Glycosaminoglycan Replacement Therapy with Intravesical Instillations of Combined Hyaluronic Acid and Chondroitin Sulfate in Patients with Recurrent Cystitis, Post-radiation Cystitis and Bladder Pain Syndrome: A Narrative Review.

Defects in the glycosaminoglycan layer (GAG) of the bladder mucosa have been identified as a significant contributor to the pathogenesis and clinical progression of chronic inflammatory diseases of the bladder, such as post-radiation cystitis, bladder pain syndrome and recurrent urinary tract infections. This narrative review aims to explore the contemporary evidence on the role of GAG reconstitution with intravesical installations of hyaluronic acid and chondroitin sulfate in the management of those patients, with a goal to provide valuable insights for clinical practice. The reviewed studies consistently demonstrate that GAG reconstitution can result in varying degrees of clinical improvement in patients with post-radiation cystitis, bladder pain syndrome and recurrent urinary tract infections, and is associated with a very favorable safety profile. While the available evidence is growing, its level is still limited, mainly by relatively low number of randomized controlled trials, with small sample sizes. Further research with larger, well-designed trials is needed to solidify the findings and optimize the clinical application of GAG reconstitution.

Comparison of Multiparametric MRI, [68Ga]Ga-PSMA-11 PET-CT, and Clinical Nomograms for Primary T and N Staging of Intermediate-to-High-Risk Prostate Cancer.

PURPOSE OF THE REPORT: Although multiparametric magnetic resonance imaging (mpMRI) is commonly used for the primary staging of prostate cancer, it may miss non-enlarged metastatic lymph nodes. Positron emission tomography-computed tomography targeting the prostate-specific membrane antigen (PSMA PET-CT) is a promising method to detect non-enlarged metastatic lymph nodes, but more data are needed. MATERIALS AND METHODS: In this single-center, prospective study, we enrolled patients with intermediate-to-high-risk prostate cancer scheduled for radical prostatectomy with pelvic node dissection. Before surgery, prostate imaging with mpMRI and PSMA PET-CT was used to assess lymph node involvement (LNI), extra-prostatic extension (EPE), and seminal vesicle involvement (SVI). Additionally, we used clinical nomograms to estimate the risk of these three outcomes. RESULTS: Of the 74 patients included, 61 (82%) had high-risk prostate cancer, and the rest had intermediate-risk cancer. Histopathology revealed LNI in 20 (27%) patients, SVI in 26 (35%), and EPE in 52 (70%). PSMA PET-CT performed better than mpMRI at detecting LNI (area under the curve (AUC, 95% confidence interval): 0.779 (0.665-0.893) vs. 0.655 (0.529-0.780)), but mpMRI was better at detecting SVI (AUC: 0.775 (0.672-0.878) vs. 0.585 (0.473-0.698)). The MSKCC nomogram performed well at detecting both LNI (AUC: 0.799 (0.680-0.918)) and SVI (0.772 (0.659-0.885)). However, when the nomogram was used to derive binary diagnoses, decision curve analyses showed that the MSKCC nomogram provided less net benefit than mpMRI and PSMA PET-CT for detecting SVI and LNI, respectively. CONCLUSIONS: mpMRI and [68Ga]Ga-PSMA-11 PET-CT are complementary techniques to be used in conjunction for the primary T and N staging of prostate cancer.

Quantification of Gleason Pattern 4 at MRI-Guided Biopsy to Predict Adverse Pathology at Radical Prostatectomy in Intermediate-Risk Prostate Cancer Patients.

