Upper Urinary Tract Urothelial Cancer After Radical Cystectomy for Bladder Cancer: Survival Outcomes After Radical Nephroureterectomy.

BACKGROUND: Systemic and local recurrences of urothelial bladder cancer (UBC) significantly impair survival after radical cystectomy (RC), but little is known about the impact of the recurrence of urothelial cancer in the upper urinary tract (UTUC). This report describes survival outcomes and their predictors for patients who underwent RC followed by radical nephroureterectomy (RNU) for UTUC. METHODS: The Surveillance, Epidemiology, and End Results database was queried to identify patients who underwent RC for UBC and subsequent RNU for UTUC. The Kaplan-Meier method and competing-risk Cox regression (CRR) were used for the survival analysis. RESULTS: Overall, 102 patients have undergone RNU within a median of 49 months (interquartile range [IQR], 27-76 months) since RC. Muscle-invasive UTUCs were predominant at RNU (n = 58; 56.7%), but organ-confined bladder tumors were most frequent at RC (n = 42, 41.5%). After RNU, the estimated 5-year overall survival (OS) was 25.9%, the cancer-specific survival (CSS) was 35.6%, the median OS was 23 months (IQR, 11-63 months), and the CSS was 34 months (IQR, 13-132 months). In the multivariable CRR, the factors predictive for CSS after RNU included male gender (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.03-5.42; p < 0.05), muscle-invasive UTUC (HR, 2.20; 95% CI, 1.13-4.28; p < 0.05), and the presence of distant metastasis (HR,11.59; 95% CI, 5.33-25.2; p < 0.001). CONCLUSIONS: In conclusion, the patients who underwent RNU for UTUC after RC for UBC experienced poor OS and CSS. The majority of RNUs were performed for locally advanced tumors. The independent risk factors for worse OS and CSS after RNU were UTUC T stage, presence of metastasis, and male gender.

Changes in the Urinary Microbiome After Transurethral Resection of Non-muscle-Invasive Bladder Cancer: Insights from a Prospective Observational Study.

BACKGROUND: This study aimed to characterize the urinary and tumor microbiomes in patients with non-muscle-invasive bladder cancer (NMIBC) before and after transurethral resection of the bladder tumor (TURBT). METHODS: This single-center prospective study included 26 samples from 11 patients with low-grade Ta papillary NMIBC. Urine samples were collected at the index TURBT and at a 1-year follow-up cystoscopy. The metagenomic analysis of bacterial and archaeal populations was performed based on the highly variable V3-V4 region of the 16S rRNA gene. RESULTS: Phylogenetic alpha diversity of the bladder microbiome detected in urine was found to be lower at the 1-year follow-up cystoscopy compared to the time of the index TURBT (p < 0.01). Actinomyces, Candidatus cloacimonas, Sphingobacterium, Sellimonas, Fusobacterium, and Roseobacter were more differentially enriched taxa in urine at the follow-up cystoscopy than at the index TURBT. Beta diversity of urine microbiome significantly changed over time (p < 0.05). Phylogenetic alpha diversity of the microbiome was greater in tumor tissues than in paired urine samples (p<0.01). Sphingomonas, Acinetobacter, Candidatus, and Kocuria were more differentially overrepresented in tumor tissues than in urine. The enrichment of the abundance of Corynebacterium and Anaerococcus species in urine collected at TURBT was observed in patients who experienced recurrence within the follow-up period. CONCLUSIONS: In patients with low-grade NMIBC, the urine microbiome undergoes changes over time after removal of the tumor. The microbiome detected in tumor tissues is more phylogenetically diverse than in paired urine samples collected at TURBT. The interplay between bladder microbiome, tumor microbiome, and their alterations requires further studies to elucidate their predictive value and perhaps therapeutic implications.

Survival outcomes of patients treated with local therapy for nonmetastatic prostate cancer with high prostate-specific antigen concentrations.

