RESUMEN

Contexto y objetivo: Presentar la guía clínica de la Asociación Europea de Urología (EAU) de 2011 del carcinoma de vejiga no músculo-invasivo (CVNMI). Adquisición de la evidencia: Se ha realizado una revisión sistemática de la literatura publicada entre 2004 y 2010 acerca del diagnóstico y el tratamiento del CVNMI. Se actualizaron las guías clínicas previas, y se asignó un nivel de evidencia (NE) y un grado de recomendación (GR). Síntesis de la evidencia: Los tumores en estadio Ta, T1 o carcinoma in situ (CIS) se agrupan como CVNMI. El diagnóstico depende de la cistoscopia y de la evaluación histológica del tejido obtenido por resección transuretral (RTU) en los tumores papilares o por biopsias de vejiga múltiples en el CIS. En las lesiones papilares, una completa RTU es esencial para el pronóstico del paciente. Cuando la primera resección es incompleta o cuando se detecta un tumor de alto grado o T1, se debe realizar una segunda RTU a las 2-6 semanas. En los tumores papilares, el riesgo tanto de recurrencia como de progresión se puede calcular de manera individual mediante los sistemas de puntuación y tablas de riesgo. La estratificación de los pacientes en grupos de riesgo bajo, intermedio y alto (separando la recidiva y la progresión) es fundamental para recomendar un tratamiento adyuvante. Para los pacientes con bajo riesgo de recurrencia y progresión se recomienda una instilación inmediata de quimioterapia. Los pacientes con riesgo intermedio o alto de recurrencia y riesgo intermedio de progresión deben recibir una instilación inmediata de quimioterapia seguida de un mínimo de un año con inmunoterapia intravesical con bacilo de Calmette-Guérin (BCG) o más instilaciones de quimioterapia. Los tumores papilares con alto riesgo de progresión y CIS deben recibir BCG intravesical durante un año. Se puede ofrecer una cistectomía a los pacientes de más alto riesgo, y por lo menos se recomienda a los pacientes en los que ha fallado la BCG. Conclusión: La versión reducida de esta guía clínica de la EAU presenta una información actualizada sobre el diagnóstico y el tratamiento del CVNMI para la incorporación a la práctica clínica (AU)

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Context and objective: To present the 2011 European Association of Urology (EAU) guidelines on non-muscle-invasive bladder cancer (NMIBC).Evidence acquisition: Literature published between 2004 and 2010 on the diagnosis and treatment of NMIBC was systematically reviewed. Previous guidelines were updated, and the level of evidence and grade of recommendation were assigned. Evidence synthesis: Tumours staged as Ta, T1, or carcinoma in situ (CIS) are grouped as NMIBC. Diagnosis depends on cystoscopy and histologic evaluation of the tissue obtained by transurethral resection (TUR) in papillary tumours or by multiple bladder biopsies in CIS. In papillary lesions, a complete TUR is essential for the patient’s prognosis. Where the initial resection is incomplete or where a high-grade or T1 tumour is detected, a second TUR should be performed within 2-6 wk. In papillary tumours, the risks of both recurrence and progression maybe estimated for individual patients using the scoring system and risk tables. The stratification of patients into low-, intermediate-, and high-risk groups (separately for recurrence and progression) is pivotal to recommending adjuvant treatment. For patients with a low risk of tumour recurrence and progression, one immediate instillation of chemotherapy is recommended. Patients with an intermediate or high risk of recurrence and an intermediate risk of progression should receive one immediate instillation of chemotherapy followed by a minimum of 1 yr of bacillus Calmette-Guérin (BCG) intravesical immunotherapy or further instillations of chemotherapy. Papillary tumours with a high risk of progression and CIS should receive intravesical BCG for 1 yr. Cystectomy may be offered to the highest risk patients, and it is at least recommended in BCG failure patients. Conclusions: These abridged EAU guidelines present updated information on the diagnosis and treatment of NMIBC for incorporation into clinical practice (AU)

Asunto(s)

Humanos , Carcinoma de Células Transicionales/diagnóstico , Carcinoma de Células Transicionales/terapia , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/terapia , Vacuna BCG/uso terapéutico , Cistectomía/métodos , Administración Intravesical , Antineoplásicos/uso terapéutico

