Upper tract urothelial carcinoma (UTUC) accounts for 10% of urothelial carcinomas (UCs) and has a substantial hereditary component. However, the majority of our knowledge of germline spectrum comes from bladder cancer (BCa) data in White populations. Here, we sequence 309 Chinese UTUC cases and identify 71 germline pathogenic/likely pathogenic (P/LP) mutations in 62 patients (20.1%). Compared with White cases, we observe disparities and similarities in inherited mutational profiles. Association analysis reveals that germline P/LP mutations in MSH2, BRCA2, BRCA1, and BRIP1 significantly increase UTUC risk in Chinese populations. Furthermore, germline P/LP mutation in homologous recombination genes indicates poor prognosis for non-metastatic UTUC. Finally, we perform paired sequencing and observe significant correlations between germline mutation patterns and tumor subtypes. This study highlights the importance of genetic testing in patients with UTUC and calls for germline data from various ethnicities to better understand this disease.
- MeSH
- karcinom z přechodných buněk * genetika MeSH
- lidé MeSH
- mutace MeSH
- nádory močového měchýře * genetika MeSH
- východní Asiaté MeSH
- zárodečné mutace genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Čína MeSH
PURPOSE: To test discontinuation rates during Active Surveillance (AS) in patients diagnosed with incidental prostate cancers (IPCa) vs. tumors diagnosed at prostate biopsies (BxPCa). METHODS: Retrospective single center analysis of 961 vs. 121 BxPCa vs. IPCa patients (2008-2020). Kaplan-Meier plots and multivariable Cox regression models tested four different outcomes: (1) any-cause discontinuation; (2) discontinuation due to ISUP GG upgrading; (3) biopsy discontinuation due to ISUP GG upgrading or > 3 positive cores; (4) biopsy discontinuation or suspicious extraprostatic extension at surveillance mpMRI. Then, multivariable logistic regression models tested rates of clinically significant PCa (csPCa) (ISUP GG ≥ 3 or pT ≥ 3a or pN1) after radical prostatectomy (RP). RESULTS: Median time follow-up was 35 (19-64) months. IPCa patients were at lower risk of any-cause (3-year survival: 79.3 vs. 66%; HR: 0.5, p = 0.001) and biopsy/MRI AS discontinuation (3-year survival: 82.3 vs. 72.7%; HR: 0.5, p = 0.001), compared to BxPCa patients. Conversely, IPCa patients exhibited same rates of biopsy discontinuation and ISUP GG upgrading over time, relative to BxPCa. In multivariable logistic regression models, IPCa patients were associated with higher rates of csPCa at RP (OR: 1.4, p = 0.03), relative to their BxPCa counterparts. CONCLUSION: AS represents a safe management strategy for IPCa. Compared to BxPCa, IPCa patients are less prone to experience any-cause and biopsy/MRI AS discontinuation. However, the two mentioned groups present similar rates of biopsy discontinuation and ISUP GG upgrading over time. In consequence, tailored AS protocols with scheduled repeated surveillance biopsies should be offered to all newly diagnosed IPCa patients.
- MeSH
- biopsie MeSH
- lidé MeSH
- nádory prostaty * patologie MeSH
- pozorné vyčkávání MeSH
- prostata * diagnostické zobrazování patologie MeSH
- retrospektivní studie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
CONTEXT: The choice of the most efficacious drug for patients with idiopathic overactive bladder (IOAB) remains challenging. OBJECTIVE: The aim of this network meta-analysis was to determine the most efficacious oral antimuscarinic or β-adrenoceptor agonist accounting for adverse events for the management of IOAB. EVIDENCE ACQUISITION: A comprehensive electronic search was done in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and Ovid for studies in any language in February 2021 considering the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. We included all randomized controlled trials assessing oral antimuscarinics or β-adrenoceptor agonists for the treatment of IOAB. We determined the effect of specific bothersome symptoms separately. EVIDENCE SYNTHESIS: Fifty-four articles were included in our analysis. The most efficacious agents considering the evaluated outcomes were oxybutynin 15 mg/d in reducing incontinence episodes, imidafenacin 0.5 mg/d together with solifenacin 10 and 5 mg/d in reducing micturition episodes, fesoterodine 4 and 8 mg/d as well as solifenacin 10 mg/d in reducing urgency episodes, imidafenacin 0.5 mg/d and solifenacin 10 mg/d in reducing urgency urinary incontinence episodes, and solifenacin 10 mg/d, vibegron 50 mg/d, and fesoterodine 8 mg/d in improving the voided volume. Gastrointestinal problems, especially due to antimuscarinic agents, were the most prevalent adverse events. CONCLUSIONS: Taken together, there is only minimal difference between the efficacy of oral antimuscarinics and that of β-adrenoceptor agonists. Although finding the best medication for all is impossible, finding the best treatment for every individual patient can be done by considering the efficacy of a medicine for the most bothersome symptom(s) in balance with drug-specific adverse events. PATIENT SUMMARY: This study aimed to find the most efficient oral medication to treat overactive bladder, taking into consideration the adverse events. Based on our study, there is a minimal difference in the efficacy between the two major drug classes used to treat overactive bladder. Gastrointestinal problems were the most common adverse events in medical treatment of overactive bladder. Selection of the best treatment is possible through shared decision-making between the doctor and the patient based on the patient's most bothersome symptom. We provide a framework for physicians to facilitate shared decision-making with each individual patient.
