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BACKGROUND AND OBJECTIVE: There is no standardized regimen for follow-up after radical cystectomy (RC) for bladder cancer (BC). To address this gap, we conducted a multicenter study involving urologist members from the European Association of Urology (EAU) bladder cancer guideline panels. Our objective was to identify consistent post-RC follow-up strategies and develop a practice-based framework based on expert opinion. METHODS: We surveyed 27 urologist members of the EAU guideline panels for non-muscle-invasive bladder cancer and muscle-invasive and metastatic bladder cancer using a pre-tested questionnaire with dichotomous responses. The survey inquired about follow-up strategies after RC and the use of risk-adapted strategies. Consistency was defined as >75% affirmative responses for follow-up practices commencing 3 mo after RC. Descriptive statistics were used for analysis. KEY FINDINGS AND LIMITATIONS: We received responses from 96% of the panel members, who provided data from 21 European hospitals. Risk-adapted follow-up is used in 53% of hospitals, with uniform criteria for high-risk (at least ≥pT3 or pN+) and low-risk ([y]pT0/a/1N0) cases. In the absence of agreement for risk-based follow up, a non-risk-adapted framework for follow-up was developed. Higher conformity was observed within the initial 3 yr, followed by a decline in subsequent follow-up. Follow-up was most frequent during the first year, including patient assessments, physical examinations, and laboratory tests. Computed tomography of the chest and abdomen/pelvis was the most common imaging modality, initially at least biannually, and then annually from years 2 to 5. There was a lack of consistency for continuing follow-up beyond 10 yr after RC. CONCLUSIONS AND CLINICAL IMPLICATIONS: This practice-based post-RC follow-up framework developed by EAU bladder cancer experts may serve as a valuable guide for urologists in the absence of prospective randomized studies. PATIENT SUMMARY: We asked urologists from the EAU bladder cancer guideline panels about their patient follow-up after surgical removal of the bladder for bladder cancer. We found that although urologists have varying approaches, there are also common follow-up practices across the panel. We created a practical follow-up framework that could be useful for urologists in their day-to-day practice.
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Background and objective: Patients with intermediate-risk non-muscle-invasive bladder cancer (IR NMIBC) have a high risk of recurrence and need effective therapies to reduce the risk of disease recurrence or progression. This phase 1b study (NCT02720367) assessed the safety and tolerability of TAR-200, an intravesical drug delivery system, in participants with IR NMIBC. Methods: Participants with recurrent IR NMIBC were eligible. Participants received either two 7-d or two 21-d TAR-200 dosing cycles over a 4-6-wk period in a marker lesion/ablation design. TAR-200 was placed in the window between the cystoscopy showing recurrent papillary disease and the subsequent complete transurethral resection of the bladder tumour. The primary endpoint was TAR-200 safety. The secondary endpoints included TAR-200 tolerability, pharmacokinetics, and preliminary efficacy. Key findings and limitations: Twelve participants received TAR-200 treatment. No TAR-200-related serious or grade ≥ 3 treatment-emergent adverse events (TEAEs) occurred. Nine participants had grade ≤ 2 TAR-200-related TEAEs, with urgency, dysuria, and haematuria being most common. Two participants refused a second dosing cycle due to urinary urgency and frequency. Insertion and removal of TAR-200 was successful in all cases. Plasma gemcitabine concentrations remained below the lower limit of detection. Five participants (42%) had complete response (CR): four had pathological CR and one had CR based on visual assessment. Conclusions and clinical implications: TAR-200 appears to be safe and well tolerated, with encouraging preliminary efficacy in participants with IR NMIBC. This study lays the groundwork for the multiple phase 2 and 3 global studies that are currently on-going for TAR-200. Patient summary: In this study, researchers evaluated the safety of the novel drug delivery system TAR-200 in participants with intermediate-risk non-muscle-invasive bladder cancer. They concluded that TAR-200 was safe and well tolerated with promising antitumour activity.