BACKGROUND: Data on Gleason pattern 4 (GP4) amount in biopsy tissue is important for prostate cancer (PC) risk assessment. We aim to investigate which GP4 quantification method predicts adverse pathology (AP) at radical prostatectomy (RP) the best in men diagnosed with intermediate-risk (IR) PC at magnetic resonance imaging (MRI)-guided biopsy. METHODS: We retrospectively included 123 patients diagnosed with IR PC (prostate-specific antigen <20 ng/mL, grade group (GG) 2 or 3, no iT3 on MRI) at MRI-guided biopsy, who underwent RP. Twelve GP4 amount-related parameters were developed, based on GP4 quantification method (absolute, relative to core, or cancer length) and site (overall, targeted, systematic biopsy, or worst specimen). Additionally, we calculated PV×GP4 (prostate volume × GP4 relative to core length in overall biopsy), aiming to represent the total GP4 volume in the prostate. The associations of GP4 with AP (GG ≥ 4, ≥pT3a, or pN1) were investigated. RESULTS: AP was reported in 39 (31.7%) of patients. GP4 relative to cancer length was not associated with AP. Of the 12 parameters, the highest ROC AUC value was seen for GP4 relative to core length in overall biopsy (0.65). an even higher AUC value was noted for PV × GP4 (0.67), with a negative predictive value of 82.8% at the optimal threshold. CONCLUSIONS: The lack of an association of GP4 relative to cancer length with AP, contrasted with the better performance of other parameters, indicates directions for future research on PC risk stratification to accurately identify patients who may not require immediate treatment. Incorporating formulas aimed at GP4 volume assessment may lead to obtaining models with the best discrimination ability.

Patient-reported pain associated with grid-based transperineal magnetic resonance imaging (MRI)/ultrasound (US) software fusion biopsy of the prostate under local anesthesia: a multicenter experience.

Background: Biopsy by transperineal (TP) approach is recommended standard for prostate cancer (PC) diagnosis. To avoid pain, patients undergoing TP biopsy may be offered sedation or general anesthesia. Our aim was to investigate the degree of patient-reported pain for magnetic resonance imaging (MRI)/ultrasound (US) fusion biopsy of the prostate being performed under local anesthesia (LA) and to study for possible factors associated with increased risk of significant pain (SP) in this setting. Methods: In this retrospective observational study, we reviewed data of consecutive patients without a prior diagnosis of PC who underwent MRI/US software fusion biopsy of the prostate under LA with lidocaine at two centers between May 2020 and April 2022, and who reported their periprocedural pain on a Wong-Baker FACES Pain Rating Scale (0-10). We defined SP as reported pain score of 6-10. Patient and procedure characteristics together with SP were studied for interdependencies. Results: A total of 299 patients were included. Median pain score was 2 (interquartile range: 2-4), with SP having been reported by 55 (18.4%) patients. Among patient characteristics, only age demonstrated association with SP [odds ratio (OR), per 10 years =0.53, 95% confidence interval (CI): 0.35-0.80, P=0.003] and patients aged 62 or above were significantly less likely to report SP (OR =0.33, 95% CI: 0.18-0.60, P<0.001). Conclusions: Performing TP MRI/US fusion prostate biopsy under LA is associated with low rates of SP, with the risk being significantly lower in older men. The results of this study can serve as evidence resource for preprocedural counselling in patients especially concerned about the risk of pain.

Polish version of the Acute Cystitis Symptom Score for patients with acute uncomplicated cystitis.

Introduction: The Acute Cystitis Symptom Score (ACSS) is a self-reporting questionnaire to evaluate the symptoms and quality of life in women with uncomplicated acute cystitis (AC). The aim of the current study was the additional cognitive and clinical validation of the Polish version. Material and methods: Professional forward and backward translations from original Russian to Polish were performed by Mapi SAS. For cognitive assessment, women with different ages and educational levels were asked to comment on each item of the Polish ACSS to establish the final study version. The clinical validation was performed as a prospective, non-interventional cohort study. Women with AC (Patients) and those without (Controls) filled in the Polish ACSS during their visits to a physician's office and at a follow-up visit. Statistical analysis included ordinary descriptive values, calculation of reliability, validity, discriminative ability, responsiveness (sensitivity, specificity), and comparative analysis. Results: The cognitive assessment was performed in 60 women with a median (range) age of 44.5 (21-88) years and different educational levels: grade school (n = 8), high school (n = 25), college (n = 22), and postgraduate education (n = 5). Forty-three patients were recruited for the clinical validation study along with 34 controls. Statistical analyses resulted in excellent values of internal consistency, discriminative ability, and validity for diagnosis of AC. At a summary score of 6 and higher in the ´Typical´ domain, positive and negative predictive values were 97% and 79%, and sensitivity and specificity were 79% and 97%, respectively. Conclusions: The Polish version of the ACSS has demonstrated benefits for diagnosis and patient-reported outcome assessment. It is objective, fast, and cost-effective, and it may help to easily confirm the accurate diagnosis of AC. The Polish ASCSS can now be recommended for use in clinical and epidemiological studies, in clinical practice, or for self-diagnosis and patient-reported outcome in women with symptoms of AC.