RESUMEN

CONTEXT AND OBJECTIVE: To present the 2011 European Association of Urology (EAU) guidelines on non-muscle-invasive bladder cancer (NMIBC). EVIDENCE ACQUISITION: Literature published between 2004 and 2010 on the diagnosis and treatment of NMIBC was systematically reviewed. Previous guidelines were updated, and the level of evidence and grade of recommendation were assigned. EVIDENCE SYNTHESIS: Tumours staged as Ta, T1, or carcinoma in situ (CIS) are grouped as NMIBC. Diagnosis depends on cystoscopy and histologic evaluation of the tissue obtained by transurethral resection (TUR) in papillary tumours or by multiple bladder biopsies in CIS. In papillary lesions, a complete TUR is essential for the patient's prognosis. Where the initial resection is incomplete or where a high-grade or T1 tumour is detected, a second TUR should be performed within 2-6 wk. In papillary tumours, the risks of both recurrence and progression may be estimated for individual patients using the scoring system and risk tables. The stratification of patients into low-, intermediate-, and high-risk groups (separately for recurrence and progression) is pivotal to recommending adjuvant treatment. For patients with a low risk of tumour recurrence and progression, one immediate instillation of chemotherapy is recommended. Patients with an intermediate or high risk of recurrence and an intermediate risk of progression should receive one immediate instillation of chemotherapy followed by a minimum of 1 yr of bacillus Calmette-Guérin (BCG) intravesical immunotherapy or further instillations of chemotherapy. Papillary tumours with a high risk of progression and CIS should receive intravesical BCG for 1 yr. Cystectomy may be offered to the highest risk patients, and it is at least recommended in BCG failure patients. CONCLUSIONS: These abridged EAU guidelines present updated information on the diagnosis and treatment of NMIBC for incorporation into clinical practice.

Asunto(s)

Carcinoma de Células Transicionales/diagnóstico , Carcinoma de Células Transicionales/terapia , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/terapia , Carcinoma de Células Transicionales/clasificación , Humanos , Neoplasias de la Vejiga Urinaria/clasificación

RESUMEN

Contexto: El Grupo de Guías Clínicas sobre el carcinoma de células uroteliales de las vías urinarias superiores (CCU-VUS) de La Asociación Europea de Urología (EAU) ha elaborado una nueva guía clínica para ayudar a los médicos a evaluar el tratamiento del CCU-VUS basado en los datos científicos, y a incorporar las presentes recomendaciones a la práctica clínica diaria. Objetivo: Este documento ofrece una breve visión general de la guía clínica de la EAU sobre el CCU-VUS como una ayuda para los médicos en su práctica diaria. Adquisición de datos científicos: Las recomendaciones proporcionadas en la guía actual se basan en una meticulosa revisión de las guías y documentos sobre CCU-VUS disponibles, identificados mediante una búsqueda sistemática en Medline. Los datos sobre neoplasias uroteliales malignas y CCU-VUS en la literatura se buscaron mediante Medline con las siguientes palabras clave: cáncer del tracto urinario, carcinomas uroteliales, tracto urinario superior, carcinoma, células de transición, pelvis renal, uréter, cáncer vesical, quimioterapia, nefroureterectomía, tratamiento adyuvante, tratamiento neoadyuvante, recidiva, factores de riesgo y supervivencia. Un equipo de expertos sopesó las referencias Síntesis de los datos científicos: Hay una falta de datos en la literatura actual para proporcionar recomendaciones consistentes, debido a la rareza de la enfermedad. Una serie de recientes estudios multicéntricos ya están disponibles, mientras que las publicaciones anteriores se basaban solo en poblaciones limitadas. Sin embargo, la mayoría de estos estudios han sido análisis retrospectivos. Se recomienda la clasificación TNM2009. Se hacen recomendaciones para el diagnóstico, así como para el tratamiento radical y conservador; también se tratan los factores pronósticos. Se proporcionan recomendaciones para el seguimiento del paciente después de diferentes opciones terapéuticas. Conclusiones: Esta guía contiene información para el diagnóstico y tratamiento de los pacientes individuales de acuerdo a un enfoque estándar actual. Al determinar el régimen de tratamiento óptimo, los médicos deben tener en cuenta las características clínicas específicas de cada paciente con respecto a la función renal, incluyendo comorbilidades médicas, localización del tumor, grado y estadio y el estado de los marcadores moleculares (AU)

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Context: The European Association of Urology (EAU) Guideline Group for urothelial cell carcinoma of the upper urinary tract (UUT-UCC) has prepared new guidelines to aid clinicians in assessing the current evidence-based management of UUT-UCC and to incorporate present recommendations into daily clinical practice. Objective: This paper provides a brief overview of the EAU guidelines on UUT-UCC as an aid to clinicians in their daily practice. Evidence acquisition: The recommendations provided in the current guidelines are based on a thorough review of available UUT-UCC guidelines and papers identified using a systematic search of Medline. Data on urothelial malignancies and UUT-UCCs in the literature were searched sing Medline with the following keywords: urinary tract cancer, urothelial carcinomas, upper urinary tract, carcinoma, transitional cell, renal pelvis, ureter, bladder cancer, chemotherapy, nephroureterectomy, adjuvant treatment, neoadjuvant treatment, recurrence, risk factors, and survival. A panel of experts weighted the references. Evidence synthesis: There is a lack of data in the current literature to provide strong recommendations due to the rarity of the disease. A number of recent multicentre studies are now available, whereas earlier publications were based only on limited populations. However, most of these studies have been retrospective analyses. The TNM classification2009 is recommended. Recommendations are given for diagnosis as well as for radical and conservative treatment; prognostic factors are also discussed. Recommendations are provided for patient follow-up after different therapeutic options. Conclusions: These guidelines contain information for the diagnosis and treatment of individual patients according to a current standardised approach. When determining the optimal treatment regimen, physicians must take into account each individual patient’s specific clinical characteristics with regard to renal function including medical comorbidities; tumour location, grade and stage; and molecular marker status (AU)