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CONTEXT: We present an overview of the updated 2023 European Association of Urology (EAU) guidelines for muscle-invasive and metastatic bladder cancer (MMIBC). OBJECTIVE: To provide practical evidence-based recommendations and consensus statements on the clinical management of MMIBC with a focus on diagnosis and treatment. EVIDENCE ACQUISITION: A broad and comprehensive scoping exercise covering all areas of the MMIBC guidelines has been performed annually since 2017. Searches cover the Medline, EMBASE, and Cochrane Libraries databases for yearly guideline updates. A level of evidence and strength of recommendation are assigned. The evidence cutoff date for the 2023 MIBC guidelines was May 4, 2022. EVIDENCE SYNTHESIS: Patients should be counselled regarding risk factors for bladder cancer. Pathologists should describe tumour and lymph nodes in detail, including the presence of histological subtypes. The importance of the presence or absence of urothelial carcinoma (UC) in the prostatic urethra is emphasised. Magnetic resonance imaging (MRI) of the bladder is superior to computed tomography (CT) for disease staging, specifically in differentiating T1 from T2 disease, and may lead to a change in treatment approach in patients at high risk of an invasive tumour. Imaging of the upper urinary tract, lymph nodes, and distant metastasis is performed with CT or MRI; the additional value of flurodeoxyglucose positron emission tomography/CT still needs to be determined. Frail and comorbid patients should be evaluated by a multidisciplinary team. Postoperative histology remains the most important prognostic variable, while circulating tumour DNA appears to be an interesting predictive marker. Neoadjuvant systemic therapy remains cisplatin-based. In motivated and selected women and men, sexual organ-preserving cystectomy results in better functional outcomes without compromising oncological outcomes. Robotic and open cystectomy have comparable outcomes and should be combined with (extended) lymph node dissection. The diversion type is an individual choice after taking patient and tumour characteristics into account. Radical cystectomy remains a highly complex procedure with considerable morbidity and risk of mortality, although lower rates are observed for higher hospital volumes (>20 cases/yr). With proper patient selection, trimodal therapy (chemoradiation) has comparable outcomes to radical cystectomy. Adjuvant chemotherapy after surgery improves disease-specific survival and overall survival (OS) in patients with high-risk disease who did not receive neoadjuvant treatment, and is strongly recommended. There is a weak recommendation for adjuvant nivolumab, as OS data are not yet available. Health-related quality of life should be assessed using validated questionnaires at baseline and after treatment. Surveillance is needed to monitor for recurrent cancer and functional outcomes. Recurrences detected on follow-up seem to have better prognosis than symptomatic recurrences. CONCLUSIONS: This summary of the 2023 EAU guidelines provides updated information on the diagnosis and treatment of MMIBC for incorporation into clinical practice. PATIENT SUMMARY: The European Association of Urology guidelines panel on muscle-invasive and metastatic bladder cancer has released an updated version of the guideline containing information on diagnosis and treatment of this disease. Recommendations are based on studies published up to May 4, 2022. Surgical removal of the bladder and bladder preservation are discussed, as well as updates on the use of chemotherapy and immunotherapy in localised and metastatic disease.
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Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Urología , Masculino , Humanos , Femenino , Neoplasias de la Vejiga Urinaria/patología , Carcinoma de Células Transicionales/patología , Calidad de Vida , Cistectomía/métodos , Músculos/patología , Invasividad NeoplásicaRESUMEN
BACKGROUND AND PURPOSE: Oral capecitabine and intravenous 5-fluorouracil (5-FU) are both used as a radiosensitizer in chemoradiotherapy (CRT). A capecitabine-based regimen is more convenient for both patients and healthcare professionals. Since large comparative studies are lacking, we compared toxicity, overall survival (OS) and disease-free survival (DFS) between both CRT-regimens in patients with muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: All patients diagnosed with non-metastatic MIBC between November 2017-November 2019 were consecutively included in the BlaZIB study. Data on patient, tumor, treatment characteristics and toxicity were prospectively collected from the medical files. From this cohort, all patients with cT2-4aN0-2/xM0/x, treated with capecitabine or 5-FU-based CRT were included in the current study. Toxicity in both groups was compared using Fisher-exact tests. Propensity score-based inverse probability treatment weighting (IPTW) was applied to correct for baseline differences between groups. IPTW-adjusted Kaplan-Meier OS and DFS curves were compared using log-rank tests. RESULTS: Of the 222 included patients, 111 (50%) were treated with 5-FU and 111 (50%) with capecitabine. Curative CRT was completed according to treatment plan in 77% of patients in the capecitabine-based group and 62% of the 5-FU group (p = 0.06). Adverse events (14 vs 21%, p = 0.29), 2-year OS (73% vs 61%, p = 0.07) and 2-year DFS (56% vs 50%, p = 0.50) did not differ significantly between groups. CONCLUSIONS: Chemoradiotherapy with capecitabine and MMC is associated with a similar toxicity profile compared to 5-FU plus MMC and no difference in survival was found. Capecitabine-based CRT, as a more patient-friendly schedule, may be considered as an alternative to a 5-FU-based regimen.
