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The objective of the current research was to explore the potential prognostic value of readily available clinical and pathologic variables in bladder cancer. The novel association found between cholesterol levels and prognosis may provide the rationale for exploring novel treatments. Patients included had histologically confirmed urothelial bladder cancer and were treated with at least 3 cycles of cisplatin-based neoadjuvant chemotherapy before radical cystectomy with lymphadenectomy. A total of 245 patients at low, intermediate and high risk, presenting with 0-1, 2 or 3-4 risk factors, including positive lymph nodes, Hb 12.8, NLR ≥2.7 and cholesterol levels ≥199, were included. Five-year cancer-specific survival rate was 0.67, 0.78 and 0.94 at high, intermediate and low risk, respectively. Total cholesterol levels at the time of cystectomy may represent a commonly assessable prognostic factor and may be incorporated in a clinically meaningful risk-group classification model.Lay abstract This present study assessed a large group of patients with urothelial bladder cancer treated with chemotherapy followed by radical cystectomy, to capture the predictive power of commonly collected clinical, pathological and biochemical factors. The design of the study highlighted that higher cholesterol levels at the time of cystectomy were associated with shorter cancer-specific survival. This finding suggests that high blood-cholesterol levels truly have a negative influence on surviving cancer. In conclusion, total cholesterol levels at the time of cystectomy may represent a commonly assessable prognostic factor and could be incorporated into a clinically meaningful and valuable risk-group classification model.

Background The use of a nephron-sparing surgery for the treatment of localized renal masses is being pushed to more challenging cases. However, this procedure is not devoid of risks, and the Radius, Exophytic/Endophytic, Nearness, Anterior/Posterior, Location (RENAL) and Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) classifications are commonly employed in the prediction of complications. Recently, the Simplified PADUA REnal (SPARE) scoring system has been proposed with the aim to provide a more simple system, to improve its reproducibility to predict postoperative risks. Objective We aim to retrospectively validate and compare the proposed new SPARE system in a multi-institutional population. Design, setting, and participants The Transatlantic Robotic Nephron-sparing Surgery (TRoNeS) study group collected data from 737 patients subjected to robot-assisted partial nephrectomy (RAPN) between 2010 and 2016 at three tertiary care referral centers. Of these patients, 536 presented complete demographic and clinical data. Outcome measurements and statistical analysis Renal masses were classified according to the SPARE, RENAL, and PADUA nephrometry scores, and surgical success was defined according to the margin, ischemia, and complication scores. Results and limitations Of 536 patients, 340 were male; the median age was 61 (53–69) yr and preoperative tumor size was 30 (22–43) mm. The margin, ischemia, and complication score was achieved in 399 of cases (74.4%). All three nephrometry scores were significant predictors of surgical outcomes both in univariate and in adjusted multivariate logistic regression model analysis. In accuracy analysis, the area under the curve (AUC) of the SPARE scoring system (0.73) was significantly higher than those of the PADUA (0.65) and RENAL (0.68) nephrometry scores in predicting surgical success. Conclusions The SPARE score appears to be a promising and reliable score for the prediction of surgical outcomes of RAPN, showing a higher accuracy relative to the traditional PADUA and RENAL nephrometry scores. Further, prospective studies are warranted before its introduction in clinical practice. Patient summary The Simplified PADUA REnal (SPARE) score is a reproducible and simple nephrometry score, offering better predictive capabilities of surgical success and complications.

Background: Bladder cancer (BC) staging is challenging. There is an important need for available and affordable predictors to assess, in combination with imaging, the presence of locally-advanced disease. Objective: To determine the role of the De Ritis ratio (DRR) and neutrophils to lymphocytes ratio (NLR) in the prediction of locally-advanced disease defined as the presence of extravescical extension (pT ⩾ 3) and/or lymph node metastases (LNM) in patients with BC treated with radical cystectomy (RC). Methods: We retrospectively analyzed clinical and pathological data of 139 consecutive patients who underwent RC at our institution. Logistic regression models (LRMs) were fitted to test the above-mentioned outcomes. Results: A total of 139 consecutive patients underwent RC at our institution. Eighty-six (61.9%) patients had a locally-advanced disease. NLR (2.53 and 3.07; p = 0.005) and DRR (1 and 1.17; p = 0.01) were significantly higher in patients with locally-advanced disease as compared to organ-confined disease. In multivariable LRMs, an increasing DRR was an independent predictor of locally-advanced disease (OR = 3.91; 95% CI: 1.282–11.916; p = 0.017). Similarly, an increasing NLR was independently related to presence of locally-advanced disease (OR = 1.28; 95% CI: 1.027–1.591; p = 0.028). In univariate LRMs, patients with DRR > 1.21 had a higher risk of locally advanced disease (OR = 2.83; 95% CI: 1.312–6.128; p = 0.008). Similarly, in patients with NLR > 3.47 there was an increased risk of locally advanced disease (OR = 3.02; 95% CI: 1.374–6.651; p = 0.006). In multivariable LRMs, a DRR > 1.21 was an independent predictor of locally advanced disease (OR = 2.66; 95% CI: 1.12–6.35; p = 0.027). Similarly, an NLR > 3.47 was independently related to presence of locally advanced disease (OR = 2.24; 95% CI: 0.95–5.25; p = 0.065). No other covariates such as gender, BMI, neoadjuvant chemotherapy or diabetes reached statistical significance. The AUC of the multivariate LRM to assess the risk of locally advanced disease was 0.707 (95% CI: 0.623–0.795). Limitations include the retrospective nature of the study and the relatively small sample size.

