Showing papers in "European urology open science in 2022"

Efficacy and Safety of First-line Systemic Therapy for Metastatic Renal Cell Carcinoma: A Systematic Review and Network Meta-analysis

Abstract: Considerable advances have been made in the first-line treatment of metastatic renal cell carcinoma (mRCC), with immunotherapy-based combinations including immunotherapy-tyrosine kinase inhibitors (IO-TKIs) and dual immunotherapy (IO-IO) favored. A lack of head-to-head clinical trials comparing these treatments means that there is uncertainty regarding their use in clinical practice.To compare and rank the efficacy and safety of first-line systemic treatments for mRCC with a focus on IO-based combinations.MEDLINE (Ovid), EMBASE, Cochrane Library, Web of Science, and abstracts of recent major scientific meetings were searched to identify the most up-to-date phase 3 randomized controlled trials (RCTs) of first-line IO-based combinations for mRCC up to June 2021. A systematic review and network meta-analysis were completed using the Bayesian framework. Primary endpoints included overall survival (OS) and progression-free survival (PFS). Secondary endpoints included the objective response rate (ORR), complete response (CR), grade 3-4 treatment-related adverse events (TRAEs), treatment-related drug discontinuation (TRDD), and health-related quality of life (HRQoL). The analysis was performed for the intention-to-treat (ITT) population as well as by clinical risk group.A total of six phase 3 RCTs were included involving a total of 5121 patients. Nivolumab plus cabozantinib (NIVO-CABO) had the highest likelihood of an OS benefit in the ITT population (surface under the cumulative ranking curve 82%). Avelumab plus axitinib (AVEL-AXI) had the highest likelihood of an OS benefit for patients with favorable risk (65%). Pembrolizumab plus AXI (PEMBRO-AXI) had the highest likelihood of an OS benefit for patients with intermediate risk (78%). PEMBRO plus lenvatinib (PEMBRO-LENV) had the highest likelihood of an OS benefit for patients with poor risk (89%). PEMBRO-LENV was associated with a superior PFS benefit across all risk groups (89-98%). Maximal ORR was achieved with PEMBRO-LENV (97%). The highest likelihood for CR was attained with NIVO plus ipilimumab (NIVO-IPI; 85%) and PEMBRO-LENV (83%). The highest grade 3-4 TRAE rate occurred with PEMBRO-LENV (95%) and NIVO-CABO (83%), but the latter was associated with the lowest TRDD rate (2%). By contrast, NIVO-IPI had the lowest grade 3-4 TRAE rate (6%) and the highest likelihood of TRDD (100%). HRQoL consistently favored NIVO-CABO (66-75%), PEMBRO-LENV (44-85%), and NIVO-IPI (65-93%) in comparison to the other treatments.IO-TKI drug combinations are associated with consistent improvements in clinically relevant outcomes for all mRCC risk groups. This benefit may be at the cost of higher TRAE rates; however, lower TRDD rates suggest a manageable side-effect profile. Longer follow-up is required to determine if the benefits of IO-TKIs will be sustained and if they should be favored in the first-line treatment of mRCC.Combination treatments based on immunotherapy agents continue to show meaningful benefits in the first-line treatment of metastatic kidney cancer. Our review and network meta-analysis shows that immunotherapy combined with another class of agents called tyrosine kinase inhibitors is promising. However, longer follow-up is needed for this treatment strategy to clarify if the benefits are long-lasting.

Global Trends in Incidence and Burden of Urolithiasis from 1990 to 2019: An Analysis of Global Burden of Disease Study Data

Abstract: Urolithiasis is among the most common urologic diagnoses globally, with substantial burden and cost on healthcare systems worldwide. Increasing evidence links urolithiasis with an array of risk factors, including diet and lifestyle trends, noncommunicable diseases such as diabetes and obesity, and global warming.To examine geographic, temporal, and sociodemographic patterns to better understand global disease burden of urolithiasis.We extracted data on age-standardized incidence rate (ASIR), deaths, and disability-adjusted life years (DALYs) attributed to urolithiasis for 21 regions, including 204 countries, for 1990-2019 from the Global Burden of Disease (GBD) study.Data were analyzed at the global, regional, and country levels, as well as stratified by the Socio-Demographic Index. The average annual percentage change (AAPC) was calculated to measure temporal trends across groups.Globally, total cases, DALYs, and deaths attributed to urolithiasis increased over the study period, while the age-standardized rates of these measures decreased. The age-standardized incidence of urolithiasis decreased from 1696.2 (95% confidence interval [CI] 1358.1-2078.1) cases per 100 000 population in 1990 to 1394.0 (95% CI, 1126.4-1688.2) cases per 100 000 population in 2019, with an AAPC of -0.7 (95% CI [-0.8, -0.6]). Of the GBD regions, Eastern Europe demonstrated a consistently higher ASIR of urolithiasis than all other regions, while the Caribbean had the highest AAPC. This study is limited by the available national and regional data, as described in the original GBD study.Worldwide, total cases, DALYs, and deaths attributed to urolithiasis have increased since 1990, while age-standardized rates have decreased, with demonstrated regional and sociodemographic variation. Multifaceted strategies to address urolithiasis prevention and treatment are necessary.In this study, we looked at trends in the global burden of stone disease using data from 204 countries from 1990 to 2019. We found that the overall burden has increased, but it varies by age, sociodemographic variables, and geographic region. We conclude that we need adaptable policies that suit the specific needs of the country to address this burden.

Role of Prophylactic Antibiotics in Transperineal Prostate Biopsy: A Systematic Review and Meta-analysis

Abstract: Transperineal prostate biopsy is associated with a significantly lower risk of infectious complications than the transrectal approach. In fact, the risk of infectious complications with transperineal prostate biopsy is so low that the utility of administering periprocedural antibiotics with this procedure has come under question.To perform a systematic review and meta-analysis to assess for differences in the rates of infectious complications (septic, nonseptic, and overall) after performing transperineal prostate biopsy with and without the administration of periprocedural antibiotic prophylaxis.Three electronic databases (PubMed, Embase, and MEDLINE) were searched, and studies were included if they included patients who underwent transperineal prostate biopsy, were published after January 2000, included information on periprocedural antibiotic administration, and reported postbiopsy complications. Preferred Reporting Items for Systematic Reviews and Meta-analyses and Agency for Healthcare Research and Quality guidelines were utilized.A total of 106 unique studies describing 112 cohorts of patients were identified, of which 98 (37 805 men) received antibiotic prophylaxis and 14 (4772 men) did not receive it. All patients were included in the analysis of septic complications. In total, there were 19/37 805 (0.05%) episodes of sepsis in the group of men who received antibiotics, which was similar to the no antibiotic group with 4/4772 (0.08%) episodes (p = 0.2). For overall infections (septic plus nonseptic), there were 403/29 880 (1.35%) versus 58/4772 (1.22%) events among men with evaluable data who received and did not receive antibiotic prophylaxis, respectively (p = 0.8). Restricting our analysis to studies with a comparable low number of biopsy cores (<25 cores), there remained no difference in the rates of sepsis between groups, but there was a small, statistically significant lower risk of infectious complications with antibiotic administration-67/12 140 (0.55%) versus 58/4772 (1.22%; p < 0.01).The likelihood of septic infections after transperineal prostate biopsy is low with and without antibiotic prophylaxis. The omission of periprocedural antibiotics with this procedure stands to benefit patients by avoiding potential drug reactions. Furthermore, this practice is in line with calls throughout the medical community for improved antibiotic stewardship.In a large systematic review and meta-analysis, we evaluated infectious complications after transperineal prostate biopsy with or without the administration of prophylactic antibiotics. We conclude that prophylactic antibiotics do not decrease the rate of postbiopsy sepsis but may have a small benefit in terms of preventing less serious infections.