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Fluorouracilo , Neoplasias de la Vejiga Urinaria , Humanos , Fluorouracilo/uso terapéutico , Capecitabina/efectos adversos , Estudios de Cohortes , Quimioradioterapia/efectos adversos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Músculos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
Fluorodeoxyglucose-based positron emission tomography/computed tomography is increasingly being used for staging of muscle-invasive bladder cancer before treatment. However, international clinical guidelines are hesitant to recommend this approach, as conclusive scientific evidence on its usefulness is lacking. The question is whether and how this evidence can be obtained.
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Radiofármacos , Neoplasias de la Vejiga Urinaria , Humanos , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Estadificación de Neoplasias , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Neoplasias de la Vejiga Urinaria/diagnóstico por imagen , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
BACKGROUND: Guidelines recommend neoadjuvant chemotherapy (NAC) for the treatment of nonmetastatic muscle-invasive bladder cancer (MIBC). NAC is, however, underutilized in practice because of its associated limited overall survival (OS) benefit and significant treatment-related toxicity. We hypothesized that the absence of circulating tumour cells (CTCs) identifies MIBC patients with such a favourable prognosis that NAC may be withheld. PATIENTS AND METHODS: The CirGuidance study was an open-label, multicentre trial that included patients with clinical stage T2-T4aN0-N1M0 MIBC, scheduled for radical cystectomy. CTC-negative patients (no CTCs detectable using the CELLSEARCH system) underwent radical surgery without NAC; CTC-positive patients (≥1 detectable CTCs) were advised to receive NAC, followed by radical surgery. The primary endpoint was the 2-year OS in the CTC-negative group with a prespecified criterion for trial success of ≥75% (95% confidence interval (CI) ±5%). RESULTS: A total of 273 patients were enrolled. Median age was 69 years; median follow-up was 36 months. The primary endpoint of 2-year OS in the CTC-negative group was 69.5% (N = 203; 95% CI 62.6%-75.5%). Two-year OS was 58.2% in the CTC-positive group (N = 70; 95% CI 45.5%-68.9%). CTC-positive patients had a higher rate of cancer-related mortality [hazard ratio (HR) 1.61, 95% CI 1.05-2.45, P = 0.03] and disease relapse (HR 1.87, 95% CI 1.28-2.73, P = 0.001) than CTC-negative patients. Explorative analyses suggested that CTC-positive patients who had received NAC (n = 22) survived longer than CTC-positive patients who had not (n = 48). CONCLUSION: The absence of CTCs in MIBC patients was associated with improved cancer-related mortality and a lower risk of disease relapse after cystectomy; however, their absence alone does not justify to withhold NAC. Exploratory analyses suggested that CTC-positive MIBC patients might derive more benefit from NAC. TRIAL REGISTRATION: Netherlands Trial Register NL3954; https://www.trialregister.nl/trial/3954.