To evaluate the feasibility, safety, and efficacy of ultrasound-guided transperineal laser ablation (TPLA) as a new minimally invasive surgical therapy (MIST) for the treatment of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). Under local anesthesia and conscious sedation up to two laser fibers for each prostatic lobe were inserted under US-guidance by a percutaneous approach. TPLA was performed using a continuous wave diode laser (SoracteLite-EchoLaserX4) able to generate a light-induced thermal heating and subsequent coagulative necrosis of the prostatic tissue. Patients were evaluated at 3, 6, and 12 months after TPLA. Twenty-two consecutive patients were prospectively enrolled (median age 61.9 years). All procedures were well tolerated and no procedural complications were recorded. Median catheterization time was 7 days, while the median hospitalization time was 1 day. Three out of twenty-two patients (13.6%) experienced acute urinary retention and two (9.1%) of them urinary tract infection requiring major antibiotic treatment. At 3, 6, and 12 months, median prostate volume significantly decreased by a − 21.3%, − 29%, and − 41%, respectively. At the same time point, median IPSS was 8 (− 63.6%), 5 (− 74%), and 6 (− 75%), while median QoL score was 1 in all the scheduled timepoints of follow-up. The median postoperative Qmax at 3, 6, and 12 months improved by + 57.8%, + 98%, and + 115.8%, respectively. Ejaculatory function was preserved in 21 out of 22 patients (95.5%). TPLA of the prostate appears to be a promising MIST for BPH. Long-term results and comparative studies against standard treatments are warranted before implementations of this technique in the urologist’s armamentarium.

Background En bloc resection (ERBT) is a valid alternative to piecemeal resection for non–muscle-invasive bladder cancer (NMIBC), guaranteeing pathological outcomes. However, very few studies investigated long-term oncological outcomes of ERBT. Objective To report long-term oncological outcome of ERBT. Design, setting, and participants This is a retrospective analysis of prospectively collected data. We included patients who underwent ERBT from June 2010 to February 2014, and were diagnosed with NMIBC at pathology evaluation. Outcome measurements and statistical analysis The primary study endpoint was recurrence-free survival at 5 yr. Secondary outcomes were presence of detrusor muscle, recurrence rate at the first follow-up cystoscopy, progression to muscle-invasive bladder cancer (MIBC) at 5 yr, and factors associated with long-term oncological outcomes. Kaplan-Meier curves were used to describe recurrence-free survival time. A univariate analysis was used to investigate factors associated with recurrence. Results and limitations Overall, 74 patients were included in this study. The median age was 71 (66–76) yr. Most of the patients presented with only one bladder tumor, and the median tumor diameter was 2 (interquartile range [IQR] 1–2.5) cm. After histopathological examination, eight, 35, and 31 patients were diagnosed with low-, intermediate-, and high-risk disease, respectively. All the en bloc resected tumors showed the presence of detrusor muscle. The median follow-up was 72 (IQR 66–90) mo. The recurrence rate at the first follow-up cystoscopy was 5.4% (four out of 74 patients). Overall, 57 (77%) patients were free of recurrence at 5 yr. No progression to MIBC was observed: progression-free survival was 100%. Limitations include retrospective design and small size. Conclusions Our findings showed that ERBT for NMIBC presents an optimal long-term oncological outcome. Further studies with larger cohorts are necessary for confirming our preliminary results and for a direct comparison with the traditional piecemeal resection. Patient summary In case of superficial bladder tumors, transurethral resection of the entire tumor and its base in one piece seems to provide good long-term results in terms of recurrence and progression rates., Take Home Message Our findings show that patients undergoing en bloc transurethral resection for non–muscle-invasive bladder cancer have very promising 5-yr recurrence- and progression-free survival rates.

This collection of cases describes some unusual urological tumors and complications related to urological tumors and their treatment. Case 1: A case of uretero-arterial fistula in a patient with long-term ureteral stenting for ureteral oncological stricture and a second case associated to retroperitoneal fibrosis were described. Abdominal CT, pyelography, cystoscopy were useful to show the origin of the bleeding. Angiography is useful for confirming the diagnosis and for subsequent positioning of an endovascular prosthesis which represents a safe approach with reduced post-procedural complications. Case 2: A case of patient who suffered from interstitial pneumonitis during a cycle of intravesical BCG instillations for urothelial cancer. The patient was hospitalized for more than two weeks in a COVID ward for a suspected of COVID-19 pneumonia, but he did not show any evidence of SARS-CoV-2 infection during his hospital stay. Case 3: A case of a young man with a functional urinary bladder paraganglioma who was successfully managed with complete removal of the tumor, leaving the urinary bladder intact. Case 4: A case of a 61 year old male suffering from muscle invasive bladder cancer who was admitted for a radical cystectomy and on the eighth postoperative day developed microangiopathic hemolytic anemia and thrombocytopenia, which clinically defines thrombotic microangiopathy.

The dogma that urine is sterile has been overturned and dysbiosis of the urinary microbiome has been linked to many urological disorders. We tested the hypothesis that the urinary microbial composition may be different between men with or without bladder cancer in catheter collected urines, bladder washouts and midstream voided urines, and may be dependent on tumor staging.Liquid samples were collected from male patients with bladder cancer, and sex and age matched nonneoplastic controls. Total DNA was extracted and processed for 16S rRNA gene sequencing. Bioinformatic analysis for microbial classification was performed to assess diversity and variations.The urinary microbiome associated with catheter collected urine samples of patients with bladder cancer was characterized by a significantly increased abundance ofThe bladder is colonized by endogenous bacteria and microbial modifications characterize the microbiome of patients with bladder cancer. Different microbial compositions can be characterized by changing sampling strategy. These results pave the way for exploring new diagnostic and therapeutic options based on the manipulation of the bacterial community.

