Unlocking the Potential of Adequate Bacillus Calmette-Guérin Immunotherapy in Very-high-risk Non-muscle-invasive Bladder Carcinoma: A Multicenter Analysis of Oncological Outcomes and Risk Dynamics.

BACKGROUND: The European Association of Urology (EAU) recommends discussing upfront radical cystectomy for all patients with very high risk (VHR) non-muscle-invasive bladder carcinoma (NMIBC), but the role of bacillus Calmette-Guérin (BCG) treatment remains controversial. OBJECTIVE: To analyze oncological outcomes in VHR NMIBC patients (EAU risk groups) treated with adequate BCG. DESIGN, SETTING, AND PARTICIPANTS: A multi-institutional retrospective study involving patients with VHR NMIBC who received adequate BCG therapy from 2007 to 2020 was conducted. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A survival analysis estimated recurrence-free survival (RFS), progression-free survival (PFS), and the cumulative incidence of cancer-specific mortality (CSM) after accounting for other causes of mortality as competing risk events and of the overall mortality (OM). Conditional survival probabilities for 0-4 yr without events were computed. Cox regression assessed the predictors of oncological outcomes. RESULTS AND LIMITATION: A total of 640 patients, with a median 47 (32-67) mo follow-up for event-free individuals, were analyzed. High-grade RFS and PFS at 5 yr were 53% (49-57%) and 78% (74-82%), respectively. The cumulative incidence of CSM and OM at 5 yr was 13% (10-16%) and 16% (13-19%), respectively. Conditional RFS, PFS, overall survival, and cancer-specific survival at 4 yr were 91%, 96%, 87%, and 94%, respectively. Cox regression identified tumor grade (hazard ratio [HR]: 1.54; 1.1-2) and size (HR: 1.3; 1.1-1.7) as RFS predictors. Tumor multiplicity predicted RFS (HR: 1.6; 1.3-2), PFS (HR: 2; 1.2-3.3), and CSM (HR: 2; 1.2-3.2), while age predicted OM (HR: 1.48; 1.1-2). CONCLUSIONS: Patients with VHR NMIBC who receive adequate BCG therapy have a more favorable prognosis than predicted by EAU risk groups, especially among those with a sustained response, in whom continuing maintenance therapy emerges as a viable alternative to radical cystectomy. PATIENT SUMMARY: Our research shows that a sustained response to bacillus Calmette-Guérin in patients can lead to favorable outcomes, serving as a viable alternative to cystectomy for select cases.

Are PARP Inhibitors Ready for Prime Time in Metastatic Prostate Cancer? Maybe Not.

While PARP inhibitors such as rucaparib and olaparib have shown activity in metastatic castration-resistant prostate cancer, they have failed to show a clear improvement in hard outcomes such as overall survival or quality of life. Because of methodological limitations, we suggest caution before implementing these treatments in routine clinical practice; offering them to patients without a BRCA1/2 mutation is probably inappropriate.

Evaluating the Certainty of Evidence in Evidence-based Medicine.

Certainty of evidence (formerly known as quality of evidence) is defined as the extent to which our confidence in an estimate of the effect is correct or our certainty that such estimate supports a particular recommendation for a clinical practice guideline. Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) is a structured and reproducible framework for assigning a level of certainty on a per-outcome basis for evidence derived from randomized and nonrandomized studies. The level of certainty starts as high or low and can be increased or decreased after considering several criteria (eg, risk of bias, inconsistency of results, publication bias, dose-response gradient, large magnitude of effect, among others). Here we describe in brief the GRADE process for summarizing and assigning a certainty rating for evidence. PATIENT SUMMARY: The GRADE framework is a way to work out how much we can trust results from medical research studies. This helps doctors in making informed decisions with their patients.

Oncological and Renal Function Outcomes in Patients Who Underwent Simultaneous Radical Cystectomy and Nephroureterectomy for Synchronous or Metachronous Panurothelial Carcinoma.

