Bladder Cancer at the time of COVID-19 Outbreak

ABSTRACT The COVID-19 outbreak has led to the deferral of a great number of surgeries in an attempt to reduce transmission of infection, free up hospital beds, intensive care and anaesthetists, and limit aerosol-generating procedures. Guidelines and suggestions have been provided to categorize Urological diseases into risk groups and recommendations are available on procedures that can be or cannot be deferred. We aim to summarise updates on diagnosis, treatment and follow up of bladder cancer during the COVID-19 outbreaks.

Generation of potent cytotoxic T lymphocytes against in male patients with non-muscle invasive bladder cancer by dendritic cells loaded with dying T24 bladder cancer cells

ABSTRACT Background In order to induce a potent cytotoxic T lymphocyte (CTL) response in dendritic cell (DC)-based immunotherapy for bladder cancer, various tumor antigens can be loaded onto DCs. Objective The aim of this study was to establish a method of immunotherapy for male patients with non-muscle invasive bladder cancer (NMIBC), using bladder cancer-specific CTLs generated in vitro by DCs. Materials and Methods Monocyte-derived DCs from bladder cancer patients were induced to mature in a standard cytokine cocktail (IL-1β, TNF-α, IL-6, and PGE2: standard DCs, sDCs) or anα-type 1-polarized DC (αDC1) cocktail (IL-1β, TNF-α, IFN-α, IFN-γ, and polyinosinic:polycytidylic acid) and loaded with the UVB-irradiated bladder cancer cell line, T24. Antigen-loaded αDC1s were evaluated by morphological and functional assays, and the bladder cancer-specific CTL response was analyzed by cytotoxic assay. Results The αDC1s significantly increased the expression of several molecules pertaining to DC maturation, regardless of whether or not the αDC1s were loaded with tumor antigens, relative to sDCs. The αDC1s demonstrated increased production of interleukin-12 both during maturation and after subsequent stimulation with CD40L that was not significantly affected by loading with tumor antigens as compared to that of sDCs. Bladder cancer-specific CTLs targeting autologous bladder cancer cells were successfully induced by αDC1s loaded with dying T24 cells. Conclusion Autologous αDC1s loaded with an allogeneic bladder cancer cell line resulted in increased bladder cancer-specific CTL responses as compared to that with sDCs, and therefore, may provide a novel source of DC-based vaccines that canbe used in immunotherapy for male patients with NMIBC.

Potential therapeutic strategies for non - muscle invasive bladder cancer based on association of intravesical immunotherapy with P-MAPA and systemic administration of cisplatin and doxorubicin

ABSTRACT The present study describes the histopathological and molecular effects of P-MAPA (Protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride) intravesical immunotherapy combined with systemic doxorubicin or cisplatin for treatment of non-muscle invasive bladder cancer (NMIBC) in an appropriate animal model. Our results showed an undifferentiated tumor, characterizing a tumor invading mucosa or submucosa of the bladder wall (pT1) and papillary carcinoma in situ (pTa) in the Cancer group. The histopathological changes were similar between the combined treatment with intravesical P-MAPA plus systemic Cisplatin and P-MAPA immunotherapy alone, showing decrease of urothelial neoplastic lesions progression and histopathological recovery in 80% of the animals. The animals treated systemically with cisplatin or doxorubicin singly, showed 100% of malignant lesions in the urinary bladder. Furthemore, the combined treatment with P-MAPA and Doxorubicin showed no decrease of urothelial neoplastic lesions progression and histopathological recovery. Furthermore, Akt, PI3K, NF-kB and VEGF protein levels were significantly lower in intravesical P-MAPA plus systemic cisplatin and in intravesical P-MAPA alone treatments than other groups. In contrast, PTEN protein levels were significantly higher in intravesical P-MAPA plus systemic cisplatin and in intravesical P-MAPA alone treatments. Thus, it could be concluded that combination of intravesical P-MAPA immunotherapy and systemic cisplatin in the NMIBC animal model was effective, well tolerated and showed no apparent signs of antagonism between the drugs. In addition, intravesical P-MAPA immunotherapy may be considered as a valuable option for treatment of BCG unresponsive patients that unmet the criteria for early cystectomy.