BACKGROUND: Patients with nonmetastatic prostate cancer (nmPCa) and high prostate-specific antigen (PSA) levels due to the high likelihood of metastasis pose a clinical dilemma regarding their optimal treatment and long-term outcomes after initial local therapy. We aimed to evaluate the oncologic outcomes of patients treated with radical prostatectomy (RP) or radiotherapy (RT) for nmPCa with high PSA levels. METHODS: We queried the Surveillance, Epidemiology, and End Results (SEER) database to identify patients diagnosed with nmPCa who received RP or RT from 2004 through 2015. We included nmPCa patients with high PSA levels categorized as ≥50 and ≥98 ng/mL, the highest level recorded in SEER. We used the Kaplan-Meier method and Cox proportional hazards to analyze cancer-specific (CSS) and overall survival (OS). RESULTS: We included 6177 patients with nmPCa and PSA ≥ 50 ng/mL at diagnosis; 1698 (27%) had PSA ≥ 98 ng/mL. Of these, 1658 (26.8%) underwent RP and 4519 (73.16%) patients received primary RT. Within a median of 113 months (interquartile range 74-150 months), the 5- and 10-year CSS estimates were 92.3% and 81.5% respectively; 10-year OS was 61%. In the PSA ≥ 98 ng/mL subgroup 5- and 10-year CSS estimates were 89.2% and 76%, respectively. In multivariable analyses for CSS, ISUP grade group (p < 0.001), N stage (p < 0.001), treatment with RP (hazard ratio [HR] = 0.60, 95% confidence interval [CI] 0.43-0.83, p < 0.001), and patient's age (p < 0.05) were associated with improved CSS. In the whole cohort of patients with PSA ≥ 50 ng/mL and RP subgroup, PSA failed to retain its independent prognostic value for CSS. CONCLUSIONS: Patients treated with local therapy for nmPCa with very high PSA at diagnosis have relatively good long-term oncological outcomes. Therefore, among well-selected patients with nmPCa, high PSA levels alone should not preclude the use of radical local therapy. Potential selection bias limits inferences about the relative effectiveness of specific local therapies in this setting.

Cancer-Specific Survival of Patients with Non-Muscle-Invasive Bladder Cancer: A Population-Based Analysis.

BACKGROUND AND PURPOSE: Non-muscle-invasive bladder cancer (NMIBC) constitutes a heterogeneous group of tumors with different prognoses. This population-based study aimed to report real-world cancer-specific survival (CSS) of NMIBC and create a prognostic nomogram based on the identified risk factors. METHODS: The Surveillance, Epidemiology, and End Results database was searched for patients diagnosed with NMIBC from 2004 to 2015, who underwent transurethral resection of the bladder tumor. The dataset was divided into development and validation cohorts. Factors associated with CSS were identified using Cox proportional hazards and used to develop a prognostic nomogram. RESULTS: In total, 98,238 patients with NMIBC were included. At the median follow-up of 124 months (IQR 81-157 months), cancer-specific mortality (CSM) was highest for T1HG (19.52%), followed by Tis (15.56%), similar for T1LG and TaHG (10.88% and 9.23%, respectively), and lowest for TaLG (3.76%). Multivariable Cox regression for CSS prediction was utilized to develop a nomogram including the following risk factors: tumor T category and grade, age, tumor size and location, histology type, primary character, race, income, and marital status. In the validation cohort, the model was characterized by an AUC of 0.824 and C-index that reached 0.795. CONCLUSIONS: To conclude, NMIBC is associated with a significant risk of long-term CSM especially, but not only, in patients with T1HG. Rarely diagnosed TaHG and T1LG tumors should be regarded as high-risk due to approximately 10% CSM. T category, grading, and age remain the most powerful determinants of CSS in NMIBC, but sociodemographic factors might also influence its prognosis.

Magnetic resonance imaging (MRI) for local staging before salvage radical prostatectomy: a meta-analysis.

