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OBJECTIVES: To investigate the role of specialised genitourinary multidisciplinary team meetings (MDTMs) in decision-making and identify factors that influence the probability of receiving a treatment plan with curative intent for patients with muscle invasive bladder cancer (MIBC). PATIENTS AND METHODS: Data relating to patients with cT2-4aN0/X-1 M0 urothelial cell carcinoma, diagnosed between November 2017 and October 2019, were selected from the nationwide, population-based Netherlands Cancer Registry ('BlaZIB study'). Curative treatment options were defined as radical cystectomy (RC) with or without neoadjuvant chemotherapy, chemoradiation or brachytherapy. Multilevel logistic regression analyses were used to examine the association between MDTM factors and curative treatment advice and how this advice was followed. RESULTS: Of the 2321 patients, 2048 (88.2%) were discussed in a genitourinary MDTM. Advanced age (>80 years) and poorer World Health Organization performance status (score 1-2 vs 0) were associated with no discussion (P < 0.001). Being discussed was associated with undergoing treatment with curative intent (odds ratio [OR] 3.0, 95% confidence interval [CI] 1.9-4.9), as was the involvement of a RC hospital (OR 1.70, 95% CI 1.09-2.65). Involvement of an academic centre was associated with higher rates of bladder-sparing treatment (OR 2.05, 95% CI 1.31-3.21). Patient preference was the main reason for non-adherence to treatment advice. CONCLUSIONS: For patients with MIBC, the probability of being discussed in a MDTM was associated with age, performance status and receiving treatment with curative intent, especially if a representative of a RC hospital was present. Future studies should focus on the impact of MDTM advice on survival data.
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Neoplasias da Bexiga Urinária , Humanos , Idoso de 80 Anos ou mais , Neoplasias da Bexiga Urinária/cirurgia , Bexiga Urinária/patologia , Cistectomia , Terapia Neoadjuvante , Equipe de Assistência ao Paciente , Invasividade NeoplásicaRESUMO
BACKGROUND: Quality of Life (QoL) of bladder cancer patients has been largely neglected. This is partly due to the lack of well-validated QoL questionnaires. The aim of this study is to examine the structural validity, reliability (i.e., internal consistency and test-retest reliability), construct validity (i.e., divergent validity and known group validity) and responsiveness of the Dutch version of the European Organisation for Research and Treatment of Cancer QoL questionnaire for muscle invasive bladder cancer (EORTC-QLQ-BLM30). METHODS: Patients with newly diagnosed muscle invasive bladder cancer (MIBC) participating in the population-based 'Blaaskankerzorg In Beeld' (BlaZIB) study who completed the EORTC-QLQ-BLM30 at baseline were included. BlaZIB is a Dutch nationwide population-based prospective cohort study collecting clinical data and QoL data of bladder cancer patients. QoL is assessed with a self-administered questionnaire at four points in time: 6 weeks (baseline), 6 months, 12 months and 24 months after diagnosis. Confirmatory factor analysis and multitrait scaling analysis were used to investigate and adapt the scale structure. Reliability, construct validity and responsiveness of the revised scales were evaluated. RESULTS: Of the 1542 patients invited to participate, 650 patients (42.2%) completed the QLQ-BLM30 at baseline. The questionnaire's scale structure was revised into seven scales and eight single items. Internal consistency and test-reliability were adequate for most scales (Cronbach's α ≥0.70 and intraclass correlation coefficient ≥ 0.70, respectively), with the exception of the revised urostomy problem scale and abdominal bloating and flatulence scale. The questionnaire exhibited little overlap with the EORTC-QLQ-C30: all correlations were < 0.40, except for the correlation between emotional function (QLQ-C30) and future worries (QLQ-BLM30). The questionnaire was able to distinguish between patient subgroups formed on the basis of physical function, but not - as hypothesized- based on stage. Changes in health due to treatment were captured by the questionnaire, indicating that the questionnaire is responsive to change. CONCLUSIONS: This study shows that the adapted scale structure of the EORTC-QLQ-BLM30 generally exhibits good measurement properties in Dutch patients, but needs to be validated in other languages and settings. TRIAL REGISTRATION: BlaZIB, NL8106, www.trialregister.nl.