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Células Neoplásicas Circulantes , Neoplasias de la Vejiga Urinaria , Anciano , Femenino , Humanos , Masculino , Músculos/patología , Terapia Neoadyuvante , Recurrencia , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
CONTEXT: A large proportion of patients with non-muscle-invasive bladder cancer (NMIBC) fall in the gap between bacillus Calmette-Guérin (BCG)-naïve and BCG-unresponsive disease. As multiple therapeutic agents move into this gray area, there is a critical need to define the disease state and establish recommendations for optimal trial design. OBJECTIVE: To develop a consensus on optimal trial design for patients with BCG-exposed NMIBC, defined as high-grade recurrence after BCG treatment that does not meet the criteria for BCG-unresponsive disease. EVIDENCE ACQUISITION: We conducted a literature review using the Cochrane Library, Medline, and Embase and a review of clinical trials in ClinicalTrials.gov as a basis to generate consensus recommendations for clinical trial design in BCG-exposed NMIBC. EVIDENCE SYNTHESIS: BCG-exposed NMIBC encompasses BCG resistance (presence of high-grade Ta or carcinoma in situ [CIS] at 3-mo evaluation after induction BCG) and delayed relapse. Randomized controlled trials are required to compare experimental therapies to a control arm receiving additional BCG, although ongoing BCG shortages may impact our ability to follow an optimal trial design. A placebo should be used in combination with BCG if the treatment arm includes BCG plus a study drug. Trials will either need to separate patients with and without CIS into two cohorts, or stratify by the presence of CIS at the time of randomization. If two cohorts are used, the primary endpoint for CIS patients should be complete response within a predetermined time. The primary endpoint in a cohort with Ta/T1 only, or if a single combined cohort is used, should be the duration of event-free survival. Suggested efficacy thresholds and corresponding sample sizes are provided. CONCLUSIONS: The International Bladder Cancer Group has developed recommendations regarding definitions, endpoints, and clinical trial design for BCG-exposed NMIBC to encourage uniformity among studies in this disease state. PATIENT SUMMARY: Our consensus provides a precise definition of the disease state for bladder cancer not invading the bladder muscle and exposed to bacillus Calmette-Guérin (BCG) treatment. Clear guidance for conducting optimal clinical trials in this disease setting was established and we believe that this will promote further progress in this field.
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Carcinoma in Situ , Neoplasias de la Vejiga Urinaria , Adyuvantes Inmunológicos/uso terapéutico , Administración Intravesical , Vacuna BCG/uso terapéutico , Carcinoma in Situ/tratamiento farmacológico , Carcinoma in Situ/patología , Ensayos Clínicos como Asunto , Humanos , Músculos/patología , Invasividad Neoplásica , Recurrencia Local de Neoplasia/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
CONTEXT: Treatment of metastatic urothelial carcinoma is currently undergoing a rapid evolution. OBJECTIVE: This overview presents the updated European Association of Urology (EAU) guidelines for metastatic urothelial carcinoma. EVIDENCE ACQUISITION: A comprehensive scoping exercise covering the topic of metastatic urothelial carcinoma is performed annually by the Guidelines Panel. Databases covered by the search included Medline, EMBASE, and the Cochrane Libraries, resulting in yearly guideline updates. EVIDENCE SYNTHESIS: Platinum-based chemotherapy is the recommended first-line standard therapy for all patients fit to receive either cisplatin or carboplatin. Patients positive for programmed death ligand 1 (PD-L1) and ineligible for cisplatin may receive immunotherapy (atezolizumab or pembrolizumab). In case of nonprogressive disease on platinum-based chemotherapy, subsequent maintenance immunotherapy (avelumab) is recommended. For patients without maintenance therapy, the recommended second-line regimen is immunotherapy (pembrolizumab). Later-line treatment has undergone recent advances: the antibody-drug conjugate enfortumab vedotin demonstrated improved overall survival and the fibroblast growth factor receptor (FGFR) inhibitor erdafitinib appears active in case of FGFR3 alterations. CONCLUSIONS: This 2021 update of the EAU guideline provides detailed and contemporary information on the treatment of metastatic urothelial carcinoma for incorporation into clinical practice. PATIENT SUMMARY: In recent years, several new treatment options have been introduced for patients with metastatic urothelial cancer (including bladder cancer and cancer of the upper urinary tract and urethra). These include immunotherapy and targeted treatments. This updated guideline informs clinicians and patients about optimal tailoring of treatment of affected patients.