PURPOSE: The reliability of magnetic resonance imaging (MRI) as a local and nodal staging tool in radio-recurrent prostate cancer (PCa) is still unclear. The present study aims at evaluating the predictive value of MRI in the detection of extracapsular extension (ECE), seminal vesical invasion (SVI) and nodal involvement (LNI) in patients after primary radio (EBRT) and/or brachytherapy (BT) before salvage radical prostatectomy (SRP). METHODS: This systematic review and meta-analysis were performed in line with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Pubmed, Scopus, and Web of Science databases were systemically reviewed to extract the data on diagnostic performance of MRI in radio-recurrent PCa. RESULTS: Four studies comprising 94 radio-recurrent PCa patients were included. The pooled prevalence of ECE, SVI, and LNI was 61%, 41%, and 20%, respectively. The pooled sensitivity for ECE, SVI and LNI detection was 53% (CI 95% 19.8-83.6%), 53% (CI 95% 37.2-68%) and 33% (CI 95% 4.7-83.1%) respectively, whereas specificity was 75% (CI 95% 40.6-92.6%), 88% (CI 95% 71.7-95.9%) and 92% (CI 95% 79.6-96.8%). The sensitivity analysis revealed that a single outlying study using only T2-weighted imaging instead of multiparametric MRI reported significantly higher sensitivity with significantly lower specificity. CONCLUSIONS: This is the first meta-analysis reporting reliability of staging MRI in a radio-recurrent setting. MRI provides poor sensitivity while maintaining high specificity for local and nodal staging before SRP. However, current evidence is limited to the low number of heterogenous studies at meaningful risk of bias.

The Cannabinoid Ligand Arachidonyl-2'-Chloroethylamide (ACEA) Ameliorates Depressive and Overactive Bladder Symptoms in a Corticosterone-Induced Female Wistar Rat Model.

There is growing need to increase the knowledge on the cannabinoid ligands in the treatment of overactive bladder. Among potential candidates, arachidonyl-2'-chloroethylamide (ACEA), a selective cannabinoid CB1 receptor agonist is proposed. The aim of this paper was to determine if ACEA, a selective cannabinoid CB1 receptor agonist, could reverse the effects of corticosterone (CORT), characteristic of depressive and bladder overactivity potential. The animals (48 female rats) were divided into four groups: I-control, II-received CORT, III-received ACEA, and IV-received the combination of CORT and ACEA. The conscious cystometry, forced swim test (FST), and locomotor activity measurements were performed 3 days after the last dose of ACEA, followed by ELISA measurements. In group IV, ACEA restored urodynamic parameters that were altered by CORT. CORT prolonged the immobility time in FST and the values were lowered by ACEA. ACEA normalized the expression of c-Fos in all the analyzed central micturition centers (group IV vs. group II). ACEA restored the CORT-induced changes in the biomarkers in urine (BDNF, NGF), bladder detrusor (VAChT, Rho kinase), bladder urothelium (CGRP, ATP, CRF, OCT-3, TRPV1), and hippocampus (TNF-α, IL-1ß and Il-6, CRF, IL-10, BDNF, NGF). In conclusion, ACEA was proven to reverse CORT-induced changes in both cystometric and biochemical parameters that are determinants of OAB/depression, which represents an example of an existing link between OAB and depression via cannabinoid receptors.

HDAC6 inhibition upregulates CD20 levels and increases the efficacy of anti-CD20 monoclonal antibodies.

Downregulation of CD20, a molecular target for monoclonal antibodies (mAbs), is a clinical problem leading to decreased efficacy of anti-CD20-based therapeutic regimens. The epigenetic modulation of CD20 coding gene (MS4A1) has been proposed as a mechanism for the reduced therapeutic efficacy of anti-CD20 antibodies and confirmed with nonselective histone deacetylase inhibitors (HDACis). Because the use of pan-HDACis is associated with substantial adverse effects, the identification of particular HDAC isoforms involved in CD20 regulation seems to be of paramount importance. In this study, we demonstrate for the first time the role of HDAC6 in the regulation of CD20 levels. We show that inhibition of HDAC6 activity significantly increases CD20 levels in established B-cell tumor cell lines and primary malignant cells. Using pharmacologic and genetic approaches, we confirm that HDAC6 inhibition augments in vitro efficacy of anti-CD20 mAbs and improves survival of mice treated with rituximab. Mechanistically, we demonstrate that HDAC6 influences synthesis of CD20 protein independently of the regulation of MS4A1 transcription. We further demonstrate that translation of CD20 mRNA is significantly enhanced after HDAC6 inhibition, as shown by the increase of CD20 mRNA within the polysomal fraction, indicating a new role of HDAC6 in the posttranscriptional mechanism of CD20 regulation. Collectively, our findings suggest HDAC6 inhibition is a rational therapeutic strategy to be implemented in combination therapies with anti-CD20 monoclonal antibodies and open up novel avenues for the clinical use of HDAC6 inhibitors.

Surgical treatment for renal masses in the elderly: analysis of oncological, surgical and functional outcomes.

PURPOSE: Radical treatment in elderly patients with renal tumor remains debatable due to uncertainties regarding the risk of surgical complications, risk of end-stage renal disease (ESRD) and survival benefit. The aim of the study was to assess outcomes of radical treatment for renal cancer in elderly patients. MATERIALS AND METHODS: This retrospective analysis enrolled 507 consecutive patients treated with partial or radical nephrectomy due to renal mass. Patients with upfront metastatic disease (n=46) and patients lost to follow-up (n=110) were excluded from the analysis. Surgical, functional (screen for ESRD development) and survival outcomes were analyzed in patients aged >75 years in comparison to younger individuals. RESULTS: The analyzed group included 55 elderly patients and 296 younger controls. Within the cohort a total of 148 and 203 patients underwent radical and partial nephrectomies respectively. The rate of surgical complications, including grade >3 Clavien- Dindo complications, did not differ between groups (3.6% vs. 4.4%, p=0.63). Median length of hospital stay was equal in both groups (7 days). During a follow-up (median 51.9 months, no difference between groups), ESRD occurred in 3.4% of controls and was not reported in elderly group (p=0.37). Younger patients demonstrated a statistically significant advantage in both overall survival and cancer-specific survival over elderly patients (OS 94.6% vs. 87% p=0.036, CSS 97.3% vs. 89.1% p=0.0008). CONCLUSIONS: Surgical treatment in elderly patients with renal tumor is as safe as in younger individuals and does not increase the risk of ESRD. However, cancer specific survival among these patients remains shorter than in younger patients.

Catheter-associated bacterial flora in patients with benign prostatic hyperplasia: shift in antimicrobial susceptibility pattern.

BACKGROUND: Men with urinary retention secondary to benign prostatic hyperplasia (BPH) are prone to genitourinary infections. Physicians should be aware of the current antimicrobial susceptibility pattern in this population if empirical treatment is needed. The goal of this study was to evaluate variations in prevalence, composition and antimicrobial susceptibility of bacterial flora in men with indwelling catheters subjected to surgery for BPH in chosen time periods since 1994. Necessary changes in empirical therapy were also assessed. METHODS: All patients with indwelling catheters admitted to a single urological center for BPH surgery in the years 1994-1996, 2004-2006, and 2011-2015 were considered. Catheterization times and results of urine cultures from samples collected at admission were evaluated. Susceptibility for selected antimicrobials was compared separately for Gram negative and Gram positive species. For each agent and for their combinations effectiveness of empirical therapy was calculated dividing the number of patients with bacteriuria susceptible to the agents by the total number of patients with bacteriuria. RESULTS: Bacteriuria was present in 70% of 169, 72% of 132, and 69% of 156 men in the respective time periods. The incidence of Gram-positive strains increased from 10 to 37% (P < 0.001). Their susceptibility to amoxicillin/clavulanate was fluctuating (81, 61, 77%; P=NS). No vancomycin-resistant strain was present. Gram-negative flora composition was stable. Their susceptibility decreased to ciprofloxacin (70 to 53%; P = 0.01) and amoxicillin/clavulanate (56 to 37%; P < 0.01) while it increased to gentamycin (64 to 88%; P < 0.001) and co-trimoxazole (14 to 62%; P < 0.001); susceptibility to amikacin remained high (> 85%). Only two cases of resistance to carbapenems in 2004-2006 were found. In vitro effectiveness of amikacin + amoxicillin/clavulanate in empirical therapy was slowly decreasing (87 to 77%; P=NS). Imipenem was found the most effective single agent (90-95%) and its efficacy was even improved by adding vancomycin (97-98%). CONCLUSIONS: Substantial rise in the incidence of Gram-positive species and fluctuations in antimicrobial susceptibility patterns were found. Empirical therapy of genitourinary infection in catheterized men with BPH should now involve antimicrobial agents effective both to Enterococci and Enterobacteriaceae. Periodic monitoring and publishing data on antimicrobial susceptibility for this population is necessary.

Clinical rationale and safety of restaging transurethral resection in indication-stratified patients with high-risk non-muscle-invasive bladder cancer.

BACKGROUND: Indications for restaging transurethral resection of the bladder tumor (reTURBT) in patients with non-muscle-invasive bladder cancer (NMIBC) remain controversial. This study was aimed at evaluation of clinical value and safety of reTURBT in different clinical indications. METHODS: This is a retrospective analysis of consecutive 141 patients who underwent TURBT followed by reTURBT in years 2011-2015 in a single department. Pathological results and surgical complications were analyzed in the whole study cohort and stratified by clinical stage (Ta, T1, Tx (no muscle in the specimen)) and grade (low-grade (LG), high-grade (HG)) of bladder cancer diagnosed at primary TURBT. RESULTS: Full data was available for 132 patients. Residual disease was found in 53 patients (40.2%) with highest rate for Ta-HG cases (57.1%) followed by T1-HG (51.4%), Tx-HG (45.2%), T1-LG (32.1%), and Tx-LG (25.8%). In the multivariate analysis, high grade (p = 0.02) was the only independent predictor of residual disease. Upstaging to muscle-invasive bladder cancer was noticed in 9 patients (6.8%). The rate of grade ≥ 2 Clavien-Dindo complications (1.5 vs. 5.3%) did not differ significantly between TURBT and reTURBT cases. CONCLUSIONS: ReTURBT is a safe procedure that remains crucial for therapeutic and staging purposes in patients with T1, Tx, or high-grade bladder cancer found in the primary resection.

What Can Be Expected from Prostate Cancer Biomarkers A Clinical Perspective.

Along with significant advances in prostate cancer biology research, we also observe the rapid development of modern diagnostic tests. New biomarkers are derived to detect disease while it is organ-confined to stratify the risk and to aid clinical decision-making. Majority of these tools have already been validated clinically, but only a few have received premarket clearance and administration approval. Superiority of novel tests is visible not only in improved detection accuracy but predominantly in the assessment of tumour aggressiveness and selection of patients eligible for conservative management. Two factors limiting the clinical implementation of validated biomarker candidates are costs and local availability. For these reasons, currently, their true clinical role starts after routine screening with prostate-specific antigen test. With this review of prostate cancer biomarkers, we attempted to draw general conclusions on clinical perspectives of these novel tools.

Safety and Efficacy of Intravesical Bacillus Calmette-Guérin Immunotherapy in Patients with Non-Muscle-Invasive Bladder Cancer Presenting with Asymptomatic Bacteriuria: A Systematic Review.

Intravesical Bacillus Calmette-Guérin (BCG) immunotherapy in bladder cancer patients with asymptomatic bacteriuria (ABU) remains a matter of debate. The aim of this systematic review was to present available evidence on the safety and efficacy of BCG immunotherapy in patients with ABU. A literature search within the Medline and the Embase databases was conducted with the following search terms: adverse events, bacteriuria, BCG, bladder cancer, cystitis, infection, pyuria, side effects and urinary tract infection (UTI). Sixteen relevant original articles were identified, including 6 articles directly presenting the safety or efficacy of BCG therapy in patients with ABU. None of them was a randomized controlled trial. Intravesical BCG instillations in patients with ABU were not associated with the increased risk of symptomatic UTI and did not affect negatively the recurrence- or progression-free survival. Routine urine analysis before BCG instillation created increased cost and potentially unnecessary delays in BCG therapy. ABU does not affect negatively the safety and efficacy of intravesical BCG immunotherapy. There is no evidence to support routine screening and treatment of ABU in patients scheduled for intravesical BCG instillations due to bladder cancer. However, this issue was not addressed adequately and needs further research.