Risk of Sepsis in Retrograde Intrarenal Surgery: A Systematic Review of the Literature

Abstract: Nowadays, urolithiasis has become a highly prevalent disease. Recent studies indicate that retrograde intrarenal surgery (RIRS) is becoming more popular among surgical treatments due to the preference of patients and providers. This minimally invasive procedure results in high stone-free rates and relatively low morbidity; however, complications resulting from infection can still occur, including acute urinary tract infection, systemic inflammatory response syndrome, and sepsis.To identify the independent risk factors for sepsis following RIRS, as well as general risk factors that may contribute to this life-threatening complication in the pre- and intraoperative periods.A literature review was conducted in April 2020 using the Medline, Scopus, and Cochrane databases. We searched the references of included papers.We screened 2306 manuscripts and selected 13 for inclusion. The sepsis rate ranged from 0.5% to 11.1%, and the septic shock rate ranged from 0.3% to 4.6%. All selected studies mentioned risks for sepsis and/or infective complications (including sepsis), but only four of them addressed independent risks for urosepsis. These independent risk factors were stone size, high irrigation pressure, prolonged stent dwelling time (>30 d), sepsis as an indication for stent insertion, female gender, positive intraoperative bladder urine culture, longer surgical time, and diabetes mellitus.RIRS is associated with a low sepsis rate, according to the latest evidence. However, given that this is a serious life-threatening complication, knowing its potential risk factors is extremely important.In this report, we looked at the outcome of sepsis after planned retrograde intrarenal surgery for stone disease in patients with and without comorbidities. This information may be useful for colleagues in their daily practice.

Diagnostic Performance of a Magnetic Resonance Imaging-directed Targeted plus Regional Biopsy Approach in Prostate Cancer Diagnosis: A Systematic Review and Meta-analysis

Abstract: Systematic biopsies are additionally recommended to maximize the diagnostic performance of the magnetic resonance imaging (MRI) diagnostic pathway for men with suspected prostate cancer (PCa) and positive scans. To reduce unnecessary systematic biopsies (SBx), MRI-directed approaches comprising targeted plus regional biopsy (TBx + RBx) are being investigated.To systematically evaluate the diagnostic performance of MRI-directed TBx + RBx approaches in comparison to MRI-directed TBx alone and TBx + SBx approaches.The MEDLINE and Embase databases were searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses process. Identified reports were critically appraised according to the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) criteria. Detection of grade group (GG) ≥2 PCa was the endpoint of interest. Fixed-effect meta-analyses were conducted to characterize summary effect sizes and quantify heterogeneity. Only MRI-positive men were included.A total of eight studies were included for analysis. Among a cumulative total of 2603 men with suspected PCa, the GG ≥2 PCa detection rate did not significantly differ between MRI-directed TBx + RBx and TBx + SBx approaches (risk ratio [RR] 0.95, 95% confidence interval [CI] 0.90-1.01; p = 0.09). The TBx + RBx results were obtained using significantly fewer biopsy cores and avoiding contralateral SBx altogether. By contrast, there was significant difference in GG ≥2 PCa detection between MRI-directed TBx + RBx and TBx approaches (RR 1.18, 95% CI 1.10-1.25; p < 0.001).MRI-directed TBx + RBx approaches showed a nonsignificant difference in detection of GG ≥2 PCa compared to the recommended practice of MRI-directed TBx + SBx. However, owing to the extensive heterogeneity among the studies included, future prospective clinical studies are needed to further investigate, optimize, and standardize this promising biopsy approach.We reviewed the scientific literature on prostate biopsy approaches using magnetic resonance imaging (MRI)-directed targeted biopsy plus regional biopsy of the prostate. The studies we identified found arguments to potentially embrace such a combined biopsy approach for future diagnostics in prostate cancer.

Primary Renal Tumour Response in Patients Treated with Nivolumab and Ipilimumab for Metastatic Renal Cell Carcinoma: Real-world Data Assessment

Abstract: Following CARMENA and SURTIME, patients with metastatic renal cell carcinoma (mRCC) and International Metastatic RCC Database Consortium (IMDC) intermediate and poor risk receive systemic therapy with the primary tumour (primary) in place, with the option of deferred cytoreductive nephrectomy (CN) in responding patients. We retrospectively analysed the safety and efficacy of first-line nivolumab/ipilimumab in 71 primary mRCC patients (42.3% IMDC poor risk; 43.6% with more than three metastatic sites). The baseline mean primary diameter was 9.3 cm and median follow-up was 11.5 mo. Of 69 patients with at least one follow-up computed tomography scan, 23 (33.3 %) had a partial response (PR) of the primary after a median of 4.8 mo, which was associated with a 91.3% overall response rate at metastatic sites (MSs) and absence of progressive disease, irrespective of the IMDC risk. The complete response (CR) rate at MSs (n = 7 [10.1%]) is similar to the CR rate in CheckMate 214. Thirteen deferred CNs were performed (18.8%) after a median of 13 mo, rendering four patients disease free. Only 4.3% of primaries progressed; grade 3-4 immune-related adverse events occurred in 31.9%. Irrespective of the IMDC risk, patients with a PR in the primary had a 1-yr overall survival rate of 89% versus 67% in those without (p = 0.012).Patients with metastatic kidney cancer receiving immunotherapy with nivolumab and ipilimumab had superior response at metastatic sites and better survival irrespective of International Metastatic RCC Database Consortium (IMDC) risk.

Learning Curve Analysis for Intracorporeal Robot-assisted Radical Cystectomy: Results from the EAU Robotic Urology Section Scientific Working Group

Abstract: The utilisation of robot-assisted radical cystectomy with intracorporeal reconstruction (iRARC) has increased in recent years. Little is known about the length of the learning curve (LC) for this procedure. To study the length of the LC for iRARC in terms of 90-d major complications (MC90; Clavien-Dindo grade ≥3), 90-d overall complications (OC90, Clavien-Dindo grades 1–5), operating time (OT), estimated blood loss (EBL), and length of hospital stay (LOS). This was a retrospective analysis of all consecutive iRARC cases from nine European high-volume hospitals with ≥100 cases. All patients had bladder cancer for which iRARC was performed, with an ileal conduit or neobladder as the urinary diversion. Outcome parameters used as a proxy for LC length were the number of consecutive cases needed to reach a plateau level in two-piece mixed-effects models for MC90, OC90, OT, EBL, and LOS. A total of 2186 patients undergoing iRARC between 2003 and 2018were included. The plateau levels for MC90 and OC90 were reached after 137 cases (95% confidence interval [CI] 80–193) and 97 cases (95% CI 41–154), respectively. The mean MC90 rate at the plateau was 14% (95% CI 7–21%). The plateau level was reached after 75 cases (95% CI 65–86) for OT, 88 cases (95% CI 70–106) for EBL, and 198 cases (95% CI 130–266) for LOS. A major limitation of the study is the difference in the balance of urinary diversion types between centres. This multicentre retrospective analysis for the iRARC LC among nine European centres showed that 137 consecutive cases were needed to reach a stable MC90 rate. We carried out a multicentre analysis of the surgical learning curve for robot-assisted removal of the bladder and bladder reconstruction in patients with bladder cancer. We found that 137 consecutive cases were needed to reach a stable rate of serious complications.

Estimated Glomerular Filtration Rate Decline at 1 Year After Minimally Invasive Partial Nephrectomy: A Multimodel Comparison of Predictors

Abstract: Long-term renal function after partial nephrectomy (PN) is difficult to predict as it is influenced by several modifiable and nonmodifiable variables, often intertwined in complex relations.To identify variables influencing long-term renal function after PN and to assess their relative weight.A total of 457 patients who underwent either robotic (n = 412) or laparoscopic PN (n = 45) were identified from a multicenter international database.The 1-yr estimated glomerular filtration rate (eGFR) percentage loss (1YPL), defined as the eGFR percentage change from baseline at 1 yr after surgery, was the outcome endpoint. Predictors evaluated included demographic data, tumor features, and operative and postoperative variables. Bayesian multimodel analysis of covariance was used to build all possible models and compare the fit of each model to the data via model Bayes factors. Bayesian model averaging was used to quantify the support for each predictor via the inclusion Bayes factor (BFincl). High-dimensional undirected graph estimation was used for network analysis of conditional independence between predictors.Several models were found to be plausible for estimation of 1YPL. The best model, comprising postoperative eGFR percentage loss (PPL), sex, ischemia technique, and preoperative eGFR, was 207 times more likely than all the other models regarding relative predictive performance. Its components were part of the top 44 models and were the predictors with the highest BFincl. The role of cold ischemia, solitary kidney status, surgeon experience, and type of renorraphy was not assessed.Preoperative eGFR, sex, ischemia technique, and PPL are the best predictors of eGFR percentage loss at 1 yr after minimally invasive PN. Other predictors seem to be irrelevant, as their influence is insignificant or already nested in the effect of these four parameters.Kidney function at 1 year after partial removal of a kidney depends on sex, the technique used to halt blood flow to the kidney during surgery, and kidney function at baseline and in the early postoperative period.

Reducing Biopsies and Magnetic Resonance Imaging Scans During the Diagnostic Pathway of Prostate Cancer: Applying the Rotterdam Prostate Cancer Risk Calculator to the PRECISION Trial Data

Abstract: Risk stratification in the diagnostic pathway of prostate cancer (PCa) can be used to reduce biopsies and magnetic resonance imaging (MRI) scans, while maintaining the detection of clinically significant PCa (csPCa). The use of highly discriminating and well-calibrated models will generate better clinical outcomes if context-dependent thresholds are used.To retrospectively assess the effect of the upfront use of the Rotterdam Prostate Cancer Risk Calculator (RPCRC) developed in a screening cohort and the RPCRC-MRI developed in a clinical cohort while exploring the need to adapt thresholds in biopsy-naïve men in the PRECISION (Prostate Evaluation for Clinically Important Disease: Sampling Using Image Guidance or Not?) trial.In the transrectal ultrasonography arm, we evaluated 188 men; in the MRI arm, we evaluated 206 (for the reduction of MRI scans) and 137 (for the reduction of targeted biopsies) men.Performance was assessed by discrimination, calibration, and clinical utility.The performance of the RPCRC was good. However, intercept adjustment was warranted. Net benefit was observed from a recalibrated probability of 32% for any PCa and 10% for csPCa. After recalibration and applying a threshold of 20% for any PCa or 10% for csPCa, 28% of all biopsies could have been reduced, missing five cases of csPCa. The uncalibrated RPCRC could reduce 35% of all MRI scans, with a threshold of 20% for any PCa or 4% for csPCa. In the MRI arm, performance was good without stressing recalibration. Net benefit was observed from a probability of 22% for any PCa and 7% for csPCa. With a threshold of 20% for any PCa or 4% for csPCa, 9% of all targeted biopsies could be reduced, missing one grade group 2 PCa.The performance of the RPCRC and RPCRC-MRI in men included in the PRECISION trial was good, but recalibration and adaptation of the risk threshold of the RPCRC are indicated to reach optimal performance.In this report, we show that risk stratification with the Rotterdam Prostate Cancer Risk Calculator has added value in reducing harm, but adjustment to reflect the characteristics of the patient cohort is indicated.

Retroperitoneal Robot-assisted Partial Nephrectomy: A Systematic Review and Pooled Analysis of Comparative Outcomes

Abstract: Robot-assisted partial nephrectomy (RAPN) has gained increasing popularity as primary minimally invasive surgical treatment for localized renal tumors, and it has preferably been performed with a transperitoneal approach. However, the retroperitoneal approach represents an alternative approach given potential advantages. To provide an updated analysis of the comparative outcomes of retroperitoneal RAPN (R-RAPN) versus transperitoneal RAPN (T-RAPN). A systematic review of the literature was performed up to September 2021 using MEDLINE, EMBASE, and Web of Science databases, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) recommendations. A sensitivity analysis was performed considering only matched-pair studies. Seventeen studies, which were published between 2013 and 2021, were retrieved. None of them was a randomized clinical trial. Among the 6,266 patients included in the meta-analysis, 2261 (36.1%) and 4,005 (63.9%) underwent R-RAPN and T-RAPN, respectively. No significant difference was found in terms of baseline features. The T-RAPN group presented a higher rate of male patients (odds ratio [OR]: 0.86, p = 0.03) and larger tumor size (weighted mean difference [WMD]: 0.2 cm; p = 0.003). The R-RAPN group reported more frequent posterior renal masses (OR: 0.23; p < 0.0001). The retroperitoneal approach presented lower estimated blood loss (WMD: 30.41 ml; p = 0.001), shorter operative time (OT; WMD: 20.36 min; p = 0.0001), and shorter length of stay (LOS; WMD: 0.35 d; p = 0.002). Overall complication rates were 13.7% and 16.05% in the R-RAPN and T-RAPN groups, respectively (OR: 1.32; p = 0.008). There were no statistically significant differences between the two groups regarding major (Clavien-Dindo classification ≥3 grade) complication rate, “pentafecta” achievement, as well as positive margin rates. When considering only matched-pair studies, no difference between groups was found in terms of baseline characteristics. Posterior renal masses were more frequent in the R-RAPN group (OR: 0.6; p = 0.03). Similar to the analysis of the entire cohort, R-RAPN reported lower EBL (WMD: 35.56 ml; p < 0.0001) and a shorter OT (WMD: 18.31 min; p = 0.03). Overall and major complication rates were similar between the two groups. The LOS was significantly lower for R-RAPN (WMD: 0.46 d; p = 0.02). No statistically significant difference was found between groups in terms of overall PSM rates. R-RAPN offers similar surgical outcomes to T-RAPN, and it carries potential advantages in terms of shorter OT and LOS. Available evidence remains limited by the lack of randomized clinical trials. In this review of the literature, we looked at comparative outcomes of two surgical approaches to robot-assisted partial nephrectomy. We found that the retroperitoneal technique offers similar surgical outcomes to the transperitoneal one, with potential advantages in terms of shorter operative time and length of hospital stay.

Online Public Interest in Urological Cancers During the COVID-19 Pandemic: What Can “Dr. Google” Teach Us?

Abstract: The coronavirus disease 2019 (COVID-19) pandemic has greatly affected health care priorities.To explore and analyse trends in public online search for urological cancers.We performed a retrospective analysis using the Google Health Trends online tool. Data related to urological cancer terms ("prostate cancer", "kidney cancer", and "bladder cancer") were extracted. We analysed trends for the whole world and for five countries: Italy, the UK, France, Sweden, and the USA.A join-point regression model was used to define significant changes in trends over time. Week percentage changes (WPCs) were estimated to summarise linear trends. The Mann-Whitney test was used to compare the search volume during the COVID-19 pandemic period (from January 2020 to April 2021) and the equivalent period of 2018 and 2019.During COVID-19, worldwide online interest decreased significantly for all urological cancers, especially prostate cancer (WPC: -13.9%, p = 0.004; WPC: -5.4%, p < 0.001; and WPC: -4.3%, p < 0.001, for prostate, kidney, and bladder cancers, respectively). The most important decline was observed in the USA. The interest for all cancers was significantly less during the COVID-19 pandemic than in the same periods of 2018 and 2019.Online interest in urological cancers decreased significantly during the COVID-19 pandemic. Future studies will tell us whether this will translate into worse oncological outcomes.Patients are increasingly searching the Internet to get information on cancer. We explored Google queries during the COVID-19 pandemic and found that online interest decreased significantly for all urological cancers, especially prostate cancer. We do not know yet whether this will translate into worse prognosis for patients.

A Phase 1b Clinical Study of Intravesical Photodynamic Therapy in Patients with Bacillus Calmette-Guérin–unresponsive Non–muscle-invasive Bladder Cancer

Abstract: A phase 1b study of photosensitizer TLD-1433–mediated photodynamic therapy (PDT) was performed in bacillus Calmette-Guérin (BCG)-unresponsive non–muscle-invasive bladder cancer (NMIBC) patients. The primary objectives were safety and tolerability of PDT, with secondary objectives of (1) pharmacokinetic (PK) properties of TLD-1433 and (2) efficacy, as evaluated by recurrence-free survival and complete response (CR) at 90 and 180 d for patients treated at the maximum recommended starting dose (0.35 mg/cm2 bladder surface area) and the therapeutic dose (0.70 mg/cm2). Six BCG-unresponsive patients were enrolled in an open-label, single-arm, dose-escalating study of PDT. TLD-1433 was instilled intravesically for 60 min preoperatively. PDT was performed under general anesthesia using intravesically delivered irradiation of the bladder wall with green light (520 nm) to a dose of 90 J/cm2. Patients were followed by standard cystoscopy and cytology for up to 18 mo to assess time to recurrence. PDT was well tolerated by all patients. All patients experienced at least one grade ≤2 adverse event (AE). There were no patient deaths or light sensitivity reactions. The most common AE was moderate bladder irritability, which resolved within the first weeks after treatment. AEs were independent of the TLD-1433 dose. TLD-1433 was cleared in the urine and from the plasma within 24 and 72 h, respectively. Of three patients treated at the therapeutic dose, two achieved a CR at 180 d, which was durable at 18 mo. The other patient was diagnosed with metastatic disease at 138 d. PDT with TLD-1433 appears safe for the treatment of BCG-unresponsive NMIBC. Early efficacy signals from full-dose photosensitizer are encouraging and warrant phase 2 trial investigation. The safety and PK results obtained support the potential for administration of consecutive PDT treatments as required. Photodynamic therapy with TLD-1433 appears to be safe and effective for the treatment of bacillus Calmette-Guérin (BCG)-unresponsive bladder cancer.

Combining Antiandrogens with Immunotherapy for Bladder Cancer Treatment

Abstract: These preclinical studies in mice using the MBT-2 model of bladder cancer suggests that the combination of antiandrogens and immunotherapy for non–muscle-invasive bladder cancer may improve response rates. Men are three to four times more likely to be diagnosed with bladder cancer (BCa) than women, who often have more aggressive tumors. Intravesical bacillus Calmette-Guerin (BCG) for non–muscle-invasive bladder cancer (NMIBC) is one of the first immunotherapies, with use of immune checkpoint inhibitors for BCa immunotherapy expanding. Sex hormones, and notably androgens, might impact the outcome of these therapies. To understand immunological sex differences in BCa and investigate androgen receptor (AR) inhibition as a novel strategy to improve the response to BCa immunotherapy. Human NMIBC tumors were freshly collected following transurethral resection. In vivo studies used the subcutaneous MBT-2 BCa model in male and female C3H mice. The AR antagonist enzalutamide was given alone or in combination with anti–programmed cell death protein-1 (anti–PD-1) or intratumoral BCG + poly(I:C) treatments. Tumor growth and survival were evaluated in vivo . Flow cytometry and RNA sequencing characterized the immune cells present in murine and human tumors. Descriptive comparisons were performed for MBT-2 tumors between sexes and with human NMIBC tumors. The MBT-2 model shows multiple similarities to the immune composition of human NMIBC tumors and recapitulates previously observed human tumor immune cell sex differences. Enzalutamide in combination with either anti–PD-1 or BCG + poly(I:C) treatment in male mice synergized to improve response rates. Notably, the proportion of complete responses in male mice treated with the combination treatment resembles that observed in female mice with either immunotherapy alone. Limitations include the sample size for murine experiments. Our results suggest that combining AR antagonism with immunotherapy in male BCa patients may potentiate the antitumor immune response and increase response rates. The MBT-2 model appears relevant to investigate immunological BCa sex differences. Our studies suggest that combining antiandrogen treatments with BCa immunotherapy may improve response rates in men. We also demonstrate the utility of the MBT-2 mouse model to study sex differences in BCa.

Real-world Early Outcomes and Retreatment Rates Following Water Vapour Ablative Therapy for Symptomatic Benign Prostatic Hyperplasia

Abstract: Rezūm water vapour ablation is an effective minimally invasive surgical therapy for the treatment of bladder outflow obstruction.To present early outcomes and reoperation rates after Rezūm, including an analysis of retreatment rates to gain an insight into optimal patient selection and the durability of the procedure.Data were prospectively collected for consecutive patients undergoing Rezūm for symptomatic benign prostatic hyperplasia between March 2017 and January 2020 at two hospital sites.Rezūm treatment of the prostate.Patients were reviewed at 6 wk and 3, 6, and 12 mo after their Rezūm procedure. We evaluated changes in urinary symptoms and the retreatment rate.A total of 461 patients undergoing Rezūm were analysed. The mean (±standard deviation) follow-up duration was 16.7 ± 10.4 mo. The mean patient age was 67.5 ± 7.8 yr and the mean prostate volume was 56.5 ± 24.0 ml. There was a significant improvement in mean maximum flow rate and postvoid residual volume and in International Prostate Symptom Score and quality-of-life scores (p < 0.0001). During the follow-up period, 21 patients (4.6%) required retreatment, of which 11 cases (2.4%) were within the first year. The retreatments included eight bladder neck incisions or resections, six transurethral resections of the prostate, four Greenlight laser photoselective vaporisations of the prostate, and three Rezūm procedures. The median length of time to a further operation was 11.5 mo (range 3-34). The most common findings at reoperation were an inadequately treated median lobe, an obstructing bladder neck, and in some cases asymmetry of the prostate cavity or recesses within the prostate gland.This study demonstrates that the beneficial effects of Rezūm observed in the pivotal phase 2 randomised study are transferable to a real-world population with a comparable early retreatment rate. A range of procedures were used for retreatment. The factors dictating which option to select were based on patient concerns regarding side effects, gland volume, symptom profile, and cystoscopy findings.We investigated outcomes for patients undergoing Rezūm, a water vapour treatment to reduce the size of the prostate in men with obstruction of the bladder outlet because of benign prostate enlargement. This technique yields significant improvements in symptoms and preserves sexual function. The proportion of men needing retreatment was 2.4% in the first year after their Rezūm procedure.

Robotic Versus Open Kidney Transplantation from Deceased Donors: A Prospective Observational Study

Abstract: While robot-assisted kidney transplantation (RAKT) from living donors has been shown to achieve favourable outcomes, there is a lack of evidence on the safety and efficacy of RAKT as compared with the gold standard open kidney transplantation (OKT) in the setting of deceased donors, who represent the source of most grafts worldwide. To compare the intraoperative, perioperative, and midterm outcomes of RAKT versus OKT from donors after brain death (DBDs). Data from consecutive patients undergoing RAKT or OKT from DBDs at a single academic centre between October 2017 and December 2020 were prospectively collected. RAKT or OKT. The primary outcomes were intraoperative adverse events, postoperative surgical complications, delayed graft function (DGF), and midterm functional outcomes. A multivariable logistic regression analysis assessed the independent predictors of DGF, trifecta, and suboptimal graft function (estimated glomerular filtration rate [eGFR] <45 ml/min/1.73 m2) at the last follow-up. Overall, 138 patients were included (117 [84.7%] OKTs and 21 [15.3%] RAKTs). The yearly proportion of RAKT ranged between 10% and 18% during the study period. The OKT and RAKT cohorts were comparable regarding all graft-related characteristics, while they differed regarding a few donor- and recipient-related factors. The median second warm ischaemic time, ureterovesical anastomosis time, postoperative complication rate, and eGFR trajectories did not differ significantly between the groups. A higher proportion of patients undergoing OKT experienced DGF; yet, at a median follow-up of 31 mo (interquartile range 19–44), there was no difference between the groups regarding the dialysis-free and overall survival. At the multivariable analysis, donor- and/or recipient-related factors, but not the surgical approach, were independent predictors of DGF, trifecta, and suboptimal graft function at the last follow-up. The study is limited by its nonrandomised nature and the small sample size. Our study provides preliminary evidence supporting the noninferiority of RAKT from DBDs as compared with the gold standard OKT in carefully selected recipients. Kidney transplantation using kidneys from deceased donors is still being performed with an open surgical approach in most transplant centres worldwide. In fact, no study has compared the outcomes of open and minimally invasive (robotic) kidney transplantation from deceased donors. In this study, we evaluated whether robotic kidney transplantation using grafts from deceased donors was not inferior to open kidney transplantation regarding the intraoperative, postoperative, and midterm functional outcomes. We found that, in experienced hands and provided that there was a time-efficient organisation of the transplantation pathway, robotic kidney transplantation from deceased donors was feasible and achieved noninferior outcomes as compared with open kidney transplantation.

Plasma and Urine Free Glycosaminoglycans as Monitoring Biomarkers in Nonmetastatic Renal Cell Carcinoma—A Prospective Cohort Study

Abstract: No liquid biomarkers are approved in renal cell carcinoma (RCC), making early detection of recurrence in surgically treated nonmetastatic (M0) patients dependent on radiological imaging. Urine- and plasma free glycosaminoglycan profiles—or free GAGomes—are promising biomarkers reflective of RCC metabolism. To explore whether free GAGomes could detect M0 RCC recurrence noninvasively. Between June 2016 and February 2021, we enrolled a prospective consecutive series of patients elected for (1) partial or radical nephrectomy for clinical M0 RCC (cohort 1) or (2) first-line therapy following RCC metachronous metastatic recurrence (cohort 2) at Sahlgrenska University Hospital, Gothenburg, Sweden. The study population included M0 RCC patients with recurrent disease (RD) versus no evidence of disease (NED) in at least one follow-up visit. Plasma and urine free GAGomes—consisting of 40 chondroitin sulfate (CS), heparan sulfate, and hyaluronic acid (HA) features—were measured in a blinded central laboratory preoperatively and at each postoperative follow-up visit until recurrence or end of follow-up in cohort 1, or before treatment start in cohort 2. We used Bayesian logistic regression to correlate GAGome features with RD versus NED and with various histopathological variables. We developed three recurrence scores (plasma, urine, and combined) proportional to the predicted probability of RD. We internally validated the area under the curve (AUC) using bootstrap resampling. We performed a decision curve analysis to select a cutoff and report the corresponding net benefit, sensitivity, and specificity of each score. We used univariable analyses to correlate each preoperative score with recurrence-free survival (RFS). Of 127 enrolled patients in total, 62 M0 RCC patients were in the study population (median age: 63 year, 35% female, and 82% clear cell). The median follow-up time was 3 months, totaling 72 postoperative visits —17 RD and 55 NED cases. RD was compatible with alterations in 14 (52%) of the detectable GAGome features, mostly free CS. Eleven (79%) of these correlated with at least one histopathological variable. We developed a plasma, a urine, and a combined free CS RCC recurrence score to diagnose RD versus NED with AUCs 0.91, 0.93, and 0.94, respectively. At a cutoff equivalent to ≥30% predicted probability of RD, the sensitivity and specificity were, respectively, 69% and 84% in plasma, 81% and 80% in urine, and 80% and 82% when combined, and the net benefit was equivalent to finding an extra ten, 13, and 12 cases of RD per hundred patients without any unnecessary imaging for plasma, urine, and combined, respectively. The combined score was prognostic of RFS in univariable analysis (hazard ratio = 1.90, p = 0.02). Limitations include a lack of external validation. Free CS scores detected postsurgical recurrence noninvasively in M0 RCC with substantial net benefit. External validity is required before wider clinical implementation. In this study, we examined a new noninvasive blood and urine test to detect whether renal cell carcinoma recurred after surgery.

Circulating Tumor DNA in Patients with Renal Cell Carcinoma. A Systematic Review of the Literature

Abstract: Over the past decade there has been increasing interest in the potential of liquid biopsies and systematic biomarkers in the diagnosis and management of kidney cancer, as they may provide a tool for early detection of disease and monitoring of treatment response.To identify and summarize relevant published data on circulating tumor DNA (ctDNA) in patients with renal cell carcinoma (RCC).We performed a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement of studies identified in PubMed, MEDLINE, EMBASE, and Cochrane Library up to January 15, 2021. Two reviewers independently screened all articles and performed the data extraction.Nineteen studies investigating ctDNA in RCC (1237 patients) were included and analyzed in the final review. The study size and design varied widely, and the studies were divided into five groups according to the method used for ctDNA detection. The outcome data included (1) the sensitivity/specificity if available; (2) the method used for ctDNA detection; and (3) the main findings in the studies.The studies highlight that the level of ctDNA in RCC appears to be low. Studies using multiple methods for ctDNA detection indicate that tumor-guided analysis improves the ctDNA detection rate and suggest that cell-free methylated DNA immunoprecipitation and high-throughput sequencing may be a very sensitive method for ctDNA detection in RCC.We systematically reviewed the literature to identify all relevant studies investigating circulating tumor DNA in patients with kidney cancer to investigate its use and potential in this highly malignant disease. We found that the level of circulating tumor DNA is low in kidney cancer and that very sensitive methods have to be used for detection in this disease.

Repair Rate and Associated Costs of Reusable Flexible Ureteroscopes: A Systematic Review and Meta-analysis

Abstract: The refined mechanics of a flexible ureteroscope (fURS) are vulnerable to damage. Sending the fURS for repair is costly and has driven interest toward estimating the resources used for fURS repairs.To systematically review available literature and to estimate the total weighted repair rate of an fURS and the average repair cost per ureteroscopy.A systematic review was conducted by searching the MEDLINE, Embase, Web of Science, and Cochrane Library databases. The average costs of all repairs identified in the included studies were extracted. A random-effect model was used to calculate the pooled total fURS repair rate. The total weighted repair rate and average cost per repair were multiplied to provide an average cost of repair per ureteroscopy procedure.We identified 18 studies that fulfilled the inclusion criteria, which included 411 repairs from 5900 investigated ureteroscopy procedures. The calculated weighted repair rate was 6.5% ± 0.745% (95% confidence interval: 5.0-7.9%; I2 = 75.3%), equivalent to 15 ureteroscopy procedures before repair. The average cost per repair was 6808 USD; according to the weighted repair rate of 6.5%, this corresponds to an average repair cost of 441 USD per procedure. Egger's regression test did not reveal a significant publication bias (p = 0.07).This is the first meta-analysis to estimate the repair rate of the fURS used for ureteroscopy. Our analysis demonstrates a repair rate of 6.5%, equivalent to 15 ureteroscopy procedures between fURS repairs and a repair cost of 441 USD per procedure. Ureteroscopy practices should consider fURS breakage rates and repair costs to optimize the use of reusable versus disposable devices.We reviewed available literature investigating the repair rate of a flexible ureteroscope (fURS). We found that fURSs are sent for repair after every 15 ureteroscopy procedures, corresponding to 441 USD per procedure in repair cost.

Red Blood Cell Distribution Width Is Associated with All-cause Mortality but Not Adverse Cancer-specific Outcomes in Men with Clinically Localized Prostate Cancer Treated with Radical Prostatectomy: Findings Based on a Multicenter Shared Equal Access Regional Cancer Hospital Registry

Abstract: Recent reports with a small number of patients showed an association of red blood cell distribution width (RDW) with prostate cancer (PCa) progression.To investigate whether preoperative RDW can serve as a prognostic marker in patients with PCa undergoing radical prostatectomy (RP) in a large, equal access, and diverse patient cohort.Data were retrospectively collected on 4756 men treated with RP at eight Veteran Affairs medical centers within the Shared Equal Access Regional Cancer Hospital (SEARCH) database from 1999 through 2017.Biochemical recurrence (BCR) was the primary outcome, while metastasis, all-cause mortality (ACM), and prostate cancer-specific mortality (PCSM) were secondary outcomes.The mean (standard deviation) age was 62 yr (6.1), and 1589 (33%) men were black. The median (interquartile range) follow-up was 82 mo (46-127). Preoperative RDW either as a continuous variable or when stratified by quartiles was not associated with BCR. Likewise, preoperative RDW was not associated with metastases or PCSM. However, higher RDW was significantly associated with higher ACM, both as a continuous variable (p < 0.001) and when stratified by quartiles in univariable and multivariable models (p < 0.001). RDW was found to be correlated with D'Amico risk classification of PCa. Study limitations include its retrospective nature and lack of data regarding advanced PCa.Preoperative RDW was not associated with PCa outcomes in men treated with RP but was associated with ACM. While RDW may be a biomarker of overall health, it is not a biomarker for PCa outcomes. These results emphasize the importance of diverse, larger sized studies in genitourinary cancer research.Prostate cancer includes a wide spectrum of diseases with different genetic, pathological, and oncological behaviors. Red blood cell distribution width is helpful in predicting the overall survival for a localized prostate cancer patient, and hence, it can help inform personalized treatment decisions and operative care.

Safety of Minimizing Intensity of Follow-up on Active Surveillance for Clinical Stage I Testicular Germ Cell Tumors

Abstract: We have recommended active surveillance as the preferred management option for clinical stage I (CSI) testicular germ cell tumors (GCTs) since 1980. Over time, the recommended intensity of surveillance has decreased; however, the impact on relapse detection has not been investigated.To examine relapse rate, time to relapse, extent of disease, and burden of treatment at relapse across decreasing surveillance intensity over time.CSI GCT patients under active surveillance from 1981 to 2021 were included in this study.Through four major iterations in both nonseminomatous (NSGCT) and seminoma surveillance schedules, visit frequency, blood testing, and imaging have been decreased successively. Low-dose, noncontrast computed tomography (CT) scans were adopted in 2011. Categorical variables and time to relapse were compared using chi-square and Fisher's exact or Kruskal-Wallis test, respectively.A total of 1583 consecutive patients (942 with seminoma and 641 with NSGCT) were included. In seminoma, chest x-rays were reduced from 13 to one and CT scans were reduced from 20 to ten. Relapse rate, time to relapse, N or M category, and International Germ Cell Cancer Collaborative Group (IGCCCG) classification did not change. In NSGCT, chest x-rays were reduced from 27 to zero and CT scans were reduced from 11 to five. Relapse rate (from 46.2% to 21.2%, p = 0.002) and the median time to relapse (from 6.54 to 4.47 mo, p = 0.025) decreased. No difference in relapsed disease burden was identified by N, M, and S category or IGCCCG classification. Treatment burden at relapse and GCT cancer deaths remained similar for seminoma and NSGCT. Limitations include the retrospective design and large time period covered.Despite considerable reductions in surveillance intensity, we did not observe an increase in disease extent, treatment burden, or GCT cancer deaths upon relapse. These results support that our current lower-intensity active surveillance schedules are safe for managing CSI GCT.Our current reduced-intensity surveillance schedules for clinical stage I germ cell tumors appear to be safe.

Clinically Significant Prostate Cancer Diagnosis Without Histological Proof: A Possibility in the Prostate-specific Membrane Antigen Era?

Abstract: Magnetic resonance imaging (MRI) has resulted in a reduction in the number of patients indicated for prostate biopsy. Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has recently shown additional value in detecting clinically significant prostate cancer (csPCa). Combining these imaging modalities allows such specific prediction of the presence of csPCa that the need for histological confirmation may be obsolete. We retrospectively analyzed PSMA PET/CT scans performed in the primary staging of PCa in the past 2 yr in our center (n = 451). All 74 patients with a PSMA ligand maximum standardized uptake value (SUVmax) of ≥16 had csPCa (grade group ≥2). Of the 185 patients with a combination of a Prostate Imaging-Reporting and Data System score ≥4 and SUVmax ≥8, 98% had csPCa. A nomogram combining predictive factors should be developed to identify patients in whom biopsy could theoretically be avoided. Nevertheless, biopsy will remain indispensable in patients with indefinite risk of csPCa and can provide important additional information.Using patient data from our center, we found that addition of a special type of scan based on prostate-specific membrane antigen could help in the diagnosis of clinically significant prostate cancer without the need for prostate biopsy. Direct therapy without biopsy confirmation of cancer might be possible for a highly select group of patients.

Prostate Cancer Patients Under Active Surveillance with a Suspicious Magnetic Resonance Imaging Finding Are at Increased Risk of Needing Treatment: Results of the Movember Foundation’s Global Action Plan Prostate Cancer Active Surveillance (GAP3) Consortium

Abstract: The inclusion criterion for active surveillance (AS) is low- or intermediate-risk prostate cancer. The predictive value of the presence of a suspicious lesion at magnetic resonance imaging (MRI) at the time of inclusion is insufficiently known.To evaluate the percentage of patients needing active treatment stratified by the presence or absence of a suspicious lesion at baseline MRI.A retrospective analysis of the data from the multicentric AS GAP3 Consortium database was conducted. The inclusion criteria were men with grade group (GG) 1 or GG 2 prostate cancer combined with prostate-specific antigen <20 ng/ml. We selected a subgroup of patients who had MRI at baseline and for whom MRI results and targeted biopsies were used for AS eligibility. Suspicious MRI was defined as an MRI lesion with Prostate Imaging Reporting and Data System (PI-RADS)/Likert ≥3 and for which targeted biopsies did not exclude the patient for AS.The primary outcome was treatment free survival (FS). The secondary outcomes were histological GG progression FS and continuation of AS (discontinuation FS).The study cohort included 2119 patients (1035 men with nonsuspicious MRI and 1084 with suspicious MRI) with a median follow-up of 23 (12-43) mo. For the whole cohort, 3-yr treatment FS was 71% (95% confidence interval [CI]: 69-74). For nonsuspicious MRI and suspicious MRI groups, 3-yr treatment FS rates were, respectively, 80% (95% CI: 77-83) and 63% (95% CI: 59-66). Active treatment (hazard ratio [HR] = 2.0, p < 0.001), grade progression (HR = 1.9, p < 0.001), and discontinuation of AS (HR = 1.7, p < 0.001) were significantly higher in the suspicious MRI group than in the nonsuspicious MRI group.The risks of switching to treatment, histological progression, and AS discontinuation are higher in cases of suspicious MRI at inclusion.Among men with low- or intermediate-risk prostate cancer who choose active surveillance, those with suspicious magnetic resonance imaging (MRI) at the time of inclusion in active surveillance are more likely to show switch to treatment than men with nonsuspicious MRI.

Human Gut Mycobiome and Fungal Community Interaction: The Unknown Musketeer in the Chemotherapy Response Status in Bladder Cancer

Abstract: Until recently, the properties of microbiome and mycobiome in humans and its relevance to disease have largely been unexplored. While the interest of microbiome and malignancy over the past few years have burgeoned with advent of new technologies, no research describing the composition of mycobiome in bladder cancer has been done. Deciphering of the metagenome and its aggregate genetic information can be used to understand the functional properties and relationships between the bacteria, fungi, and cancer.The aim of this project is to characterize the compositional range of the normal versus bladder cancer mycobiome of the gut.An internal transcribed spacer (ITS) survey of 52 fecal samples was performed to evaluate the gut mycobiome differences between noncancer controls and bladder cancer patients.Our study evaluated the differences in mycobiome among patients with bladder cancer, versus matched controls. Our secondary analysis evaluated compositional differences in the gut as a function of response status with neoadjuvant chemotherapy. Data demultiplexing and classification were performed using the QIIME v.1.1.1.1 platform. The Ion Torrent-generated fungal ITS sequence data were processed using QIIME (v.1.9.1), and the reads were demultiplexed, quality filtered, and clustered into operation taxonomic units using default parameters. Alpha and beta diversity were computed and plotted in Phyloseq, principal coordinate analysis was performed on Bray-Curtis dissimilarity indices, and a one-way permutational multivariate analysis of variance was used to test for significant differences between cohorts. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was applied to infer functional categories associated with taxonomic composition.We found distinctive mycobiome differences between control group (n = 32) and bladder cancer (n = 29) gut flora, and identified an increasing abundance of Tremellales, Hypocreales, and Dothideales. Significant differences in alpha and beta diversity were present between the groups (control vs bladder; p = 0.002), noting distinct compositions within each cohort. A subgroup analysis by sex and neoadjuvant chemotherapy status did not show any further differences in mycobiome composition and diversity. Our results indicate that the gut mycobiome may modulate tumor response to preoperative chemotherapy in bladder cancer patients. We propose that patients with a "favorable" mycobiome composition (eg, high diversity, and low abundance of Agaricomycetes and Saccharomycetes) may have enhanced systemic immune response to chemotherapy through antigen presentation.Our study is the first to characterize the enteric mycobiome in patients with bladder cancer and describe complex ecological network alterations, indicating complex bacteria-fungi interactions, particularly highlighted among patients with complete neoadjuvant chemotherapy response.Our study has demonstrated that the composition of stool mycobiome (fungal inhabitants of the gastrointestinal tract) in patients with bladder cancer is different from that in noncancer individuals. Furthermore, when evaluating how patients respond to chemotherapy given prior to their surgery, our study noted significant differences between patients who responded and those who did not.

What Is the Most Effective Management of the Primary Tumor in Men with Invasive Penile Cancer: A Systematic Review of the Available Treatment Options and Their Outcomes

Abstract: The primary lesion in penile cancer is managed by surgery or radiation. Surgical options include penile-sparing surgery, amputative surgery, laser excision, and Moh's micrographic surgery. Radiation is applied as external beam radiotherapy (EBRT) and brachytherapy. The treatment aims to completely remove the primary lesion and preserve a sufficient functional penile stump.To assess whether the 5-yr recurrence-free rate and other outcomes, such as sexual function, quality of life, urination, and penile preserving length, vary between various treatment options.The EMBASE, MEDLINE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL; Cochrane HTA, DARE, HEED), Google Scholar, and ClinicalTrials.gov were searched for publications from 1990 through May 2021. Randomized controlled trials, nonrandomized comparative studies (NRCSs), and case series (CSs) were included.The systematic review included 88 studies, involving 9578 men from 16 NRCSs and 72 CSs. The cumulative mean 5-yr recurrence-free rates were 82.0% for penile-sparing surgery, 83.9% for amputative surgery, 78.6% for brachytherapy, 55.2% for EBRT, 69.4% for lasers, and 88.2% for Moh's micrographic surgery, as reported from CSs, and 76.7% for penile-sparing surgery and 93.3% for amputative surgery, as reported from NRCSs. Penile surgery affects sexual function, but amputative surgery causes more appearance concerns. After brachytherapy, 25% of patients reported sexual dysfunction. Both penile-sparing surgery and amputative surgery affect all aspects of psychosocial well-being.Despite the poor quality of evidence, data suggest that penile-sparing surgery is not inferior to amputative surgery in terms of recurrence rates in selected patients. Based on the available information, however, broadly applicable recommendations cannot be made; appropriate patient selection accounts for the relative success of all the available methods.We reviewed the evidence of various techniques to treat penile tumor and assessed their effectiveness in oncologic control and their functional outcomes. Penile-sparing as well as amputative surgery is an effective treatment option, but amputative surgery has a negative impact on sexual function. Penile-sparing surgery and radiotherapy are associated with a higher risk of local recurrence, but preserve sexual function and quality of life better. Laser and Moh's micrographic surgery could be used for smaller lesions.

Surgical Results and Complications for Open, Laparoscopic, and Robot-assisted Radical Prostatectomy: A Reverse Systematic Review

Abstract: The advantages of minimally invasive surgery for radical prostatectomy (RP) have been demonstrated in a number of systematic reviews (SRs). However, the rigorous study selection process for SR means that a lot of information can be excluded, leading to a very specific clinical scenario that is often unrepresentative of real life. Our new reverse SR methodology generates a heterogeneous population database that covers a wide range of clinical scenarios.To compare perioperative surgical results and complications for open retropubic RP (RRP), laparoscopic RP (LRP), and robot-assisted RP (RARP) in a reverse SR.Eight databases were searched for SRs on RRP, LRP, or RARP between 2000 and 2020 (80 SRs). All references used in these SRs were captured for analysis (1724 articles). Perioperative outcomes and complications were compared among the RRP, LRP, and RARP approaches.We identified 559 (32.4%) reports on RRP, 413 (23.9%) on LRP, and 752 (43.7%) on RARP, involving 1 353 485 patients overall. RARP showed a significantly higher annual volume of surgery per surgeon (AVSS) in comparison to RRP and LRP (mean 64.29, 43.26, and 41.47, respectively), a higher percentage of low-risk patients (prostate-specific antigen <10 ng/ml, Gleason <7, stage

TERT Promoter Mutations in Keratinizing and Nonkeratinizing Squamous Metaplasia of the Urinary Tract

Abstract: We identified urothelial tract biopsy and resection specimens with keratinizing squamous metaplasia (KSM), nonkeratinizing squamous metaplasia (NKSM), and urothelial and squamous carcinomas over a 20-yr period, focusing on cases with neurogenic lower urinary tract dysfunction (NLUTD) and/or those with spatial or temporal variation in sampling. TERT promoter mutations as assessed via allele-specific polymerase chain reaction were surprisingly common in our testing cohort, identified not only in 15 (94%) invasive cancer foci but also in 13 (68%) examples of KSM and seven (70%) examples of NKSM. TERT promoter mutations were present in 23 foci from NLUTD specimens and 11 foci from bladder diverticula, including in foci of KSM, NKSM, and unremarkable urothelium from cases with no clinical association with previous, concurrent, or subsequent cancer. Our demonstration of temporally and spatially persistent TERT promoter mutation in examples of KSM and NKSM in cases of bladder cancer and in morphologically benign cases with neurogenic dysfunction suggests a molecular mechanism by which such pre-neoplastic lesions can potentially progress and develop into overt carcinoma. Given the interest in TERT promoter mutations as a potential biomarker for the development of bladder cancer, these findings possibly explain the association between conditions with chronic urinary bladder injury (such as the natural history of NLUTD) and higher risk of bladder cancer. TERT promoter mutations may represent an early event in bladder cancer tumorogenesis, and our findings expand on the clinical ramifications and predictive value of TERT promoter mutations in this context.Mutations in the TERT gene are the most common genetic changes in bladder cancer. We found that these mutations are also sometimes present in patients with chronic bladder irritation such as neurogenic bladder dysfunction and changes to the lining of the bladder that pathologists would consider "benign." This finding might explain why such conditions are associated with the development of bladder cancer.

Is Mini Percutaneous Nephrolithotomy a Game Changer for the Treatment of Renal Stones in Children?

Abstract: Mini percutaneous nephrolithotomy (MPCNL) is a newer surgical procedure that has changed the management of paediatric renal stones.To evaluate MPCNL morbidity and success rates for renal stones as a function of patient age in a paediatric cohort.This was a retrospective case series that included 143 consecutive patients younger than 17 yr who underwent MPCNL at our institution between January 2016 and November 2020. The patients were categorised into three different age groups: <6 yr (n = 71, 49.7%), 6-11 yr (n = 44, 30.8%), and 12-17 yr (n = 28, 19.6%). MPCNL was performed in all patients through 16-20Fr tracts.The stone-free rate, perioperative complications, tract number, operative time, postoperative haemoglobin change, and hospitalisation time were evaluated for each age group.MPCNL was performed in 143 paediatric patients (88 boys and 55 girls; mean age 6.53 yr). The mean stone burden (± standard deviation) was 2.096 ± 1.01 cm in group one, 2.05 ± 1.05 cm in group two, and 3.46 ± 19.94 cm in group three; group three was significantly larger (p = 0.001). After a single MPCNL session, 92.42% of patients experienced complete stone clearance. All age groups were similar in terms of stone-free rate (p = 0.82), hospitalisation time (p = 0.94), postoperative haemoglobin change (p = 0.06), and perioperative complications (p = 0.62). However, stone size (p = 0.009), stone complexity (p = 0.001), number of access points (p = 0.03), and operative time (p = 0.009) were higher in the group aged 12-17 yr.MPCNL is an effective and safe procedure in younger as well as older children. Age should not be considered a limiting factor for MPCNL in children, and MPCNL should be considered the primary option for treating paediatric renal stones when PCNL is indicated.Our results show that surgical removal of kidney stones through an incision in the skin and using miniaturised instruments is an effective and safe procedure for children.

Metastatic Potential of Small Testicular Germ Cell Tumors: Implications for Surveillance of Small Testicular Masses

Abstract: Incidental detection of urogenital tumors has increased in recent decades owing to the greater use of ultrasonography and cross-sectional imaging. For patients with low-risk prostate cancer or small renal masses, active surveillance represents a valid treatment option. Similarly, for men with small testicular masses <10 mm, active surveillance has been discussed as an alternative to surgery, although little is known regarding the behavior of small testicular germ cell tumors (GCTs). In the Swiss Austrian German Testicular Cancer Cohort Study we identified 849 patients (546 seminoma, 303 nonseminoma) treated with radical inguinal orchiectomy for GCT with a median tumor diameter of 35 mm. A tumor diameter <10 mm was observed in 25 patients (13 seminoma, 12 nonseminoma). Of these, five patients (20%) presented with primary metastatic disease, all of whom had elevated tumor markers and nonseminomatous GCTs. Two patients (8%) with initially localized disease (1 seminoma, 1 nonseminoma) and without elevated tumor markers experienced relapse at 4 mo (nonseminoma) and 14 mo (seminoma) after orchiectomy, despite the fact that the latter had received adjuvant chemotherapy. These findings highlight the metastatic potential of small testicular GCTs and raise the question of whether active surveillance for small testicular masses is safe.This study on testicular cancer assesses the metastatic potential of small testicular germ cell tumors. Men with small testicular masses should be counseled about the malignant potential of small testicular germ cell tumors.