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Models predicting the risk of adverse pathology (ie, International Society of Urological Pathology [ISUP] grade group ≥3, pT3, and/or pN1) among patients operated by radical prostatectomy (RP) have been proposed to expand active surveillance (AS) inclusion criteria. We aimed to test these models in a set of 1062 low-risk and favorable intermediate-risk prostate cancer (PCa) patients diagnosed by multiparametric magnetic resonance imaging (MRI) and MRI-targeted biopsy. We hypothesized that the inclusion of radiological features into a novel model would improve patient selection. Performance was assessed using discrimination, calibration, and decision curve analysis (DCA). Available models were characterized by poor discrimination (areas under the receiver operating characteristic curve [AUCs] of 59% and 60%), underestimation of predicted risk on calibration plots, and a small amount of net benefit against a probability threshold of 40-50% at the DCA. The development of a novel model slightly improved discrimination (AUC of 63% vs 59%, p = 0.001, and 63% vs 60%, p = 0.07) and net benefit against threshold probabilities of ≥30%. This first multicenter study demonstrated the poor performance of models predicting adverse pathology and that implementation of MRI and MRI-targeted biopsy in this setting was not associated with a clear improvement in patient selection. Patients harboring low-risk or favorable intermediate-risk PCa and candidates for RP cannot be referred accurately to an AS program without a non-negligible risk of misclassification. PATIENT SUMMARY: We tested prediction models that could expand the selection of prostate cancer patients for active surveillance. Models were inaccurate and associated with a high risk of misclassification despite the implementation of multiparametric magnetic resonance imaging and targeted biopsies.

Urinary microbiota has been found to play a key role in numerous urological diseases. The aim of this systematic review is to depict the role of urinary microbiota in the pathogenesis, diagnosis, prognosis, and treatment of urological tumors, including bladder cancer (BCa), prostate cancer (PCa) and renal cell carcinoma (RCC).A systematic PubMed and Scopus search was undergone from inception through June 2021 for studies investigating urinary microbiota alterations in urological tumors. Study selection followed the PRISMA statement. Phylum, family, genus and species of each bacterium in cancer patients and controls were recorded.Twenty-one studies with 1194 patients (748 cancer patients and 446 controls) were included in our final analysis. Certain bacterial phylum, family, genus, and species were more predominant in each of BCa, PCa and RCC patients compared to controls. Abundance and specificity of urinary microbiota were prognosticators for: (1) recurrence, distinguishing recurrent from non-recurrent BCa, (2) disease stage, distinguishing non-muscle invasive from muscle invasive BCa, and (3) disease grade, distinguishing high- vs. low-grade PCa and BCa. Dietary, environmental and geographic patterns influenced urinary microbiota. Urinary microbiota of benign prostatic hyperplasia was different from PCa.Urological cancer patients have an altered urinary microbiota compared to controls. This may predict recurrence, disease stage and disease grade of these tumors. Further prospective studies are needed to depict a potential influence on therapeutic outcomes.

To assess the most efficient biopsy method to improve International Society of Urological Pathology (ISUP) grade group accuracy with final pathology of the radical prostatectomy (RP) specimen in the era of magnetic resonance imaging (MRI)-driven pathway.A total of 753 patients diagnosed by transrectal MRI-targeted and systematic biopsies (namely "standard method"), treated by RP, between 2016 and 2021 were evaluated. Biopsy methods included MRI-targeted biopsy, side-specific systematic biopsies relative to index MRI lesion and combination of both. Number of MRI-targeted biopsy cores and positive cores needed per index MRI lesion were assessed. Multivariable analysis was performed to analyze predictive factors of upgrading using MRI targeted and ipsilateral systematic biopsies method.Overall, ISUP grade group accuracy varied among biopsy methods with upgrading rate of 35%, 49%, 27%, and 24% for MRI targeted, systematic, MRI targeted and ipsilateral systematic biopsies and standard methods, respectively (p 0.001). A minimum of two positive MRI-targeted biopsies cores per index MRI lesion were required when testing MRI targeted and ipsilateral systematic biopsies method to reach equivalent accuracy compared to standard method. Omitting contralateral systematic biopsies spared an average of 5.9 cores per patient. At multivariable analysis, only the number of positive MRI-targeted biopsy cores per index MRI lesion was predictive of upgrading.MRI targeted and ipsilateral systematic biopsies allowed an accurate definition of ISUP grade group and appears to be an interesting alternative when compared with standard method, reducing total number of biopsy cores needed.