Open partial nephrectomy for entirely intraparenchymal tumors: a matched case-control study of oncologic outcome and complication rate.

PURPOSE: To compare the oncologic and clinical outcomes for open partial nephrectomy (OPN) performed in patients with entirely intraparenchymal tumors versus casematched controls, with exophytic lesions. MATERIAL AND METHODS: Patients having undergone OPN between 2007 and 2012 were investigated. Exclusion criteria included patients with a benign tumor, advanced malignancy, malignancies other than renal cell carcinoma, end-stage renal failure, or 3 or more co-existing chronic diseases. Individuals with tumors that were invisible at the renal surface were identified, and then matched with 2 controls chosen for tumor size, pathology, age, follow-up period, and presence of a solitary kidney. Oncological status, perioperative, and postoperative data were collected and compared between groups. RESULTS: 17 individuals with entirely endophytic RCC tumors and available oncologic status were identified. For five patients, only one suitable control could be identified, bringing the control group number to 29. All tumors were clear cell carcinomas staged at pT1a. Median tumor size was 25mm for endophytic lesions, and 27mm for exophytic masses (P=0.32). The operative period was extended by 20 minutes for intrarenal tumors (P=0.03), with one case of a positive surgical margin in each group (P=0.7). There were no significant differences in perioperative or postoperative complications. Median follow-up was 47 and 43 months for patients with endophytic and exophytic tumors respectively. Disease recurrence was recorded in one patient after endophytic tumor resection, and in four controls (P=0.4). CONCLUSIONS: OPN shows equivalent safety and efficacy for both intrarenal RCC tumors and exophytic tumors of the same size and type.

B-cell receptor signaling in the pathogenesis of lymphoid malignancies.

B-cell receptor (BCR) signaling pathway plays a central role in B-lymphocyte development and initiation of humoral immunity. Recently, BCR signaling pathway has been shown as a major driver in the pathogenesis of B-cell malignancies. As a result, a vast array of BCR-associated kinases has emerged as rational therapeutic targets changing treatment paradigms in B cell malignancies. Based on high efficacy in early-stage clinical trials, there is rapid clinical development of inhibitors targeting BCR signaling pathway. Here, we describe the essential components of BCR signaling, their function in normal and pathogenic signaling and molecular effects of their inhibition in vitro and in vivo.

Oncologic outcomes of patients treated with kidney-sparing surgery or radical nephroureterectomy for upper urinary tract urothelial cancer: a population-based study.

PURPOSE: Although kidney-sparing surgery (KSS) is a nonminor option for low-risk upper urinary tract urothelial cancer (UTUC), its oncological benefits in high-risk UTUC remain unclear when compared to radical nephroureterectomy (RNU). This study aimed to compare the oncological outcomes of RNU and KSS in patients with UTUC. METHODS: We searched the SEER database for patients treated for primary non-metastatic UTUC with either RNU or a kidney-sparing approach (segmental ureterectomy (SU) or local tumor excision (LTE)) between 2004 and 2018. RESULTS: The study included 6,659 patients with primary non-metastatic UTUC treated with surgery; 2,888 (43.4%) and 3,771 (56.6%) patients presented with ureteral and renal pelvicalyceal tumors, respectively. Finally, 5,479 (82.3%) patients underwent RNU, 799 (12.0%) were treated with SU, and 381 (5.7%) patients received LTE. For confounder control, propensity score matching (PSM) of patients treated with SU and RNU was performed to adjust for T stage, grade, age, gender, tumor size, and lymphadenectomy performance. PSM analysis included 694 patients treated with RNU and 694 individuals who underwent SU. In multivariable Cox regression and Kaplan-Meier analyses, we found no difference in either CSS or OS between RNU and SU, even in the subgroup of high-grade and/or muscle-invasive UTUC including pT3-T4 tumors (all p > 0.05). CONCLUSION: In this population-based study, SU provides equivalent CSS and OS compared to RNU, even in high-risk and locally advanced ureteral cancer. Due to the unavoidable risk of selection bias, further prospective studies are expected to overcome the limitations of this study and support the wider implementation of KSS.