Asunto(s)

Humanos , Carcinoma de Células Transicionales/patología , Urotelio/patología , Neoplasias Urológicas/patología , Neoplasias Urológicas/terapia , Biomarcadores de Tumor/análisis , Pelvis Renal/patología , Neoplasias Ureterales/patología , Laparoscopía

RESUMEN

CONTEXT: The European Association of Urology (EAU) Guideline Group for urothelial cell carcinoma of the upper urinary tract (UUT-UCC) has prepared new guidelines to aid clinicians in assessing the current evidence-based management of UUT-UCC and to incorporate present recommendations into daily clinical practice. OBJECTIVE: This paper provides a brief overview of the EAU guidelines on UUT-UCC as an aid to clinicians in their daily practice. EVIDENCE ACQUISITION: The recommendations provided in the current guidelines are based on a thorough review of available UUT-UCC guidelines and papers identified using a systematic search of Medline. Data on urothelial malignancies and UUT-UCCs in the literature were searched using Medline with the following keywords: urinary tract cancer, urothelial carcinomas, upper urinary tract, carcinoma, transitional cell, renal pelvis, ureter, bladder cancer, chemotherapy, nephroureterectomy, adjuvant treatment, neoadjuvant treatment, recurrence, risk factors, and survival. A panel of experts weighted the references. EVIDENCE SYNTHESIS: There is a lack of data in the current literature to provide strong recommendations due to the rarity of the disease. A number of recent multicentre studies are now available, whereas earlier publications were based only on limited populations. However, most of these studies have been retrospective analyses. The TNM classification 2009 is recommended. Recommendations are given for diagnosis as well as for radical and conservative treatment; prognostic factors are also discussed. Recommendations are provided for patient follow-up after different therapeutic options. CONCLUSIONS: These guidelines contain information for the diagnosis and treatment of individual patients according to a current standardised approach. When determining the optimal treatment regimen, physicians must take into account each individual patient's specific clinical characteristics with regard to renal function including medical comorbidities; tumour location, grade and stage; and molecular marker status.

Asunto(s)

Carcinoma de Células Transicionales/diagnóstico , Carcinoma de Células Transicionales/terapia , Neoplasias Renales/diagnóstico , Neoplasias Renales/terapia , Neoplasias Ureterales/diagnóstico , Neoplasias Ureterales/terapia , Vacuna BCG/administración & dosificación , Vacuna BCG/uso terapéutico , Biomarcadores de Tumor/análisis , Carcinoma de Células Transicionales/epidemiología , Carcinoma de Células Transicionales/patología , Quimioterapia Adyuvante , Diagnóstico por Imagen/métodos , Medicina Basada en la Evidencia , Humanos , Neoplasias Renales/epidemiología , Neoplasias Renales/patología , Laparoscopía , Mitomicina/administración & dosificación , Mitomicina/uso terapéutico , Clasificación del Tumor , Invasividad Neoplásica , Estadificación de Neoplasias , Nefrectomía , Nefrostomía Percutánea , Pronóstico , Radioterapia Adyuvante , Factores de Riesgo , Neoplasias Ureterales/epidemiología , Neoplasias Ureterales/patología , Ureteroscopía

RESUMEN

OBJECTIVES: Urine cytology is the gold standard in the diagnosis and follow-up of bladder cancer. Cytology, however, exhibits variable sensitivity depending on tumour grade and interpretation of urine specimens is highly dependent on the skill of the examiner. Positive cytology, classes IV and V by Papanicolaou classification, is a strong predictor for coexisting or subsequent malignancy, while the role of suspicious cytology, class III, is controversial. The objective of the study was to evaluate the role of the suspicious finding in cytological analysis, and whether it should be considered as a negative or positive sign for coexisting malignancy. MATERIAL AND METHODS: Six hundred and fifty-two consecutive patients with bladder cancer were studied in a prospective multicenter trial. One hundred and fifty-one of the patients were newly diagnosed, and the remaining 501 patients were under follow-up. A voided urine sample was obtained prior to TURB or prior to routine follow-up cystoscopy in those under the surveillance and split for culture and cytology. The cytopathological results were analyzed by a central review and only patients with samples available for review analysis were included. Sensitivity and specificity, as well as positive (PPV) and negative (NPV) predictive values of urine cytology were calculated by classifying the class III samples as negative or positive. RESULTS: A total of 570 patients were evaluable. One hundred and twenty nine (22.6%) were newly diagnosed and 441 were under follow-up, of whom 117 (26.5%) had recurrence. Cytology was classified as suspicious in 33/129 (25.6%) patients with primary tumour, and in 41/441 (9.3%) of those under the follow-up, of whom 20 (48.8%) had recurrence. Sensitivity increased from to 31.0% to 56.6% in primary tumours (p < 0.001) and from 17.8% to 34.7% in recurrent tumours (p < 0.001) if class III was determined as positive, whereas the specificity decreased from 96.6% to 90.1% (p < 0.001). Accordingly, the NPV increased from 76.3% to 79.1% and the PPV decreased from 65.6% to 56.2%. CONCLUSIONS: The poor sensitivity of voided urine cytology improved significantly when suspicious samples were determined as positive while the specificity remained high, a clear advantage compared with most of the new tumour marker tests. In addition, nearly half of the follow-up patients with suspicious class III cytology had recurrence implying that this patient category is at substantial risk for co-existing malignancy. Therefore, it is recommended that suspicious class III cytology together with class IV and V specimens should be considered positive.