Background Magnetic resonance imaging (MRI) has been proposed as a staging tool for bladder cancer (BC), but its use has been limited by its high costs and limited availability. Microultrasound (mUS) is a novel technology capable of providing high-resolution images of the prostate. Objective To test the feasibility of high-resolution mUS in patients diagnosed with BC and its ability to differentiate between non-muscle-invasive BC (NMIBC) and muscle-invasive BC (MIBC). Design, setting, and participants This is an observational prospective study performed in 23 patients with a diagnosis of primary BC scheduled for an endoscopic treatment. Surgical procedure Micro-US was performed before transurethral resection of bladder tumor using the ExactVu system with an EV29L 29-MHz side-fire transducer (Exact Imaging, Markham, Canada). Measurements The endpoints were to test the feasibility, describe the normal bladder wall anatomy, identify the lesions, and compare the mUS findings with the histopathological results. Results and limitations Micro-US was accurate in differentiating the three layers of the bladder wall in all cases. Bladder cancers were clearly identified as heterogeneous structures protruding from the normal bladder wall. In 14 cases the lesions appeared confined to the lamina propria, and in all cases NMIBC was confirmed by the final pathological report. In the other patients, the lesions seemed to extend into the muscular layer, but MIBC was confirmed in five out of seven cases (71.4%) from the pathologist. The small sample size was the main limitation of the current study. Conclusions Our findings showed that mUS is able to differentiate the bladder wall layers and identify the bladder cancer stage. Further studies with a larger population and imaging correlation with MRI are warranted before its introduction in clinical practice. Patient summary In this report, a new imaging technique was tested for the characterization of bladder cancer. Microultrasound appears to be feasible and capable of discriminating between superficial and invasive tumors.

Background The adoption of robotic technology in the treatment of prostate cancer (PCa) could lead to improvement in outcomes. Objective To evaluate feasibility, to compare functional outcomes, and to assess the economic benefits of removing catheter on the postoperative day (POD) 3 versus POD 5 after robot-assisted radical prostatectomy (RARP). Design, setting, and participants From September 2016 to May 2017, patients selected to undergo RARP for clinically localized PCa at a high-volume center were prospectively randomized into group 1 (POD 3; n = 72) versus group 2 (POD 5, n = 74). Intervention All patients underwent RARP with anatomical posterior and anterior reconstruction. Outcome measurements and statistical analysis The primary endpoint was to compare acute urinary retention (AUR) and urinary leakage rate in the two groups. The secondary endpoints were early and mid-term postoperative functional outcomes assessed through questionnaires (ICIQ-MLUTS, IPSS), early continence rate, and postoperative pain/discomfort (visual analog scale score). The economic impact of early catheter removal was also assessed. Results and limitations AUR was reported in two (1.4%) cases, one for each study group (p = 0.9). One case of vesicourethral leakage was reported (0.7%) in group 1. Urethral discomfort and pain at discharge was significantly higher in group 2 (p = 0.03). In our clinical practice, POD 3 catheter removal approach would determine a saving of approximately €80 000 and 405 d of hospitalization yearly. The main limitation is the small sample size. Conclusions Early catheter removal after RARP does not lead to an increase in perioperative complications. No negative effect on early and mid-term functional outcomes was observed. A significant impact on saving economic resources was reported. Patient summary We demonstrated that early catheter removal has no negative effect on spontaneous voiding, complications, or urinary continence recovery after robot-assisted radical prostatectomy.

INTRODUCTION AND OBJECTIVE:MRI improved the detection of clinically significant PCa (csPCa), yet the consistent number of csPCa missed at MRI-target biopsy prevents us from omitting systematic biop...

INTRODUCTION AND OBJECTIVE:Natural history of Low-risk Non-Muscle-Invasive Bladder Cancers (NMIBCs) is characterized by a high recurrence rate and a very low progression rate. Active Surveillance (...

INTRODUCTION AND OBJECTIVE:At present no clear indication exists regarding the optimal treatment for non-muscle invasive micropapillary bladder cancer (NMI-MPBC). We compared cancer-specific surviv...

INTRODUCTION AND OBJECTIVE:Recently, micro-ultrasound (microUS) has been proposed as an alternative to multiparametric magnetic resonance imaging for the diagnosis of clinically significant Prostat...

INTRODUCTION AND OBJECTIVE:Multiparametric MRI (MRI) has consolidated its role in the diagnosis of prostate cancer (PCa). High-resolution micro-ultrasound (mUS) is a new imaging modality enabling r...