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Qualidade de Vida , Neoplasias da Bexiga Urinária , Humanos , Reprodutibilidade dos Testes , Estudos Prospectivos , Inquéritos e Questionários , Psicometria , MúsculosRESUMO
PURPOSE: Little is known about the prevalence of occult lymph node metastases (LNM) in muscle-invasive bladder cancer (MIBC) patients with pathological downstaging of the primary tumor. We aimed to estimate the prevalence of occult LNM in patients without residual MIBC at radical cystectomy (RC) with or without neoadjuvant chemotherapy (NAC) or neoadjuvant radiotherapy (NAR), and to assess overall survival (OS). METHODS: Patients with cT2-T4aN0M0 urothelial MIBC who underwent RC plus pelvic lymph node dissection (PLND) with curative intent between January 1995-December 2013 (retrospective Netherlands Cancer Registry (NCR) cohort) and November 2017-October 2019 (prospective NCR-BlaZIB cohort (acronym in Dutch: BlaaskankerZorg In Beeld; in English: Insight into bladder cancer care)) were identified from the nationwide NCR. The prevalence of occult LNM was calculated and OS of patients with <(y)pT2N0 vs. <(y)pT2N+ disease was estimated by the Kaplan-Meier method. RESULTS: In total, 4657 patients from the NCR cohort and 760 patients from the NCR-BlaZIB cohort were included. Of 1374 patients downstaged to <(y)pT2, 4.3% (N = 59) had occult LNM 4.1% (N = 49) of patients with cT2-disease and 5.6% (N = 10) with cT3-4a-disease. This was 4.0% (N = 44) in patients without NAC or NAR, 4.5% (N = 10) in patients with NAC, and 13.5% (N = 5) in patients with NAR but number of patients treated with NAR and downstaged disease was small. The prevalence of <(y)pT2N+ disease was 4.2% (N = 48) in the NCR cohort and 4.6% (N = 11) in the NCR-BlaZIB cohort. For patients with <(y)pT2N+ and <(y)pT2N0, median OS was 3.5 years (95% CI 2.5-8.9) versus 12.9 years (95% CI 11.7-14.0), respectively. CONCLUSION: Occult LNM were found in 4.3% of patients with cT2-4aN0M0 MIBC with (near-) complete downstaging of the primary tumor following RC plus PLND. This was regardless of NAC or clinical T-stage. Patients with occult LNM showed considerable worse survival. These results can help in counseling patients for bladder-sparing treatments.
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Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/cirurgia , Cistectomia , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia , Idoso , Carcinoma de Células de Transição/tratamento farmacológico , Cistectomia/métodos , Humanos , Metástase Linfática , Terapia Neoadjuvante , Invasividade Neoplásica , Neoplasia Residual , Países Baixos , Estudos Prospectivos , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/tratamento farmacológicoRESUMO
BACKGROUND: Prediction of side-specific extraprostatic extension (EPE) is crucial in selecting patients for nerve-sparing radical prostatectomy (RP). OBJECTIVE: To develop and externally validate nomograms including multiparametric magnetic resonance imaging (mpMRI) information to predict side-specific EPE. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of 1870 consecutive prostate cancer patients who underwent robot-assisted RP from 2014 to 2018 at three institutions. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Four multivariable logistic regression models were established, including combinations of patient-based and side-specific variables: prostate-specific antigen (PSA) density, highest ipsilateral International Society of Urological Pathology (ISUP) biopsy grade, ipsilateral percentage of positive cores on systematic biopsy, and side-specific clinical stage assessed by both digital rectal examination and mpMRI. Discrimination (area under the curve [AUC]), calibration, and net benefit of these models were assessed in the development cohort and two external validation cohorts. RESULTS AND LIMITATIONS: On external validation, AUCs of the four models ranged from 0.80 (95% confidence interval [CI] 0.68-0.88) to 0.83 (95% CI 0.72-0.90) in cohort 1 and from 0.77 (95% CI 0.62-0.87) to 0.78 (95% CI 0.64-0.88) in cohort 2. The three models including mpMRI staging information resulted in relatively higher AUCs compared with the model without mpMRI information. No major differences between the four models regarding net benefit were established. The model based on PSA density, ISUP grade, and mpMRI T stage was superior in terms of calibration. Using this model with a cut-off of 20%, 1980/2908 (68%) prostatic lobes without EPE would be found eligible for nerve sparing, whereas non-nerve sparing would be advised in 642/832 (77%) lobes with EPE. CONCLUSIONS: Our analysis resulted in a simple and robust nomogram for the prediction of side-specific EPE, which should be used to select patients for nerve-sparing RP. PATIENT SUMMARY: We developed a prediction model that can be used to assess accurately the likelihood of tumour extension outside the prostate. This tool can guide patient selection for safe nerve-sparing surgery.