Asunto(s)

Neoplasias de la Vejiga Urinaria/diagnóstico , Orina/citología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico , Valor Predictivo de las Pruebas , Estudios Prospectivos , Sensibilidad y Especificidad , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/orina

RESUMEN

The purpose of the study was to determine, in addition to well-known prognostic factors, histological grade, stage, tumour size and multiplicity, the correlation of BTA stat Test on disease free interval (DFI) on primary superficial bladder cancer. A total of 116 patients with newly diagnosed bladder cancer were evaluated in a prospective multicentre study. A voided urine sample was obtained prior to TURB and split for culture, cytology and BTA stat testing. Follow-up data for the patients were collected until the first recurrence or the last visit and the DFI was analysed by Kaplan-Meier method and Cox analysis. Ninety-seven of the 116 (83.6%) patients were eligible for analysis. The BTA stat Test was positive in 73 (75.3%) patients, whereas cytology detected 20 (20.6%) cases. The DFI was found to be shorter among patients with a positive BTA stat Test, and also among those with intermediate or high-grade tumours. The BTA stat Test result divided patients with grade 2 tumours into two prognostic groups, in that those testing positive had 68.6% risk of recurrence during the first year compared to 42.9% risk of those with a negative test result (P = 0.041). Although the effect of tumour size on DFI was notable, the difference did not reach statistical significance (P = 0.064). Number of tumours was not related to DFI, nor was the difference between different stage of tumour of significance. BTA stat Test is not only sensitive in detection of primary bladder cancer, but also might have some independent prognostic significance.

Asunto(s)

Biomarcadores de Tumor/análisis , Carcinoma de Células Transicionales/patología , Factor H de Complemento/análisis , Neoplasias de la Vejiga Urinaria/patología , Adulto , Anciano , Anciano de 80 o más Años , Antígenos de Neoplasias/análisis , Carcinoma de Células Transicionales/genética , Cromatografía , Factor H de Complemento/genética , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunoensayo , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Neoplasias de la Vejiga Urinaria/genética

RESUMEN

OBJECTIVES: To evaluate the role of a positive BTA stat Test result in patients with negative cystoscopic findings. METHODS: Five hundred one consecutive patients in follow-up for bladder cancer were studied. A voided urine sample was obtained before cystoscopy and split for culture, cytology, and BTA stat testing. In the case of a positive BTA stat Test, but negative cystoscopic findings, patients underwent additional investigations. RESULTS: Of 501 patients, 133 (26.5%) had bladder cancer recurrence at cystoscopy, of which the BTA stat Test detected 71 (53.4%); only 21 of the cases (17.9%) were detected by cytologic examination. Of the remaining 368 patients with no visible tumor at cystoscopy, 96 (26.1%) had a positive BTA stat Test result. Fifty-five of those (57.3%) underwent intravenous urography or renal ultrasound and random biopsies, and an additional 9 recurrences (16.4%) were detected. Of those 46 patients who had a true false-positive BTA stat Test, 3 (3 of 43, 7.0%) had recurrence at the next follow-up cystoscopy, 4 (8.7%) had a urine infection, and 8 (17.4%) had ongoing intravesical instillations; the latter two percentages were significantly higher than among those with true-negative BTA stat Test results (0% and 6.8%, respectively). CONCLUSIONS: Patients with a positive BTA stat Test result but negative cystoscopic findings have about a 16% risk of an undetected recurrence. False-positive results may be due to present instillation treatment and urine infection, and the predictive value of a BTA stat Test for subsequent recurrence seems relatively low.