Background Literature lacks clear evidence regarding the optimal treatment for non–muscle-invasive micropapillary bladder cancer (MPBC) due to its rarity and the presence of only small sample size and single-centre studies. Objective To assess cancer-specific mortality (CSM) and overall mortality (OM) between immediate radical cystectomy (RC) and conservative management among T1 high-grade (HG) MPBC. Design, setting, and participants We retrospectively analysed a multicentre dataset including 119 T1 HG MPBC patients treated between 2005 and 2019 at 15 tertiary referral centres. The median follow-up time was 35 mo (interquartile range: 19–64). Intervention Patients underwent immediate RC versus conservative management with bacillus Calmette-Guerin. Outcomes measurements and statistical analysis Cumulative incidence functions and Kaplan-Meier methods were applied to estimate survival outcomes. Multivariable Cox analyses were performed to assess independent predictors of disease recurrence and disease progression after conservative management; covariates consisted of pure MPBC, concomitant lymphovascular invasion (LVI), and carcinoma in situ at initial diagnosis. Results and limitations Immediate RC and conservative management were performed in 27% and 73% of patients, respectively. CSM and OM did not differ significantly among patient treated with immediate RC versus conservative management (Pepe-Mori test p = 0.5 and log-rank test p = 0.9, respectively). Overall, 66.7% and 34.5% of patients experienced disease recurrence and disease progression after conservative management, respectively. At multivariable Cox analyses, concomitant LVI was an independent predictor of disease recurrence (p = 0.01) and progression (p = 0.03), while pure MPBC was independently associated with disease progression (p = 0.03). The absence of a centralised re-review and the retrospective design represent the main limitations of our study. Conclusions Conservative management could achieve satisfactory results among T1 HG MPBC patients with neither pure MPBC nor LVI at initial diagnosis. Patient summary Bacillus Calmette-Guerin seems to be an effective therapy for T1 micropapillary bladder cancer patients with neither pure micropapillary disease nor lymphovascular invasion at initial diagnosis.

Active surveillance (AS) has been proposed as an alternative to transurethral resection (TUR) in selected patients with recurrent low-risk non–muscle-invasive bladder cancer (NMIBC). Here we report long-term results for patients on AS and investigate features associated with AS failure. Cases with recurrence after diagnosis of low-grade (LG) pTa/pT1a NMIBC were enrolled in the Bladder Italian Active Surveillance (BIAS) project. Over 251 AS events, we observed 130 failures (51.8%). In these patients, final pathology showed 25 benign lesions (19.2%) and 92 LG Ta (70.7%), 12 high-grade Ta/T1 (9.2%), and one T2 (0.7%) tumor. The treatment-free probability at 12, 18, 24, and 36 mo was 59.7%, 54.5%, 46.3%, and 40.4%, respectively. We identified 95 patients (37.8%) who remained on AS for >18 mo. A multivariable Cox regression model confirmed that patients with a history of multiple TURs (hazard ratio [HR] 1.59, 95% confidence interval [CI] 1.01–2.51) and those with more than one lesion at AS entry (HR 1.63, 95% CI 1.05–2.54) were significantly more likely to experience AS failure. Our results confirm that well-selected patients with NMIBC can safely remain on AS for a long period of time. Multiple TURs and multiple lesions at AS enrollment are associated with a higher risk of AS failure. Patient summary Active surveillance has been proposed as an alternative to surgery for patients with recurrent low-risk superficial bladder cancer. Our report confirms that well-selected patients can safely avoid or postpone surgery.

Purpose This study reports the safety and efficacy of Oncofid−P-B, a novel compound under development by Fidia Farmaceutici S.p.A. with specific binding to CD44 receptor, in patients with CIS unresponsive or intolerant to BCG. Materials and Methods This is a phase 1 open-label, single arm, multicenter European study to assess safety, tolerability and efficacy of Oncofid-P-B administered in 20 patients with CIS ± Ta-T1, unresponsive or intolerant to BCG, unwilling or unfit for cystectomy. Oncofid-P-B was administered by intravesical instillation for 12 consecutive weeks (intensive phase) followed, in CR patients, by 12 monthly instillations (maintenance phase). The primary objective was the overall safety profile. Secondary objectives included: i) any evidence of antitumor activity, ii) patient's compliance, iii) systemic absorption. The CR was defined as a negative cystoscopy, negative biopsy of the urothelium and negative cytology. Results At the end of the intensive phase, 15 of the 20 enrolled patients (75%), achieved the CR. Patients still in CR after 3, 6, 9 and 12 months of maintenance phase were 13 (65%), 12 (60%), 9 (45%) and 8 (40%), respectively. Only seven (5 mild and 2 moderate) drug-related AEs were reported in three patients. No drug related serious AEs and no drug related withdrawals have been reported. In all plasma samples, the drug concentratiosn was below the LLOQ (1ng/ml). Conclusions Oncofid-P-B is very safe, well tolerated and highly effective (75% CR) when administered weekly for up to 12 consecutive weeks (75% CR), with 40% CR still after 15 months from treatment start.

Aim: To investigate the prognostic role of neutrophil percentage-to-albumin ratio (NPAR) in muscle-invasive bladder cancer (MIBC) patients treated with neoadjuvant chemotherapy (NAC) and radical cystectomy (RC). Patients & methods: 213 patients were included. Inclusion criteria: Nonmetastatic, MIBC (cT2-T4aN0M0), at least three cycles of NAC, undergone RC and with blood count within 30 days before NAC. Results: Five-years overall survival (OS) with NPAR >18 was 34.06% (95% CI: 18.3–50.5) and 65.37% (95% CI: 52.4–75.6) with NPAR 18 was 42.9% (95% CI: 23.9–60.7) and 74.5% (95% CI: 62.6–83.1) with NPAR, Lay abstract This research demonstrated that presence of a high neutrophil percentage-to-albumin ratio in patients with muscle-invasive bladder cancer prior neoadjuvant chemotherapy and radical cystectomy is associated with worse outcomes and reduced overall and cancer-specific survival. Thus, neutrophil percentage-to-albumin ratio could be a useful biological marker in clinical practice to help predict outcomes for patients with muscle-invasive bladder cancer.