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Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Urología , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/patología , Cisplatino , Femenino , Humanos , Masculino , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
Bacillus Calmette-Guérin (BCG) is the most widely used vaccine worldwide and has been used to prevent tuberculosis for a century. BCG also stimulates an anti-tumour immune response, which urologists have harnessed for the treatment of non-muscle-invasive bladder cancer. A growing body of evidence indicates that BCG offers protection against various non-mycobacterial and viral infections. The non-specific effects of BCG occur via the induction of trained immunity and form the basis for the hypothesis that BCG vaccination could be used to protect against the severity of coronavirus disease 2019 (COVID-19). This Perspective article highlights key milestones in the 100-year history of BCG and projects its potential role in the COVID-19 pandemic.
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Adyuvantes Inmunológicos/historia , Vacuna BCG/historia , Vacunas contra la COVID-19 , COVID-19/prevención & control , Inmunoterapia/historia , Animales , Bovinos , Historia del Siglo XIX , Historia del Siglo XX , Humanos , LactanteAsunto(s)
Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Neoplasias Urológicas , Antígeno B7-H1 , Carcinoma de Células Transicionales/tratamiento farmacológico , Humanos , Inhibidores de Puntos de Control Inmunológico , Platino (Metal)/uso terapéutico , Pronóstico , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias Urológicas/tratamiento farmacológicoRESUMEN
BACKGROUND: Radical cystectomy with pelvic lymph node dissection (PLND) and urinary diversion in patients with bladder cancer is known for its high risk of complications. Although open radical cystectomy (ORC) is regarded as the standard treatment, robot-assisted radical cystectomy (RARC) is increasingly used in practice, despite the fact that high-quality evidence comparing the effectiveness of both techniques is lacking. OBJECTIVE: To study the effectiveness of RARC compared with that of ORC, in terms of 90 d complications (Clavien-Dindo), health-related quality of life (HRQOL), and clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS: A prospective comparative effectiveness study was conducted in 19 Dutch centres, expert in either ORC or RARC. Follow-up visits were scheduled at 30, 90, and 365 d. INTERVENTION: Standard ORC or RARC with PLND, using a standardised perioperative protocol. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was any-grade complications after 90 d. Secondary outcomes included HRQOL, complications (minor, major, 30 d, and 365 d), and clinical outcomes. Differences were calculated as risk differences (RDs) between the groups with 95% confidence intervals (CIs), adjusted for potential baseline differences by means of propensity score-based inverse probability of treatment weighting. RESULTS AND LIMITATIONS: Between March 2016 and November 2018, 348 patients were included (n = 168 for ORC, n = 180 for RARC). At 90 d, any-grade complication rates were 63% for ORC and 56% for RARC (RD -6.4%, 95% CI -17 to 4.5). Major complication rates were 15% for ORC and 16% for RARC (RD 0.9%, 95% CI -7.0 to 8.8). Total minor complication rates were 57% for ORC and 49% for RARC (RD -7.6%, 95% CI -19 to 3.6). Analyses showed no statistically significant differences in HRQOL between ORC and RARC. Some differences were found in the secondary outcomes in favour of either RARC or ORC. The major drawback inherent to the design comprises residual confounding. CONCLUSIONS: This multicentre comparative effectiveness study showed no statistically significant differences between ORC and RARC in terms of complications and HRQOL. PATIENT SUMMARY: This multicentre study did not show differences in overall complication rates, health-related quality of life, mortality, and clinical and oncological outcomes between open and robot-assisted radical cystectomy in bladder cancer patients.