Paradox of life among survivors of bladder cancer and treatments / Paradoja de la vida entre supervivientes del cáncer de vejiga y tratamientos / Paradoxo da vida entre sobreviventes do câncer de bexiga e tratamentos

Abstract OBJECTIVE: To interpret the meanings attributed to the experience of bladder cancer among survivors in therapeutic follow-up. METHOD: Qualitative methodological approach, based on medical anthropology and narrative methodology. After approval by the research ethics committee of a public university hospital, data were collected from January 2014 to February 2015, by means of recorded semi-structured interviews, direct observation and field journal entries on daily immersion with a group of six men and six women, aged between 57 and 82 years, in therapeutic follow-up. Narratives were analyzed by means of inductive thematic analysis. RESULTS: The meanings revealed difficulties with the processes of disease and treatment, such as breakdown of normal life, uncertainty about the future due to possible recurrence of the disease, difficulty with continuity of care and emotional control, relating it to conflicting ways of understanding the present life. Thus, the meaning of this narrative synthesis is paradox. CONCLUSION: Interpretation of the meaning of experience with bladder cancer among patients provides nurses with a comprehensive view of care, which encompasses biological, psychological and social dimensions, and thereby systematizes humanized care.

Resumen OBJETIVO: Interpretar el significado atribuido a la experiencia del cáncer de vejiga entre supervivientes en seguimiento terapéutico. MÉTODO: Se empleó el abordaje metodológico cualitativo, fundado en la antropología médica y el método narrativo. Después de la aprobación del Comité de Ética, los datos fueron recogidos de enero de 2014 a febrero de 2015, por medio de entrevistas semiestructuradas grabadas, observación directa y registros en el diario de inmersión con grupo de seis hombres y seis mujeres, entre 57 y 82 años, en seguimiento terapéutico en un hospital público universitario. Las narrativas fueron analizadas mediante el análisis temático inductivo. RESULTADOS: Los sentidos desvelan las dificultades con el progreso de la enfermedad y del tratamiento, como rupturas en la vida futura incierta por la posibilidad de recidiva de la enfermedad, continuidad del tratamiento y control emocional, relacionándose con las ponderaciones contradictorias de la vida actual. Así, el significado de esta síntesis narrativa es de paradoja. CONCLUSIÓN: La interpretación del significado de la experiencia con cáncer de vejiga entre los enfermos le permite al enfermero una mirada integrada del cuidado que supere las dimensiones biopsicosociales de los enfermos y, con eso, sistematice la asistencia de manera humanizada.

Resumo OBJETIVO: Interpretar o significado atribuído à experiência do câncer de bexiga entre sobreviventes em seguimento terapêutico. MÉTODO: Empregou-se a abordagem metodológica qualitativa, embasado pela antropologia médica e método narrativo. Após aprovação do Comitê de Ética, os dados foram coletados de janeiro 2014 a fevereiro de 2015, por meio de entrevistas semiestruturadas gravadas, observação direta e registros no diário de imersão com grupo de seis homens e seis mulheres, entre 57 e 82 anos, em seguimento terapêutico em um hospital público universitário. As narrativas foram analisadas por meio da análise temática indutiva. RESULTADOS: Os sentidos revelam as dificuldades com o processo da doença e do tratamento, como rupturas na vida, futuro incerto pela possibilidade de recidiva da doença, continuidade do tratamento e controle emocional, relacionando-se com as ponderações contraditórias da vida atual. Assim, o significado desta síntese narrativa é de paradoxo. CONCLUSÃO: A interpretação do significado da experiência com câncer de bexiga entre os adoecidos permite ao enfermeiro um olhar integralizado do cuidado que perpasse as dimensões biopsicossociais dos adoecidos e, com isso, sistematize a assistência de maneira humanizada.

Are we following the guidelines on non-muscle invasive bladder cancer?