Background: To investigate the impact of COVID-19 outbreak on the diagnosis and treatment of non-muscle invasive bladder cancer (NMIBC). Methods: A retrospective analysis was performed using an Italian multi-institutional database of TURBT patients with high-risk urothelial NMIBC between January 2019 and February 2021, followed by Re-TURBT and/or adjuvant intravesical BCG. Results: A total of 2591 patients from 27 institutions with primary TURBT were included. Of these, 1534 (59.2%) and 1056 (40.8%) underwent TURBT before and during the COVID-19 outbreak, respectively. Time between diagnosis and TURBT was significantly longer during the COVID-19 period (65 vs. 52 days, p = 0.002). One thousand and sixty-six patients (41.1%) received Re-TURBT, 604 (56.7%) during the pre-COVID-19. The median time to secondary resection was significantly longer during the COVID-19 period (55 vs. 48 days, p &lt, 0.0001). A total of 977 patients underwent adjuvant intravesical therapy after primary or secondary resection, with a similar distribution across the two groups (n = 453, 86% vs. n = 388, 86.2%). However, the proportion of the patients who underwent maintenance significantly differed (79.5% vs. 60.4%, p &lt, 0.0001). Conclusions: The COVID-19 pandemic represented an unprecedented challenge to our health system. Our study did not show significant differences in TURBT quality. However, a delay in treatment schedule and disease management was observed. Investigation of the oncological impacts of those differences should be advocated.

Introduction We aimed to test the hypothesis that the immune-modulatory effect of statins may improve survival outcomes in patients with non-muscle invasive bladder cancer (NMIBC). We focused on a cohort of patients diagnosed with high risk NMIBC, that were treated with intravesical BCG immunotherapy. Patients and methods We included patients at first diagnosis of T1 high grade NMIBC after transurethral resection of bladder (TURB). All procedures were performed at 18 different tertiary institutions between January 2002 and December 2012. Univariable and multivariable models were used to test differences in terms of residual tumour, disease recurrence, disease progression and overall mortality (OM) rates. Results Overall, 1510 patients with T1 high grade NMIBC at TURB were included in our analyses. Of these, 402 (26.6%) were statin users. At multivariable analysis, statin use was associated with a higher rates of high grade BC at re-TURB (OR: 1.37, 95%CI: 1.04-1.78; p=0.022), while at follow-up it was not independently associated with OM (HR: 0.71, 95%CI: 0.50-1.03; p=0.068) and disease progression rates (HR: 0.97, 95%CI: 0.79-1.19; p=0.753). Conversely, statin use has been shown to be independently associated with a lower risk of recurrence (HR:0.80, 95%CI: 0.67-0.95; p=0.009). The median recurrence-free survival was 47 (95%CI 40-49) months for those classified as non-statin users vs. 53 (95%CI 48-68) months in those classified as statin users. Conclusions Statin daily intake do not compromise oncological outcomes in high risk NMIBC patients treated with BCG. Moreover, statin may have a beneficial effect on recurrence rates in this cohort of patients.

BACKGROUND: There are sex differences in vulnerability to Coronavirus disease 2019 (COVID-19). The coronavirus S protein mediates viral entry into target cells employing the host cellular serine protease TMPRSS2 for S-protein priming. The TMPRSS2 gene expression is responsive to androgen stimulation and it could partially explain sex differences. We hypothesized that men chronically exposed to 5-alpha reductase inhibitors (5ARIs) for benign prostate hyperplasia (BPH) have a lower risk of hospitalization for COVID-19. METHODS: This is a population-based case-control study on consecutive patients positive for SARS-CoV-2 virus who required hospitalization for COVID-19 (cases), age-matched to beneficiaries of the Lombardy Regional Health Service (controls). Data were collected by two high-volume COVID-19 regional centers of Lombardy (Italy). The primary outcome was to compare the prevalence of patients chronically exposed to 5ARIs, who required hospitalization for COVID-19, with the one of controls. RESULTS: Overall, 943 males were enrolled; 45 (4.77%) were exposed to 5ARI. COVID-19 patients aged >55 years under 5ARI treatment were significantly less than expected on the basis of the prevalence of 5ARI treatment among age-matched controls (5.57 vs. 8.14%; p=0.0083, 95%CI=0.75-3.97%). This disproportion was higher for men aged >65 (7.14 vs. 12.31%; p=0.0001, 95%CI=2.83-6.97%). Eighteen 5ARIs-patients died; the mean age of men who died was higher than those who did not: 75.98±9.29 vs. 64.78±13.57 (p

Background An accurate and early diagnosis of bladder cancer (BC) is essential to offer patients the most appropriate treatment and the highest cure rate. For this reason, patients need to be best stratified by class and risk factors. We aimed to develop a score able to better predict cancer outcomes, using serum variables of inflammation. Methods A total of 1,510 high-risk non-muscle invasive bladder cancer (NMIBC) patients were included in this retrospective observational study. Patients with pathologically proven T1 HG/G3 at first TURBT were included. Systemic combined inflammatory score (SCIS) was calculated according to systemic inflammatory markers (SIM), modified Glasgow prognostic score (mGPS), and prognostic nutritional index (PNI) dichotomized (final score from 0 to 3). Results After 48 months of follow-up (IQR 40.0-73.0), 727 patients recurred (48.1%), 485 progressed (32.1%), 81 died for cancer (7.0%), and 163 died for overall causes (10.8%). Overall, 231 (15.3%) patients had concomitant Cis, 669 (44.3%) patients had multifocal pathology, 967 (64.1%) patients had tumor size >3 cm. Overall, 357 (23.6%) patients received immediate-intravesical therapy, 1,356 (89.8%) received adjuvant intravesical therapy, of which 1,382 (91.5%) received BCG, 266 (17.6%) patients received mitomycin C, 4 (0.5%) patients received others intravesical therapy. Higher SCIS was independently predictive of recurrence (hazard ratio HR 1.5, 1.3 and 2.2) and cancer specific mortality for SCIS 0 and 3 (HR: 1.61 and 2.3), and overall mortality for SCIS 0 and 3 (HR: 2.4 and 3.2). Conversely, SCIS was not associated with a higher probability of progression. Conclusions The inclusion of the SCIS in clinical practice is simple to apply and can help improve the prediction of cancer outcomes. It can identify patients with high-grade BC who are more likely to experience disease mortality.

