Adjuvant intravesical therapy in intermediate-risk non-muscle-invasive bladder cancer.

OBJECTIVE: To evaluate the impact of adjuvant therapy on oncological outcomes in patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC), as due to the poorly-defined and overlapping diagnostic criteria optimal decision-making remains challenging in these patients. PATIENTS AND METHODS: In this multicentre study, patients treated with transurethral resection of bladder tumour for Ta disease were retrospectively analysed. All patients with low- or high-risk NMIBC were excluded from the analysis. Associations between adjuvant therapy administration with recurrence-free survival (RFS) and progression-free survival (PFS) rates were assessed in Cox regression models. RESULTS: A total of 2206 patients with intermediate-risk NMIBC were included in the analysis. Among them, 1427 patients underwent adjuvant therapy, such as bacille Calmette-Guérin (n = 168), or chemotherapeutic agents, such as mitomycin C or epirubicin (n = 1259), in different regimens up to 1 year. The median (interquartile range) follow-up was 73.3 (38.4-106.9) months. The RFS at 1 and 5 years in patients treated with adjuvant therapy and those without were 72.6% vs 69.5% and 50.8% vs 41.3%, respectively. Adjuvant therapy was associated with better RFS (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.70-0.89, P < 0.001), but not with PFS (P = 0.09). In the subgroup of patients aged ≤70 years with primary, single Ta Grade 2 <3 cm tumours (n = 328), adjuvant therapy was not associated with RFS (HR 0.71, 95% CI 0.50-1.02, P = 0.06). While in the subgroup of patients with at least one risk factor including patient age >70 years, tumour multiplicity, recurrent tumour and tumour size ≥3 cm (n = 1878), adjuvant intravesical therapy was associated with improved RFS (HR 0.78, 95% CI 0.68-0.88, P < 0.001). CONCLUSION: In our study, patients with intermediate-risk NMIBC benefit from adjuvant intravesical therapy in terms of RFS. However, in patients without risk factors, adjuvant intravesical therapy did not result in a clear reduction in the recurrence rate.

Overactive bladder negatively affects erectile function and promotes premature ejaculation: findings from large representative population-level study.

PURPOSE: The effect of overactive bladder (OAB) on sexual health has been evaluated extensively for women but much less for men. Therefore, the aim of this study was to evaluate the relationship between OAB and men's sexual activity and the effect of OAB on erectile dysfunction (ED) and premature ejaculation (PE) in a large representative cohort of men at the population level. METHODS: This study was based on computer-assisted web interviews that used validated questionnaires. The most recent census and the sample size estimation calculations were employed to produce a population-representative pool. RESULTS: The study included 3001 men, representative of the population in terms of age and place of residence. The frequency of sexual intercourse was higher for respondents without OAB symptoms compared with persons who had OAB (p = 0.001), but there was no association between OAB symptoms and number of sexual partners (p = 0.754). Regression models did not confirm the effect of OAB on sexual activity (odds ratio 0.993, CI 0.974-1.013, p = 0.511). Both ED and PE were more prevalent in respondents with OAB symptoms compared with persons who lacked those symptoms (p < 0.001). Importantly, the effect of OAB on ED or PE was independent of age, comorbidities, and lifestyle habits (regression coefficients of 0.13 and 0.158 for ED and PE, respectively). CONCLUSION: Overactive bladder did not significantly affect men's sexual activity, but it significantly correlated with ED and PE. Our results suggest a need in daily clinical practice to screen for OAB symptoms for persons who report ED or PE.

Impact of disease volume on survival efficacy of triplet therapy for metastatic hormone-sensitive prostate cancer: a systematic review, meta-analysis, and network meta-analysis.