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Nomogramas , Neoplasias da Próstata , Humanos , Masculino , Próstata/patologia , Próstata/cirurgia , Antígeno Prostático Específico , Prostatectomia/métodos , Neoplasias da Próstata/patologia , Estudos RetrospectivosRESUMO
BACKGROUND: Despite the embedding of bladder cancer management in European guidelines, large variation in clinical practice exists for applied diagnostics and treatments. This variation may affect patients' outcomes including complications, disease recurrence, progression, survival, and health-related quality of life (HRQL). Lack of detailed clinical data and HRQL data hampers a comprehensive evaluation of bladder cancer care. Through prospective data registration, this study aims to provide insight in bladder cancer care in the Netherlands and to identify barriers and modulators of optimal bladder cancer care. METHODS: This study is a nationwide prospective cohort study including all patients who were newly diagnosed with high-risk non-muscle invasive bladder cancer (HR-NMIBC; Tis and/or T1, N0, M0/x) or non-metastatic muscle invasive bladder cancer (MIBC; ≥T2, N0/x-3, M0/x) in the Netherlands between November 1st 2017 and October 31st 2019. Extensive data on patient- and tumor characteristics, diagnostics, treatment and follow-up up to 2 years after diagnosis will be collected prospectively from electronic health records in the participating hospitals by data managers of the Netherlands Cancer Registry (NCR). Additionally, patients will be requested to participate in a HRQL survey shortly after diagnosis and subsequently at 6, 12 and 24 months. The HRQL survey includes six standardized questionnaires, e.g. SCQ Comorbidity score, EQ-5D-5 L, EORTC-QLQ-C30, EORTC-QLQ-BLM30, EORTC-QLQ-NMIBC24 and BCI. Variation in care and deviation from the European guidelines will be assessed through descriptive analyses and multivariable multilevel analyses. Survival analyses will be used to assess the association between variation in care and relevant outcomes such as survival. DISCUSSION: The results of this observational study will guide modifications of clinical practice and/or adaptation of guidelines and may set the agenda for new specific research questions in the management of bladder cancer. TRIAL REGISTRATION: Retrospectively registered in the Netherlands Trial Register. Trial identification number: NL8106. Registered on October 22nd 2019.
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Avaliação das Necessidades/normas , Guias de Prática Clínica como Assunto/normas , Qualidade da Assistência à Saúde/normas , Qualidade de Vida , Neoplasias da Bexiga Urinária/terapia , Seguimentos , Humanos , Países Baixos , Prognóstico , Estudos ProspectivosRESUMO
INTRODUCTION: To establish oncological safe nerve-sparing robot-assisted radical prostatectomy, accurate assessment of extraprostatic extension (EPE) is critical. A recently developed nomogram including magnetic resonance imaging parameters accurately predicted side-specific EPE in the development cohort. The aim of this study is to assess this model's performance in an external patient population. PATIENTS AND METHODS: Model fit was assessed in a cohort of 550 patients who underwent robot-assisted radical prostatectomy in 2014 to 2017 for prostate cancer. Model calibration was evaluated using calibration slopes. Discriminative ability was quantified using the area under the receiver operating characteristic curve. Model updating was done by adjusting the linear predictor to minimize differences in expected and observed risk for EPE. RESULTS: A total of 792 prostate lobes were included for model validation. Discriminative ability expressed in terms of receiver operating characteristic curve was 0.78, 95%CI 0.75-0.82. Graphical evaluation of the calibration showed poor fit with a high disagreement between predicted probabilities and observed probabilities of EPE in the population. Model updating resulted in excellent agreement between mean predicted and observed probabilities. However, calibration plots showed substantial miscalibration; including both under- and overestimation. CONCLUSION: External validation of the novel nomogram for the prediction of side specific EPE developed by Martini and co-workers showed good discriminative ability but poor calibration. After updating, substantial miscalibration was still present. Use of this nomogram for individualized risk predictions is therefore not recommended.
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Nomogramas , Prostatectomia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos , Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Prostatectomia/métodos , Estudos RetrospectivosRESUMO
PURPOSE: Available published studies evaluating the association between nerve sparing robot-assisted radical prostatectomy and risk of ipsilateral positive surgical margins were subject to selection bias. In this study we overcome these limitations by using multivariable regression analysis. MATERIALS AND METHODS: Patients undergoing robot-assisted radical prostatectomy for prostate cancer at 4 institutions from 2013 to 2018 were included in the study. A multilevel logistic random intercept model, including covariates on patient level and side specific factors on prostate lobe level, was used to evaluate the association between nerve sparing and risk of ipsilateral positive margins. RESULTS: A total of 5,148 prostate lobes derived from 2,574 patients who underwent robot-assisted radical prostatectomy were analyzed. Multivariable analysis showed nerve sparing was an independent predictor for ipsilateral positive margins (OR 1.42, 95% CI 1.14-1.82). Other significant predictors for positive margins were prostate specific antigen density (OR 3.64, 95% CI 2.36-5.90) and side specific covariates including highest preoperative ISUP (International Society of Urological Pathology) biopsy grade (OR 1.58, 95% CI 1.13-2.53; OR 1.62, 95% CI 1.13-2.69; OR 2.11, 95% CI 1.39-3.59 and OR 4.43, 95% CI 3.17-10.12 for ISUP grade 2, 3, 4 and 5, respectively), presence of extraprostatic extension on magnetic resonance imaging (OR 1.42, 95% CI 1.03-1.91) and percentage of positive cores on systematic biopsy (OR 3.82, 95% CI 2.50-5.86). CONCLUSIONS: Nerve sparing was associated with an increased risk of ipsilateral positive surgical margins. The increased risk of positive margins should be considered when counseling patients who opt for nerve sparing robot-assisted radical prostatectomy.
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Margens de Excisão , Tratamentos com Preservação do Órgão , Prostatectomia , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Prospectivos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/patologiaRESUMO
OBJECTIVES: It has consistently been shown that women who are diagnosed with bladder cancer have lower survival than men, but the exact mechanism remains unknown. Most studies assumed that the sex-specific mortality ratio is constant over time, possibly resulting in inaccurate estimates in various periods of follow-up. This study aimed to investigate the sex-specific excess mortality in bladder cancer patients and its variation over follow-up time. METHODS: Observational cohort study. Using data from the population-based Netherlands Cancer Registry, we studied 24,169 patients diagnosed between 2003 and 2014 with histologically confirmed ≥T1 bladder cancer with follow-up until January 2018. We used flexible parametric relative survival models to estimate excess mortality as a function of time for each sex and to explore the effect of covariates on these functions. RESULTS: Female patients (24%) had worse clinical tumor, node, and metastasis-stage at diagnosis and more often a nonurothelial tumor histology. The excess mortality ratio of sex was not constant over time; in the first two years after diagnosis excess mortality rates for women were higher than for men, but lower thereafter; this applied to both nonmuscle-invasive and muscle-invasive bladder cancer subgroups. Baseline differences in age, tumor, node, and metastasis-stage and histology accounted for only part of the excess mortality gap. CONCLUSIONS: The assumption of proportional hazards over time leads to underestimation of the excess mortality ratio for women in the first two years and overestimation thereafter, when excess mortality is comparable for women and men. Clinicians should incorporate the initial sex-specific poorer outcome in their considerations regarding prognosis and treatment options for female patients, e.g., more invasive treatment and neo-adjuvant treatment. These findings also point towards a mechanism of micrometastatic disease, warranting assessment of sex-specific efficacy in randomized controlled trials on treatments in this patient population.
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Neoplasias da Bexiga Urinária/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos de Coortes , Cistectomia , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Países Baixos/epidemiologia , Prognóstico , Sistema de Registros/estatística & dados numéricos , Fatores de Risco , Fatores Sexuais , Taxa de Sobrevida , Fatores de Tempo , Bexiga Urinária/patologia , Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/terapia , Adulto JovemRESUMO
INTRODUCTION: Several techniques can be used to treat intravesical chemohyperthermia (ChHT). We compared radiofrequency-induced hyperthermia (RF-HT) with conductive hyperthermia (C-HT) for their ability to induce bladder wall temperatures of >40.5 °C, the target temperature for ChHT. MATERIALS AND METHODS: Fresh porcine bladders (n = 12) were placed in a temperature-controlled saline bath to simulate body temperature and circulation. HT was induced with RF-HT (43 °C) or C-HT (inflow temperature 44 and 46 °C) using a custom-made device. In two additional bladders, we varied intravesical solution and volume. Temperatures were recorded with a three-way catheter containing three mucosal and two urethral thermocouples (TCs) and a 915 MHz RF antenna, and with external TCs in the bladder wall at three different levels and three different locations. RESULTS: Target temperature (40.5 °C) was reached in the submucosa at all locations by both techniques. In the detrusor, target temperature was reached by RF-HT at the bladder neck and side wall. C-HT46 reached significantly higher submucosal temperatures at the side wall. The bladder dome seemed best heated by C-HT, although a high inflow temperature (46 vs. 44 °C) was required (ns). Intravesical saline resulted in higher temperatures than sterile water for RF-HT. A volume of 100 mL resulted in higher bladder dome temperatures for RF-HT, and higher bladder neck with lower dome temperatures for C-HT. CONCLUSION: Our results indicate a slightly superior heating capacity for RF-HT compared to C-HT, whereas for the bladder dome, the reverse seems true. Comparative studies are warranted to evaluate whether HT efficacy differs between both techniques, with emphasis on tumor location.
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Hipertermia Induzida/métodos , Neoplasias da Bexiga Urinária/terapia , Administração Intravesical , Animais , Feminino , Humanos , Ondas de Rádio , Suínos , Neoplasias da Bexiga Urinária/patologiaRESUMO
BACKGROUND: Despite the fact that the cost-effectiveness of robot-assisted radical cystectomy (RARC) is not yet proven, and open radical (ORC) cystectomy is recommended as the standard of care in patients with high-risk non-muscle-invasive and muscle-invasive bladder cancer, the use of RARC is still increasing. The objective of the current ongoing comparative effectiveness trial therefore is to study the (cost-)effectiveness of RARC compared to ORC, both in terms of objective (complication rates, oncological outcomes) and patient-reported (health-related quality of life) outcome measures. METHODS: This study is designed as a non-randomized, multicentre comparative effectiveness trial. Centres with an annual caseload of > 20 radical cystectomies can include patients after informed consent has been given. Centres that perform RARC must have passed the (initial) learning curve of 40 cases. A total of 338 (2 × 169) patients will be enrolled from 23 participating centres (12 ORC, 10 RARC and 1 LRC). Follow-up visits will be scheduled at 1, 3, 6 and 12 months. During each follow-up visit, clinical data and health-related quality of life questionnaires will be administered. Costs will be studied using a monthly resource usage questionnaire. Impact on complications and quality of life will be calculated as the average difference between the groups with 95% confidence intervals, adjusted for potential baseline differences by means of propensity score matching. DISCUSSION: This study aims to contribute to the development of evidence-based guidelines regarding the most cost-effective surgical technique for radical cystectomy. TRIAL REGISTRATION: Nederlands Trial Register/Dutch Trial Registry, trial identifying number: NTR5362. Registered on 14 August 2015. ( http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=5362 ).
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Cistectomia/efeitos adversos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Neoplasias da Bexiga Urinária/cirurgia , Adulto , Idoso , Feminino , Humanos , Laparoscopia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/patologia , Qualidade de Vida , Fatores de Risco , Resultado do Tratamento , Neoplasias da Bexiga Urinária/epidemiologia , Neoplasias da Bexiga Urinária/patologiaRESUMO
PURPOSE: To evaluate the oncological impact of postponing radical cystectomy (RC) to allow further conservative therapies prior to progression in a large multicentre retrospective cohort of T1-HG/G3 patients initially treated with BCG. METHODS: According to the time of RC, the population was divided into 3 groups: patients who did not progress to muscle-invasive disease, patients who progressed before radical cystectomy and patients who experienced progression at the time of radical cystectomy. Clinical and pathological outcomes were compared across the three groups. RESULTS: Of 2451 patients, 509 (20.8%) underwent RC. Patients with tumors > 3 cm or with CIS had earlier cystectomies (HR = 1.79, p = 0.001 and HR = 1.53, p = 0.02, respectively). Patients with tumors > 3 cm, multiple tumors or CIS had earlier T3/T4 or N + cystectomies. In patients who progressed, the timing of cystectomy did not affect the risk of T3/T4 or N + disease at RC. Patients with T3/T4 or N + disease at RC had a shorter disease-specific survival (HR = 4.38, p < 0.001), as did patients with CIS at cystectomy (HR = 2.39, p < 0.001). Patients who progressed prior to cystectomy had a shorter disease-specific survival than patients for whom progression was only detected at cystectomy (HR = 0.58, p = 0.024) CONCLUSIONS: Patients treated with RC before experiencing progression to muscle-invasive disease harbor better oncological and survival outcomes compared to those who progressed before RC and to those upstaged at surgery. Tumor size and concomitant CIS at diagnosis are the main predictors of surgical treatment while tumor size, CIS and tumor multiplicity are associated with extravesical disease at surgery.
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Vacina BCG/uso terapêutico , Carcinoma de Células de Transição/cirurgia , Cistectomia/métodos , Recidiva Local de Neoplasia/patologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/cirurgia , Idoso , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/patologia , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologiaRESUMO
OBJECTIVE: To evaluate the antitumor effect of cyclodextrin-curcumin complex (CDC) on human and rat urothelial carcinoma cells in vitro and to evaluate the effect of intravesical instillations of CDC, BCG, and the combination in vivo in the AY-F344 orthotopic bladder cancer rat model. Curcumin has anticarcinogenic activity on urothelial carcinoma and is therefore under investigation for the treatment of non-muscle invasive bladder cancer. Curcumin and BCG share immunomodulating pathways against urothelial carcinoma. METHODS: Curcumin was complexed with cyclodextrin to improve solubility. Four human urothelial carcinoma cell lines and the AY-27 rat cell line were exposed to various concentrations of CDC in vitro. For the in vivo experiment, the AY-27 orthotopic bladder cancer F344 rat model was used. Rats were treated with consecutive intravesical instillations of CDC, BCG, the combination of CDC+BCG, or NaCl as control. RESULTS: CDC showed a dose-dependent antiproliferative effect on all human urothelial carcinoma cell lines tested and the rat AY-27 urothelial carcinoma cell line. Moreover, intravesical treatment with CDC and CDC+BCG results in a lower percentage of tumors (60% and 68%, respectively) compared to BCG (75%) or control (85%). This difference with placebo was not statistically significant (p=0.078 and 0.199, respectively). However, tumors present in the placebo and BCG-treated rats were generally of higher stage. CONCLUSIONS: Cyclodextrin-curcumin complex showed an antiproliferative effect on human and rat urothelial carcinoma cell lines in vitro. In the aggressive orthotopic bladder cancer rat model, we observed a promising effect of CDC treatment and CDC in combination with BCG.
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Carcinoma de Células de Transição/tratamento farmacológico , Curcumina/uso terapêutico , Ciclodextrinas/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Animais , Vacina BCG , Humanos , Ratos , Ratos Endogâmicos F344RESUMO
The NCI Bladder Cancer Task Force convened a Clinical Trials Planning Meeting (CTPM) Workshop focused on Novel Therapeutics for Non-Muscle Invasive Bladder Cancer (NMIBC). Meeting attendees included a broad and multi-disciplinary group of clinical and research stakeholders and included leaders from NCI, FDA, National Clinical Trials Network (NCTN), advocacy and the pharmaceutical and biotech industry. The meeting goals and objectives were to: 1) create a collaborative environment in which the greater bladder research community can pursue future optimally designed novel clinical trials focused on the theme of molecular targeted and immune-based therapies in NMIBC; 2) frame the clinical and translational questions that are of highest priority; and 3) develop two clinical trial designs focusing on immunotherapy and molecular targeted therapy. Despite successful development and implementation of large Phase II and Phase III trials in bladder and upper urinary tract cancers, there are no active and accruing trials in the NMIBC space within the NCTN. Disappointingly, there has been only one new FDA approved drug (Valrubicin) in any bladder cancer disease state since 1998. Although genomic-based data for bladder cancer are increasingly available, translating these discoveries into practice changing treatment is still to come. Recently, major efforts in defining the genomic characteristics of NMIBC have been achieved. Aligned with these data is the growing number of targeted therapy agents approved and/or in development in other organ site cancers and the multiple similarities of bladder cancer with molecular subtypes in these other cancers. Additionally, although bladder cancer is one of the more immunogenic tumors, some tumors have the ability to attenuate or eliminate host immune responses. Two trial concepts emerged from the meeting including a window of opportunity trial (Phase 0) testing an FGFR3 inhibitor and a second multi-arm multi-stage trial testing combinations of BCG or radiotherapy and immunomodulatory agents in patients who recur after induction BCG (BCG failure).
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After an infectious complication caused by bacillus Calmette-Guérin (BCG), consider a dose reduction. Treatment of a mycotic aneurysm with an endostent seems safe; however, continuation of BCG after mycotic aneurysm treatment is not advised.
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BACKGROUND: To answer the research questions: (a) what were the training pathways followed by the first generation of robot urologists; and (b) what are their opinions on the ideal training for the future generation? METHODS: Data were gathered with a questionnaire and semi-structured interviews in a mixed-method research design. RESULTS: The results show that training approaches differed from hardly any formal training to complete self-initiated training programmes, with all available learning resources. The median number of supervised procedures at the start of robot-assisted laparoscopy was five (range 0-100). Before patient-related console time, respondents indicated that the minimum training of robot trainees should consist of: live observations (94% indicated this as essential), video observations (90%), knowledge (88%), table assisting (87%) and basic skills (70%). CONCLUSION: The first generation of robot urologists used different training approaches to start robotic surgery. There is a need for a structured and compulsory training programme for robotic surgery. Copyright © 2014 John Wiley & Sons, Ltd.
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PURPOSE: We determined the positive and negative predictive values of multiparametric magnetic resonance imaging for extraprostatic extension at radical prostatectomy for different prostate cancer risk groups. MATERIALS AND METHODS: We evaluated a cohort of 183 patients who underwent 3 Tesla multiparametric magnetic resonance imaging, including T2-weighted, diffusion weighted magnetic resonance imaging and dynamic contrast enhanced sequences, with an endorectal coil before radical prostatectomy. Pathological stage at radical prostatectomy was used as standard reference for extraprostatic extension. The cohort was classified into low, intermediate and high risk groups according to the D'Amico criteria. We recorded prevalence of extraprostatic extension at radical prostatectomy and determined sensitivity, specificity, positive predictive value and negative predictive value of multiparametric magnetic resonance imaging for extraprostatic extension in each group. Univariate and multivariate analyses were performed to identify predictors of extraprostatic extension at radical prostatectomy. RESULTS: The overall prevalence of extraprostatic extension at radical prostatectomy was 49.7% ranging from 24.7% to 77.1% between low and high risk categories. Overall staging accuracy of multiparametric magnetic resonance imaging for extraprostatic extension was 73.8%, with sensitivity, specificity, positive predictive value and negative predictive value of 58.2%, 89.1%, 84.1% and 68.3%, respectively. Positive predictive value of multiparametric magnetic resonance imaging for extraprostatic extension was best in the high risk cohort with 88.8%. Negative predictive value was highest in the low risk cohort with 87.7%. With an odds ratio of 10.3 multiparametric magnetic resonance imaging is by far the best preoperative predictor of extraprostatic extension at radical prostatectomy. CONCLUSIONS: For adequate patient counseling, knowledge of predictive values of multiparametric magnetic resonance imaging for extraprostatic extension is of utmost importance. High negative predictive value, important for decisions on nerve sparing strategies at radical prostatectomy, is only reached in low risk subjects.
Assuntos
Imageamento por Ressonância Magnética/métodos , Neoplasias da Próstata/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Valor Preditivo dos Testes , Prostatectomia , Neoplasias da Próstata/cirurgia , Reto , Medição de RiscoRESUMO
BACKGROUND: Previous studies on the effects of different prostate cancer treatments on quality of life, were confounded because patients were not comparable. This study examined treatment effects in more comparable groups. METHODS: From 2008-2011, 240 patients with localised prostate cancer were selected to be eligible for both radical prostatectomy (RP) and external beam radiotherapy (EBRT). Brachytherapy (BT) was a third option for some. Health-related quality of life was measured by expanded prostate cancer index composite (EPIC) up to 12 months after treatment. RESULTS: In the sexual domain, RP led to worse summary scores (P<0.001) and more often to a clinically relevant deterioration from baseline than BT and EBRT (79%, 33%, 34%, respectively). In the urinary domain, RP also led to worse summary scores (P=0.014), and more deterioration from baseline (41%, 12%, 19%, respectively). Only on the irritative/obstructive urinary scale, more BT patients (40%) showed a relevant deterioration than RP (17%) and EBRT patients (11%). In the bowel domain, the treatment effects did not differ. CONCLUSION: This study provides a more unbiased comparison of treatment effects, as men were more comparable at baseline. Our results suggest that, for quality of life, radiotherapy is as least as good an option as RP for treating localised prostate cancer.
Assuntos
Braquiterapia/efeitos adversos , Prostatectomia/efeitos adversos , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Qualidade de Vida , Idoso , Braquiterapia/métodos , Disfunção Erétil , Nível de Saúde , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Prostatectomia/métodos , Inquéritos e Questionários , Resultado do Tratamento , Incontinência UrináriaRESUMO
BACKGROUND AND PURPOSE: Postprostatectomy radiotherapy (RT) improves survival in adjuvant and salvage settings. The implantation technique and complications rate of gold markers in the prostate bed for high-precision RT were analyzed. PATIENTS AND METHODS: Patients undergoing postprostatectomy RT for prostate-specific antigen (PSA) relapse or high-risk disease were enrolled in the study. Under transrectal ultrasound guidance, three fine gold markers were implanted in the prostate bed and the technical difficulties of insertion were documented. Patients received our self-designed questionnaires concerning complications and pain. The influence of anticoagulants and coumarins on bleeding was analyzed, as was the effect of potential risk factors on pain. RESULTS: In 77 consecutive patients, failure of marker implantation or marker migration was seen in six cases. Rectal bleeding was reported by 10 patients and 1 had voiding complaints. No macroscopic hematuria persisting for more than 3 days was observed. Other complications included rectal discomfort (n = 2), nausea (n = 1), abdominal discomfort (n = 1), and pain requiring analgesics (n = 4). No major complications were reported. On a 0-10 visual analogue scale (VAS), the mean pain score was 3.7. No clinically significant risk factors for complications were identified. CONCLUSION: Transrectal implantation of gold markers in the prostate bed is feasible and safe. Alternatives like cone beam computed tomography (CBCT) should be considered, but the advantages of gold marker implantation for high-precision postprostatectomy RT would seem to outweigh the minor risks involved.