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

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

The Impact of the Ongoing COVID-19 Epidemic on the Increasing Risk of Adverse Pathology in Prostate Cancer Patients Undergoing Radical Prostatectomy.

We aimed to assess whether the ongoing course of the COVID-19 epidemic has been associated with an increased risk of adverse pathology (AP) findings in prostate cancer (PC) patients treated with radical prostatectomy (RP). We performed a retrospective data analysis which included 408 consecutive, non-metastatic, previously untreated PC patients who underwent RP in our institution between March 2020 and September 2021. Patients were divided into two equally numbered groups in regard to the median surgery date (Early Epidemic [EE] and Late Epidemic [LE]) and compared. Adverse pathology was defined as either grade group (GG) ≥ 4, pT ≥ 3a or pN+ at RP. Patients in the LE group demonstrated significantly higher rates of AP than in the EE group (61 vs. 43% overall and 50 vs. 27% in preoperative non-high-risk subgroup, both p < 0.001), mainly due to higher rates of upgrading. On multivariable analysis, consecutive epidemic week (odds ratio: 1.02, 95% confidence interval: 1.00−1.03, p = 0.009) as well as biopsy GG ≥ 2 and a larger prostate volume (mL) were associated with AP in non-high-risk patients. The study serves as a warning call for increased awareness of risk underassessment in contemporarily treated PC patients.

Diagnostic Performance of Preoperative Choline-PET/CT in Patients Undergoing Salvage Lymph Node Dissection for Recurrent Prostate Cancer: A Multicenter Experience.

We aimed to retrospectively analyze consecutive prostate cancer patients diagnosed with biochemical or clinical recurrence after local treatment with curative intent, with no evidence of distant metastases, who underwent positron emission tomography/computed tomography (PET/CT) with choline followed by salvage lymph node dissection (SLND) in three academic centers between 2013 and 2020. A total of 27 men were included in the analyses. Sensitivity, specificity, positive and negative predictive values, and accuracy of choline-PET/CT in predicting pathology-proven lymph node involvement were 75%, 43%, 79%, 38% and 67% on per-patient and 70%, 86%, 80%, 78%, and 79% on per-site analyses, respectively, with the differences in specificity and NPV between per-patient and per-site analyses being statistically significant (p = 0.03 and 0.04, respectively). The study provides further insight into the role of preoperative choline-PET/CT in patients undergoing SLND for recurrent PC.

Non-Invasive Biomarkers in the Diagnosis of Upper Urinary Tract Urothelial Carcinoma-A Systematic Review.

Beyond laboratory, imaging and endoscopic procedures, new diagnostic tools are increasingly being sought for the diagnosis of upper urinary tract urothelial carcinoma (UTUC), especially those that are non-invasive. In this systematic review, we aimed to determine the effectiveness of non-invasive tests in the diagnosis of UTUC. PubMed and Embase electronic databases were searched to identify studies assessing effectiveness of non-invasive tests in the primary diagnosis of UTUC. The study protocol was registered with PROSPERO (CRD42020216480). Among 10,084 screened publications, 25 were eligible and included in the analysis. Most of them were conducted on small samples of patients and the control groups were heterogenous. The test used in the largest number of studies was voided urinary cytology, which has poor sensitivity (11-71.1%) with favorable specificity (54-100%). Fluorescence in situ hybridization in diagnostic cytology showed higher sensitivity (35-85.7%) with equally good specificity (80-100%). There were also studies on the use of tests known to diagnose bladder cancer such as NMP22, uCYT or BTA test. Other urine or blood tests have been the subject of only isolated studies, with varying results. To conclude, currently there is a lack of high-quality data that could confirm good effectiveness of non-invasive tests used in the diagnosis of UTUC.

High-Intensity Focused-Ultrasound Focal Therapy Versus Laparoscopic Radical Prostatectomy: A Comparison of Oncological and Functional Outcomes in Low- and Intermediate-Risk Prostate Cancer Patients.