BACKGROUND: Triplet therapy, androgen receptor signaling inhibitors (ARSIs) plus docetaxel plus androgen-deprivation therapy (ADT), is a novel guideline-recommended treatment for metastatic hormone-sensitive prostate cancer (mHSPC). However, the optimal selection of the patient most likely to benefit from triplet therapy remains unclear. METHODS: We performed a systematic review, meta-analysis, and network meta-analysis to assess the oncologic benefit of triplet therapy in mHSPC patients stratified by disease volume and compare them with doublet treatment regimens. Three databases and meeting abstracts were queried in March 2023 for randomized controlled trials (RCTs) evaluating patients treated with systemic therapy for mHSPC stratified by disease volume. Primary interests of measure were overall survival (OS). We followed the PRISMA guideline and AMSTAR2 checklist. RESULTS: Overall, eight RCTs were included for meta-analyses and network meta-analyses (NMAs). Triplet therapy outperformed docetaxel plus ADT in terms of OS in both patients with high-(pooled HR: 0.73, 95%CI 0.64-0.84) and low-volume mHSPC (pooled HR: 0.71, 95%CI 0.52-0.97). There was no statistically significant difference between patients with low- vs. high-volume in terms of OS benefit from adding ARSI to docetaxel plus ADT (p = 0.9). Analysis of treatment rankings showed that darolutamide plus docetaxel plus ADT (90%) had the highest likelihood of improved OS in patients with high-volume disease, while enzalutamide plus ADT (84%) had the highest in with low-volume disease. CONCLUSIONS: Triplet therapy improves OS in mHSPC patients compared to docetaxel-based doublet therapy, irrespective of disease volume. However, based on treatment ranking, triplet therapy should preferably be considered for patients with high-volume mHSPC while those with low-volume are likely to be adequately treated with ARSI + ADT.

Clinical value of cholinesterase in patients treated with radical nephroureterectomy for upper urinary tract carcinoma.

PURPOSE: To evaluate the prognostic value and the clinical impact of preoperative serum cholinesterase (ChoE) levels on decision-making in patients treated with radical nephroureterectomy (RNU) for clinically non-metastatic upper tract urothelial cancer (UTUC). METHODS: A retrospective review of an established multi-institutional UTUC database was performed. We evaluated preoperative ChoE as a continuous and dichotomized variable using a visual assessment of the functional form of the association of ChoE with cancer-specific survival (CSS). We used univariable and multivariable Cox regression models to establish its association with recurrence-free survival (RFS), CSS, and overall survival (OS). Discrimination was evaluated using Harrell's concordance index. Decision curve analysis (DCA) was used to assess the impact on clinical decision-making of preoperative ChoE. RESULTS: A total of 748 patients were available for analysis. Within a median follow-up of 34 months (IQR 15-64), 191 patients experienced disease recurrence, and 257 died, with 165 dying of UTUC. The optimal ChoE cutoff identified was 5.8 U/l. ChoE as continuous variable was significantly associated with RFS (p < 0.001), OS (p < 0.001), and CSS (p < 0.001) on univariable and multivariable analyses. The concordance index improved by 8%, 4.4%, and 7% for RFS, OS, and CSS, respectively. On DCA, including ChoE did not improve the net benefit of standard prognostic models. CONCLUSION: Despite its independent association with RFS, OS, and CSS, preoperative serum ChoE has no impact on clinical decision-making. In future studies, ChoE should be investigated as part of the tumor microenvironment and assessed as part of predictive and prognostic models, specifically in the setting of immune checkpoint-inhibitor therapy.

Bipolar spectrum in prostate cancer patients and its role in stress related symptoms.

BACKGROUND: Studies show significant co-occurrence of bipolar disorder and prostate cancer, as well as the presence of shared genes associated with both diseases. Our aim was to evaluate whether prostate cancer patients present bipolar spectrum symptoms and to establish their possible associations with stress related symptoms during diagnosis and the course of the cancer therapy. METHODS: 200 participants were enrolled to this study: 100 prostate cancer patients and 100 healthy males. Bipolar spectrum symptoms were measured with the use of Mood Disorder Questionnaire and Hypomania Checklist-32 (HCL-32). Stress related symptoms were rated with The Impact of Events Scale-Revised (IES-R), Perceived Stress Scale-10 (PSS-10) and Generalised Self-Efficacy Scale (GSES). RESULTS: In comparison to healthy controls group, prostate cancer patients have shown higher HCL-32 scores. Mood Disorder Questionnaire measures were associated with more severe stress related to prostate cancer diagnosis and treatment reflected by higher scores of IES-R and its subscales (Avoidance, Intrusions and Hyperarousal). Mood Disorder Questionnaire, HCL-32, PSS-10, IES-R and GSES measures were not associated with clinical characteristics of prostate cancer severity. LIMITATIONS: Cross-sectional study model precluded identification of causal relationship among variables. Bipolar spectrum symptoms and stress related measures were based on auto-questionnaires. CONCLUSIONS: To our best knowledge, this is the first study evaluating bipolar spectrum symptoms in prostate cancer patients. We have shown that this clinical group presents increased bipolarity traits compared to healthy individuals. Moreover, bipolar spectrum symptoms were associated with more severe stress related to the prostate cancer diagnosis and its treatment, reflected in avoidance, hyperarousal, and intrusions.