- MeSH
- adrenergní receptory terapeutické užití MeSH
- antagonisté muskarinových receptorů terapeutické užití MeSH
- benzhydrylové sloučeniny MeSH
- hyperaktivní močový měchýř * diagnóza farmakoterapie MeSH
- inkontinence moči * farmakoterapie MeSH
- lidé MeSH
- síťová metaanalýza MeSH
- solifenacin sukcinát škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- systematický přehled MeSH
Radical cystectomy with pelvic lymphadenectomy and urinary diversion is the standard treatment for patients diagnosed with localized muscle-invasive bladder cancer. Enhanced recovery after surgery (ERAS) is a multimodal perioperative care pathway comprising recommendations on different items with variable evidence that are aimed at improving outcomes. This review provides an overview of the application of specific elements of the ERAS guidelines. Forty-eight series were identified through our literature search. The studies reported a median of 16 out of the 22 ERAS steps (72.7%). The elements were applied in 79.3% of cases (interquartile range 61.1-85%) if mentioned in the studies, decreasing to 73.5% in the postoperative period. PATIENT SUMMARY: Guidelines on enhanced recovery after surgery recommend steps to follow and cover all areas of the patient's journey through the surgical process. We looked at the application of the elements for patients with bladder cancer. We found inconsistent reporting and use.
- MeSH
- lidé MeSH
- nádory močového měchýře * chirurgie MeSH
- urychlená pooperační rehabilitace * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: Among various clinicopathologic factors used to identify low-risk upper tract urothelial carcinoma (UTUC), tumor grade and stage are of utmost importance. The clinical value added by inclusion of other risk factors remains unproven. OBJECTIVE: To assess the performance of a tumor grade- and stage-based (GS) model to identify patients with UTUC for whom kidney-sparing surgery (KSS) could be attempted. DESIGN, SETTING, AND PARTICIPANTS: In this international study, we reviewed the medical records of 1240 patients with UTUC who underwent radical nephroureterectomy. Complete data needed for risk stratification according to the European Association of Urology (EAU) and National Comprehensive Cancer Network (NCCN) guidelines were available for 560 patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Univariable and multivariable logistic regression analyses were performed to determine if risk factors were associated with the presence of localized UTUC. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the GS, EAU, and NCCN models in predicting pathologic stage were calculated. RESULTS AND LIMITATIONS: Overall, 198 patients (35%) had clinically low-grade, noninvasive tumors, and 283 (51%) had ≤pT1disease. On multivariable analyses, none of the EAU and NCCN risk factors were associated with the presence of non-muscle-invasive UTUC among patients with low-grade and low-stage UTUC. The GS model exhibited the highest accuracy, sensitivity, and negative predictive value among all three models. According to the GS, EAU, and NCCN models, the proportion of patients eligible for KSS was 35%, 6%, and 4%, respectively. Decision curve analysis revealed that the net benefit of the three models was similar within the clinically reasonable range of probability thresholds. CONCLUSIONS: The GS model showed favorable predictive accuracy and identified a greater number of KSS-eligible patients than the EAU and NCCN models. A decision-making algorithm that weighs the benefits of avoiding unnecessary kidney loss against the risk of undertreatment in case of advanced carcinoma is necessary for individualized treatment for UTUC patients. PATIENT SUMMARY: We assessed the ability of three models to predict low-grade, low-stage disease in patients with cancer of the upper urinary tract. No risk factors other than grade assessed on biopsy and stage assessed from scans were associated with better prediction of localized cancer. A model based on grade and stage may help to identify patients who could benefit from kidney-sparing treatment of their cancer.