ABSTRACT Objectives To evaluate the clinical practice of non-muscle invasive bladder cancer (NMIBC) treatment in Brazil in relation to international guidelines: Sociedade Brasileira de Urologia (SBU), European Association of Urology (EAU) and American Urological Association (AUA). Materials and Methods Cross-sectional study using questionnaires about urological practice on treatment of NMIBC during the 32nd Brazilian Congress of Urology. A total of 650 question forms were answered. Results There were 73% of complete answers (total of 476 question forms). In total, 246 urologists (51.68%) lived in the southeast region and 310 (65.13%) treat 1 to 3 cases of NMIBC per month. Low risk cancer: Only 35 urologists (7.5%) apply the single intravesical dose of immediate chemotherapy with Mitomicin C recommended by the above guidelines. Adjuvant therapy with BCG 2 to 4 weeks after TUR is used by 167 participants (35.1%) and 271 urologists (56.9%) use only TUR. High risk tumors: 397 urologists (83.4%) use adjuvant therapy, 375 (78.8%) use BCG 2 to 4 weeks after TUR, of which 306 (64.3%) referred the use for at least one year. Intravesical chemotherapy with Mitomicin C (a controversial recommendation) was used by 22 urologists (4.6%). BCG dose raised a lot of discrepancies. Induction doses of 40, 80 and 120mg were referred by 105 (22%), 193 (40.4%) and 54 (11.3%) respectively. Maintenance doses of 40, 80 and 120mg were referred by 190 (48.7%), 144 (37.0%) and 32 (8.2%) urologists, respectively. Schemes of administration were also varied and the one cited by SWOG protocol was the most used: 142 (29.8%). Conclusion SBU, EAU and AUA guidelines are partially respected by Brazilian urologists, particularly in low risk tumors. In high risk tumors, concordance rates are comparable to international data. Further studies are necessary to fully understand the reasons of such disagreement.

Cancer de la vessie : aspects épidémiologiques, diagnostiques et thérapeutiques au service d'OncoHématologie de l'Hôpital National de Niamey : à propos de 159 cas colligés de 2007 à 2014

Titre : CANCER DE LA VESSIE : aspects épidémiologiques, diagnostiques et thérapeutiques au service d'Onco-Hématologie de l'Hôpital National de Niamey. A propos de 159 cas colligés de 2007 à 2014. Objectifs : Objectif Général :  Contribuer à l'amélioration la prise en charge du cancer de la vessie. PATIENTS ET METHODES : Il s'agit d'une étude rétrospective sur huit (8) ans, réalisé du 1er Janvier 2007 au 31 Décembre 2014. L'étude a inclus les patients des deux sexes, tout âge confondu qui ont été pris en charge pour cancer vésical avec ou sans confirmation histologique au service d'OncoHématologie de l'HNN. RESULTATS : Au terme de notre étude, nous avons colligé 159 cas de tumeurs de la vessie. L'âge moyen est de 41 ans avec des extrêmes de 11 et 71 ans. La majorité des patients était des cultivateurs (38,36%) et des ménagères (27%) et proviennent de la région de Tillabéry (33,96%). Le sexe masculin était prédominant (69,20%) et sex ratio de 2,24. L'hématurie est le signe clinique le plus fréquent avec 69,18%. L'échographie abdomino-pelvienne a été réalisée chez 73,58% des patients, la radiographie pulmonaire dans 67,92% des cas, cystoscopie dans 59,75%, cytologie urinaire dans 9,43%, examen histologique dans 8,18% des cas et le carcinome épidermoïde retrouvé dans 77,77% des cas. La chimiothérapie a constitué le principal traitement dans 58,49% des cas et la chirurgie 5,66% des cas. Conclusion : Le cancer de la vessie est fréquent à l'HNN. Malgré les moyens d'explorations relativement limités, les patients bénéficient d'une prise en charge multi-disciplinaire. Le retard de consultation constitue un frein pour cette prise en charge et dans la majorité des cas la tumeur est diagnostiquée à un stade très avancé de maladie d'où un fort taux de décès est enregistré

Recurrencia y progresión del carcinoma transicional de alto grado superficial de vejiga tratado con Bacilo de Calmette-Guerín (BCG) en lesiones únicas o múltiples / Recurrence and progression of transitional cell carcinoma of high - grade surface treated with bacillus Calmette - Guerin (BCG) in single or multiple lesions

Introducción: El carcinoma transicional de vejiga ocupa el segundo lugar en frecuencia, detrás del adenocarcinoma de la próstata, dentro de los tumores malignos del tracto genitourinario. Entre el 75-85% de los pacientes afectos de carcinoma vesical se presentan en formas confinadas a la mucosa o a la submucosa. Son los considerados carcinomas superficiales de vejiga y se estima que entre el 10-20% de ellos su evolución es hacia formas clínicas invasoras músculo-infiltrantes y un 50-70% evolucionaránhacia la recurrencia de la enfermedad. Objetivo: Evaluar la incidencia de la recurrencia y progresión en pacientes con Carcinoma en estadio T1 tratados con BCG, teniendo en cuenta la uni o multifocalidad de las lesiones vesicales al diagnóstico. Materiales y métodos: Criterios de inclusión: Paciente con diagnóstico de carcinoma transicional de vejiga de alto grado superficial de Febrero del 2010 a Agosto del 2014, con un seguimiento de al menos 12 meses. Tratados conBCG endocavitario. Los criterios de exclusión fueron; controles cistoscópicos irregulares, ciclos incompletos de BCG y seguimiento menor a 12 meses. Resultados: 81 HC; Grupo “A” con lesión única, 54 pacientes (66.7%) y Grupo “B” con dos o más lesiones, 27 pacientes (33.3%). Grupo “A” 50 % de recurrencia, 16,6 % de progresión y 33,4 % libres de enfermedad. Grupo “B” 66,6 % de recurrencia, 18,6 % de progresión y 14,8 % libres de enfermedad Conclusión: La inmunoterapia intravesical con BCG después de la resección transuretral completa de una lesión por un carcinoma transicional de vejiga de alto grado superficial, se considera un tratamiento con resultados aceptables.