Evaluation of grade and invasiveness of bladder urothelial carcinoma using infrared imaging and machine learning.

Urothelial bladder carcinoma (BC) is primarily diagnosed with a subjective examination of biopsies by histopathologists, but accurate diagnosis remains time-consuming and of low diagnostic accuracy, especially for low grade non-invasive BC. We propose a novel approach for high-throughput BC evaluation by combining infrared (IR) microscopy of bladder sections with machine learning (partial least squares-discriminant analysis) to provide an automated prediction of the presence of cancer, invasiveness and grade. Cystoscopic biopsies from 50 patients with clinical suspicion of BC were histologically examined to assign grades and stages. Adjacent tissue cross-sections were IR imaged to provide hyperspectral datasets and cluster analysis segregated IR images to extract the average spectra of epithelial and subepithelial tissues. Discriminant models, which were validated using repeated random sampling double cross-validation, showed sensitivities (AUROC) ca. 85% (0.85) for the identification of cancer in epithelium and subepithelium. The diagnosis of non-invasive and invasive cases showed sensitivity values around 80% (0.84-0.85) and 76% (0.73-0.80), respectively, while the identification of low and high grade BC showed higher sensitivity values 87-88% (0.91-0.92). Finally, models for the discrimination between cancers with different invasiveness and grades showed more modest AUROC values (0.67-0.72). This proves the high potential of IR imaging in the development of ancillary platforms to screen bladder biopsies.

No differences in miRNA expression in the stroma of ERG+ and ERG- prostate cancers.

Prostate cancer (PC) is one of the most common cancers in males. A significant proportion of PCs bear TMPRSS2-ETS translocation and overexpress ERG transcription factor, allowing classification into ERG+ and ERG- groups, which differ in several features including the tumor microenvironment. The aim of the study was to verify whether they differ in expression of the miRNA in the microenvironment. The material consisted of 150 radical prostatectomies. Immunohistochemistry (IHC) for ERG was done using a routine method. FISH for TMPRSS2-ETS translocation was done with a ZytoLight SPEC ERG/TMPRSS2 TriCheck Probe. From each case, a representative section was selected, and tumor and non-tumor were microdissected with the LMD7000 device. RNA was isolated using the RNeasy Mini Kit system (Qiagen) and miRNA libraries were prepared with the NEBNext Multiplex Small RNA Library Prep Set for Illumina and their sequencing was performed on the NexSeq 500. Statistical analysis was done with Statistica and R software. When analyzing the expression of miRNAs some differences could be seen, but after correction for multiple comparisons was applied, these were found to be non- significant.

Impact of preoperative plasma levels of interleukin 6 and interleukin 6 soluble receptor on disease outcomes after radical cystectomy for bladder cancer.

BACKGROUND: Preoperative plasma levels of Interleukin 6 (IL6) and its soluble receptor (IL6sR) have previously been associated with oncologic outcomes in urothelial carcinoma of the bladder (UCB); however, external validation in patients treated with radical cystectomy (RC) for UCB is missing. PATIENTS/METHODS: We prospectively collected preoperative plasma from 1,036 consecutive patients at two institutes. These plasma specimens were assessed for levels of IL6 and IL6sR. Logistic and Cox regression analyses were used to assess the correlation of plasma levels with pathologic and survival outcomes. The additional clinical net benefits of preoperative IL6 and IL6sR were evaluated using decision curve analysis (DCA). RESULTS: Median IL6 and IL6sR plasma levels were significantly higher in patients with adverse pathologic features. Elevated biomarker levels were independently associated with an increased risk for lymph node metastasis and ≥ pT3 disease. Both biomarkers were independently associated with recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). The addition to, respectively, fitted pre- and postoperative prognostic models improved the predictive accuracy for lymph node metastasis, ≥ pT3 disease, RFS and CSS on DCA. INTERPRETATION: We confirmed that elevated preoperative plasma levels of IL6 and IL6sR levels are associated with worse oncological disease survival in patients treated with RC for UCB in a large multicenter study. Both biomarkers hold potential in identifying patients with adverse pathological features that may benefit from intensified/multimodal therapy and warrant inclusion into predictive/prognostic models. They demonstrated the ability to improve the discriminatory power of such models and thus guide clinical decision making.

Immune cells lacking Y chromosome show dysregulation of autosomal gene expression.