Asunto(s)

Antígenos de Neoplasias/orina , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/orina , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/orina , Orina/citología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Transicionales/diagnóstico , Carcinoma de Células Transicionales/orina , Cistoscopía , Reacciones Falso Positivas , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Prospectivos , Sensibilidad y Especificidad

RESUMEN

Immunoreactivity of p21WAF1/CIP1 and cyclin D1 proteins was assessed in a cohort of 207 patients with superficial (pTa-pT1) bladder cancer followed up for a mean of 4.9 years. The results of the immunostainings were compared with T category, WHO grade, tumor cell proliferation rate (MIB-1 score), the expressions of p53 and bcl-2 as well as survival. Sixty-eight percent and 75% of the tumors were p21WAF1/CIP1 positive (> or = 5% of cells positive) and cyclin D1 positive (> or = 10% of cells positive), respectively. The p21WAF1/CIP1 expression was related to cyclin D1 immunolabelling (P < 0.001) but not to the other variables studied. The expression of cyclin D1 was inversely associated with T category (P = 0.001), WHO grade (P = 0.006), MIB-1 score (P = 0.014), p53 expression (P = 0.001), and bcl-2 (P = 0.011) immunoreactivity. In univariate analysis, T category (P = 0.0001), WHO grade (P < 0.0001), MIB-1 score (P < 0.0001), bcl-2 (P = 0.0092), p53 (P = 0.0016) and p21WAF1/CIP1 (P = 0.009) expressions were significant prognostic factors with regard to tumor progression, whereas cyclin D1 was without any prognostic significance (P = 0.1). Out of 123 p21 positive tumors 21 progressed, whereas only 2 out of 58 p21 negative tumors progressed. In multivariate analysis, the MIB-1 score was the only independent predictor of cancer-specific survival (P = 0.03), whereas tumor grade (P = 0.002) and cyclin D1 expression (P = 0.04) were independent predictors of tumor recurrence. Only the WHO grade (P = 0.04) retained its prognostic value indicating the risk of progression. We suggest that in superficial bladder cancer p21WAF1/CIP1 and cyclin D1 immunohistochemistry provide no additional prognostic information compared with already established prognostic factors for predicting the risk of progressive disease.

Asunto(s)

Carcinoma de Células Transicionales/metabolismo , Carcinoma de Células Transicionales/patología , Ciclina D1/metabolismo , Ciclinas/metabolismo , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Adulto , Anciano , Anciano de 80 o más Años , División Celular , Inhibidor p21 de las Quinasas Dependientes de la Ciclina , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto

RESUMEN

PURPOSE: We evaluated alternatives to bacillus Calmette-Guerin (BCG) monotherapy using a new combination of chemotherapy and immunotherapy for recurrent superficial bladder carcinoma. MATERIALS AND METHODS: A total of 236 patients with frequently recurrent stage Ta or T1 bladder tumors were enrolled in our prospective, randomized, multicenter Finnbladder IV study. The initial mitomycin C instillation was instilled in all patients perioperatively after transurethral resection, followed by 4 weekly instillations of mitomycin C. Thereafter patients were randomized to receive monthly for up to 1 year BCG only or interferon-alpha2b and BCG alternating monthly. Primary end points were time to initial recurrence, recurrence rate (number of recurrences per patient-year) and recurrence index (number of recurrent tumors per patient-year). RESULTS: Of the 236 randomized patients 205 were eligible for study with a median overall followup of 30.7 months. Monthly BCG was superior to alternating monthly interferon-alpha and/or BCG with respect to time to initial recurrence (log rank test p <0.00001) as well as recurrence rate (0.4 versus 0.9, p <0.00001) and index (0.9 versus 3.0, p <0.00001). Side effects were limited. CONCLUSIONS: Monthly BCG given for up to 1 year preceded by perioperative and an additional 4 weekly mitomycin C instillations is a well tolerated mode of instillation therapy, providing excellent tumor control comparable to that of the best reported instillation regimens. No benefit was obtained by alternating interferon-alpha2b with BCG.

Asunto(s)

Adyuvantes Inmunológicos/administración & dosificación , Antibióticos Antineoplásicos/administración & dosificación , Antineoplásicos/administración & dosificación , Vacuna BCG/administración & dosificación , Carcinoma Papilar/prevención & control , Interferón-alfa/administración & dosificación , Mitomicina/administración & dosificación , Recurrencia Local de Neoplasia/prevención & control , Neoplasias de la Vejiga Urinaria/prevención & control , Administración Intravesical , Anciano , Terapia Combinada , Esquema de Medicación , Femenino , Humanos , Interferón alfa-2 , Masculino , Estudios Prospectivos , Proteínas Recombinantes

RESUMEN

PURPOSE: We compared the sensitivity of the BTA statdagger test, a rapid, noninvasive, qualitative urine test that detects bladder tumor associated antigen (human complement factor H related protein) in urine, to that of voided urine cytology in patients with primary bladder cancer. We also assessed the effect of tumor size, number, histological grade and stage on test sensitivity. MATERIALS AND METHODS: We evaluated 151 patients with newly diagnosed bladder cancer in a prospective multicenter study. A voided urine sample obtained before transurethral bladder tumor resection was divided for culture, cytology and BTA stat testing. RESULTS: Overall sensitivity of the BTA stat test and urine cytology for detecting primary bladder cancer was 81.5% and 30.3%, respectively (p <0.0001). The sensitivity of each test increased as tumor size, number, histological grade and stage increased. CONCLUSIONS: Sensitivity of the BTA stat test was superior to that of voided urine cytology in all tumor categories. This noninvasive, easy to perform, point of care test may have the potential to replace cytology for diagnosing bladder cancer.