Introduction: The transitional bladder cell carcinoma is the secondone in frequency after the adenocarcinoma of prostate, withinmalignant tumors of the genitourinary tract. Between 75-85% ofpatients with bladder carcinoma are presented in ways confined tothe mucous membrane or submucous. These are consideredsuperficial bladder carcinomas and it is estimated that between 10-20% of them evolution is toward muscle-invasive clinical forms andevolve towards 50-70% recurrence of the disease.Objectives: To evaluate the incidence of recurrence andprogression in patients with carcinoma stage T1 treated with(BCG), taking into account the uni or multifocal lesions of bladderdiagnosis.Material and methods: Inclusion criteria: Patient diagnosed withtransitional bladder cell carcinoma of high-grade surface fromFebruary 2010 to August 2014, with a follow up of at least 12months treated with endocavity BCG. Exclusion criteria were;irregular cystoscopic controls, incomplete cycles of BCG and lowertrack of 12 months.Results: HC 81 was obtained; Group "A" with single lesion, 54patients (66.7%) and Group "B" with two or more lesions, 27patients (33.3%). Group "A": 50% of recurrence, 16.6% of disease progression and 33.4% of free disease. Group "B": 66.6% of recurrence, 18.6% of disease progression and 14.8% of freedisease Conclusion: Intravesical immunotherapy with BCG after completetransurethral resection of a lesion, by a transitional bladdercarcinoma of grade high surface, is considered a treatment with acceptable results.

Targeting PPM1D by lentivirus-mediated RNA interference inhibits the tumorigenicity of bladder cancer cells

Protein phosphatase magnesium/manganese-dependent 1D (PPM1D) is a p53-induced phosphatase that functions as a negative regulator of stress response pathways and has oncogenic properties. However, the functional role of PPM1D in bladder cancer (BC) remains largely unknown. In the present study, lentivirus vectors carrying small hairpin RNA (shRNA) targeting PPM1D were used to explore the effects of PPM1D knockdown on BC cell proliferation and tumorigenesis. shRNA-mediated knockdown of PPM1D significantly inhibited cell growth and colony forming ability in the BC cell lines 5637 and T24. Flow cytometric analysis showed that PPM1D silencing increased the proportion of cells in the G0/G1 phase. Downregulation of PPM1D also inhibited 5637 cell tumorigenicity in nude mice. The results of the present study suggest that PPM1D plays a potentially important role in BC tumorigenicity, and lentivirus-mediated delivery of shRNA against PPM1D might be a promising therapeutic strategy for the treatment of BC.

Cistectomia com reconstrução de neobexiga ortotópica ileal para tratamento de bexiga contraída após aplicação de bacilo de Calmette-Guérin intravesical / Cystectomy with orthotopic ileal neobladder reconstruction for treatment of bladder contracture after intravesical bacillus Calmette-Guerin therapy

O câncer de bexiga é um importante problema de saúde mundial, tanto pelas elevadas taxas de prevalência, quanto pelos custos relacionados ao tratamento. Desde a introdução da imunoterapia intravesical adjuvante com bacilo Calmette-Guérin, vem sendo observada diminuição na taxa de recorrência. As principais complicações são de pequeno porte e simples resolução a partir de medidas locais e orientações. A bexiga contraída, uma complicação local rara e grave, mas incapacitante em alguns casos, é observada principalmente em doentes com um programa de manutenção. Relatamos aqui o caso de um paciente masculino submetido a ressecção transuretral da bexiga por um carcinoma urotelial T1 de alto grau, que desenvolveu tal complicação durante tratamento com bacilo Calmette-Guérin, sendo portanto submetido à cistoprostatectomia com realização de neobexiga ortotópica ileal.