BackgroundThree or four cycles of cisplatin-based chemotherapy is the standard neoadjuvant treatment prior to cystectomy in patients with muscle-invasive bladder cancer. Although NCCN guidelines recommend 4 cycles of cisplatin-gemcitabine, three cycles are also commonly administered in clinical practice. In this multicenter retrospective study, we assessed a large and homogenous cohort of patients with urothelial bladder cancer (UBC) treated with three or four cycles of neoadjuvant cisplatin-gemcitabine followed by radical cystectomy, in order to explore whether three vs. four cycles were associated with different outcomes.MethodsPatients with histologically confirmed muscle-invasive UBC included in this retrospective study had to be treated with either 3 (cohort A) or 4 (cohort B) cycles of cisplatin-gemcitabine as neoadjuvant therapy before undergoing radical cystectomy with lymphadenectomy. Outcomes including pathologic downstaging to non-muscle invasive disease, pathologic complete response (defined as absence of disease -ypT0), overall- and cancer-specific- survival as well as time to recurrence were compared between cohorts A vs. B.ResultsA total of 219 patients treated at 14 different high-volume Institutions were included in this retrospective study. Patients who received 3 (cohort A) vs. 4 (cohort B) cycles of neoadjuvant cisplatin-gemcitabine were 160 (73,1%) vs. 59 (26,9%).At univariate analysis, the number of neoadjuvant cycles was not associated with either pathologic complete response, pathologic downstaging, time to recurrence, cancer specific, and overall survival. Of note, patients in cohort B vs. A showed a worse non-cancer specific overall survival at univariate analysis (HR= 2.53; 95 CI= 1.05 - 6.10; p=0.046), although this finding was not confirmed at multivariate analysis.ConclusionsOur findings suggest that 3 cycles of cisplatin-gemcitabine may be equally effective, with less long-term toxicity, compared to 4 cycles in the neoadjuvant setting.

Objective: Overview of bladder cancer (BC) management in Italy during the first month of the COVID-19 pandemic (March 2020) with head to head comparison of the data from March 2019, considered “usual activity” period. The aim is to analyze performance of different Italian Centers in North, Center and South, with a special eye for Lombardy (the Italian epicenter). Patients and methods: During April 2020, a survey containing 14 multiple-choice questions focused on general staffing and surgical activity related to BC during the months of March 2019 and March 2020 was sent to 32 Italian Centers. Statistical analysis was performed using IBM SPSS Statistics (v26) software. A Medline search was performed, in order to attempt a comparative analysis with published papers. Results: 28 Centers answered, for a response rate of 87.5%. Most of the urology staff in the Lombardy region were employed in COVID wards (p = 0.003), with a statistically significant reduction in the number of radical cystectomies (RC) performed during that time (p = 0.036). The total amount of RC across Italy remained the same between 2019 and 2020, however there was an increase in the number of surgeries performed in the Southern region. This was most likely due to travel restrictions limiting travel the North. The number of Trans-Urethral Resection of Bladder Tumors (TURBT) (p = 0.046) was higher in Academic Centers (AC) in 2020 (p = 0.037).Conclusions: The data of our survey, although limited, represents a snap shot of the management of BC during the first month of the COVD-19 pandemic, which posed a major challenge for cancer centers seeking to provide care during an extremely dynamic clinical and political situation which requires maximum flexibility to be appropriately managed.

Objectives: Real-life overview of bladder cancer (BC) surgical management in Italy during the first month of COVID-19 pandemic (March 2020) with head to head comparison of the data from March 2019, considered “usual activity” period. The aim is to confront performance of Academic Centers (AC) vs Non Academic Centers (NAC) as well as non-COVID Centers (nCC) and COVID Centers (CC). Patients and methods: During April 2020, an e-mail survey was sent to 32 Sections of Urology across Italy. It contained 14 multiple-choice questions focused on activities during March 2019 and March 2020. Statistical analysis was performed using IBM SPSS Statistics (v26) software. Results28 centers answered to survey. AC and NAC showed statistically significant differences (chi-square test pConclusionThe COVID-19 pandemic represents an important challenge for cancer centers, in the context of an extremely dynamic clinical and political situation which requires maximum flexibility to be appropriately managed.

Background: The new severe acute respiratory syndrome virus (SARS-CoV-2) outbreak is a huge health, social and economic issue and has been declared a pandemic by the World Health Organization. Bladder cancer, on the contrary, is a well-known disease burdened by a high rate of affected patients and risk of recurrence, progression and death. Summary: The coronavirus disease (COVID-19 or 2019-nCoV) often involves mild clinical symptoms but in some cases, it can lead to pneumonia with acute respiratory distress syndrome and multiorgan dysfunction. Factors associated with developing a more severe disease are increased age, obesity, smoking and chronic underlying comorbidities (including diabetes mellitus). High-risk non-muscle-invasive bladder cancer (NMIBC) progression and worse prognosis are also characterized by a higher incidence in patients with risk factors similar to COVID-19. Immune system response and inflammation have been found as a common hallmark of both diseases. Most severe cases of COVID-19 and high-risk NMIBC patients at higher recurrence and progression risk are characterized by innate and adaptive immune activation followed by inflammation and cytokine/chemokine storm (interleukin [IL]-2, IL-6, IL-8). Alterations in neutrophils, lymphocytes and platelets accompany the systemic inflammatory response to cancer and infections. Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio for example have been recognized as factors related to poor prognosis for many solid tumors, including bladder cancer, and their role has been found important even for the prognosis of SARS-CoV-2 infection. Key Messages: All these mechanisms should be further analyzed in order to find new therapeutic agents and new strategies to block infection and cancer progression. Further than commonly used therapies, controlling cytokine production and inflammatory response is a promising field.

ImportanceThere are gender differences in vulnerability to the Coronavirus disease 2019 (COVID-19), with men experiencing more severe disease at any age. The use of anti-androgen drugs, like 5-alpha reductase inhibitors (5ARIs), could protect from severe pulmonary disease.ObjectiveTo determine whether men who received 5ARIs for benign prostatic hyperplasia (BPH) have a lower risk of hospitalization for COVID-19.DesignThis is a case-control study on patients hospitalized for COVID-19 (cases), matched to beneficiaries of the Lombardy Regional Health Service (controls).SettingData were collected by two high-volume COVID-19 regional centres of Lombardy (Italy) from 1st March to 24th April 2020.ParticipantsConsecutive patients positive for SARS-CoV-2 virus according to the WHO guidance, who required hospitalization.ExposureBPH treatment with 5ARIs (finasteride/dutasteride) in the last six months.Main Outcome(s) and Measure(s)The primary outcome was to compare the prevalence of male patients chronically exposed to 5ARIs, who required hospitalization for COVID-19, with the one of age-matched males in Lombardy.ResultsOverall, 1,432 COVID-19 patients were included. Among the 943 males, 45 (4.77%) patients were exposed to chronic 5ARI therapy. COVID-19 patients aged >55 years under 5ARI treatment were significantly less than expected on the basis of the prevalence of 5ARI treatment among age-matched controls (5.57 vs. 8.14%; p=0.0083, 95%CI=0.75-3.97%). This disproportion was even higher for men aged >65 (7.14 vs. 12.31%; p=0.0001, 95%CI=2.83-6.97%).Eighteen 5ARIs-patients died; the mean age of men who died was higher than those who did not: 75.98±9.29 vs. 64.78±13.57 (pConclusions and RelevanceIn this case-control study the use of 5ARIs was less frequent among patients hospitalized for COVID-19 than among controls, suggesting that men exposed to 5ARIs might be less vulnerable to severe COVID-19. This observation further supports the idea to test in randomized clinical trials whether anti-androgen therapies can prevent the transition from paucisymptomatic SARS-CoV-2 infection to overt pulmonary disease.KEY POINTSQuestionMay treatment of benign prostatic hyperplasia with 5-alpha reductase inhibitors (5ARIs) impact on COVID-19-related hospitalization risk?FindingsIn this case-control study, which compared 943 adult males hospitalized for COVID-19 with age-matched men from Lombardy (all beneficiaries of the Regional Health Service), the proportion of patients aged >55 years, who were exposed to 5ARIs (dutasteride, finasteride), was significantly lower (5.57%) than that of the general male population (8.14%) (p=0.0083, 95%CI=0.75-3.97%).MeaningThe use of 5ARIs was associated with a potential reduced risk of hospitalization for COVID-19 in men older than >55 years. This suggests the opportunity to test whether anti-androgen therapies can prevent the transition from paucisymptomatic SARS-CoV-2 infection to overt pulmonary disease.

INTRODUCTION AND OBJECTIVE:Active surveillance (AS) represents an important alternative to active treatment strategies in patients diagnosed with low-risk prostate cancer (PCa). We investigated the...

INTRODUCTION AND OBJECTIVE:Stone components and physical properties were important data in setting the laser lithotripter. The aim of the study was to investigate the hypothesis that a senior endou...

BACKGROUND: Basophils, eosinophils and monocytes may be involved in BCG-induced immune responses and be associated with outcomes of bladder cancer patients receiving intravesical BCG. Our objective was to explore the association of baseline counts of basophils, eosinophils and monocytes with outcomes of patients with high-grade T1 bladder cancer receiving a standard course of intravesical BCG. METHODS: We retrospectively reviewed medical records of patients with primary T1 HG/G3 bladder cancer. After re-TURBT, patients were treated with a 6-week course of intravesical BCG induction followed by intravesical BCG every week for 3 weeks given at 3, 6, 12, 18, 24, 30 and 36 months from initiation of therapy The analysis of potential risk factors for recurrence, muscle invasion and cancer-specific and overall survival was performed using univariable Cox regression models. Those factors that presented, at univariate analysis, an association with the event at a liberal p

Purpose To evaluate the predictive factors of pT0 at repeated transurethral resection of the bladder (re-TURB) in pT1 high-grade (HG) nonmuscle invasive bladder cancer in order to explore the possibility to avoid it in well-selected patients. Methods This multicenter retrospective study included patients with pT1HG nonmuscle invasive bladder cancer from 4 different centers who underwent a complete TURB. Re-TURB was defined as a second resection which involved the site of the first TURB performed within 2-6 weeks from the previous resection. A multivariable logistic-regression model was performed to evaluate the predictors of pT0 at re-TURB. A nomogram was built to calculate the probability of obtaining a negative histology at re-TURB. The performance of the nomogram and its net benefit were tested with the decision curve analysis. Results Overall, 321 patients were included in the study. On multivariable logistic regression, detrusor muscle in the specimen (HR 1.99, P = 0.02), concomitant carcinoma in situ (HR 0.29, P = 0.005) and resection performed with en-bloc technique (HR 7.71, P = 0.01) were independent predictors of pT0 at re-TURB. Decision curve analysis showed a net benefit for the nomogram for each probability over 0.35 compared to the strategy to perform a re-TURB in all pT1HG tumors. Conclusions The presence of detrusor muscle in TURB specimen, the absence of concomitant carcinoma in situ and the en-bloc resection were able to predict a negative histology at re-TURB, opening the door to the possibility to avoid it in an extremely well-selected cohort of patients. External validations and prospective studies are urgently needed.