Asunto(s)

Carcinoma de Células Transicionales/diagnóstico , Factor H de Complemento/química , Neoplasias de la Vejiga Urinaria/diagnóstico , Carcinoma de Células Transicionales/patología , Carcinoma de Células Transicionales/orina , Femenino , Humanos , Masculino , Estudios Prospectivos , Juego de Reactivos para Diagnóstico , Sensibilidad y Especificidad , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/orina , Orina/citología

RESUMEN

PURPOSE: To study short-term events in the mechanism of action of BCG with an emphasis on the interaction between BCG and T24 cell line cells. MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMNC) or/and several tumor cell lines were incubated with BCG (Oncotice) using various clinical and subclinical BCG concentrations. RESULTS: 3 h BCG incubation of PBMNC at 10(7) - 5*10(5) CFU/ml., followed by a 4 h cytotoxicity test, resulted in a significant augmentation of cytotoxicity of PBMNC against T24 cells, and the augmentation was almost significant at 10(5) CFU/ml. Overnight BCG incubation of PBMNC further augmented that cytotoxicity at all concentrations down to 10(4) CFU/ml. The minimum overall time (incubation with BCG + cytotoxicity test), where stimulation of PBMNC could be detected, was only 4 h. The BCG enhanced cytotoxicity of PBMNC could be demonstrated against all the tested cell line cells in a 4 h cytotoxicity test by using a preceding overnight BCG incubation of PBMNC, and against the majority of the cell lines by using a preceding 3 h BCG incubation of PBMNC. No convincing evidence was obtained to support the hypothesis that BCG should be first processed by T24 cells to make these cells more susceptible to cell mediated lysis by PBMNC. CONCLUSIONS: Clinical and subclinical concentrations of BCG are directly stimulatory to PBMNC, which become, in a minimum time of a few hours, more capable of killing tumor cells, without a need for preceding interaction between BCG and tumor cells.

Asunto(s)

Adyuvantes Inmunológicos/farmacología , Vacuna BCG/farmacología , Carcinoma de Células Transicionales/inmunología , Carcinoma de Células Transicionales/patología , Neoplasias de la Próstata/inmunología , Neoplasias de la Próstata/patología , Linfocitos T Citotóxicos/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Masculino , Células Tumorales Cultivadas

RESUMEN

OBJECTIVE: A prospective randomized study was undertaken to determine whether cell proliferation indices (M/V index, MIB1), papillary status, the expression of p53 and epidermal growth factor receptor (EGFr) have prognostic value in superficial (pTa-pT1) bladder cancer (SBC). METHODS: 207 patients with primary SBC were followed up over a period of 4.9 (range 3.7-6.0) years. M/V index and papillary status were assessed by light microscopy, and expression of MIB1, p53 and EGFr was assessed by immunohistochemistry. The results of histopathological analyses were related to the survival data of the patients. RESULTS: Using univariate analysis, stage (p < 0.001), grade (p < 0.001), papillary status (p < 0.001), MIB1 (p < 0.001), M/V index (p < 0.001), EGFr (p < 0.001) and p53 (p = 0.002) were significant predictors of progression. Using multivariate analysis, MIB-1 score and papillary status were independent predictors of progressive disease and cancer-specific survival. Tumor grade was the only independent predictor of recurrence. CONCLUSION: Evaluation of tumor cell proliferation rate by M/V index or by MIB1 immunohistochemistry and assessment of papillary status by light microscopy are useful prognostic tools in tailoring treatment and follow-up schedule of patients with SBC.

Asunto(s)

Biomarcadores de Tumor/análisis , Carcinoma de Células Transicionales/patología , Receptores ErbB/análisis , Genes p53 , Índice Mitótico , Proteínas Nucleares/análisis , Neoplasias de la Vejiga Urinaria/patología , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Carcinoma de Células Transicionales/mortalidad , Carcinoma de Células Transicionales/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estadificación de Neoplasias , Pronóstico , Estudios Prospectivos , Sensibilidad y Especificidad , Análisis de Supervivencia , Tasa de Supervivencia , Neoplasias de la Vejiga Urinaria/mortalidad , Neoplasias de la Vejiga Urinaria/terapia