Bladder cancer is an important health problem worldwide due to high prevalence rates and costs related to treatment. A reduction in recurrence rates has been observed since the introduction of adjuvant intravesical immunotherapy with bacillus Calmette-Guerin. There are mild complications that are easily solved by local measures and orientations. Bladder contracture, a rare and severe local complication, in some cases leading to disability, is observed primarily in patients in a maintenance program. In this article we reported the case of a male patient who underwent transurethral resection of the bladder because of a high-grade T1 urothelial carcinoma and developed this complication during treatment with bacillus Calmette-Guerin. For this reason he was submitted to cystoprostatectomy with orthotopic ileal neobladder reconstruction.

Polymorphism at P21 codon 31 and dinucleotide polymorphism of P73 gene and susceptibility to bladder cancer in individuals from North India.

BACKGROUND AND AIM: p73, a novel P53 homolog and plays an important role in modulating cell cycle control, apoptosis and cell growth while P21, functions to negatively control the cell cycle. P53 up regulates p21 expression in response to deoxyribonucleic acid damage leading to cell cycle arrest at G1 checkpoint. In the present study, we are targeting p21 codon 31 and p73 gene variants of G4C14‑to‑A4T14 (Exon 2) polymorphism for bladder cancer (BC) risk in North Indians. MATERIALS AND METHODS: The above gene variants of P21 and P73 were assessed in the case‑control study comprising of 200 BC cases and 200 healthy controls of the same age, gender and similar ethnicity. Genotyping was performed by polymerase chain reaction (PCR) restriction fragment length polymorphism method and PCR‑based confronting two‑pair primers (PCR with CTPP). RESULTS: The variant genotype of p73Exon 2 polymorphism showed significant risk for BC (p = 0.014). While combining with heterozygous genotype, variant genotype of p73Exon2 showed a significant association with BC risk (p = 0.010). While in case of p21 codon31 showed no significant association for BC risk at genotypic level. Significant association between p73Exon2 polymorphism and smoking was observed for BC risk. Furthermore, gene combination analysis revealed that AT/AT‑Ser/Ser is associated with risk for BC. Variant genotype of P73Exon2 was associated with reduced risk of recurrence (p = 0.039) in superficial BC patients receiving Bacillus Calmette‑Guerin treatment thus showing least survival (log rank = 0.029). CONCLUSION: Our study provided evidence that the p73 G4C14 > A4T14 (Exon2) polymorphisms were associated with higher risk of BC in North Indian population.

Superficial bladder tumours: recurrence and progression

To determine various presentations of superficial bladder cancer, its management, recurrence and progression rates. Case series. Department of Urology, Jinnah Postgraduate Medical Centre, Karachi, From January 2002 to December 2009. Patients with pathologically proven superficial transitional cell carcinoma [TCC] with minimal 2 years of follow-up were included. Their clinical presentations and management was recorded. Complete transurethral resection of bladder tumour [TURBT] was attempted in all patients. Tumour grading and staging was performed. Intra-vesical single instillation of mityomycin-C was given postoperatively in selected patients. Cystoscopic surveillance was used to assess recurrence in all patients according to standard protocol. Metastatic work-up and biopsy record of follow-up TURBT was used to document progression in high risk patients. Results were described as simple descriptive statistics. A total of 92 patients were studied. The median age of patient was 62 years, with male preponderance [88%]. Hematuria with lower urinary tract symptoms [LUTS] was most common presentation [47.8%], followed by hematruia alone [25.7%], LUTS alone [9.2%] and upper tract symptom in 1.8% of patients. Complete TURBT in first attempt was possible in 72 patients [78.3%]. Multiple tumours were seen in 34 patients [39.6%]. Intravesical mitomycin was given in 70% patients. Over-all recurrence rate of 68.4% was noted. Patients with TaG2-3 showed recurrence rate of 58.8% which occurred late with good recurrence free interval. T1G2-3 patients have more and early recurrences [80.4%]. Progression seen in 13 patients [14%], 6 patients have up-grading, four showed stage progression, one developed pelvic lymphadenopathy and another one had bone metastasis. One female patient [TaG2] developed right renal pelvic recurrence and progression while her bladder disease was well controlled. The number of patients with T1 disease was 45% in this study which is comparatively higher than other studies. Early recurrences and progression were observed with T1G2-3, while late recurrence were seen with Ta disease, having tumour free interval between 6 months to 2 years. Early radical cystectomy was advised to T1G3 disease and with multiple recurrences, but patient's compliance was poor