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Procedimientos Quirúrgicos Robotizados , Robótica , Neoplasias de la Vejiga Urinaria , Cistectomía/efectos adversos , Humanos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios Prospectivos , Calidad de Vida , Procedimientos Quirúrgicos Robotizados/efectos adversos , Resultado del Tratamiento , Neoplasias de la Vejiga Urinaria/cirugíaRESUMEN
BACKGROUND: Heterogenous outcome reporting in non-muscle-invasive bladder cancer (NMIBC) effectiveness trials of adjuvant treatment after transurethral resection (TURBT) has been noted in systematic reviews (SRs). This hinders comparing results across trials, combining them in meta-analyses, and evidence-based decision-making for patients and clinicians. OBJECTIVE: We aimed to systematically review the extent of reporting and definition heterogeneity. METHODS: We included randomized controlled trials (RCTs) identified from SRs comparing adjuvant treatments after TURBT or TURBT alone in patients with NMIBC (with or without carcinoma in situ) published between 2000-2020. Abstracts and full texts were screened independently by two reviewers. Data were extracted by one reviewer and checked by another. RESULTS: We screened 807 abstracts; from 15 SRs, 57 RCTs were included. Verbatim outcome names were coded to standard outcome names and organised using the Williamson and Clarke taxonomy. Recurrence (98%), progression (74%), treatment response (in CIS studies) (40%), and adverse events (77%) were frequently reported across studies. However, overall (33%) and cancer-specific (33%) survival, treatment completion (17%) and treatment change (37%) were less often reported. Quality of Life (3%) and economic outcomes (2%) were rarely reported. Heterogeneity was evident throughout, particularly in the definitions of progression and recurrence, and how CIS patients were handled in the analysis of studies with predominantly papillary patients, highlighting further issues with the definition of recurrence and progression vs treatment response for CIS patients. Data reporting was also inconsistent, with some trials reporting event rates at various time-points and others reporting time-to-event with or without Hazard Ratios. Adverse events were inconsistently reported. QoL data was absent in most trials. CONCLUSIONS: Heterogenous outcome reporting is evident in NMIBC effectiveness trials. This has profound implications for meta-analyses, SRs and evidence-based treatment decisions. A core outcome set is required to reduce heterogeneity. PATIENT SUMMARY: This systematic review found inconsistencies in outcome definitions and reporting, pointing out the urgent need for a core outcome set to help improve evidence-based treatment decisions.
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En un esfuerzo por disminuir las tasas de recurrencia y progresión en el cáncer de vejiga no músculo- invasivo (NMIBC), la resección transuretral de un tumor de vejiga es seguida por instilaciones intravesicales usando Mitomicina-C (MMC) y Bacillus Calmette-Guérin (BCG). A pesar de estas modalidades de tratamiento adyuvante, las tasas de recurrencia y progresión siguen siendo altas. Debido a estas limitaciones de la terapia estándar actual y la escasez de BCG, hay una necesidad de desarrollar formas alternativas de tratamiento para NMIBC. La MMC intravesical combinada con hipertermia, especialmente la quimiohipertermia (QHT) inducida por RF que se ha investigado de manera más exhaustiva en los últimos 20 años, es una de estas alternativas para NMIBC de riesgo intermedio y alto. Existen varias técnicas y dispositivos diferentes para generar hipertermia en la pared de la vejiga y elevar las temperaturas hasta 40,5-44,00C. La hipertermia puede ser el resultado de ondas de ultrasonido, conducción térmica directa o campos electromagnéticos. En esta revisión se hará una descripción general de los sistemas de hipertermia con respecto a sus aspectos técnicos, los resultados del tratamiento y los eventos adversos (EA). En pacientes que fracasan con el tratamiento estándar que no están en forma o no desean someterse a cirugía, se debe considerar la QHT inducida por RF. Además de QHT, hay más formas de tratamiento actualmente en investigación en NMIBC como la Administración electromotriz (EMDA) y quimioterapia intravesical neoadyuvante, estas requieren más ensayos clínicos para determinar la selección y la eficiencia del paciente
