data System (PI-RADS) score of the lesions, were all found to be predictors of this. Our model had a good discriminative ability (concordance index = 0.70). The results from our decision curve analysis show that this model provides a higher net clinical benefit than either biopsying all men or omitting biopsy in all patients when the threshold probability is <30%. CONCLUSION: We found that omitting concurrent systematic biopsy in men undergoing TRUS/MRI-fusion-guided biopsy would miss significant disease in more than one in 10 patients. We propose a prediction model with good discriminative ability that can be used to improve patient selection for performing concurrent systematic biopsy in order to minimise the number of missed significant cancers. It is important that our model is validated in external cohorts before being employed in routine clinical practice.

The utility of PET-based imaging for prostate cancer biochemical recurrence: a systematic review and meta-analysis.

INTRODUCTION: Conventional imaging modalities have been poor in characterizing the true extent of disease in men with biochemical recurrence following primary treatment for prostate cancer. Functional imaging with positron emission tomography (PET) has shown promise of being a superior imaging modality. We conducted a systematic review and meta-analysis to define the diagnostic accuracy of PET/CT using 11C-choline, 18F-FACBC, or 68Ga-PSMA in detecting recurrent prostate cancer. METHODS: We searched multiple databases in line with the preferred reporting items for systematic review and meta-analysis (PRISMA) statement to define the diagnostic accuracy of 11C-choline, 18F-FACBC, or 68Ga-PSMA PET/CT. Only studies secondarily staging participants with biochemical recurrence and those with an appropriate reference standard (pathology, further imaging, and/or clinical response) were eligible for analysis. RESULTS: Twenty-one studies with 3202 participants met the inclusion criteria. Of these, 11C-choline, 18F-FACBC, and 68Ga-PSMA were the tracer investigated in 16, 5, and 1 studies, respectively. The summary sensitivity for each tracer was 80.9% (95% CI 70.4-88.3%), 79.7% (95% CI 51.9-93.4%), and 76.4% (95% CI 68.3-82.9%), respectively. The corresponding summary specificity was 84.1% (95% CI 70.2-92.2%), 61.9% (95% CI 41.1-79.0%), and 99.8% (95% CI 97.5-100%), respectively. Detection rates ranged between 58.6 and 82.8%. All included studies were judged to be at high risk of bias primarily due to study limitations pertaining to the reference standard. CONCLUSION: There is a lack of high-quality data to verify the accuracy of PET-based imaging using 11C-choline, 18F-FACBC, or 68Ga-PSMA. The early results are encouraging that these techniques are superior to conventional imaging modalities, which would allow salvage therapies to be optimized.

Extended versus standard lymph node dissection for urothelial carcinoma of the bladder in patients undergoing radical cystectomy.

BACKGROUND: In the treatment of urothelial carcinoma of the bladder, we are currently uncertain of the benefits and harms of standard pelvic lymph node dissection (PLND) compared to extended PLND. OBJECTIVES: To assess the effects of extended versus standard PLND in patients undergoing cystectomy to treat muscle-invasive (cT2 and cT3) and treatment-refractory, non-muscle-invasive (cT1 with or without carcinoma in situ) urothelial carcinoma of the bladder. SEARCH METHODS: We performed a comprehensive literature search using multiple databases (PubMed, Embase, Cochrane Controlled Trials, Web of Science, and LILACS), trial registries, and conference proceedings published up to April 29, 2019, with no restrictions on the language or status of publication. SELECTION CRITERIA: We included randomized controlled trials in which participants underwent radical cystectomy (RC) for muscle-invasive or therapy-refractory non-muscle-invasive urothelial carcinoma of the bladder with either an extended PLND with a superior extent reaching as far cranially as the inferior mesenteric vein, or a standard PLND with a superior extent of the bifurcation of the internal and external iliac artery, with otherwise the same anatomical boundaries. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the included studies and extracted data from them for the primary outcomes: time to death from any cause, time to death from bladder cancer and Clavien-Dindo classification of surgical complications grade III-V, and the secondary outcomes: time to recurrence, Clavien-Dindo I-II complications and disease-specific quality of life.We performed statistical analyses using a random-effects model and rated the certainty of evidence according to the GRADE approach. MAIN RESULTS: The search identified one multicenter trial based in Germany that enrolled 401 participants with histologically confirmed T1 grade 3 or muscle-invasive urothelial carcinoma. The median age was 67 years (range: 59 to 74) and the majority of participants were male (78.3%). No participant received neoadjuvant chemotherapy; a small subset received adjuvant chemotherapy (14.5%).Primary outcomesOur results indicate that extended PLND may reduce the risk of death from any cause over time as compared to standard PLND, but the confidence interval includes the possibility of no effect (hazard ratio [HR]: 0.78, 95% confidence interval [CI]: 0.57 to 1.07, 401 participants, low-certainty evidence). After five years of follow-up, this may result in 83 fewer deaths (95% CI: 174 fewer to 24 more overall deaths) per 1000 participants: 420 deaths for extended PLND compared to 503 deaths per 1000 for standard PLND. We downgraded the certainty of evidence by two levels due to study limitations and imprecision.Our results indicate that extended PLND may reduce the risk of death from bladder cancer over time as compared to standard PLND but, again, the confidence interval includes the possibility of no effect (HR: 0.70, 95% CI: 0.45 to 1.07, participants = 401, low-certainty evidence). After five years of follow-up, this corresponds to 91 fewer deaths per 1000 participants (95% CI: 176 fewer to 19 more bladder cancer deaths): 264 deaths for extended PLND compared to 355 deaths per 1000 for standard PLND. We downgraded the certainty of evidence by two levels due to study limitations and imprecision.Based on follow-up of up to 30 days, we are uncertain whether extended PLND leads to more grade III-V complications as compared to standard PLND, because of study limitations and imprecision (risk ratio [RR]: 1.13, 95% CI: 0.84 to 1.52, participants = 401, very low-certainty evidence).Secondary outcomesWe are uncertain whether extended PLND reduces the risk of recurrence over time as compared to standard PLND, because of study limitations and imprecision (HR: 0.84, 95% CI: 0.58 to 1.22, participants = 401, very low-certainty evidence).Based on follow-up of up to 30 days, we are uncertain whether extended PLND leads to similar grade I-II complications as compared to standard PLND because of study limitations and imprecision (RR: 0.94, 95% CI: 0.74 to 1.19, participants = 401, very low-certainty evidence).We found no trials that reported on disease-specific quality of life. AUTHORS' CONCLUSIONS: Results from a single trial indicate that extended PLND in patients undergoing radical cystectomy for invasive urothelial carcinoma of the bladder may reduce death from any cause and death from bladder cancer over time; however, the results include the possibility of no effect. We are uncertain whether the risk of serious complications up to 30 days may be increased. We are also uncertain as to whether the risk of recurrence over time or the risk of minor complications up to 30 days changes. We were unable to conduct any of the preplanned subgroup analyses, in particular, analyses based on extended lymph node dissection templates, clinical tumor stage, and use of neoadjuvant chemotherapy that may be important effect modifiers. Important additional data is expected from a larger, ongoing trial that will also consider the role of neoadjuvant chemotherapy. Inclusion of this trial in the meta-analysis may help address the issue of imprecision which was a common reason for downgrading the certainty of the evidence.