Epidemiological investigations show that mosaic loss of chromosome Y (LOY) in leukocytes is associated with earlier mortality and morbidity from many diseases in men. LOY is the most common acquired mutation and is associated with aberrant clonal expansion of cells, yet it remains unclear whether this mosaicism exerts a direct physiological effect. We studied DNA and RNA from leukocytes in sorted- and single-cells in vivo and in vitro. DNA analyses of sorted cells showed that men diagnosed with Alzheimer's disease was primarily affected with LOY in NK cells whereas prostate cancer patients more frequently displayed LOY in CD4 + T cells and granulocytes. Moreover, bulk and single-cell RNA sequencing in leukocytes allowed scoring of LOY from mRNA data and confirmed considerable variation in the rate of LOY across individuals and cell types. LOY-associated transcriptional effect (LATE) was observed in ~ 500 autosomal genes showing dysregulation in leukocytes with LOY. The fraction of LATE genes within specific cell types was substantially larger than the fraction of LATE genes shared between different subsets of leukocytes, suggesting that LOY might have pleiotropic effects. LATE genes are involved in immune functions but also encode proteins with roles in other diverse biological processes. Our findings highlight a surprisingly broad role for chromosome Y, challenging the view of it as a "genetic wasteland", and support the hypothesis that altered immune function in leukocytes could be a mechanism linking LOY to increased risk for disease.

The Multiple Sclerosis Intimacy and Sexuality Questionnaire (MSISQ-15): translation, adaptation and validation of the Polish version for patients with multiple sclerosis and spinal cord injury.

BACKGROUND: Polish physicians and researchers lack an extensive and precise instrument in their native language for evaluating sexual dysfunction in individuals with neurogenic disorders. The aim of this study was to create a culturally adapted, validated, Polish language version of the Multiple Sclerosis Intimacy and Sexuality Questionnaire (MSISQ-15) for persons with multiple sclerosis (MS) and spinal cord injury (SCI). METHODS: International recommendations and standardized methods for instrument validation were followed. Sexually active patients with MS and SCI completed the MSISQ-15, International Index of Erection Function (IIEF-15, men), and Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-31, women). IIEF-15 and PISQ-31 were used as reference questionnaires. Responses were collected at baseline (test) and after 2 weeks (re-test). RESULTS: We recruited 299 Polish-speaking patients with MS or SCI. Interviews disclosed that the translated questionnaire had optimal content validity/cross-cultural adaptation. MSISQ-15 scores correlated significantly with the severity of sexual dysfunction as evaluated by IIEF-15 (r = - 0.487) and PISQ-31 (r = - 0.709). These correlations substantiated the high quality construct/criterion validity. An analysis of reliability presented good internal consistency (Cronbach's alpha of 0.93 for the total score of MS patients and 0.86 for the total score of SCI patients) and reproducibility (intraclass correlation coefficients of 0.91 for the total score of MS patients and 0.92 for the total score of SCI patients). There were no ceiling or floor effects. CONCLUSIONS: The Polish version of MSISQ-15 exhibited excellent measurement properties. It is a suitable and reliable instrument to assess sexual dysfunction in MS and SCI individuals. The Polish MSISQ-15 will enhance routine clinical practice and assist research for neurogenic patients in Poland.

Prognostic value of the preoperative albumin-globulin ratio in patients with upper urinary tract urothelial carcinoma treated with radical nephroureterectomy: results from a large multicenter international collaboration.

OBJECTIVE: To assess the value of preoperative albumin to globulin ratio for predicting pathologic and oncological outcomes in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy in a large multi-institutional cohort. MATERIALS AND METHODS: Preoperative albumin to globulin ratio was assessed in a multi-institutional cohort of 2492 patients. Logistic regression analyses were performed to assess the association of the albumin to globulin ratio with pathologic features. Cox proportional hazards regression models were performed for survival endpoints. RESULTS: The optimal cut-off value was determined to be 1.4 according to a receiver operating curve analysis. Lower albumin to globulin ratios were observed in 797 patients (33.6%) compared with other patients. In a preoperative model, low preoperative albumin to globulin ratio was independently associated with nonorgan-confined diseases (odds ratio 1.32, P = 0.002). Patients with low albumin to globulin ratios had worse recurrence-free survival (P < 0.001), cancer-specific survival (P = 0.001) and overall survival (P = 0.020) in univariable and multivariable analyses after adjusting for the effect of standard preoperative prognostic factors (recurrence-free survival: hazard ratio (HR) 1.31, P = 0.001; cancer-specific survival: HR 1.31, P = 0.002 and overall survival: HR 1.18, P = 0.024). CONCLUSIONS: Lower preoperative albumin to globulin ratio is associated with locally advanced disease and worse clinical outcomes in patients treated with radical nephroureterectomy for upper tract urothelial carcinoma. As it is difficult to stage disease entity, low preoperative serum albumin to globulin ratio may help identify those most likely to benefit from intensified care, such as perioperative systemic therapy, and the extent and type of surgery.

Polish versions of the ICIQ-FLUTS and the ICIQ-FLUTS LF: translation, adaptation, and validation of female-specific instruments for evaluation of lower urinary tract symptoms.

INTRODUCTION AND HYPOTHESIS: Previously, there was no specific questionnaire in the Polish language for overall assessment of lower urinary tract symptoms (LUTS) in women. The aim of this study was to translate, culturally adapt, and validate Polish versions of the International Consultation on Incontinence Modular Questionnaire on Female Lower Urinary Tract Symptoms (ICIQ-FLUTS and ICIQ-FLUTS LF, short and long forms) for use in clinical practice and research in Poland. METHODS: The original English ICIQ-FLUTS and ICIQ-FLUTS LF were adapted to Polish according to international standards and recommended procedures. Adult women with LUTS who were seen at the Department of Urology at the Jagiellonian University, Krakow, Poland, completed the ICIQ-FLUTS and ICIQ-FLUTS LF at baseline and 2 weeks later. Control participants completed the questionnaires once. Validity and reliability were determined. RESULTS: One hundred and eighty Polish-speaking women who had LUTS completed the questionnaires. Content validity was high. Significant differences between women with LUTS and controls for both ICIQ-FLUTS and ICIQ-FLUTS LF confirmed optimal construct validity. An intercorrelation analysis revealed that internal consistency was good for ICIQ-FLUTS and ICIQ-FLUTS LF (Cronbach's alpha >0.7). Test-retest reliability (reproducibility) demonstrated strong stability (intraclass correlation coefficient > 0.7). Floor and ceiling effects were absent from women with LUTS, whereas a floor effect was detected in the control group. CONCLUSIONS: The Polish ICIQ-FLUTS and ICIQ-FLUTS LF are valid, reliable, and consistent measures of overall evaluation of LUTS in women. They are equivalent to the original English versions, and they retained the psychometric properties of the original questionnaires.

The urinary disorder-specific quality of life in patients after spinal cord injury: Polish translation, adaptation and validation of the Qualiveen and SF-Qualiveen.

STUDY DESIGN: Prospective cohort validation study. OBJECTIVES: In spinal cord injury (SCI), neurogenic lower urinary tract dysfunction is associated with a reduced quality of life. No specific questionnaire has been translated, culturally adapted, and validated into Polish language to assess urinary disorder-specific quality of life in people after SCI. In this study, we translated, adapted, and validated the Polish versions of the Qualiveen and SF-Qualiveen in individuals with SCI. SETTING: University Hospital in Krakow, Poland. METHODS: Translation and cross-cultural adaptation of the Qualiveen and SF-Qualiveen were done using international recommendations and well-established methods. Adult patients with SCI from the Department of Urology at the University Hospital in Krakow, Poland completed the Polish versions of the Qualiveen, SF-Qualiveen, and International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) at baseline and 2 weeks later. The ICIQ-SF served as the reference instrument. Validity and reliability were determined. RESULTS: Polish-speaking patients with SCI (n = 178) were included. Content validity/cross-cultural adaptation of the translated questionnaires was investigated during face-to-face interviews. Construct/criterion validity was assessed, and positive correlations were found between the Qualiveen and ICIQ-SF as well as the SF-Qualiveen and ICIQ-SF. A reliability study revealed good internal consistency (Cronbach's alpha > 0.8) and reproducibility (intraclass correlation coefficients > 0.8) for both adapted questionnaires. We did not identify floor or ceiling effect. CONCLUSIONS: The Polish versions of the Qualiveen and SF-Qualiveen showed good measurement properties. Polish healthcare providers can now reliably and directly assess the urinary disorder-specific quality of life in individuals after SCI.

Association between Lower Urinary Tract Symptoms and Sleep Quality of Patients with Depression.

Background and Objectives: In the general population, sleep disorders are associated with lower urinary tract symptoms (LUTS) including urinary incontinence (UI). This connection has not been explored fully in specific patient groups. Thus, we investigated the association between sleep quality and LUTS for patients with depression. Materials and Methods: This study was prospective and cross-sectional. We analyzed questionnaire data on depression, sleep quality, LUTS, and UI from depressed patients treated in our department of adult psychiatry. We used the Hamilton Rating Scale for Depression, the Holland Sleep Disorders Questionnaire, the International Prostate Symptom Score, and the International Consultation on Incontinence Questionnaire-Short Form. Results: In total, 102 patients treated for depression were enrolled. We found a statistically significant correlation between depression severity and sleep quality. A significant correlation was also investigated for sleep quality and LUTS severity. The group of depressed patients with moderate or severe LUTS had greater sleep problems compared with patients who had mild urinary tract symptoms or no symptoms. With regression analysis, we further demonstrated that the relationships between LUTS and sleep quality as well as UI and sleep quality in depressed patients are independent from age and sex. Conclusions: In the cohort of patients treated for depression, sleep quality correlated with LUTS including UI. We suggest that the negative effect of LUTS and UI on sleep quality that we observed should lead to the re-evaluation of current recommendations for diagnosis and treatment of sleep problems among patients with depression.

Robot-assisted vs open radical cystectomy for bladder cancer in adults.

BACKGROUND: It has been suggested that, in comparison with open radical cystectomy (ORC), robot-assisted radical cystectomy (RARC) results in less blood loss, shorter convalescence and fewer complications, with equivalent short-term oncological and functional outcomes; however, uncertainty remains as to the magnitude of these benefits. OBJECTIVES: To assess the effects of RARC vs ORC in adults with bladder cancer. SEARCH METHODS: We conducted a comprehensive search, with no restrictions on language of publication or publication status, for randomized controlled trials (RCTs) that compared RARC with ORC. The date of the last search was 1 July 2018. Databases searched included the Cochrane Central Register of Controlled Trials, MEDLINE (1999 to July 2018), PubMed Embase (1999 to July 2018), Web of Science (1999 to July 2018), Cancer Research UK (www.cancerresearchuk.org/), and the Institute of Cancer Research (www.icr.ac.uk/). We also searched the following trial registers: ClinicalTrials.gov (clinicaltrials.gov/); BioMed Central International Standard Randomized Controlled Trials Number (ISRCTN) Registry (www.isrctn.com); and the World Health Organization International Clinical Trials Registry Platform. The review was based on a published protocol. Primary outcomes of the review were recurrence-free survival and major postoperative complications (Clavien grade III to V). Secondary outcomes were minor postoperative complications (Clavien grades I and II), transfusion requirement, length of hospital stay (days), quality of life, and positive surgical margins (%). Three review authors independently assessed relevant titles and abstracts of records identified by the literature search to determine which studies should be assessed further. Two review authors assessed risk of bias using the Cochrane risk-of-bias tool and rated the quality of evidence according to GRADE. We used Review Manager 5 to analyse the data. RESULTS: We included in the review five RCTs comprising a total of 541 participants. Total numbers of participants included in the ORC and RARC cohorts were 270 and 271, respectively. We found that RARC and ORC may result in a similar time to recurrence (hazard ratio 1.05, 95% confidence interval [CI] 0.77 to 1.43; two trials, low-certainty evidence). In absolute terms at 5 years of follow-up, this corresponds to 16 more recurrences per 1000 participants (95% CI 79 fewer to 123 more) with 431 recurrences per 1000 participants for ORC. We downgraded the certainty of evidence because of study limitations and imprecision. RARC and ORC may result in similar rates of major complications (risk ratio [RR] 1.06, 95% CI 0.76 to 1.48; five trials, low-certainty evidence). This corresponds to 11 more major complications per 1000 participants (95% CI 44 fewer to 89 more). We downgraded the certainty of evidence because of study limitations and imprecision. We were very uncertain whether RARC reduces minor complications (very-low-certainty evidence). We downgraded the certainty of evidence because of study limitations and very serious imprecision. RARC probably results in substantially fewer transfusions than ORC (RR 0.58, 95% CI 0.43 to 0.80; two trials, moderate-certainty evidence). This corresponds to 193 fewer transfusions per 1000 participants (95% CI 262 fewer to 92 fewer) based on 460 transfusion per 1000 participants for ORC. We downgraded the certainty of evidence because of study limitations. RARC may result in a slightly shorter hospital stay than ORC (mean difference -0.67, 95% CI -1.22 to -0.12; five trials, low-certainty evidence). We downgraded the certainty of evidence because of study limitations and imprecision. RARC and ORC may result in a similar quality of life (standardized mean difference 0.08, 95% CI 0.32 lower to 0.16 higher; three trials, low-certainty evidence). We downgraded the certainty of evidence because of study limitations and imprecision. RARC and ORC may result in similar positive surgical margin rates (RR 1.16, 95% CI 0.56 to 2.40; five trials, low-certainty evidence). This corresponds to eight more (95% CI 21 fewer to 67 more) positive surgical margins per 1000 participants, based on 48 positive surgical margins per 1000 participants for ORC. We downgraded the certainty of evidence because of study limitations and imprecision. CONCLUSIONS: We conclude that RARC and ORC may have similar outcomes with regard to time to recurrence, rates of major complications, quality of life, and positive surgical margin rates (all low-certainty evidence). We are very uncertain whether the robotic approach reduces rates of minor complications (very-low-certainty evidence), although it probably reduces the risk of blood transfusions substantially (moderate-certainty evidence) and may reduce hospital stay slightly (low-certainty evidence). We were unable to conduct any of the preplanned subgroup analyses to assess the impact of patient age, pathological stage, body habitus, or surgeon expertise on outcomes. This review did not address issues of cost-effectiveness.