In an effort to decrease recurrence and progression rates in non-muscle-invasive bladder cancer (NMIBC), transurethral resection of a bladder tumor is followed by intravesical instillations using Mitomycin-C (MMC) and Bacillus Calmette-Guérin (BCG). In spite of these adjuvant treatment modalities, recurrence and progression rates remain high. Because of these limitations of current standard therapy and the shortage of BCG, there is a search for alternative forms of treatment in NMIBC. Intravesical MMC combined with hyperthermia, especially RF-induced QHT being most extensively investigated in the past 20 years, is one of these alternatives for intermediate- and high-risk NMIBC. There are several different techniques and devices to create hyperthermia of the bladder wall raising temperatures up to 40.5-44.0 º C. Hyperthermia can be the result of ultrasound waves, direct thermal conduction, or electromagnetic fields. An overview of hyperthermia systems concerning their technical aspects, treatment outcomes and adverse events (AEs) will be described in this review. In patients failing standard treatment who are not fit or unwilling to undergo surgery, RF-induced QHT should be considered. Besides QHT, there are more forms of treatment currently being investigated in NMIBC like EMDA and neoadjuvant intravesical chemotherapy, these require more clinical trials to determine patient selection and efficiency
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Humanos , Hipertermia Inducida , Antibióticos Antineoplásicos/administración & dosificación , Neoplasias de la Vejiga Urinaria/terapia , Administración Intravesical , Terapia Combinada , Invasividad Neoplásica , Neoplasias de la Vejiga Urinaria/patología , PredicciónRESUMEN
CONTEXT: Invasive bladder cancer is a frequently occurring disease with a high mortality rate despite optimal treatment. The European Association of Urology (EAU) Muscle-invasive and Metastatic Bladder Cancer (MIBC) Guidelines are updated yearly and provides information to optimise diagnosis, treatment, and follow-up of this patient population. OBJECTIVE: To provide a summary of the EAU guidelines for physicians and patients confronted with muscle-invasive and metastatic bladder cancer. EVIDENCE ACQUISITION: An international multidisciplinary panel of bladder cancer experts reviewed and discussed the results of a comprehensive literature search of several databases covering all sections of the guidelines. The panel defined levels of evidence and grades of recommendation according to an established classification system. EVIDENCE SYNTHESIS: Epidemiology and aetiology of bladder cancer are discussed. The proper diagnostic pathway, including demands for pathology and imaging, is outlined. Several treatment options, including bladder-sparing treatments and combinations of treatment modalities (different forms of surgery, radiation therapy, and chemotherapy) are described. Sequencing of these modalities is discussed. Potential indications and contraindications, such as comorbidity, are related to treatment choice. There is a new paragraph on organ-sparing approaches, both in men and in women, and on minimal invasive surgery. Recommendations for chemotherapy in fit and unfit patients are provided including second-line options. Finally, a follow-up schedule is provided. CONCLUSIONS: The current summary of the EAU Muscle-invasive and Metastatic Bladder Cancer Guidelines provides an up-to-date overview of the available literature and evidence dealing with diagnosis, treatment, and follow-up of patients with metastatic and muscle-invasive bladder cancer. PATIENT SUMMARY: Bladder cancer is an important disease with a high mortality rate. These updated guidelines help clinicians refine the diagnosis and select the appropriate therapy and follow-up for patients with metastatic and muscle-invasive bladder cancer.
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Adyuvantes Inmunológicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Vacuna BCG/uso terapéutico , Carcinoma de Células Transicionales/terapia , Cistectomía , Cistoscopía , Radioterapia , Neoplasias de la Vejiga Urinaria/terapia , Carcinoma de Células Transicionales/patología , Carcinoma de Células Transicionales/secundario , Europa (Continente) , Humanos , Músculo Liso/patología , Invasividad Neoplásica , Metástasis de la Neoplasia , Sociedades Médicas , Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/patología , UrologíaRESUMEN
OBJECTIVE: To determine the relationship of age to side-effects leading to discontinuation of treatment in patients with stage Ta-T1 non-muscle-invasive bladder cancer (NMIBC) treated with maintenance bacille Calmette-Guérin (BCG). PATIENTS AND METHODS: We evaluated toxicity for 487 eligible patients with intermediate- or high-risk Ta-T1 (without carcinoma in situ) NMIBC randomised to receive 3 years of maintenance BCG therapy (247 BCG alone and 240 BCG + isoniazid) in European Organisation for Research and Treatment of Cancer Genito-Urinary Group trial 30911. The percentage of patients who stopped for toxicity and the number of treatment cycles that they received were compared in four age groups, ≤60, 61-70, 71-75 and >75 years, using the Mantel-Haenszel chi-square test for trend. RESULTS: The percentage of patients stopping BCG for toxicity was 17.9% in patients aged ≤60 years, 21.9% in patients aged 61-70 years, 22.9% in patients aged 71-75 years, and 16.4% in patients aged >75 years (P = 0.90). For both systemic and local side-effects, there was likewise no significant difference. CONCLUSION: In patients with intermediate- and high-risk Ta-T1 NMIBC treated with BCG, no differences in toxicity as a reason for stopping treatment were detected based on patient age.