Introduction: Multiple trials are currently studying the additional effect of immunotherapy on neoadjuvant chemotherapy (NAC) in nonmetastatic muscle-invasive bladder cancer. Methods: We performed a systematic review of the literature that summarizes all ongoing trials, with their results when available. Results: From an initial 269 trials identified, 17 were included. Pathological response and pathological complete response rates of the immunotherapy + NAC combination in the cisplatin-eligible population varied between 56.6–75% and 34.0–66.7%, respectively. Two studies published their results in the cisplatin-ineligible population, with pathological complete response rates of 18 and 45.2%. Conclusion: Neoadjuvant immunochemotherapy in platinum-eligible patients results in response rates higher than those reported for NAC alone. Strong preliminary results are still lacking in the platinum-ineligible population.

Everyday clinical decisions are based on “statistically” significant or non-significant results, with an exaggerated credit given to statistics. This is due to the interesting dichotomy that statistics respond to: to perform a surgery or not, to give a treatment or not. However, statistics rely on the law of probability and cannot provide definite judgments. This manuscript aims to highlight the statistical flaws in clinical practice from a simple perspective for surgeons.

In May 2024, all medical devices in Europe will require to comply with the new Medical Device Regulation 2017/745, including those we have been using for years. Currently, there are major delays and problems associated with this new certification. As clinicians, we express our serious concerns regarding whether the system will be ready on time to ensure that all the medical devices that we use will be available for patient care.

This systematic review aims to assess all the prospective studies published to date on the efficacy of CAR-T cell therapy in solid tumors. Databases searched were PubMed and Google Scholar from inception through May 1st 2021. Search query was (Chimeric antigen receptor) or (CAR-T) or (T-CAR). Twenty-nine prospective studies (265 patients) were included. Most published clinical trials are phase I. Clinical benefit was 100% in epithelial ovarian cancer, 70-82% in gastrointestinal tumors, 79% in mesothelioma, 63% in small-cell lung cancer, 24-67% in sarcoma, 50-62% in prostate cancer, and 45-50% in central nervous system tumors. No serious CAR-T cell specific serious toxicities were noted.

Antibody-drug conjugates (ADCs) reflect a new promising approach in prostate cancer, even more so after the practice-changing results in other malignancies, either hematologic or solid. ADCs consist of monoclonal antibodies (mAb) targeted at specific antigens overly expressed on cancer cells compared to normal cells. A cytotoxic payload is attached to the mAb using a stable linker. In prostate cancer, PSMA, STEAP1, TROP2, CD46 and B7-H3 are antigens currently being studied as targets for ADCs. In this paper, we discuss the composition of ADCs and focus on their application and challenges as treatment options in prostate cancer.

COVID-19 is the pandemic that hit the world starting December 2019. Recent studies and international statistics have shown an increased prevalence, morbidity as well as mortality of this disease in male patients compared to female patients. The aim of this brief communication is to describe the pathophysiology of this sex-discrepancy, based on the infectivity mechanism of the coronavirus including the Angiotensin-Converting Enzyme 2 (ACE2), the Type II transmembrane Serine Protease (TMPRSS2), and the androgen receptor. This could help understand the susceptibility of urological patients, especially those receiving androgen deprivation therapy for prostate cancer, and testosterone replacement therapy.

Male gender has been shown to be a risk factor for COVID-19 infection, and men are more likely to develop severe disease. The aim of this study was to evaluate the effect of androgen deprivation therapy (ADT) on the incidence of infection and severity of SARS-CoV-2 in prostate cancer patients.A systematic review and meta-analysis were performed after searching PubMed, Scopus, and ClinicalTrial.org databases, between January 2020 and March 2022. Analyses were interpreted through forest plots for the following parameters: risk of infection, hospitalization, intensive care admission, and SARS-CoV-2-related death, with random or fixed-effects models.Fifteen articles were included in the systematic review and ten in the meta-analysis. Seven studies evaluated risk of infection in patients on ADT: OR=1.11 (95 % IC : [0.48-2.58] ; P=0.81). Six studies evaluated the risk of hospitalization in patients on ADT: TDA : OR=1.58 (95 % IC : [0.94-2.64] ; P=0.08). Seven studies evaluated risk of ICU admission in patients on ADT: OR=0.90 (95 % IC : [0.71-1.13] ; P=0.37). Nine studies evaluated mortality risk in patients on ADT: OR=1.07 (95 % IC : [0.61-1.87] ; P=0.82).ADT does not protect against SARS-CoV-2 in prostate cancer patients, nor does it protect against hospitalization, ICU admission, or mortality. These results remain questionable given the retrospective nature of the majority of studies included in our meta-analysis.

Radical cystectomy with pelvic lymphadenectomy and urinary diversion is the standard treatment for patients diagnosed with localized muscle-invasive bladder cancer. Enhanced recovery after surgery (ERAS) is a multimodal perioperative care pathway comprising recommendations on different items with variable evidence that are aimed at improving outcomes. This review provides an overview of the application of specific elements of the ERAS guidelines. Forty-eight series were identified through our literature search. The studies reported a median of 16 out of the 22 ERAS steps (72.7%). The elements were applied in 79.3% of cases (interquartile range 61.1-85%) if mentioned in the studies, decreasing to 73.5% in the postoperative period. PATIENT SUMMARY: Guidelines on enhanced recovery after surgery recommend steps to follow and cover all areas of the patient's journey through the surgical process. We looked at the application of the elements for patients with bladder cancer. We found inconsistent reporting and use.

To assess the prognostic value of sex for non-muscle-invasive/muscle-invasive bladder urothelial carcinoma (NMIBC/MIBC) treated with radical surgery.The PubMed, Web of Science, and Scopus databases were searched in November 2021 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Studies were deemed eligible if they involved the comparison of the overall, cancer-specific, progression, and recurrence-free survival of patients with NMIBC/MIBC. Formal sex-stratified meta-analyses of these outcomes were performed.Thirty-one studies, which included 32,525 patients with NMIBC, and 63 studies, which included 85,132 patients with MIBC, were eligible for review and meta-analysis. Female sex was associated with worse cancer-specific survival (pooled hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.11-1.31) and overall survival (pooled HR, 1.02; 95% CI, 1.00-1.05) in patients with MIBC. In contrast, however, sex was not associated with cancer-specific survival (pooled HR, 1.01; 95% CI, 0.70-1.46), progression-free survival (pooled HR, 1.04; 95% CI, 0.88-1.24), and recurrence-free survival (pooled HR, 1.06; 95% CI, 0.98-1.16) in patients with NMIBC.Sex is associated with an increased risk of worse survival outcomes in patients with MIBC but not in those with NMIBC. Given the genetic and social differences between sexes, sex may represent a key factor in the clinical decision-making process.

A trend towards greater benefit from adjuvant chemotherapy (ACT) in pN+ bladder cancer (BCa) has been observed in multiple randomized controlled trials. However, it is still unclear which patients might benefit the most from this approach. We retrospectively analyzed a multicenter cohort of 1381 patients with pTany pN1-3 cM0 R0 urothelial BCa treated with radical cystectomy (RC) with or without cisplatin-based ACT. The main endpoint was overall survival (OS) after RC. We performed 1:1 propensity score matching to adjust for baseline characteristics and conducted a classification and regression tree (CART) analysis to assess postoperative risk groups and Cox regression analyses to predict OS. Overall, 391 patients (28%) received cisplatin-based ACT. After matching, two cohorts of 281 patients with pN+ BCa were obtained. CART analysis stratified patients into three risk groups: favorable prognosis (≤pT2 and positive lymph node [PLN] count ≤2; odds ratio [OR] 0.43), intermediate prognosis (≥pT3 and PLN count ≤2; OR 0.92), and poor prognosis (pTany and PLN count ≥3; OR 1.36). Only patients with poor prognosis benefitted from ACT in terms of OS (HR 0.51; p 0.001). We created the first algorithm that stratifies patients with pN+ BCa into prognostic classes and identified patients with pTany BCa with PLN ≥3 as the most suitable candidates for cisplatin-based ACT. PATIENT SUMMARY: We found that overall survival among patients with bladder cancer and evidence of lymph node involvement depends on cancer stage and the number of positive lymph nodes. Patients with more than three nodes affected by metastases seem to experience the greatest overall survival benefit from cisplatin-based chemotherapy after bladder removal. Our study suggests that patients with the highest risk should be prioritized for cisplatin-based chemotherapy after bladder removal.

Platinum-based combination chemotherapy is the standard treatment for advanced or metastatic urothelial carcinoma (AMUC). However, data comparing the efficacy of different platinum agents are limited.This review aimed to assess the efficacy of carboplatin as a first-line treatment for AMUC using phase 3 randomized trial data.Multiple databases were searched for articles published until August 2021. Studies that compared overall survival (OS), complete response (CR), and objective response rates (ORRs) in chemotherapy-eligible patients with AMUC were deemed eligible.Four studies were included. Compared with immune checkpoint inhibitor (ICI) monotherapy, neither cisplatin- nor carboplatin-based chemotherapy was associated with significant OS (hazard ratio [HR]: 0.97, 95% confidence interval [CI]: 0.85-1.11, p = 0.64 and HR: 0.90, 95% CI: 0.78-1.04, p = 0.16, respectively) and CR (odds ratio [OR]: 1.16, 95% CI: 0.70-1.92, p = 0.57 and OR: 0.89, 95% CI: 0.52-1.53, p = 0.67, respectively benefits, while both were associated with a favorable ORR (OR: 0.54, 95% CI: 0.40-0.74, p0.001 and OR: 0.58, 95% CI: 0.42-0.80, p0.001, respectively). A network meta-analysis (NMA)-based indirect comparison between carboplatin and cisplatin revealed that while cisplatin was slightly better than carboplatin in terms of OS, CR, and ORR, no significant difference was noted.Cisplatin- and carboplatin-based chemotherapies offer similar OS/CR benefits to ICI monotherapy and elicit a greater ORR than ICI monotherapy. Moreover, our NMA demonstrated that both cisplatin- and carboplatin-based chemotherapy have a similar efficacy in terms of OS, CR, and ORR. Given that carboplatin-based chemotherapy is shown to be more effective in contemporary series than in historical controls, it is strongly recommended that carboplatin be re-examined for its value in the era of ICIs and beyond.Cisplatin- as well as carboplatin-based chemotherapy is as effective as immune checkpoint inhibitors in terms of survival and eliciting a positive response. It is currently believed that cisplatin provides greater benefits than carboplatin; this requires re-evaluation.

Purpose of review The role of a re-transurethral resection (TUR) is clearly demonstrated in T1 high-grade nonmuscle invasive bladder cancer. However, its role remains controversial for Ta high-risk tumors and the recent European guidelines stated that the second look procedure could be avoided for these patients despite harboring a high-risk of both disease recurrence and progression. We aimed to evaluate the added benefit on staging, response to bacillus Calmette-Guerin and oncological outcomes of re-TUR in patients with Ta high-grade nonmuscle invasive bladder cancer. Recent findings Overall, we identified 15 studies, including 3912 patients from which 743 harbored Ta high-grade disease. Delay between first and second TUR was ranging from 2 to 12 weeks (median 5.6 weeks). The rate of residual disease was 52.8% (range 17-67%). The rate of overall upstaging to T1 and muscle-invasive disease were 10.9 and 4.7%, respectively. Although there was a trend toward improvement of recurrence-free survival outcomes, no definitive conclusions can be drawn due to the retrospective design of the studies included. Summary Residual tumor is common after initial TUR for Ta high-grade. Re-TUR is useful in reducing the rates of residual disease, may improve staging, response to bacillus Calmette-Guerin and oncological outcomes.

Simple Summary Intravesical immunotherapy with bacillus Calmette-Guerin (BCG) is the standard therapy for high-risk non-muscle invasive bladder cancer. Different BCG strains are currently available and the superiority of any BCG strain over another could not be demonstrated yet. We compared the efficacy of two BCG strains: RIVM and TICE, respectively. In this propensity-score matched cohort study, we showed no particular survival benefit of TICE vs RIVM in the case of high-risk disease. Nevertheless, stratifying our data for re-staging procedures and for those who received BCG maintenance, we identified BCG TICE to improve RFS independently. Herein, we corroborated the importance of performing a routine secondary resection followed by an adequate maintenance course of BCG. Future larger prospective randomized head-to-head trials are needed to further elucidate this important topic, especially in this era of BCG shortage. Background: Intravesical immunotherapy with bacillus Calmette-Guerin (BCG) is the standard therapy for high-risk non-muscle invasive bladder cancer (NMIBC). The superiority of any BCG strain over another could not be demonstrated yet. Methods: Patients with NMIBCs underwent adjuvant induction +/- maintenance schedule of intravesical immunotherapy with either BCG TICE or RIVM at two high-volume tertiary institutions. Only BCG-naive patients and those treated with the same strain over the course of follow-up were included. One-to-one (1:1) propensity score matching (PSM) between the two cohorts was utilized to adjust for baseline demographic and tumor characteristics imbalances. Kaplan-Meier estimates and multivariable Cox regression models according to high-risk NMIBC prognostic factors were implemented to address survival differences between the strains. Sub-group analysis modeling of the influence of routine secondary resection (re-TUR) in the setting of the sole maintenance adjuvant schedule for the two strains was further performed. Results: 852 Ta-T1 NMIBCs (n = 719, 84.4% on TICE; n = 133, 15.6% on RIVM) with a median of 53 (24-77) months of follow-up were reviewed. After PSM, no differences at 5-years RFS, PFS, and CSS at both Kaplan-Meier and Cox regression analyses were detected for the whole cohort. In the sub-group setting of full adherence to European/American Urology Guidelines (EAU/NCCN), BCG TICE demonstrated longer 5-years RFS compared to RIVM (68% vs. 43%, p = 0.008; HR: 0.45 95% CI 0.25-0.81). Conclusion: When routinely performing re-TUR followed by a maintenance BCG schedule, TICE was superior to RIVM for RFS outcomes. However, no significant differences were detected for PFS and CSS, respectively.

Predicting the risk of side-specific extracapsular extension (ECE) is essential for planning nerve-sparing radical prostatectomy (RP) in patients with prostate cancer (PCa).To externally validate available models for prediction of ECE.Sixteen models were assessed in a cohort of 737 consecutive PCa patients diagnosed via multiparametric magnetic resonance imaging (MRI)-targeted and systematic biopsies and treated with RP between January 2016 and November 2021 at eight referral centers.Model performance was evaluated in terms of discrimination using area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analysis (DCA).Overall, ECE was identified in 308/1474 (21%) prostatic lobes. Prostatic lobes with ECE had higher side-specific clinical stage on digital rectal examination and MRI, number of positive biopsy cores, and International Society of Urological Pathology grade group in comparison to those without ECE (all p 0.0001). Less optimistic performance was observed in comparison to previous published studies, although the models described by Pak, Patel, Martini, and Soeterik achieved the highest accuracy (AUC ranging from 0.73 to 0.77), adequate calibration for a probability threshold40%, and the highest net benefit for a probability threshold8% on DCA. Inclusion of MRI-targeted biopsy data and MRI information in models improved patient selection and clinical usefulness. Using model-derived cutoffs suggested by their authors, approximately 15% of positive surgical margins could have been avoided. Some available models were not included because of missing data, which constitutes a limitation of the study.We report an external validation of models predicting ECE and identified the four with the best performance. These models should be applied for preoperative planning and patient counseling.We validated several tools for predicting extension of prostate cancer outside the prostate gland. These tools can improve patient selection for surgery that spares nerves affecting recovery of sexual potency after removal of the prostate. They could potentially reduce the risk of finding cancer cells at the edge of specimens taken for pathology, a finding that suggests that not all of the cancer has been removed.

Patients with upper tract urothelial carcinoma (UTUC) often have a delayed diagnosis and by then, present with advanced disease which has been shown to be associated with lymphovascular invasion (LVI). It has been suggested to be involved in the metastatic cascade of the disease. In this review, we provide an extensive up-to-date summary of the current knowledge about the prognostic impact of LVI in patients undergoing radical nephroureterectomy (RNU). A systematic search of PubMed/MEDLINE, Scopus, EMBASE, and Web of Science for all reports published from 2010 through 2021 was performed. We performed pooled analyses of hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) of series that evaluated LVI as a prognostic factor in adults with UTUC who underwent RNU. The assessed oncological outcomes were disease recurrence, cancer-specific and overall survival. A meta-regression analysis was used to explore potential heterogeneity. A total of 58 series met the eligibility criteria for qualitative and quantitative synthesis. We included 29,829 patients, ranging from 101 to 2492 per study. All series were retrospective. LVI was present in 7,818 patients (26.2%). The median age of the patients was 69 years and the median follow-up was 40 months. In 40 of 58 studies (68.9%), adjuvant chemotherapy was given. The pooled HRs show that LVI predicts a greater risk of recurrence of the disease (pooled HR 1.43, 95% CI: 1.31-1.55, P = 0.000; I