Prognostic value of T1 substaging on oncological outcomes in patients with non-muscle-invasive bladder urothelial carcinoma: a systematic literature review and meta-analysis.

PURPOSE: To evaluate the prognostic value of substaging on oncological outcomes in patients with T (or pT1) urothelial carcinoma of the bladder. METHODS: A literature search using PubMed, Scopus, Web of Science, and Cochrane Library was conducted on March 2019 to identify relevant studies according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. The pooled disease recurrence (DR) and disease progression (DP) rate in T1(or pT1) patients were calculated using a fixed or random effects model. RESULTS: Overall 36 studies published between 1994 and 2018 including a total of 6781 bladder cancer patients with T1(or pT1) stage were selected for the systematic review and meta-analysis. Twenty-nine studies reported significant association between tumor infiltration depth or muscularis mucosa (MM) invasion and oncological outcomes. Totally 12 studies were included in the meta-analysis. MM invasion (T1a/b/c [or pT1a/b/c] or T1a/b [or pT1a/b] substaging system) was associated with DR (pooled HR: 1.23, 95%CI: 1.01-1.49) and DP (pooled HR: 2.61, 95%CI: 1.61-4.23). Tumor infiltration depth (T1 m/e [or pT1 m/e] substaging system) was also associated with DR (pooled HR: 1.49, 95%CI: 1.11-2.00) and DP (pooled HR: 3.29, 95%CI: 2.39-4.51). CONCLUSIONS: T1(or pT1) substaging in patients with bladder cancer is of prognostic value as it is associated with oncologic outcomes. Inclusion of this factors into the clinical decision-making process of this heterogeneous tumor may improve outcomes, while avoiding over- and under-treatment for T1(or pT1) bladder cancer.

Expression of urokinase-type plasminogen activator system in non-metastatic prostate cancer.

PURPOSE: To investigate the prognostic role of expression of urokinase-type plasminogen activator system members, such as urokinase-type activator (uPA), uPA-receptor (uPAR), and plasminogen activator inhibitor-1 (PAI-1), in patients treated with radical prostatectomy (RP) for prostate cancer (PCa). METHODS: Immunohistochemical staining for uPA system was performed on a tissue microarray of specimens from 3121 patients who underwent RP. Cox regression analyses were performed to investigate the association of overexpression of these markers alone or in combination with biochemical recurrence (BCR). Decision curve analysis was used to assess the clinical impact of these markers. RESULTS: uPA, uPAR, and PAI-1 were overexpressed in 1012 (32.4%), 1271 (40.7%), and 1311 (42%) patients, respectively. uPA overexpression was associated with all clinicopathologic characteristics of biologically aggressive PCa. On multivariable analysis, uPA, uPAR, and PAI-1 overexpression were all three associated with BCR (HR: 1.75, p < 0.01, HR: 1.22, p = 0.01 and HR: 1.20, p = 0.03, respectively). Moreover, the probability of BCR increased incrementally with increasing cumulative number of overexpressed markers. Decision curve analysis showed that addition of uPA, uPAR, and PAI-1 resulted in a net benefit compared to a base model comparing standard clinicopathologic features across the entire threshold probability range. In subgroup analyses, overexpression of all three markers remained associated with BCR in patients with favorable pathologic characteristics. CONCLUSION: Overexpression of uPA, uPAR, and PAI-1 in PCa tissue were each associated with worse BCR. Additionally, overexpression of all three markers is informative even in patients with favorable pathologic characteristics potentially helping clinical decision-making regarding adjuvant therapy and/or intensified follow-up.

Polish versions of the Qualiveen and the SF-Qualiveen: Translation and validation of urinary disorder-specific instruments in patients with multiple sclerosis.

AIMS: No specific questionnaire to date has been available in Polish for evaluating health-related quality of life for urinary dysfunctions associated with multiple sclerosis (MS). The aim of this study was to translate, culturally adapt, and validate Polish versions of the Qualiveen and SF-Qualiveen for use in patients with MS. METHODS: Cross-cultural adaptation of the original English Qualiveen and SF-Qualiveen into Polish was performed according to international recommended and standard procedures. Adult patients with MS of the Department of Urology at the Jagiellonian University, Krakow, Poland, completed the Qualiveen, SF-Qualiveen, and International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) twice: at baseline and 2 weeks later. RESULTS: One hundred eighty-nine Polish-speaking patients with MS completed the questionnaires. An intercorrelation study revealed that internal consistency was good for the total Qualiveen and SF-Qualiveen (Cronbach's α >0.8). Test-retest reliability (reproducibility) demonstrated strong stability (intraclass correlation coefficient >0.8). Content validities were optimal. Significant relationships between the Qualiveen and the ICIQ-SF, as well as the SF-Qualiveen and the ICIQ-SF, confirmed good construct/criterion validity. CONCLUSION: The Polish Qualiveen and SF-Qualiveen are reliable, valid, and consistent measures of urinary disorder-specific quality of life in patients with MS. After years of no appropriate Polish instrument being available for healthcare professionals to evaluate patients with MS, we provide these versions and recommend their use in research and clinical practice in Poland.

Neurogenic bladder symptom score: Polish translation, adaptation and validation of urinary disorder-specific instrument for patients with neurogenic lower urinary tract dysfunction.

INTRODUCTION: There is no comprehensive and specific questionnaire translated, adapted and validated in the Polish language for evaluating symptoms, quality of life and complications associated with the neurogenic lower urinary tract dysfunction (NLUTD). The aim of this study was to translate, culturally adapt and validate a Polish version of the Neurogenic Bladder Symptom Score (NBSS) for patients who experience NLUTD. MATERIAL AND METHODS: Standardised guidelines and well-established methods were used for translation and cross-cultural adaptation of the NBSS. Adult patients with multiple sclerosis and spinal cord injury completed the NBSS, the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), the International Prostate Symptom Score (IPSS) and the SF-Qualiveen. Responses were recorded twice within a 14-day period. RESULTS: Two hundred seventy-four Polish-speaking patients with NLUTD were included in the study. Content validity was optimal. Significant relationships between NBSS (Incontinence) and ICIQ-SF, NBSS (Storage and Voiding) and IPSS, and NBSS (Quality of Life) and SF-Qualiveen confirmed good construct/criterion validity. An intercorrelation study revealed that internal consistency was good for the total NBSS and specific domains (Cronbach's alpha >0.7). Test-retest reliability (reproducibility) demonstrated strong stability (intra-class correlation coefficients >0.7 for the total NBSS). No ceiling or floor effects were present. CONCLUSIONS: The Polish NBSS demonstrated good measurement properties for a large cohort of patients with NLUTD. It is a suitable tool to assess NLUTD symptoms, consequences and quality of life. The Polish NBSS will support routine clinical practice of all types of physicians in Poland who care for patients with NLUTD.

Image analysis discloses differences in nuclear parameters between ERG+ and ERG- prostatic carcinomas.

Prostatic carcinoma (PC) is the most frequent urologic cancer and one of the most frequent cancers in males; it is a heterogeneous disease, in terms of molecular features, morphology and prognosis. About half of cases depends on TMPRSS2-ETS translocation which leads to a production of ERG transcription factor. ERG+ and ERG- cancers seem to differ in a number of features, which could lead to an altered nuclear structure; the aim of the study was to test this hypothesis. The material consisted of total 39 PC cases, representing ERG+ and ERG-, as well as Gleason pattern 3 and 4. Filtering by color deconvolution and automatic segmentation were used, and the properly detected nuclei were manually selected. From each case fifty nuclei were obtained; then geometric features and texture parameters were assessed. The analysis of the collected data showed differences both between ERG+/ERG- and Gleason pattern 3 and 4 cases in most of the features analyzed. Our results suggest that indeed the ERG status, thus likely TMPRSS2-ETS translocation, has an impact on morphology of nuclei in PC, and their differences are evident enough to be detectable by image analysis.