BACKGROUND: Identifying those of patients with metastatic renal cell carcinoma (mRCC) who are most likely to benefit from cytoreductive nephrectomy (CN) is challenging. We tested the association between preoperative value of Systemic Immune-Inflammation Index (SII) and overall survival (OS) as well as cancer-specific survival (CSS) in mRCC patients treated with CN. METHODS: mRCC patients treated with CN at different institutions were included. After assessing for the optimal pretreatment SII cut‐off value, we found 710 to have the maximum Youden Index value. The overall population was therefore divided into two SII groups using this cut‐off (low, <710 vs. high, ≥710). Univariable and multivariable Cox regression analyses tested the association SII and OS as well as CSS. The discrimination of the model was evaluated with the Harrel's Concordance Index (C-Index). The clinical value of the SII was evaluated with decision curve analysis (DCA). RESULTS: Among 613 mRCC patients, 298 (49%) patients had a SII≥710. Median follow-up was 31 (IQR 16-58) months. On univariable analysis, high preoperative serum SII was significantly associated with worse OS (HR: 1.28, 95% CI: 1.07-1.54, P=0.01) and CSS (HR: 1.29, 95% CI: 1.08-1.55, P=0.01). On multivariable analysis, which adjusted for the effect of established clinicopathologic features, SII≥710 was associated with OS (HR: 1.25, 95% CI: 1.04-1.50, P=0.02) and CSS (HR: 1.26, 95% CI: 1.05-1.52, P=0.01). The addition of SII only slightly improved the discrimination of a base model that included established clinicopathologic features (C-index: 0.637 vs. 0.629). On DCA, the inclusion of SII did not improve the net-benefit of the prognostic model. On multivariable analyses, SII≥710 remained independently associated with the worse OS and CSS in IMDC intermediate risk group (both: HR: 1.31, 95% CI: 1.02-1.67, P=0.03). In the subgroup analyses based on the BMI, among patients with BMI ≥ 25, SII was significantly associated with OS (HR: 1.29, 95% CI: 1.04-1.61, P=0.02) and CSS (HR: 1.31, 95% CI: 1.05-1.63, P=0.02). CONCLUSIONS: We found an independent association of high SII prior to CN with unfavorable clinical outcomes, particularly in patients with intermediate risk mRCC and patients with increased BMI. Despite these results, it does not seem to add any prognostic or clinical benefit beyond that obtained by currently available clinicopathologic characteristics as sole worker.
- MeSH
- cytoredukční chirurgie * MeSH
- karcinom z renálních buněk * imunologie patologie chirurgie MeSH
- lidé MeSH
- nádory ledvin * imunologie patologie chirurgie MeSH
- nefrektomie * metody MeSH
- předoperační péče MeSH
- prognóza MeSH
- zánět imunologie patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
CONTEXT: The role of a placebo response in the management of overactive bladder (OAB) remains unclear. OBJECTIVE: The aim of this review is to methodically study the placebo response extracted from the control arms of randomized clinical trials assessing therapy in patients with OAB. EVIDENCE ACQUISITION: Medline (PubMed), The Cochrane Library, EMBASE, and Scopus were searched to identify randomized controlled trials (RCTs) published until September 2019. Randomized placebo-controlled trials investigating oral drug therapy for OAB were included. The articles were critically appraised by two reviewers. The primary outcomes were the placebo response in the main patient-reported urinary outcomes together with assessing the impact of patient demographic factors on the placebo response. EVIDENCE SYNTHESIS: The initial search resulted in 1982 records after reviewing the titles and abstracts, and reference lists of other systematic reviews; 57 studies with an overall estimated 12 901 patients were included in the meta-analysis. The included studies were of overall high/acceptable quality. The standardized mean difference was -0.45 (95% confidence interval [CI] -0.51 to -0.40; p<0.001) for daily micturition episodes, -0.33 (95% CI -0.42 to -0.24; p<0.001) for daily nocturia episodes, -0.46 (95% CI -0.55 to -0.37; p<0.001) for urgency urinary incontinence episodes, -0.50 (95% CI -0.61 to -0.39; p<0.001) for daily urgency episodes, -0.51 (95% CI -0.60 to -0.43; p<0.001) for daily incontinence episodes, and 0.25 (95% CI 0.211-0.290; p<0.001) for volume voided per micturition. The meta-regression of age-related impact of the placebo response on nocturia showed a slope of -0.02 (p<0.001). CONCLUSIONS: Placebo has a statistically significant effect on improving symptoms and signs associated with OAB; this effect is age dependent. However, there is no consensus on what change of OAB symptoms and signs is clinically meaningful for the affected patient. Taken together, the placebo response seems to be non-negligible in OAB, supporting the need for placebo control in RCTs. PATIENT SUMMARY: Placebo is an inert treatment method often used in clinical research for comparison with active treatment. However, studies show that placebo has an effect of its own. A placebo response means the total improvement resulting from receiving a placebo. In our study, placebo had a significant role in improving the symptoms of overactive bladder.
INTRODUCTION: Although upper tract urothelial carcinoma (UTUC) is more common in the elderly, outcomes of neoadjuvant chemotherapy (NAC) in this population have never been explored. The objective of the study was to assess the impact of NAC on pathologic response and oncological outcomes stratified by age. PATIENTS AND METHODS: This multicenter study included 164 patients treated with NAC and radical nephroureterectomy (RNU) for clinically non-metastatic, high-risk UTUC. The cohort was stratified into two groups according to median age. Patients received either cisplatin-based or non-cisplatin-based chemotherapies. Pathologic responses were defined as pathologic objective response (pOR; ≤ ypT1N0) and pathologic complete response (pCR; ypT0N0). Univariable and multivariable logistic and Cox regression analyses were performed to identify predictors for pathologic response and survival outcomes. RESULTS: The cohorts' median age was 68 years with the elderly group (> 68 years) comprising 74 patients. Neoadjuvant chemotherapy included methotrexate-vinblastine-doxorubicin-cisplatin (MVAC) in 66 (40%), gemcitabine cisplatin (GC) in 66 (40%) and non-cisplatin chemotherapy in 32 patients (20%). Younger patients received more often MVAC (50% vs. 28%) while elderly received more GC (34% vs. 47%) or non-cisplatin chemotherapy (16% vs. 24%) (P = .02). Overall, pOR and pCR were similar across age groups (52% vs. 47%; P = .5 and 10% vs. 8%; P = .7). While GC and non-cisplatin chemotherapy showed a lower pCR of 5% and 3%, respectively, MVAC revealed a pCR of 17% (P = .03) and was independently associated with a higher pCR (OR 4.31; P = .03). Kaplan-Meier analysis showed no difference in recurrence-free and cancer-specific survival, whereas a lower rate was seen in overall survival for the elderly. CONCLUSION: Elderly patients with high-risk UTUC eligible for cisplatin-based NAC prior to RNU may benefit from this multimodal therapy equally as their younger counterparts. Cisplatin-ineligible patients undergoing non-cisplatin-based NAC appeared to have lower response rates and should be considered for immediate RNU.
- MeSH
- cisplatina terapeutické užití MeSH
- karcinom z přechodných buněk * patologie MeSH
- lidé MeSH
- nádory močového měchýře * patologie MeSH
- neoadjuvantní terapie škodlivé účinky MeSH
- protokoly antitumorózní kombinované chemoterapie MeSH
- retrospektivní studie MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- MeSH
- epigeneze genetická MeSH
- epigenomika metody MeSH
- lidé MeSH
- management nemoci MeSH
- metylace DNA * MeSH
- náchylnost k nemoci MeSH
- nádorové biomarkery * MeSH
- nádory prostaty rezistentní na kastraci krev diagnóza genetika terapie MeSH
- prognóza MeSH
- stanovení celkové genové exprese MeSH
- tekutá biopsie * metody MeSH
- výpočetní biologie metody MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- dopisy MeSH
- práce podpořená grantem MeSH
OBJECTIVE: To investigate the predictive value of tumour-infiltrating immune cells (TIICs) on oncological outcomes and response to BCG treatment in patients with non-muscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS: A systematic review and meta-analysis was performed using PubMed, Scopus and the Cochrane Library in July 2020 to identify relevant studies according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The pooled recurrence-free survival (RFS) rate was calculated using a fixed-effect model. RESULTS: We retrieved 15 studies (including 791 patients) evaluating the effect of TIICs on oncological outcomes in patients with NMIBC treated with intravesical BCG. TIICs were reported to be a significant predictor of oncological outcomes and response to BCG treatment in 10 studies. Tumour-associated macrophages were associated with worse RFS (pooled hazard ratio 2.30, 95% confidence interval 1.64-3.22). CONCLUSIONS: Based on these data, TIICs are significant predictors of RFS and response to BCG treatment in patients with NMIBC; therefore, incorporation of TIICs into risk stratification models may help patients and physicians in the clinical decision-making process in order to achieve the maximum possible benefit from BCG treatment.
- MeSH
- adjuvancia imunologická aplikace a dávkování MeSH
- aplikace intravezikální MeSH
- BCG vakcína aplikace a dávkování MeSH
- lidé MeSH
- nádory močového měchýře farmakoterapie imunologie patologie MeSH
- tumor infiltrující lymfocyty * MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- systematický přehled MeSH