OBJECTIVE: To assess clinical outcomes of patients who underwent simultaneous radical cystectomy (RC) and radical nephroureterectomy (RNU) for panurothelial carcinoma (PanUC). MATERIALS AND METHODS: A retrospective analysis of 67 patients who underwent simultaneous RC and unilateral RNU for PanUC, from 1996 to 2017. Kaplan-Meier estimates for remnant urothelium recurrence-free survival, metastasis-free survival, overall survival (OS), and cancer-specific survival (CSS) were performed. Cox multivariate models were constructed. RESULTS: The median follow-up was 38 months, 29.8% of patients had a recurrence, 34.3% had metastasis, 67.2% of patients died from any cause, and 37.3% died from urothelial carcinoma. Overall survival and CSS rates at 5 years were 44% and 61%, respectively. In multivariate analysis, progression to muscle-invasive bladder cancer before surgery, presence of muscle-invasive stages at RC and/or RNU, and prostatic urethra involvement were predictors for worse metastasis-free survival and CSS. Forty-one patients (61.2%) had an estimated glomerular filtration rate (eGFR) <60 mL/min before surgery and the number rose to 56 (83.5%) after surgery; 29.8% patients needed renal function replacement therapy after surgery (16 haemodialysis and 4 renal transplant). CONCLUSION: Patients with PanUC who undergo simultaneous surgery have adverse oncological (only 4 out of every 10 remain alive at 5 years) and functional outcomes (1 out of 3 will need renal function replacement therapy after surgery). Up to a third of the patients had a recurrence (urethra or contralateral kidney) within 18 months, justifying close surveillance or considering prophylactic urethrectomy. These data should help in counsel on morbidity and life expectancy.

Evidence-based Medicine: Perceptions, Attitudes, and Skills Among European Urology Residents.

Background: Evidence-based medicine (EBM) was introduced as a concept in the early 1990s as an integration of the best available evidence with clinical expertise and patient values. Objective: To evaluate the current status of EBM training and EBM perception, attitudes, and self-perceived skills among European urology residents. Design setting and participants: Our online open survey comprised 28 multiple-choice items, including ten questions with responses on a five-point Likert scale ranging from 1 = strongly disagree to 5 = strongly agree. The survey was distributed via the mailing lists and social media accounts of the European Society of Residents in Urology, German Society of Residents in Urology, French Society of Urologists in Training, Spanish Urology Residents Working Group, Italian Society of Residents in Urology, and the Urology Social Media Working Group in two rounds (May-July 2019 and July 2020). We excluded responses from non-European countries. Outcome measurements and statistical analysis: The online open survey comprised 28 multiple-choice items. These included ten questions with answers on a five-point Likert scale with response items ranging from strongly disagree (score of 1) to strongly agree (score of 5). Results and limitations: We received 210 responses, of which 181 from 23 European countries were eligible. Approximately three-quarters (73.7%) of the respondents were male, with a mean age of 31 yr. Only 28.2% reported EBM training as part of their urology curriculum and 19.3% felt that the training they received was sufficient to guide their daily practice. An overwhelming majority (91.5%) stated that they would be interested in more formalized EBM training or additional training. There was a strong level of agreement (median score 5, interquartile range 4-5) that EBM is important for daily medical and surgical practice and that it improves patient care. Overall, the mean self-perceived understanding of basic EBM concepts was good. Limitations include concerns about generalizability given its internet-based format, the inability to calculate a response rate, poor representation from some European regions, and limited sample size. Conclusions: Our survey suggests that European urology residents receive a limited amount of EBM training despite considerable appreciation, interest, and self-perceived deficits for more advanced concepts. Formal integration of EBM teaching in all European residency programs should be considered. Patient summary: We performed an online survey of urology residents in Europe. We found that residents have positive perceptions of and attitudes to evidence-based medicine but most programs lack formal training in this area.

Accuracy of the CUETO, EORTC 2016 and EAU 2021 scoring models and risk stratification tables to predict outcomes in high-grade non-muscle-invasive urothelial bladder cancer.

PURPOSE: Non-muscle-invasive bladder cancers (NMIBC) constitute 3-quarters of all primary diagnosed bladder tumors. For risk-adapted management of patients with NMIBC, different risk group systems and predictive models have been developed. This study aimed to externally validate EORTC2016, CUETO and novel EAU2021 risk scoring models in a multi-institutional retrospective cohort of patients with high-grade NMIBC who were treated with an adequate BCG immunotherapy. METHODS: The Kaplan-Meier estimates for recurrence-free survival and progression-free survival were performed, predictive abilities were assessed using the concordance index (C-index) and area under the curve (AUC). RESULTS: A total of 1690 patients were included and the median follow-up was 51 months. For the overall cohort, the estimates recurrence-free survival and progression-free survival rates at 5-years were 57.1% and 82.3%, respectively. The CUETO scoring model had poor discrimination for disease recurrence (C-index/AUC for G2 and G3 grade tumors: 0.570/0.493 and 0.559/0.492) and both CUETO (C-index/AUC for G2 and G3 grade tumors: 0.634/0.521 and 0.622/0.525) EAU2021 (c-index/AUC: 0.644/0.522) had poor discrimination for disease progression. CONCLUSION: Both the CUETO and EAU2021 scoring systems were able to successfully stratify risks in our population, but presented poor discriminative value in predicting clinical events. Due to the lack of data, model validation was not possible for EORTC2016. The CUETO and EAU2021 systems overestimated the risk, especially in highest-risk patients. The risk of progression according to EORTC2016 was slightly lower when compared with our population analysis.

Recirculating hyperthermic intravesical chemotherapy with mitomycin C (HIVEC) versus BCG in high-risk non-muscle-invasive bladder cancer: results of the HIVEC-HR randomized clinical trial.

PURPOSE: The purpose of the study was to compare the outcomes of high-risk non-muscle-invasive bladder cancer (HR-NMIBC) patients treated with BCG vs recirculating hyperthermic intravesical chemotherapy (HIVEC) with mitomycin C (MMC). METHODS: A pilot phase II randomized clinical trial was conducted including HR-NMIBC patients, excluding carcinoma in situ. Patients were randomized 1:1 to receive intravesical BCG for 1 year (once weekly for 6 weeks plus subsequent maintenance) or HIVEC with 40 mg MMC, administered using the Combat BRS system (once weekly instillations were given for 6 weeks, followed by once monthly instillation for 6 months). Total recirculating dwell time for HIVEC was 60 min at a target temperature of 43° ± 0.5 °C. Primary endpoint was recurrence-free survival. Secondary endpoints were time to recurrence, progression-free survival, cancer-specific survival, and overall survival at 24 months. Adverse events were routinely assessed. RESULTS: Fifty patients were enrolled. Mean age was 73.5 years. Median follow-up was 33.7 months. Recurrence-free survival at 24 months was 86.5% for HIVEC and 71.8% for BCG (p = 0.184) in the intention-to-treat analysis and 95.0% for HIVEC and 75.1% for BCG (p = 0.064) in the per protocol analysis. Time to recurrence was 21.5 and 16.1 months for HIVEC and BCG, respectively. Progression-free survival for HIVEC vs BCG was 95.7% vs 71.8% (p = 0.043) in the intention-to-treat analysis and 100% vs 75.1% (p = 0.018) in the per protocol analysis, respectively. Cancer-specific survival at 24 months was 100% for both groups and overall survival was 91.5% for HIVEC vs 81.8% for BCG. CONCLUSION: HIVEC provides comparable safety and efficacy to BCG and is a reasonable alternative during BCG shortages. TRIAL REGISTRATION: EudraCT 2016-001186-85. Date of registration: 17 March 2016.

Evidence-based urology: understanding GRADE methodology.

Grading of Recommendations Assessment, Development, and Evaluation (GRADE) is a methodologically rigorous and transparent framework for grading the certainty of evidence and moving from evidence to recommendations in guidelines. Certainty of evidence can be rated as high, moderate, low, or very low, and some domains may lead to an increase or decrease in the certainty of evidence. Once evidence is summarized, the certainty, balance of desirable and undesirable outcomes, patients' values and preferences, equity, acceptability, and feasibility are taken into consideration in order to give a strong or weak recommendation for or against an intervention. In this review we summarize the GRADE approach using urology-related examples. PATIENT SUMMARY: GRADE is a well-established system for determining how much confidence we can place in research evidence and how guideline panels can make recommendations for patient care and health care policy. Recommendations can be strong or weak for or against a treatment strategy. Guideline developers should consider the certainty of the evidence, the balance of desirable and undesirable outcomes, patients' values and preferences, and resource use.

Long surgical waiting list times are associated with an increased rate of negative ureteroscopies.

INTRODUCTION: Negative ureteroscopy (NURS) is "a ureteroscopy in which no stone is found during the procedure." We aimed to determine the association between the surgical waiting list time (WLT) and the NURS rate. METHODS: We retrospectively analyzed all patients scheduled for ureteroscopy in our center between January 2017 and July 2019. The inclusion criterion was unilateral, semirigid ureteroscopy for a single ureteral stone; exclusion criteria were renal-only stones, incomplete ureteroscopy, and stones >10 mm. We analyzed age; gender; body mass index; stone size, density, and location; presence of a temporary double-J (DJ) stent; use of medical expulsive therapy; and WLT. Complications while waiting for surgery were also collected and analyzed. RESULTS: We included 219 patients, 41 (18.7%) of whom had NURS. The median WLT was 74 days (interquartile range [IQR] 45-127). Variables protective against NURS were large stone size (odds ratio [OR] 0.78, 95% confidence interval [CI] 0.66-0.93), presence of a temporary DJ stent (OR 0.43, 95% CI 0.2-0.8), and radiopaque stones (OR 0.44, 95% CI 0.21-0.88). A long WLT ((≥60 days) increased the risk of NURS (OR 2.18, 95% CI 1.02-4.61). Complications requiring emergency department visits while waiting for surgery were documented in 58/137 (42.3%) patients with indwelling DJ stents; nonetheless, a WLT greater than the median was not associated with an increased risk of complications (p=0.38). CONCLUSIONS: Long WLT has an independent, direct, and linear correlation with NURS rates. Patients at higher risk of NURS, may be offered preoperative re-evaluation with a computed tomography scan in a resource-limited setting.

Analgesic refractory colic pain: Is prolonged conservative management appropriate?

OBJECTIVES: To propose a clear definition and management pathway of patients with analgesic refractory colic pain (ARCP). PATIENTS AND METHODS: Prospective cohort study from February 2018 to February 2019 including patients with ARCP defined as ongoing renal colic pain after one dose of IV NSAID, IV paracetamol, and a parenteral opioid, given sequentially in that order. Patients were observed in-hospital under full parenteral analgesic management for 8-12 h, whenever patients had minimal or absent pain after conservative management (CM) they were discharged, and followed-up with new imaging within four weeks. If the pain was not controlled after CM, surgical management (double-J stent or ureteroscopy) was performed. We excluded patients with any other indication for urgent intervention or in cases where CM was deemed inappropriate (sepsis, acute renal failure, stones >10 mm in size, suspected concomitant urinary tract infection, bilateral ureteral stones, pregnancy, patients with a single kidney, kidney transplant recipients, difficult access to medical care or refusal to undergo CM). RESULTS: Data from 60 patients was collected. The only variable associated with an increased risk of failed CM was a history of previous renal colic (OR 3.98 [95% CI 1.14-13.84], p = 0.02). Neither gender, age, stone size, location, or hydronephrosis grade were able to predict CM failure. 41.6% of patients were successfully managed conservatively and only 8% of them required scheduled surgical management at follow-up. CONCLUSION: Our results show that a high proportion of patients with ARCP may be successfully managed conservatively with an extended observation period without complications at follow-up. These results should be replicated in a randomized controlled trial to confirm them.

Quality of life and adverse events in patients with nonmuscle invasive bladder cancer receiving adjuvant treatment with BCG, MMC, or chemohyperthermia.

INTRODUCTION: Chemohyperthermia (CHT) with mitomycin C (MMC) is together with Bacillus Calmette-Guérin (BCG), and passive MMC, a treatment option for patients with non muscle-invasive bladder cancer. There are no data published about the impact of CHT in quality of life (QoL). We evaluated QoL and adverse events (AE) in this 3-arm observational study. PATIENTS AND METHODS: Prospective observational study from September 2016 to March 2017, we recruited consecutive patients that received adjuvant treatment after transurethral resection of bladder tumor. Patients received induction courses of either BCG, CHT, or passive MMC. Patients filled the questionnaires Functional assessment of cancer therapy for bladder cancer patients (FACT-Bl) and International prostate symptom score (IPSS) before, during, and after the induction course. A urologist documented AE using Common Terminology Criteria for AE (CTCAE criteria). RESULTS: A total of 56 patients, receiving a total of 296 bladder instillations (BCG n = 27, CHT n = 14 and MMC n = 15). FACT-Bl showed statistically significant differences in the fourth week in favor of CHT versus BCG, IPSS did not show statistically significant differences before, during, and after induction course in all 3 arms. All patients recovered their baseline QoL at the end of the induction treatment. Overall 55.5%, 50% and 20% of patients presented any grade of AE in the BCG, CHT and MMC groups respectively. About 7% of patients in BCG and CHT arms had to discontinue treatment due to AE. BCG and CHT showed a similar rate of AE but in CHT were mostly grade I and BCG had grade I, II, and IV. Passive MMC had the safest profile. CONCLUSION: There are no clinically significant differences between BCG, CHT, and passive MMC regarding QoL and lower urinary tract symptoms during the induction course. CHT has a more favorable AE profile when compared with BCG.

Diagnostic accuracy of ureteroscopic biopsy in predicting stage and grade at final pathology in upper tract urothelial carcinoma: Systematic review and meta-analysis.

OBJECTIVE: To assess the accuracy of ureteroscopic (URS) biopsies in predicting stage and grade at final pathology in upper tract urothelial carcinoma (UTUC). MATERIALS AND METHODS: The meta-analysis was performed in accordance with the PRISMA statement. Studies providing data on tumor stage and grade at URS biopsy and surgical specimens were included. The negative predictive value (NPV) implies concordance between the absence of subepithelial connective tissue invasion or the presence of low-grade tumors at URS biopsy and the absence of a muscle-invasive disease in the final pathology. RESULTS: A total of 23 studies were included (3547 patients). The stage-to-stage match between URS biopsy/final pathology showed a positive predictive value (PPV) for cT1+/muscle-invasive disease of 94% (95% CI: 84%-100%) and a NPV for cTa-Tis/non-muscle-invasive disease of 60% (95% CI: 52%-68%). The grade-to-grade match between URS biopsy/final pathology was 66% (95% CI: 55%-77%) for low-grade (cLG/pLG) tumors and 97% (95% CI: 94%-98%) for high-grade (cHG/pHG) tumors. The PPV for cHG/muscle-invasive disease was 60% (95% CI: 54%-66%) and the NPV for cLG/non-muscle-invasive disease was 77% (95% CI: 73%-82%). The undergrading and understaging rates were 32% (95%CI: 25%-38%) and 46% (95% CI: 38%-54%), respectively. CONCLUSIONS: There is a substantial correlation between tumor grade at URS biopsy and the final pathology. The identification of cHG tumors and subepithelial connective tissue invasion (cT1+) in URS biopsy showed a moderate and a strong correlation with invasive UTUC, respectively. Nevertheless, a certain risk of undergrading and understaging should be assumed.

Social media influence in the COVID-19 Pandemic

ABSTRACT Never before in human history has it been possible to communicate so quickly during a pandemic, social media platforms have been a key piece for the dissemination of information; however, there are multiple advantages and disadvantages that must be considered. Responsible use of these tools can help quickly disseminate important new information, relevant new scientific findings, share diagnostic, treatment, and followup protocols, as well as compare different approaches globally, removing geographic boundaries for the first time in history. In order to use these tools in a responsible and useful way, it is recommended to follow some basic guidelines when sharing information on social networks in the COVID-19 era. In this paper, we summarize the most relevant information on the influence, and advantages, and disadvantages of the use of social networks during the COVID-19 pandemic.

Social media influence in the COVID-19 Pandemic.

Never before in human history has it been possible to communicate so quickly during a pandemic, social media platforms have been a key piece for the dissemination of information; however, there are multiple advantages and disadvantages that must be considered. Responsible use of these tools can help quickly disseminate important new information, relevant new scientific findings, share diagnostic, treatment, and follow-up protocols, as well as compare different approaches globally, removing geographic boundaries for the first time in history. In order to use these tools in a responsible and useful way, it is recommended to follow some basic guidelines when sharing information on social networks in the COVID-19 era. In this paper, we summarize the most relevant information on the influence, and advantages, and disadvantages of the use of social networks during the COVID-19 pandemic.

A global knowledge, attitudes and practices survey on anatomical endoscopic enucleation of prostate for benign prostatic hyperplasia among urologists.

There is an increasing use of the procedure, anatomical endoscopic enucleation of the prostate, as an alternative to conventional transurethral resection of prostate for surgical treatment of benign prostatic hyperplasia. However, barriers to adoption of this procedure remain and no prior studies explored this important aspect till date. The aim of this study is to identify the predictors and barriers of surgeon-related practices in this area. The study findings may also provide valuable insight into current practice trends worldwide. To achieve the objectives, we conducted an online, cross-sectional, questionnaire-based study between 1st September 2019 and 5th October 2019 to investigate the knowledge, attitudes and practices among urologists worldwide. Our findings showed that the main barriers for adoption of the procedure were lack of mentorship, a steep learning curve, and unavailability of morcellator, bipolar or laser energy sources. Fear of urinary incontinence, bleeding and bladder injury were not major hindrance to adoption of this technique. The results also demonstrated that there will be continued increase in utility of the procedure in the future.

New case of secondary bladder amyloidosis with massive hematuria-role of intravesical instillations with dimethyl sulfoxide.

Secondary bladder amyloidosis is a rare condition with less than 60 cases published in the world. It is usually secondary to chronic inflammatory processes such as rheumatologic diseases. Hematuria is its predominant and most important symptom, and usually occurs after a bladder catheterization. The diagnostic confirmation is made through a pathological and immunohistochemical study. The treatment must be staggered from less to more invasive. Our objectives are to present a new case of secondary bladder amyloidosis in a woman with a history of chronic bronchiectasis after tuberculosis and frequent super infections, whose main manifestation was a massive hematuria, and review this rare pathology. We have obtained very good initial results using intravesical instillations with dimethyl sulfoxide (DMSO) with complete resolution of the hematuria, the patient remaining asymptomatic for 6 months. After that, there was a recurrence of the hematuria that was treated with embolization of the hypogastric arteries, with good results. We can conclude that, despite being a rare condition, we must consider secondary bladder amyloidosis in patients who have already been diagnosed with systemic amyloidosis and/or chronic pathologies who develop hematuria after bladder catheterization. Based on our experience, instillations with dimethyl sulfoxide are a safe option and provide a quick and temporary resolution of hematuria symptoms.