RESUMEN

PURPOSE: We evaluated the efficacy of single dose of interferon or epirubicin administered immediately after transurethral resection compared with transurethral resection only on the recurrence of primary (not recurrent) superficial bladder cancer. MATERIALS AND METHODS: A total of 283 patients with stages Ta to T1 primary superficial, grades 1 to 3 bladder cancer was randomized into study groups 1-transurethral resection only, 2-transurethral resection plus 50 million units interferon-a2b and 3-transurethral resection plus 100 mg. epirubicin. Eligible for final analysis were 200 patients, including 66 in group 1, 66 in group 2 and 68 in group 3. Patients were followed with cystoscopy every 3 months for 2 years or until the initial recurrence. RESULTS: Group 3 had the most favorable outcome, since 45 of the 68 patients (66%) were without recurrence after 2 years compared to 24 of the 66 (37%) in group 2 and 26 of the 66 (40%) in group 1 (log rank test p <0.001). Side effects were mostly mild and transient, and no differences were found among the groups. CONCLUSIONS: A single 100 mg. dose of epirubicin given intravesically immediately after transurethral resection is safe, and significantly decreases the recurrence of primary superficial bladder cancer. A 50 million unit dose of interferon-alpha2b is well tolerated but it has no effect on recurrence as a single dose. The long-term effect of this treatment remains to be studied.

Asunto(s)

Antineoplásicos/administración & dosificación , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/cirugía , Epirrubicina/administración & dosificación , Interferón-alfa/administración & dosificación , Recurrencia Local de Neoplasia/prevención & control , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/cirugía , Administración Intravesical , Carcinoma de Células Transicionales/patología , Carcinoma de Células Transicionales/prevención & control , Terapia Combinada , Femenino , Humanos , Masculino , Estadificación de Neoplasias , Estudios Prospectivos , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/prevención & control

Asunto(s)

Afasia/rehabilitación , Equipos de Comunicación para Personas con Discapacidad , Microcomputadores , Anciano , Gráficos por Computador , Femenino , Finlandia , Humanos , Programas Informáticos

RESUMEN

A survey on superficial, local urinary bladder cancer, its prognostic factors, and instillation treatments is presented on the basis of experience with approximately 1,000 patients over a period of 20 years, experimental investigations, and the literature. Personal opinions and practical recommendations are presented in 11 conclusive theses.

Asunto(s)

Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/prevención & control , Oncología Médica/tendencias , Medicina Preventiva/tendencias , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/prevención & control , Urología/tendencias , Administración Intravesical , Humanos

RESUMEN

PURPOSE: We attempted to prove if alternating chemoprophylactic and immunoprophylactic instillations improved efficacy and decreased toxicity in patients with recurrent superficial bladder cancer. MATERIALS AND METHODS: A total of 188 patients with rapidly recurring stage Ta or T1 cancer was randomly treated with mitomycin C (group 1) or alternating mitomycin C and Pasteur strain bacillus Calmette-Guerin (BCG) instillations (group 2) for 2 years. Mean followup was 34 months. RESULTS: Median times to initial recurrence were 12 months in group 1 and 7 months in group 2 (p = 0.976), and treatment failed in 21.5% and 18.9%, respectively. Recurrence rates during the instillation period were 1.01 in group 1 and 0.86 in group 2 (p = 0.376). There was no difference in the disease-free interval between the 2 groups (p = 0.976). Instillations were discontinued because of adverse effects in 6 cases (6%) in both groups. CONCLUSIONS: Efficacy of alternating mitomycin C and BCG was equal to mitomycin C monotherapy, and both methods were effective in prophylaxis of recurrent papillary bladder cancer. Less toxicity occurred in the alternating treatment group compared to earlier BCG monotherapy results.

Asunto(s)

Adyuvantes Inmunológicos/administración & dosificación , Antibióticos Antineoplásicos/administración & dosificación , Vacuna BCG/administración & dosificación , Carcinoma de Células Transicionales/terapia , Mitomicinas/administración & dosificación , Recurrencia Local de Neoplasia/prevención & control , Neoplasias de la Vejiga Urinaria/terapia , Administración Intravesical , Anciano , Carcinoma de Células Transicionales/patología , Esquema de Medicación , Femenino , Humanos , Masculino , Estadificación de Neoplasias , Estudios Prospectivos , Neoplasias de la Vejiga Urinaria/patología

RESUMEN

PURPOSE: Our aim was to prove if alternating chemotherapeutic and immunotherapeutic instillations improved efficacy and reduced toxicity in patients with carcinoma in situ of the bladder. MATERIALS AND METHODS: Of 68 carcinoma in situ patients randomly treated with instillations 40 received mitomycin C and 28 received mitomycin C and Pasteur bacillus Calmette-Guerin (BCG) in alternating courses. Mean followup was 33 months. RESULTS: The complete response rates with mitomycin C and mitomycin C/BCG were 45% and 71% at 3 months, 59% and 82% at 12 months, and 47% and 74% at 24 months, respectively (p = 0.041). The disease-free interval showed the superiority of alternating therapy (p = 0.043). Recurrence rates during the instillation period were 1.834 with mitomycin C and 0.922 with mitomycin C/BCG (p = 0.013). No remarkable side effects developed in the alternating group. CONCLUSIONS: Therapy of carcinoma in situ with alternating mitomycin C and BCG is more effective than mitomycin C alone. Compared to BCG monotherapy only few side effects occur.