To compare oncological and functional outcomes of high-intensity focused-ultrasound (HIFU) focal therapy (FT) versus laparoscopic radical prostatectomy (LRP) in patients treated for low- or intermediate-risk prostate cancer (PCa), we retrospectively analyzed data of consecutive patients comprising 30 men, who underwent HIFU-FT, and 96 men who underwent LRP, in an academic center. Oncological outcomes were assessed based on the follow-up prostate-specific antigen values. We used the International Index of Erectile Function short form score to assess erectile function (EF). Urinary continence status was defined based on the number of pads used per day. Median follow-up was 12.5 and 19.1 months in the LRP and HIFU-FT groups, respectively. The effects were computed after propensity score matching and expressed as average treatment effect (ATE). Compared to LRP, HIFU-FT was associated with increased risk of treatment failure (ATE 0.103-0.164, depending on definition, p < 0.01) and lower risk of urinary incontinence (ATE -0.808 at 12 months, p < 0.01). Risk of erectile dysfunction was higher in the LRP group (ATE 5.092, p < 0.01). Our results demonstrate that HIFU-FT may be a reasonable treatment option in selected PCa patients, willing to preserve their EF and urinary continence yet accepting a higher risk of treatment failure.

piRNAs and PIWI Proteins as Diagnostic and Prognostic Markers of Genitourinary Cancers.

piRNAs (PIWI-interacting RNAs) are small non-coding RNAs capable of regulation of transposon and gene expression. piRNAs utilise multiple mechanisms to affect gene expression, which makes them potentially more powerful regulators than microRNAs. The mechanisms by which piRNAs regulate transposon and gene expression include DNA methylation, histone modifications, and mRNA degradation. Genitourinary cancers (GC) are a large group of neoplasms that differ by their incidence, clinical course, biology, and prognosis for patients. Regardless of the GC type, metastatic disease remains a key therapeutic challenge, largely affecting patients' survival rates. Recent studies indicate that piRNAs could serve as potentially useful biomarkers allowing for early cancer detection and therapeutic interventions at the stage of non-advanced tumour, improving patient's outcomes. Furthermore, studies in prostate cancer show that piRNAs contribute to cancer progression by affecting key oncogenic pathways such as PI3K/AKT. Here, we discuss recent findings on biogenesis, mechanisms of action and the role of piRNAs and the associated PIWI proteins in GC. We also present tools that may be useful for studies on the functioning of piRNAs in cancers.

Predictors of Clinically Significant Prostate Cancer in Patients with PIRADS Categories 3-5 Undergoing Magnetic Resonance Imaging-Ultrasound Fusion Biopsy of the Prostate.

Prostate biopsy is recommended in cases of positive magnetic resonance imaging (MRI), defined as Prostate Imaging Reporting and Data System (PIRADS) category ≥ 3. However, most men with positive MRIs will not be diagnosed with clinically significant prostate cancer (csPC). Our goal was to evaluate pre-biopsy characteristics that influence the probability of a csPC diagnosis in these patients. We retrospectively analyzed 740 consecutive men with a positive MRI and no prior PC diagnosis who underwent MRI-ultrasound fusion biopsies of the prostate in three centers. csPC detection rates (CDRs) for each PIRADS category were calculated. Patient, disease, and lesion characteristics were studied for interdependencies with the csPC diagnosis. The CDR in patients with PIRADS categories 3, 4, and 5 was 10.5%, 30.7%, and 54.6%, respectively. On both uni- and multivariable regression models, older age, being biopsy-naïve, prostate specific antigen ≥ 10 ng/mL, smaller prostate volume, PIRADS > 3, a larger maximum lesion size, a lesion in the peripheral zone, and a positive digital rectal examination were associated with csPC. In this large, multicenter study, we provide new data regarding CDRs in particular PIRADS categories. In addition, we present several strong predictors that further alter the risk of csPC in MRI-positive patients. Our results could help in refining individual risk assessment, especially in PIRADS 3 patients, in whom the risk of csPC is substantially low.

Human kidney injury molecule-1 as a urine biomarker differentiating urothelial and renal cell carcinoma.