Mycobacterial Infection after Intravesical Bacillus Calmette-Guerin Treatment for Bladder Cancer: A Case Report / 대한진단검사의학회지

Bacillus Calmette-Guerin (BCG) has been traditionally used as a vaccine against tuberculosis. Further, intravesical administration of BCG has been shown to be effective in treating bladder cancer. Although BCG contains a live attenuated strain of Mycobacterium bovis, complications such as M. bovis BCG infection caused by BCG administration are extremely rare. Here, we report a case of BCG infection occurring after intravesical BCG therapy. A 67-yr-old man presented with azotemia and weight loss. He had been diagnosed with bladder cancer 4 yr back, and had undergone transurethral resection of the bladder tumor and intravesical BCG (Tice strain) therapy at that time. An acid-fast bacterial strain was isolated from his urine sample. We did not detect Mycobacterium tuberculosis protein 64 (MPT-64) antigen in the isolates obtained from his sample, and multiplex PCR and PCR-reverse blot hybridization assay indicated that the isolate was a member of the M. tuberculosis complex, but was not M. tuberculosis. Finally, sequence analysis of 16S ribosomal RNA and DNA gyrase, subunit B (gyrB) suggested that the organism was M. bovis or M. bovis BCG. Although we could not confirm that M. bovis BCG was the causative agent, the results of the 3 molecular methods and the MPT-64 antigen assay suggest this finding. This is an important finding, especially because M. bovis BCG cannot be identified using common commercial molecular genetics tools.

Intravesical therapy for urothelial carcinoma of the urinary bladder: a critical review

The management of non-muscle-invasive urothelial carcinoma of the bladder (UCB) is a challenge for physicians and patients alike. This is largely due to the heterogeneous natural history of this disease, in which tumors range from indolent to rapidly progressive and eventually fatal. Moreover, the high rate of recurrence and progression cause significant morbidity, expense, and detriment to quality of life. The advent of effective and safe intravesical therapies has improved the management of non-muscle-invasive UCB. Nevertheless, despite over 30 years of research and clinical experience, the mechanism, risks, benefits, and optimal regimens and treatment algorithms remain unclear. Although immunotherapy with bacillus Calmette-Guerin (BCG) has been the mainstay of intravesical treatment and represents a significant advance in the interaction of immunology and oncology, its clinical effectiveness is accompanied by a wide range of adverse events. Here, we review the literature on intravesical immunotherapy and chemotherapy with the aim of evaluating the clinical utility of the different treatments and providing recommendations. Many studies over the years have compared efficacy and toxicities of different agents and regimens, and certain conclusions are now well supported by high-level evidence. Future perspectives and promising advances in drug development are discussed and areas of improvement are identified in order to promote better cancer control and decrease the rate and severity of side-effects.

Determinan el pronóstico y la influencia de la terapia endovesical en la recurrencia del cáncer vesical / Predictive factors and influence of intravesical therapy for recurrence of non-muscle invasive bladder cancer

Introducción: Evaluamos, en cuanto a recurrencia, los factores pronósticos en el cáncer vesical no infiltrante de músculo y el efecto de la terapia intravesical. Material y métodos: Estudiamos 419 neoplasias vesicales. Realizamos análisis univariados y multivariados sobre 24 variables de estas neoplasias y valoramos distintos tratamientos. Resultados: Existieron diferencias significativas en el tiempo libre hasta la recurrencia, que fue menor en los tumores que recurrieron en menos de 12 meses, en los tumores múltiples (3 o más tumores) y de cúpula; además existieron diferencias estadísticamente significativas cuando se estudiaron dos grupos homogéneos de cirujanos.El empleo de instilaciones vesicales incrementó de forma independiente el tiempo hasta la recidiva. Se demostró que la recurrencia se produjo significativamente más tarde cuando se habían empleado dosis altas de BCG y terapia de mantenimiento. Conclusiones: Los siguientes factores resultaron independientes para explicar menor tiempo libre hasta la recurrencia superficial: recidiva en el primer año, multiplicidad, técnica quirúrgica, no empleo de lavados intravesicales, tratamiento con dosis bajas de BCG y terapia de inducción frente a mantenimiento. El empleo de instilaciones vesicales, con dosis altas de BCG y terapia de mantenimiento, incrementó de forma independiente el tiempo hasta la recidiva.