(A)voiding misdiagnosis: prediction of detrusor underactivity vs. bladder outlet obstruction using pre-urodynamic nomogram in male patients with LUTS.

PURPOSE: Our study aimed to develop a noninvasive model using a combination of the set of clinical data and uroflowmetry (UFL) to differentiate between detrusor underactivity (DU) and bladder outlet obstruction (BOO) in non-neurogenic male patients with lower urinary tract symptoms (LUTS). METHODS: Data from 229 men with LUTS, diagnosed with DU or BOO on a pressure-flow study (PFS), were retrospectively analyzed, including medical history, Core Lower Urinary Tract Symptoms score (CLSS) questionnaire, UFL and PFS. Uni- and multivariate logistic regression were utilized for the prediction analyses. RESULTS: Of the cohort, 128 (55.9%) patients were diagnosed with DU. A multivariate logistic regression analysis identified less prevalent nocturia (OR 0.27, p < 0.002), more prevalent intermittency (OR 2.33, p = 0.03), less prevalent weak stream (OR 0.14, p = 0.0004), lower straining points in CLSS (OR 0.67, p = 0.02), higher slow stream points in CLSS (OR 1.81, p = 0.002), higher incomplete emptying points in CLSS (OR 1.31, p < 0.02), lower PVR ratio (OR 0.20, p = 0.03), and present features of fluctuating (OR 2.00, p = 0.05), fluctuating-intermittent (OR 3.09, p < 0.006), and intermittent (OR 8.11, p = 0.076) UFL curve shapes as independent predictors of DU. The above prediction model demonstrated satisfactory accuracy (c-index of 0.783). CONCLUSION: Our 10-factor model provides a noninvasive approach to differentiate DU from BOO in male patients with non-neurogenic LUTS, offering a valuable alternative to invasive PFS.

The impact of smoking on recurrence and progression of non-muscle invasive bladder cancer: a systematic review and meta-analysis.

OBJECTIVES: Although smoking is a well-recognized causative factor of urothelial bladder cancer and accounts for 50% of cases, less is known about the prognostic significance of smoking on non-muscle invasive bladder cancer (NMIBC) prognosis. This systematic review and meta-analysis aimed to evaluate the effect of smoking on the risk of NMIBC recurrence and progression. MATERIALS AND METHODS: We systematically searched Medline, Web of Science and Scopus databases for original articles published before October 2021 regarding the effect of smoking on NMIBC recurrence and progression. Information about smoking status and the number of events or odds ratio or hazard ratio for event-free survival must have been reported to include the study in the analysis. Quality In Prognosis Studies tool was utilized for the risk of bias assessment. RESULTS: We selected 64 eligible studies, including 28 617 patients with NMIBC with available data on smoking status. In a meta-analysis of 28 studies with 7885 patients, we found that smokers (current/former) were at higher risk for recurrence (OR = 1.68; 95% CI 1.34-2.09; P < 0.0001) compared to never smokers. Subgroup analysis of 2967 patients revealed that current smokers were at a 1.24 higher risk of recurrence (OR = 1.24; 95% CI 1.02-1.50; P = 0.03) compared to former smokers. A meta-analysis of the hazard ratio revealed that smokers are at higher risk of recurrence (HR = 1.31; 95%CI 1.15-1.48; P < 0.0001) and progression (HR = 1.18; 95%CI 1.08-1.29; P < 0.001) compared to never smokers. Detrimental prognostic effect of smoking on progression, but not for recurrence risk was also noted in the subgroup analysis of high-risk patients (HR = 1.30; 95%CI 1.09-1.55; P = 0.004) and BCG-treated ones (HR = 1.15; 95%CI 1.06-1.25; P < 0.001). CONCLUSION: In conclusion, patients with non-muscle invasive bladder cancer and a history of smoking have a worse prognosis regarding recurrence-free and progression-free survival compared to non-smokers.