INTRODUCTION: Urine concentration of human kidney injury molecule-1 (KIM-1) is suggested to be increased in patients with renal cell carcinoma (RCC). However, it has never been tested in patients with urothelial tumors, while preoperative differentiation between RCC and upper tract urothelial carcinoma (UTUC) plays an essential role in therapeutic decisions.The aim of the study was to evaluate the role of urinary KIM-1 expression in preoperative differentiation between RCC and urothelial carcinoma (UC). MATERIAL AND METHODS: Sixty-four participants were enrolled in the study, including 30 patients with RCC and 27 with UC (16 with UTUC and 11 with bladder tumor). Preoperative urinary KIM-1 levels were measured using a commercially available ELISA kit and normalized to urinary creatinine levels. RESULTS: The median concentration of urinary KIM-1 normalized to urinary creatinine was lower in patients with RCC compared to UC (1.35 vs 1.86 ng/mg creatinine, p = 0.04). The comparison between RCC and UTUC shows even more significant difference (1.33 vs 2.23 ng/mg creatinine, p = 0.02). Urinary KIM-1 concentration did not correlate with tumor stage nor grade in any of the groups. ROC analysis to identify UC revealed AUC of 0.657 with sensitivity 33.3% and specificity 96.7% at the cut-off value of 3.226 ng/mg creatinine. Among patients with eGFR ≥60 mL/min/1.73 m², ROC analysis to detect UC achieved AUC of 0.727 with sensitivity 69.5% and specificity 70.2%. CONCLUSIONS: Urine KIM-1 can potentially differentiate UC from RCC. However, a wide range of observed results and limited sensitivity and specificity requires caution in making clinical decisions before confirmatory studies.

Oncological outcomes of laparoscopic versus open nephroureterectomy for the treatment of upper tract urothelial carcinoma: an updated meta-analysis.

BACKGROUND: During the past two decades, laparoscopic radical nephroureterectomy (LRNU) has been proposed as an alternative technique to open radical nephroureterectomy (ORNU) and has become increasingly accepted for the treatment of patients with upper tract urothelial carcinoma (UTUC). Nevertheless, the oncologic efficacy of LRNU remains controversial, especially for the treatment of locally advanced (T3/T4 and/or N+) UTUC. In this meta-analysis, we aimed to cumulatively compare the oncological outcomes of LRNU versus ORNU. MATERIALS AND METHODS: The present meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A search was conducted of three electronic databases, namely, Medline, Embase, and Cochrane Library. Outcome measurements of cancer-specific survival (CSS), overall survival (OS), intravesical recurrence-free survival (IVRFS), and recurrence-free survival (RFS), including hazard ratios (HRs) and 95% confidence intervals (CIs), were extracted and pooled. RESULTS: Eighteen articles published from 2007 to 2020 were included in the final quantitative analysis. One study was a randomized controlled trial (RCT), and the remaining articles had a retrospective design. Among a total of 10,730 participants in the selected papers, 5959 (55.5%) and 4771 (44.5%) underwent ORNU and LRNU, respectively. The results of pooled analyses revealed no significant differences in CSS (HR 0.84, 95% CI 0.60-1.19, p = 0.33), OS (HR 0.84, 95% CI 0.62-1.13, p = 0.25), IVRFS (HR 1.08, 95% CI 0.85-1.39, p = 0.52), and RFS (HR 1.09, 95% CI 0.94-1.25, p = 0.26) between LRNU and ORNU groups. Furthermore, the results of subgroup analyses for pT3/T4 and pTany N+ populations did not confirm any statistically significant differences between LRNU and ORNU in terms of any survival parameter. CONCLUSIONS: Our present meta-analysis of current evidence suggests that LRNU and ORNU have comparable oncological outcomes in patients with UTUC, even in those with locally advanced disease. Further multicenter RCTs with large sample sizes and uniform data regarding specific surgical procedures, such as bladder cuff excision, are required to establish definitive conclusions.

Assessment of the oncological outcomes of three different bacillus Calmette-Guérin strains in patients with high-grade T1 non-muscle-invasive bladder cancer.

OBJECTIVE: : To determine whether there are significant differences in oncological outcomes between three different bacillus Calmette-Guérin (BCG) strains used for adjuvant intravesical immunotherapy in patients with high-grade T1 (T1HG) non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: : Data of 590 patients with a diagnosis of primary T1HG NMIBC were retrospectively reviewed. The study included 138 (23.4%) patients who were treated with the Moreau, 272 (46.1%) with the TICE, and 180 (30.5%) with the RIVM strains. All patients included in the analysis received at least five instillations of an induction course and at least two installations of a maintenance course. Due to existing differences in baseline patient characteristics, the association between oncological outcomes and strain groups was investigated by complementary analysis with the implementation of inverse probability weighting (IPW). RESULTS: : The 5-year recurrence-free survival (RFS) rate was 70.5%, 66.7% and 55.2% for the Moreau, TICE and RIVM groups, respectively (P = 0.016). The 5-year progression-free survival (PFS) rates were 84.4%, 85% and 77.8% in the Moreau, TICE and RIVM groups, respectively (P = 0.215). The IPW-adjusted Cox proportional hazard regression analysis did not show any differences in RFS between the Moreau and TICE groups (P = 0.69), whereas the RIVM strain was significantly associated with worse RFS compared to the Moreau (hazard ratio [HR] 1.69 for RIVM; P = 0.034) and TICE (HR 1.87 for RIVM; P = 0.002) strains. The IPW-adjusted analysis did not show any significant differences between study groups in terms of PFS. CONCLUSIONS: : The results of the present study suggest that the Moreau and TICE strains might be superior to the RIVM strain in terms of RFS in patients with T1HG NMIBC.Abbreviations: CIS: carcinoma in situ; IPW: inverse probability weighting; IQR: interquartile range; HR: hazard ratio; HG: high grade; LVI: lymphovascular invasion; MP: muscularis priopria; NMIBC: non-muscle-invasive bladder cancer; PFS: progression-free survival; RCT: randomised controlled trial; RFS: recurrence-free survival; T1HG, high-grade T1; (re-)TURB: (re-staging) transurethral resection of bladder; VH: variant histology.

En-bloc resection of urinary bladder tumour - a prospective controlled multicentre observational study.

INTRODUCTION: Transurethral resection of bladder tumour (TURBT) is one of the most commonly performed urologic procedures. Because of the shortcomings of conventional TURBT, the en-bloc resection concept was created. AIM: To analyse the influence of en-bloc technique on surgical and oncological outcomes of TURBT performed with electric current. MATERIAL AND METHODS: This non-randomized, prospective controlled multicentre study enrolled 427 consecutive patients undergoing TURBT performed by five experienced endourologists in five academic institutions. Choice of procedure was at the discretion of the surgeon. The vast majority of patients underwent monopolar resection. The en-bloc procedure was performed with Collin's knife or the classic resection loop. Study end-points were surgery, catheterization and hospitalization time, presence of muscularis propria (MP) in the specimen and 3-month recurrence-free survival (RFS). RESULTS: The study included 427 (274 conventional TURBT vs. 153 en-bloc) patients with mean age of 69 years (range: 18-99). There were more cases with MP present in the specimen in the en-bloc group (91.3% vs. 75.5%; p < 0.001). Surgery and hospitalization times were statistically shorter in the en-bloc group (both p < 0.05). A borderline significant difference was noted when the number of residual tumours in reTURBTs was analysed, with fewer cases of residual tumour in the en-bloc group (p = 0.051). RFS at 3 months was higher in the en-bloc group (88.4% vs. 80.1%; p = 0.027). After propensity score matching, differences in MP presence, hospitalization time and 3-month RFS status remained statistically significant. CONCLUSIONS: When compared to conventional TURBT, en-bloc resection of bladder tumour is associated with higher percentage of MP presence in histopathological specimen, higher 3-month RFS and shorter hospitalization time.

Systematic review and meta-analysis on bipolar versus monopolar transurethral resection of bladder tumors.

BACKGROUND: Transurethral resection of bladder tumour (TURB) is the initial and crucial step in the management of non-muscle invasive bladder cancer (NMIBC), having both diagnostic and therapeutic role. For many years, the gold standard for TURB was monopolar TURB (mTURB), however, it is associated with several complications related to its technical details. To overcome limitations of mTURB, TURB using bipolar technology (bTURB) has been developed. So far, making unequivocal statement about definitive advantage of bTURB over mTURB was difficult. The aim of this study was to systematically evaluate and compare the efficacy and safety of bTURB with mTURB. METHODS: A systematic search was conducted independently by two authors on the 4 electronic databases, including PubMed, Scopus, Embase and Cochrane Library, according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Nine comparative prospective studies with randomization (8 RCTs and 1 post-hoc analysis of RCT) were eligible to be included in this meta-analysis. RESULTS: After extraction, data were pooled to conduct the meta-analysis. The following outcomes were analysed: operation time, catheterization time, length of hospital stay, decrease in postoperative haemoglobin level, obturator nerve reflex rate, bladder perforation rate, transfusion rate, TUR syndrome rate, one year recurrence rate, failures of detrusor muscle detection. bTURB was associated with decreased operation and hospitalization time. There were no statistically significant differences between bTURB and mTURB in terms of catheterization time, decrease in haemoglobin level, postoperative complications rates, recurrence rates and pathologic outcomes. CONCLUSIONS: This meta-analysis corroborates that bTURB shows significant advantage over mTURB in terms of operation and hospitalization time while other outcomes are comparable.

Impact of Adjuvant Chemotherapy on Survival of Patients with Advanced Residual Disease at Radical Cystectomy following Neoadjuvant Chemotherapy: Systematic Review and Meta-Analysis.

BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) with pelvic lymph-node dissection is the standard treatment for cT2-4a cN0 cM0 muscle-invasive bladder cancer (MIBC). Despite the significant improvement of primary-tumor downstaging with NAC, up to 50% of patients are eventually found to have advanced residual disease (pT3-T4 and/or histopathologically confirmed nodal metastases (pN+)) at RC. Currently, there is no established standard of care in such cases. The aim of this systematic review and meta-analysis was to assess differences in survival rates between patients with pT3-T4 and/or pN+ MIBC who received NAC and surgery followed by adjuvant chemotherapy (AC), and patients without AC. MATERIALS AND METHODS: A systematic search was conducted in accordance with the PRISMA statement using the Medline, Embase, and Cochrane Library databases. The last search was performed on 12 November 2020. The primary end point was overall survival (OS) and the secondary end point was disease-specific survival (DSS). RESULTS: We identified 2124 articles, of which 6 were selected for qualitative and quantitative analyses. Of a total of 3096 participants in the included articles, 2355 (76.1%) were in the surveillance group and 741 (23.9%) received AC. The use of AC was associated with significantly better OS (hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.75-0.94; p = 0.002) and DSS (HR 0.56, 95% CI 0.32-0.99; p = 0.05). Contrary to the main analysis, in the subgroup analysis including only patients with pN+, AC was not significantly associated with better OS compared to the surveillance group (HR 0.89, 95% CI 0.58-1.35; p = 0.58). CONCLUSIONS: The administration of AC in patients with MIBC and pT3-T4 residual disease after NAC might have a positive impact on OS and DSS. However, this may not apply to N+ patients.

MCM5 urine expression (ADXBLADDER) is a reliable biomarker of high-risk non- muscle-invasive bladder cancer recurrence: A prospective matched case-control study.

BACKGROUND: Mini Chromosome Maintenance 5 (MCM5) is considered as a urinary biomarker of bladder cancer. ADXBLADDER is a commercially available test to detect MCM5 antibodies. OBJECTIVE: External validation of ADXBLADDER test as a urinary biomarker of histopathologically confirmed non-muscle invasive bladder cancer (NMIBC) recurrence. METHODS: The study enrolled 119 consecutive patients with a history of NMIBC and 37 healthy volunteers matched as controls. Single, full-void urine samples were collected from patients before cystoscopy ± TUR. To measure MCM5 expression, Arquer Diagnostics ADXBLADDER test was used. The study protocol was registered within the clinical trials database (NCT03796299). RESULTS: Among patients with NMIBC history, recurrence was diagnosed in 83 patients (69.7%). ADXBLADDER demonstrated sensitivity of 73.5% (95% confidence interval (CI) 62.7%-82.6%), specificity of 33.3% (95% CI 18.6% to 51%), overall negative predictive value (NPV) of 35.3% (95% CI 23.3% to 49.5%) and overall positive predictive value of 71.8% (95% CI 66.1% to 76.8%) for detecting recurrence. In a control group, false positive ADXBLADDER results were noticed in 18 patients (48.6%). The sensitivity and NPV were the highest in invasive tumors (100% and 100%, respectively) and in high-grade recurrences (81.8% and 94.1%, respectively). CONCLUSIONS: ADXBLADDER has a moderate sensitivity and poor specificity in detecting NMIBC recurrence. However, it properly diagnoses patients with T1+ stage recurrence or high-grade tumors.