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Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/efectos adversos , Vacuna BCG/efectos adversos , Carcinoma de Células Transicionales/tratamiento farmacológico , Quimioterapia de Mantención , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Privación de Tratamiento/estadística & datos numéricos , Factores de Edad , Anciano , Carcinoma de Células Transicionales/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Factores de Tiempo , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
A history of urinary bladder cancer (UBC) in first-degree relatives increases UBC risk by twofold. The influence of positive family history on UBC prognosis is unknown. Here, we investigated association of first-degree UBC family history with clinicopathological characteristics and prognosis of UBC patients. Detailed clinical data of 1,465 non-muscle-invasive bladder cancer (NMIBC) and 250 muscle-invasive or metastatic bladder cancer (MIBC) patients, diagnosed from 1995 to 2010, were collected through medical file review. Competing risk analyses were used to compare recurrence-free survival (RFS) and progression-free survival (PFS) of NMIBC patients according to self-reported UBC family history. Overall survival in MIBC patients was estimated using Kaplan-Meier analysis. The added value of family history in prediction of NMIBC prognosis was quantified with Harrell's concordance-index. Hundred (6.8%) NMIBC and 14 (5.6%) MIBC patients reported UBC in first-degree relatives. Positive family history was statistically significantly associated with smaller tumor size and non-significantly with more favorable distribution of other tumor characteristics. In univariable analyses, positive family history correlated with longer RFS (p = 0.11) and PFS (p = 0.04). Hazard ratios for positive vs. negative family history after adjustment for clinicopathological characteristics were 0.75 (95% CI = 0.53-1.07) and 0.45 (95% CI = 0.18-1.12) for RFS and PFS, respectively. Five familial and 48 sporadic MIBC patients (Kaplan-Meier 10-year risk: 41% and 25%) died within 10 years. Family history did not improve the c-index of prediction models. This study shows that a first-degree family history of UBC is not clearly associated with NMIBC prognosis. Family history does not aid in prediction of NMIBC recurrence or progression.
Asunto(s)
Predisposición Genética a la Enfermedad , Recurrencia Local de Neoplasia/genética , Neoplasias de la Vejiga Urinaria/genética , Anciano , Progresión de la Enfermedad , Familia , Femenino , Estudios de Seguimiento , Humanos , Masculino , Clasificación del Tumor , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/mortalidad , Estadificación de Neoplasias , Países Bajos/epidemiología , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Tasa de Supervivencia , Neoplasias de la Vejiga Urinaria/epidemiología , Neoplasias de la Vejiga Urinaria/mortalidadRESUMEN
OBJECTIVES: To explore whether urinary cytokine and chemokine (CK) levels differed between cold mitomycin-C (cold-MMC)-treated patients and chemohyperthermia (C-HT)-treated patients, to shed light on the possible molecular mechanisms that might explain the superior outcome of C-HT. Furthermore, CK-differences were explored between C-HT responders and C-HT non-responders. METHODS: Twelve NMIBC patients were included. Nine received six-weekly C-HT, and three received four-weekly cold-MMC instillations. Urine was collected on 8-12 time points before and after every treatment. MDC, IL-2, IL-6, IL-8, IP-10, MCP-1 and RANTES were determined by Luminex(®)-analysis. RESULTS: Elevated urinary CK levels were observed in both groups after treatment. In general, CK-peaks were lower in the cold-MMC group in comparison with levels in the C-HT group. Significant higher MCP-1 and IL-6 levels were observed in C-HT-treated patients. Additionally, significant cumulative effects were observed for IP-10 and IL-2. However, IP-10 and IL-2 levels did not significantly differ between treatments. MDC levels after the first week of treatment were significantly higher in the C-HT responders compared with the non-responders. CONCLUSION: MMC treatment leads to elevated urinary CK levels with significantly higher MCP-1 and IL-6 levels in C-HT-treated patients. Increased MDC levels after the first C-HT instillation appear to be related to good clinical outcome and might be of additional value to personalize treatment. Studies involving more patients and longer follow-up are needed to substantiate this observation.