The aim of this multicenter study was to investigate the prognostic role of neutrophil-to-lymphocyte ratio (NLR) and to validate the NLR cutoff of 3 in a large multi-institutional cohort of patients with primary T1 HG/G3 non-muscle-invasive bladder cancer (NMIBC)., M.D.V. is supported by the Scholarship Foundation of the Republic of Austria - OeAD and by the EUSP Scholarship - European Association of Urology.

Background It has been shown that active surveillance (AS) is feasible and effective in a subset of patients with recurrent low-grade (LG) non–muscle-invasive bladder cancer (NMIBC). Objective To update a previous preliminary series and investigate pathological outcomes for patients who failed to remain on AS. Design, setting, and participants Prospective observational cohort study started in February 2008, and currently still active, at a tertiary university hospital, including patients with pathologically confirmed NMIBC who experienced recurrence during follow-up. Intervention AS monitoring consisted of cytology and in-office flexible cystoscopy every 3 mo for the first year, and every 6 mo thereafter. Outcome measurements and statistical analysis The primary endpoint was pathological results for patients who failed to remain on AS. The secondary outcome was an update of clinical results from our previous series. Data were complemented by descriptive statistical analysis and univariable and multivariable proportional hazards Cox regression. Results and limitations Overall, 167 patients were included. Of 181 AS events, 61 (33.7%) were deemed to require treatment because of positive cytology (n = 10), gross haematuria (n = 11), and increases in the tumour number (n = 15), or size (n = 17), or both (n = 8). The median time on AS was 12 mo (interquartile range 4–26). Pathological specimens from AS failures did not show any malignancy in 20 cases. Histopathology identified urothelial hyperplasia and oedema, submucosal vascular ectasia, mucosal erosion, polypoid cystitis, von Brunn nest hyperplasia, and squamous metaplasia. The time from first transurethral resection to AS start was inversely associated with recurrence-free survival (hazard ratio 0.97, 95% confidence interval 0.96–1.00; p = 0.024). The study lacks statistical subanalyses focusing on patients with failure and negative neoplastic pathological outcomes. Conclusions AS might be a reasonable strategy in patients presenting with small LG pTa/pT1a recurrent bladder tumours. Approximately 30% of patients deemed to have AS failure did not harbour any neoplastic lesion, strengthening the role of AS. Patient summary Patients with small low-grade pTa/pT1a recurrent papillary bladder tumours could benefit from an active surveillance protocol with no significant risk of pathological progression to muscle-invasive cancer.

Context Repeat transurethral resection (reTUR) is advocated as a fundamental step towards complete clearance and appropriate staging of T1 bladder cancer tumors. Objective To assess the impact of reTUR in T1 bladder cancer via a systematic review of the literature and meta-analysis of available data sets. Evidence acquisition After definition of the population and of the outcome, a systematic search of English language articles in the literature from 1980 to 2016 was performed. The pooled prevalence of residual tumor and of upstaging at reTUR were assessed and computed using a random effects model to take into account heterogeneity showed by I 2 and Cochran's Q values. A sensitivity analysis was conducted to exclude excessive influence by a single study. Evidence synthesis Among the papers identified, 29 were selected. A total of 3566 and 2556 cases formed the study population for assessment of the prevalence of residual tumor and upstaging, respectively. The corresponding numbers for the subgroup with detrusor muscle involvement at the initial TUR were 1565 and 1187. The pooled prevalence was 0.56 (95% confidence interval [CI] 0.48–0.63) for residual tumor and 0.1 (95% CI 0.06–0.14) for upstaging to T2 at reTUR. The corresponding rates for the detrusor muscle subgroup were 0.47 (95% CI 0.33–0.62) and 0.1 (95% CI 0.06–0.14). The sensitivity analysis excluded an excessive influence of each of the studies examined. Conclusions Pooled prevalence rates for residual tumor (∼50%) and upstaging to invasive disease (10%) at reTUR in T1 cases were high, and were stable among studies in different decades and for cases with detrusor muscle involvement at the initial TUR. Therefore, reTUR remains a fundamental procedure. Patient summary Repeat transurethral resection after a diagnosis of stage T1 bladder cancer is recommended given the high risk of misallocation to the proper treatment.

Purpose: 68Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography may represent the most promising imaging modality to identify and risk stratify prostate cancer in patients with contraindications to or negative multiparametric magnetic resonance imaging.Materials and Methods: In this prospective observational study we analyzed 68Ga labeled prostate specific membrane antigen positron emission tomography/computerized tomography in a select group of patients with persistently elevated prostate specific antigen and/or Prostate Health Index suspicious for prostate cancer, negative digital rectal examination and at least 1 negative biopsy. The cohort comprised men with equivocal multiparametric magnetic resonance imaging (Prostate Imaging-Reporting and Data System, version 2 score of 2 or less), or an absolute or relative contraindication to multiparametric magnetic resonance imaging. Sensitivity, specificity and CIs were calculated compared to histopathology finding...