Asunto(s)

Adyuvantes Inmunológicos/administración & dosificación , Antibióticos Antineoplásicos/administración & dosificación , Vacuna BCG/administración & dosificación , Carcinoma in Situ/terapia , Mitomicina/administración & dosificación , Neoplasias de la Vejiga Urinaria/terapia , Administración Intravesical , Anciano , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos

RESUMEN

The activity of lymphokine (interleukin-2) activated killer (LAK) cells from 9 patients with transitional cell carcinoma (TCC) was tested against autologous, freshly purified transitional carcinoma cells. Cytotoxicity was relatively low. Bacillus Calmette-Guérin (BCG) substantially augmented both LAK activity and the cytolytic activity of non-stimulated peripheral blood mononuclear cells (PBMC) against autologous TCC when tested with 6 additional TCC patients. A similar enhancing effect of BCG was noted with leucocytes obtained from normal donors when tested against an allogenic T24 cell line. Both natural killer (NK) cells and T cells appeared to be responsible for the increased cytolytic activity caused by BCG. No cytolytic activity was noted against normal transitional epithelial cells. Sensitisation of TCC cells to the immune system may explain the clinical effects of BCG.

Asunto(s)

Antígenos Bacterianos/inmunología , Carcinoma de Células Transicionales/inmunología , Citotoxicidad Inmunológica/inmunología , Mycobacterium bovis/inmunología , Neoplasias de la Vejiga Urinaria/inmunología , Relación Dosis-Respuesta Inmunológica , Humanos , Células Asesinas Activadas por Linfocinas/inmunología , Leucocitos Mononucleares/inmunología , Complejo Mayor de Histocompatibilidad/inmunología , Células Tumorales Cultivadas

RESUMEN

The cytostatic activity of five Bacillus Calmette-Guérin (BCG) strains (Pasteur, Evans, Tice, RIVM and Connaught) on human transitional cell cancer T24 cells was examined. A striking effect was noted even in 2-day cultures, and the effect was more pronounced when the cells were incubated for 5 days with different BCG strains alone. The concentrations needed were about the same as those used in clinical practice (10(9) colony-forming units of Pasteur strain in 100 ml buffered saline solution). Combination with mitomycin C or interferon-alpha-2b potentiated the cytostatic effect. A slight difference in cytostatic activity between different BCG strains was found.

Asunto(s)

Vacuna BCG/uso terapéutico , Carcinoma de Células Transicionales/terapia , Neoplasias de la Vejiga Urinaria/terapia , Vacuna BCG/administración & dosificación , Carcinoma de Células Transicionales/tratamiento farmacológico , Terapia Combinada , Humanos , Interferón-alfa/administración & dosificación , Mitomicina/administración & dosificación , Especificidad de la Especie , Células Tumorales Cultivadas/efectos de los fármacos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico

RESUMEN

There is still much controversy about the diagnostics and therapy of carcinoma in situ (TIS/CIS) of the bladder. Reliance on cytological possibilities in the primary diagnosis and grading varies in separate centres. Hence, the small series published hitherto are often incomparable due to different start points and end points of trials. We regard cytology as the key examination in TIS. Complete response (CR) and progressive disease (PD) are end points which can be defined by histology/cytology and the timer factor. Our philosophy concerning the evaluation of therapy-principles in superficial bladder cancer is mainly based on our own experience. The efficacy of MMC and of BCG was equally modest in the Finnbladder I study: the CRs 38% and 40%; the PDs 8% and 20%, respectively. The interim of the ongoing Finnbladder II study are more promising after 6 months follow-up: the CR with MMC 67% and with alternating therapy with MMC and BCG 80%; there were no progressions so far. The primary grade of TIS has been a significant prognostic factor for instillation therapy in our earlier series of 62 pts since 1976. There were no progressions of grade I but 19% of grade II and 13% of grade III. A wide consensus of concepts dominates as to the superficial bladder cancer (Ta-T1). The recurrence rate (RR) and the recurrence index (RI/m) as the end points of prophylactic trials are capable of indicating the recurrence-preventive efficacy of different instillations, allow the use of a patient as his own control, and are suitable for statistical evaluation (table I).(ABSTRACT TRUNCATED AT 250 WORDS)

Asunto(s)

Antineoplásicos/uso terapéutico , Vacuna BCG/uso terapéutico , Carcinoma in Situ/terapia , Carcinoma Papilar/terapia , Mitomicinas/uso terapéutico , Neoplasias de la Vejiga Urinaria/terapia , Administración Intravesical , Antineoplásicos/administración & dosificación , Carcinoma in Situ/tratamiento farmacológico , Carcinoma in Situ/patología , Carcinoma Papilar/tratamiento farmacológico , Carcinoma Papilar/patología , Terapia Combinada , Femenino , Humanos , Masculino , Mitomicina , Mitomicinas/administración & dosificación , Recurrencia Local de Neoplasia , Inducción de Remisión , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología