Muscle-invasive Progression Research Articles

Surveillance for Nonmuscle Invasive Bladder Cancer: Identifying the Point of Diminishing Returns

To characterize first and second recurrence patterns using 26years of cohort-level follow-up and microsimulation modeling. Patients diagnosed with nonmuscle-invasive bladder cancer in Stockholm County between 1995 and 1996 were included. Clinical, pathological, and longitudinal follow-up data were gathered. Logistic regressions, Kaplan Meier curves, and Cox proportional hazards models were run to generate assumptions for a microsimulation model, simulating first and second recurrence and progression for 10,000 patients. Three hundred eighty-six patients were included: 67.4% were male; >50% were TaLG; and 37.5% were American Urological Association high-risk. Median time to recurrence was 300days. Three patients had missing data. Cohort follow-up has been carried out for 26years. For simulated first-recurrences, low-risk patients recurred at 56.6% over 15years of follow-up, with 2.2% muscle-invasive (MI) progression; intermediate-risk patients recurred at 62.8%, with 4.3% MI progression; high-risk patients recurred at 48.7% over 15years, with MI progression at 14.3%. For second recurrences, 70.7%, 75.7%, and 84.7% of low, medium, and high-risk patients recurred. No patients were seen to have first recurrences after 9years, with low, but notable, rates beyond 5years. These data suggest that low-, intermediate-, and high-risk patients without recurrence at 5years may be potentially transitioned to less invasive monitoring.

Somatic Features of Response and Relapse in Non–muscle-invasive Bladder Cancer Treated with Bacillus Calmette-Guérin Immunotherapy

BackgroundHigh-risk non–muscle-invasive bladder cancer (NMIBC) is treated with bacillus Calmette-Guérin (BCG), but relapse is common. Improvement of patient outcomes requires better understanding of links between BCG resistance and genomic driver alterations. ObjectiveTo validate the prognostic impact of common genomic alterations in NMIBC pretreatment and define somatic changes present in post-BCG relapses. Design, setting, and participantsWe retrieved tumour tissues and outcomes for 90 patients with BCG-naive NMIBC initiating BCG monotherapy. Post-BCG tissue was available from 34 patients. All tissues underwent targeted sequencing of tumour and matched normal. Outcome measurements and statistical analysisAssociations between clinical outcomes and genomics were determined using Cox proportional hazard models. Results and limitationsOf the patients, 58% were relapse free at data cut-off, 24% had NMIBC recurrence, and 18% experienced muscle-invasive progression. The risk of relapse was associated with ARID1A mutation (hazard ratio [HR] = 2.00; p = 0.04) and CCNE1 amplification (HR = 2.61; p = 0.02). Pre- and post-BCG tumours shared truncal driver alterations, with mutations in TERT and chromatin remodelling genes particularly conserved. However, shifts in somatic profiles were common and clinically relevant alterations in FGFR3, PIK3CA, TSC1, and TP53 were temporally variable, despite apparent clonal prevalence at one time point. Limitations include the difficulty of resolving the relative impact of BCG therapy versus surgery on genomics at relapse and biopsy bias. ConclusionsSomatic hypermutation and alterations in CCNE1 and ARID1A should be incorporated into future models predicting NMIBC BCG outcomes. Changes in tumour genomics over time highlight the importance of recent biopsy when considering targeted therapies, and suggest that relapse after BCG is due to persisting and evolving precursor populations. Patient summaryChanges in key cancer genes can predict bladder cancer relapse after treatment with bacillus Calmette-Guérin. Relapses after treatment can be driven by large-scale genetic changes within the cancer. These genetic changes help us understand how superficial bladder cancer can progress to be treatment resistant.

MP73-08 INTRAVESICAL GEMCITABINE AND DOCETAXOL IN HEAVILY PRE-TREATED PATIENTS WITH NON-MUSCLE INVASIVE BLADDER CANCER (NMIBC)

You have accessJournal of UrologyBladder Cancer: Non-invasive IV (MP73)1 Apr 2020MP73-08 INTRAVESICAL GEMCITABINE AND DOCETAXOL IN HEAVILY PRE-TREATED PATIENTS WITH NON-MUSCLE INVASIVE BLADDER CANCER (NMIBC) Adele Caruso*, Roshan Ravishankar, Keith VanArsdalen, and Stanley Malkowicz Adele Caruso*Adele Caruso* More articles by this author , Roshan RavishankarRoshan Ravishankar More articles by this author , Keith VanArsdalenKeith VanArsdalen More articles by this author , and Stanley MalkowiczStanley Malkowicz More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000959.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Therapeutic options are limited for BCG resistant/ refractory NMIBC patients who are unfit or refuse radical cystectomy. Combination chemotherapy is not regularly used due to additive toxicity. The non-desiccant properties of Gemcitabine allow for combined therapy not previously employed. Docetaxol as a single agent demonstrates significant activity with acceptable toxicity. The objective of this study was to evaluate combination intravesical chemotherapy for its initial response and therapeutic durability in those patients heavily pre-treated with BCG. METHODS: Patients who had failed or were intolerant to BCG therapy were offered combination intravesical therapy per the following regimen 1000 mg of GEM in 100 cc’s of saline instilled for two hours followed by bladder emptying and reinstallation of 37.5 mg DOC in 50 mls saline. This was done weekly for 6 weeks. At twelve weeks patients underwent cystoscopy with full bladder mapping and cytology. Cystoscopy was performed every 3 months for one year and at 3 months or 6 months thereafter. Further biopsiy or resection was performed for positive cytology, distinct recurrent tumor or suspicious areas on cystoscopy. Failure was defined as positive cytology, tumor recurrence or distant failure. RESULTS: Between 12/2015 and 6/2019, thirty patients were recruited. 26 are eligible for evaluation and had a mean of 3.2 prior induction courses of intravesical therapy. There were 20 men and 6 women with a mean age of 77 (range 68-94). Twenty four of 26 patients demonstrated an initial negative evaluation. 16/26 patients recurred during this time period with a mean disease free interval of 12.45 months (range 3-34 months). Ten patients are NED for a mean of 9.6 months (range 3-15 months) 11 failures were local (2 muscle invasive progression), 4 cytology only, 1 pelvic lymph node progression. The regimen was well tolerated per patient complaints and AUA voiding scores. CONCLUSIONS: Sequential, combination Gemcitabine and Docetaxol intravesical chemotherapy is an active regimen in BCG pretreated patients who are unfit or unwilling to undergo cystectomy. A near universal initial response with a complete response maintained for over one year in responders suggests a role for maintenance therapy and supports continued study of this intravesical regimen. Source of Funding: NONE © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1124-e1124 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Adele Caruso* More articles by this author Roshan Ravishankar More articles by this author Keith VanArsdalen More articles by this author Stanley Malkowicz More articles by this author Expand All Advertisement PDF downloadLoading ...

Low-risk non-muscle-invasive bladder cancer: Further prognostic stratification into the "very-low-risk" group based on tumor size.

To validate the significance of the entity of "very-low-risk" bladder cancer by analyzing the clinical outcomes of low-risk bladder cancer when further stratified by tumor size. We accessed our prospectively maintained, single-institution, electronic bladder cancer registry to extract the clinicopathological data of patients who were diagnosed with primary, solitary, Ta, low-grade tumors that were <3cm. Patients were divided into two prognostic groups based on tumor size (≤1.0cm vs >1.0cm). The survival data of the two groups were compared for recurrence, progression and mortality. A total of 165 patients were followed up for a median period of 79months (interquartile range 47-118months). A total of 45% (75/165) of the study cohort had tumors that were ≤1.0cm. Recurrences were found in 40% (66/165) of the study cohort. On Kaplan-Meier analysis, patients with tumor size ≤1.0cm had significantly longer time to recurrence (P<0.001, log-rank test). Using multivariate Cox modeling, only tumor size >1.0cm was significantly associated with shorter time to recurrence (HR 2.54, 95% CI 1.35-4.77, P=0.004). Tumor size was not significantly associated with any differences in time to overall progression, muscle-invasive progression or overall mortality (P=0.108, P=0.362 and P=0.225, respectively, log-rank test). Low-risk bladder cancer can be further stratified based on tumor size. Larger tumors (>1.0cm) are significantly associated with shorter time to recurrence compared with smaller tumors (≤1.0cm). However, there were no significant differences in the probability of developing disease progression or overall mortality between larger and smaller tumors.

Multiple recurrences and risk of disease progression in patients with primary low-grade (TaG1) non-muscle-invasive bladder cancer and with low and intermediate EORTC-risk score.

AimTo assess the prognostic value of multiple recurrences on the risk of progression in a large cohort of TaG1 bladder cancer of low and intermediate risk based on the EORTC score and to evaluate prognostic factors of multiple recurrences.Materials and methodsWe retrospectively analyzed a French cohort of 470 patients with primary TaG1 bladder cancer diagnosed between 1986 and 2010 and followed until 2012. They were classified at low and intermediate risk using the EORTC risk score. Associations between the number of recurrences and the risk of progression to high grade Ta/T1 bladder cancer and progression to muscle-invasive disease were assessed. The characteristics of recurrences, as occurrence time or localization, and risk of other recurrences were evaluated.ResultsOut of 470 patients, 251 had recurrence, 34 progressed to high grade Ta/T1 and 17 to muscle-invasive disease, including 4 who had non muscle-invasive progression first. The median follow-up was 7.2 years (interquartile range: 4.2–10.9). In half the progressions, no previous recurrence was observed. No association between the number of recurrences and the risk of progression was detected. Even after 5 years free of event, patients had a 15% risk of recurrence. History of two or more recurrences increased by 4.5 the risk of subsequent recurrence. Time between two recurrences inferior to six months and multifocal localization increased the risk of recurrence.ConclusionSurveillance of patients with TaG1 should be continued beyond 5 years of follow-up. However, cystoscopy exams could be spaced after 5 years. Multiple TaG1 recurrences did not appear to be prognostic for disease progression, but increased significantly the risk of subsequent recurrences. Short time between two recurrences and multifocal localization may serve to adapt monitoring of patients with TaG1 Bladder cancer.

Combined Chemohyperthermia: 10-Year Single Center Experience in 160 Patients with Nonmuscle Invasive Bladder Cancer

Nonmuscle invasive bladder cancer is characterized by a high recurrence rate. New adjuvant treatments are needed to decrease this high number ofrecurrences. We present the results of more than 10 years of experience with chemohyperthermia in patients with nonmuscle invasive bladder cancer. Using standardized medical record forms we prospectively collected patient and tumor characteristics of patients treated with chemohyperthermia between 2002 and 2013. Median followup was 75.6 months. Recurrence-free survival was the primary objective. The secondary objective was to observe recurrence-free survival differences in 1) the epirubicin group vs the mitomycin group and 2) the highly recurrent (greater than 2 recurrences in 24 months) nonmuscle invasive bladder cancer group vs the other groups. A total of 160 patients with nonmuscle invasive bladder cancer were included in study, including 20 (13%) treated with epirubicin and 129 (81%) previously treated with bacillus Calmette-Guérin. One and 2-year recurrence-free survival was 60% and 47%, respectively. Muscle invasive progression was seen in 4% of cases. Two-year recurrence-free survival in the epirubicin and mitomycin groups was 55% and 46%, respectively (p = 0.30). The highly recurrent nonmuscle invasive bladder cancer group had significant decreased recurrence-free survival compared to other groups (p <0.01). Patients treated with 2 or fewer vs greater than 2 transurethral bladder tumor resections before chemohyperthermia had higher recurrence-free survival (p = 0.01). On multivariable analysis the highly recurrent cancer criteria remained independently associated with decreased recurrence-free survival (HR 2.40, 95% CI 1.30-4.43, p = 0.01). Chemohyperthermia is an effective approach to nonmuscle invasive bladder cancer for which standard intravesical treatments fail. Patients with highly recurrent disease before chemohyperthermia have lower recurrence-free survival. Furthermore, recurrence-free survival appears to improve with earlier chemohyperthermia. No significant differences were observed between the 2 chemotherapy agents.

1131 EPIGENETIC INACTIVATION OF METHYLATION-CONTROLLED J PROTEIN (MCJ) IN BLADDER CANCER

You have accessJournal of UrologyBladder Cancer: Basic Research (III)1 Apr 20131131 EPIGENETIC INACTIVATION OF METHYLATION-CONTROLLED J PROTEIN (MCJ) IN BLADDER CANCER Noemi Pompas-Veganzones, Virginia Sandonis, Pilar Gonzalez-Peramato, Patricia Moya, Joan Palou, Oscar Rodriguez, Ferran Algaba, Mercedes Rincon, and Marta Sanchez-Carbayo Noemi Pompas-VeganzonesNoemi Pompas-Veganzones Madrid, Spain More articles by this author , Virginia SandonisVirginia Sandonis Madrid, Spain More articles by this author , Pilar Gonzalez-PeramatoPilar Gonzalez-Peramato Madrid, Spain More articles by this author , Patricia MoyaPatricia Moya Madrid, Spain More articles by this author , Joan PalouJoan Palou Barcelona, Spain More articles by this author , Oscar RodriguezOscar Rodriguez Barcelona, Spain More articles by this author , Ferran AlgabaFerran Algaba Barcelona, Spain More articles by this author , Mercedes RinconMercedes Rincon Burlington, Canada More articles by this author , and Marta Sanchez-CarbayoMarta Sanchez-Carbayo Madrid, Spain More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.746AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Methylation-controlled J protein (MCJ) is a member of the DnaJ family of cochaperones. The DNAJ proteins participate in processes such as protein folding and translocation, cell cycle control by DNA tumor viruses, and regulaton of protein kinases. To our knowledge, MCJ has not been evaluated in bladder cancer to date. In this report we aimed at evaluating the potential relevance of MCJ in bladder cancer progression and in the response to Bacille of Calmette-Guerin therapy in high-risk T1 high grade bladder cancer. METHODS The methylation status of MCJ promoter was evaluated by methylation-specific polymerase chain reaction (MS-PCR) analyses in bladder cancer cells (n=14), bladder tumors (n=150), and urinary samples (n=60) of bladder cancer patients and controls. The epigenetic silencing of MCJ by hypermethylation was tested in bladder cancer cells (n=10) before and after azacytidine treatment. MCJ expression patterns were analyzed by immunohistochemistry on tissue arrays containing bladder tumors for which MCJ methylation was assessed. RESULTS MCJ was frequently methylated in bladder cancer cells (86%). MCJ hypermethylation was associated with gene expression, being increased in vitro by azacytidine, a demethylating agent. MCJ was revealed to be frequently methylated in bladder tumors (78%). MCJ methylation was significantly associated with tumor stage (p<0.001) and tumor grade (p<0.05). In a series of patients treated with BCG, the presence of a low MCJ expression alone, or combined with MCJ methylation, were associated with poor BCG response in terms of muscle-invasive progression (p<0.05). Moreover, MCJ methylation in urinary specimens distinguished patients with bladder cancer from controls (p<0.05). CONCLUSIONS MCJ was identified to be epigenetically modified in bladder cancer. MCJ methylation and protein expression patterns associated with cancer progression and clinical outcome and BCG response. Together with its potential to detect bladder cancer patients using urinary specimens suggests further assessment of the utility of MCJ methylation and protein evaluations for the clinical management of patients affected by uroepithelial neoplasias. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e462 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Noemi Pompas-Veganzones Madrid, Spain More articles by this author Virginia Sandonis Madrid, Spain More articles by this author Pilar Gonzalez-Peramato Madrid, Spain More articles by this author Patricia Moya Madrid, Spain More articles by this author Joan Palou Barcelona, Spain More articles by this author Oscar Rodriguez Barcelona, Spain More articles by this author Ferran Algaba Barcelona, Spain More articles by this author Mercedes Rincon Burlington, Canada More articles by this author Marta Sanchez-Carbayo Madrid, Spain More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Non-metastatic Upper Tract Transitional Cell Carcinoma: Single Center Experience

Upper tract transitional cell carcinomas (UTCC) are relatively uncommon but prognosis is generally worse than TCC of bladder. Between March 2004 and June 2012, patients with initial non- metastatic UTCC were assessed in the Medical Oncology and Urology Departments of Ataturk Training and Research Hospital. A total of 11 patients with initially non-metastatic UTCC were detected in the 8 year period, all males. Median age of was 62 (range, 38-74). Six lesions were located in the renal pelvis and 5 in the ureter. Nephroureterectomy was performed in 9 patients, and distal ureterectomy and cuff excision of the bladder in the remaining 2. The majority (n= 9) had high grade tumors. Median primary tumor diameter was 3.5 cm (range, 0.7-10). Five patients (45.5%) were stage I, 2 (18.2%) were stage II, and 4 (36.4%) were stage III. While adjuvant chemotherapy was not applied for stage I and II disease (n= 7), 4 to 6 courses were applied for 3 of the stage III patients. Also one stage III case received adjuvant radiotherapy. Up to 100 months follow-up, median overall survival was 13 months (range, 5-100 months). While stage I and II patients are following-up without muscle-invasive progression, 2 of stage III patients demonstrated progression. We need more collaborative studies to determine management of especially pT3-pT4 patients with UTCC.

Weekly intravesical bacillus Calmette-Guerin (BCG) alternating with epirubicin in Ta and T1 urothelial bladder cancer: An approach to decrease BCG toxicity

Context:Bacillus Calmette-Guerin (BCG) therapy is the standard treatment for nonmuscle-invasive bladder cancer (NMIBC). However, its toxicity is a major concern.Aim:If we reduce the number of BCG doses by half and replace the second half with epirubicin, we may have a lower toxicity while maintaining the same efficacy of BCG. To test this hypothesis, we conducted this study as an update of our previous report.Setting and Design:The study included 607 patients with Ta and T1 NMIBC between January 1994 and December 2008.Materials and Methods:After transurethral resection of bladder tumor (TURBT), the patients received weekly doses of 120 mg BCG alternating with 50 mg epirubicin for six weeks (three weekly doses of each). Maintenance was given. Recurrence, progression rates, and toxicity were assessed. End points were progression, recurrence, and cancer-specific survival.Results:A total of 532 patients were eligible for evaluation (mean age: 58 years; median follow-up: 45 months). Of these, 291 (55%) were free, 157 (29.5%) showed recurrence, and 84 (15.8%) showed muscle-invasive progression. Toxicity developed in 221 patients. These were mild in the majority (167), whereas 10 developed hematuria, 30 severe cystitis, and five systemic complications. The rate of permanent therapy discontinuation was 3.8%.Statistical Analysis Used:SPSS package version 16 and Kaplan-Meier curves were used to evaluate survival.Conclusions:Reducing the frequency of BCG instillations by half and replacing the second half with epirubicin results in a similar efficacy and a lower toxicity compared with historical cases receiving BCG alone. However, further trials are required to support these results.

Abstract 2996: The prognostic value of a cell cycle proliferation gene signature in bladder cancer

Abstract An important aspect of personalized medicine involves the identification of high risk patients likely to benefit from neoadjuvant or adjuvant therapy. In the case of bladder cancer, this entails identifying the 20-30% of patients with non-muscle invasive (NMI) tumors that will progress to muscle-invasive (MI) disease, and the approximately 50% of patients diagnosed with MI tumors who do not survive past 5 years. In breast cancer, independently derived prognostic gene signatures are enriched with cell cycle proliferation (CCP) genes. Recently, a CCP score obtained from the average expression level of 31 genes was found to predict recurrence free and disease specific survival (DSS) in prostate cancer. Here, we assess the importance of CCP correlated genes for prognosis in bladder cancer and the prognostic value of the CCP score in 8 publicly available and heterogeneous microarray datasets (N = 762), with samples obtained from both cystectomy and transurethral resection of the bladder (TURBT) and profiled on 7 microarray platforms. Clusters of correlated and predictive genes for stage, grade, and DSS were identified using an iterative subtractive method. A gene set enrichment analysis on the predictive clusters found that CCP was the only consistently enriched class of genes (P &amp;lt; 0.05) for each clinical variable. We then analyzed the extent in which the performance of predictive gene signatures, composed of the top 10-100 genes in step sizes of 10, depended on genes that correlated with the CCP gene signature. When the gene expression data was adjusted for the 31 CCP genes, the predictive ability of the gene signatures was significantly and negatively impaired in most datasets. We next evaluated the CCP score for its prognostic value. Without optimizing the CCP signature for bladder cancer, we found the CCP score to be significantly higher in MI compared to NMI tumors in 3/4 cystectomy datasets (P &amp;lt; 0.05), with AUC ranging from 0.62 to 0.84, and in 2/4 TURBT datasets (P &amp;lt; 0.05) with AUC ranging from 0.60 to 0.75. CCP score was significantly higher in high grade tumors compared to low grade tumors in 3/4 cystectomy datasets (P &amp;lt; 0.05), with AUC ranging from 0.63 to 0.88, and in all 5 TURBT datasets (P &amp;lt; 0.05), with AUC ranging from 0.76 to 0.91. Most notably, although nodal staging was the most consistent predictor of DSS in cystectomy datasets (P &amp;lt; 0.05), CCP score was the only clinical variable marginally predictive of DSS (P &amp;lt; 0.10) in multiple cystectomy datasets when only preoperative variables were considered. In TURBT datasets, CCP score was the only variable predictive of DSS (P &amp;lt; 0.05) in multiple datasets. Finally, CCP score was predictive of NMI to MI progression in low grade tumors (AUC = 0.73, P = 0.020). Altogether, these results indicate that the prognostic value of gene signatures in bladder cancer depend on genes that correlate with CCP and that optimization of the CCP signature may yield clinically relevant prognostic markers in bladder cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2996. doi:1538-7445.AM2012-2996

Recurrence, Progression, and Follow-Up in Non–Muscle-Invasive Bladder Cancer

Abstract Non–muscle-invasive bladder cancer (NMIBC) is characterized by a high risk of recurrence after transurethral resection of an initial tumor; the 1-yr recurrence rate is 15–61%, and the 5-yr recurrence rate is 31–78%. These figures represent the heterogeneous character of NMIBC. The treatment and follow-up (FU) strategy vary depending on initial and subsequent clinical and histopathological characteristics. Clinical prognostic factors for recurrence and progression are size, multiplicity, reaction to intravesical therapy, grade, stage, and the presence of carcinoma in situ. In addition, recurrence anywhere in the bladder at first FU cystoscopy after transurethral resection is one of the most important prognostic factors for time to progression. The major goals in treating patients with NMIBC are to prevent the high number of recurrences and to prevent muscle-invasive progression. In this review, risks of recurrence and progression are analyzed and discussed in separate sections, including clinical and pathological results, applied treatments, and diagnostics. Finally, means and recommendations for FU are discussed.

Efecto terapéutico de mitomicina c en el postoperatorio inmediato de pacientes con tumores vesicales no músculo invasores de bajo riesgo

AbstractTherapeutic effect of mitomycin c in the immediate postoperatory in patients with low-risk non-muscle-invasive bladder tumours IntroductiónBladder cancer is a disease with a high prevalence due to its recurrence rate. Transurethral resection of the bladder (TURB) is the treatment in initial stages. Nevertheless, a high percentage of non-muscle-invasive tumors treated will have a recurrence 1-2 years afterwards. Adjuvant quemotherapy or immunotherapy after TURB has been administered in order to decrease the rate of recurrence and to prevent progression Patients and methodsA prospectived, controlled and randomized study was performed. We included 100 patients with non-muscle-invasive and bladder tumors the low grade. All patients had initially a TURB performed and were randomized to either receive or not a single dose mitomycin C (MMC) in the immediate postoperatory ResultsAll low grade tumors was less than 3 cm. Mean follow-up was 26,43±7,65 months. MMC was administered in 49 patients, of these, 67,3% had no recurrence and 32,7% had a non-muscle-invasive recurrence. Of the 51 patients in the non mitomycin, 51% had no recurrence while 47% had a non-muscle-invasive recurrence, and 2% had a muscleinvasive progression. We found significantly differences in time to recurrence among the two groups SummaryWe found a greater time to recurrence in the group of single dose adjuvant MMC being this difference statistically significantly when comparing with the other group

Efecto terapéutico de Mitomicina C en el postoperatorio inmediato de pacientes con tumores vesicales no músculo invasores de riesgo intermedio

IntroductionApproximately 70-85% of transitional bladder cell carcinomas are non-muscle-invasive. After an initial surgery, around 60-90% will have a recurrence, being the highest risk period the first two years. Urothelium instability could be the main reason for recurrence in mid grade tumours, reason why a single dose of a chemotherapy after transurethral resection of the bladder (TURB) might be insufficient. That is why a deferred therapy in occasions associated with maintenance is recommended. Patients and methodsA prospective, controlled and randomized study was performed. We included non-muscle-invasive mid risk bladder tumours. All patients had initially a TURB performed and were randomized to receive a single dose of mitomycin C (MMC), in the immediate postoperative period. ResultsA total of 105 patients were included. Mean follow-up was 22, 70±8, 15 months. MMC was administered to 53 patients. Of these 66, 0% had no recurrence and 34,0% had a non-muscle-invasive recurrence. Of the 52 patients in the non MMC group, 53,8% had no recurrence and 44,2% had a non-muscle-invasive recurrence and only 1 patient had a muscleinvasive progression. We did not find significantly differences in time to recurrence in mid risk tumours when using immediate postoperative single dose of MMC or deferred therapy. There was only one case of myelosuppression. DiscussionIn mid risk non-muscle-invasive tumors, some studies suggest that early intravesical instillation of chemotherapy reduces the risk of recurrence after TURB. We could not show significantly differences when comparing postoperatorive MMC versus traditional deferred instillations.

Recurrence and Progression of T1G3 Transitional Cell Carcinoma of the Bladder Treated with Intravesical Bacillus Calmette-Guérin

Objective: To examine the incidence of recurrence and progression in patients with stage T1, grade-3 carcinoma of the bladder treated with endovesical bacillus Calmette-Guérin (BCG) after complete transurethral resection. Material and Methods: From May 1995 to June 2002, 937 patients with superficial bladder cancer underwent transurethral resection. 46 patients (4.9%) had T1G3 tumors. All patients received endovesical BCG therapy 2–3 weeks after transurethral resection, given in 6 sessions as weekly instillations of 120 ml Pasteur strain BCG in 50 ml saline. Success was defined by normal cytology and cystoscopy, and normal bladder biopsies. Recurrent tumors were resected and a second or third cycle of therapy was given according to pathological status. Progressive tumors were managed by radical cystectomy, radiotherapy and/or chemotherapy depending on the nature of the tumor or clinical status of the patient. Results: During follow-up 60.7% of the patients (28 of 46) remained tumor free after only 1 BCG cycle and 73.9% (34 of 46) after the third BCG cycle, and the bladder was preserved in all. Muscle-invasive progression was noted in 10 (21.7%) patients at the end of the BCG cycles. Radical cystectomy was done in 10 patients. The tumor-free survival rate of all patients including those who underwent cystectomy is 84.8% (39 of 46) with a median follow-up of 61 (range 39–118) months. Conclusion: Adjuvant immunotherapy with BCG after complete transurethral resection of the bladder tumor represents a highly effective treatment for bladder preservation in stage pT1, grade-3 carcinoma of the bladder. pT1G3 tumors with early high-grade recurrence after failed immunotherapy should be regarded as candidates for early radical cystectomy.

RECURRENCE AND PROGRESSION OF STAGE T1, GRADE 3 TRANSITIONAL CELL CARCINOMA OF THE BLADDER FOLLOWING INTRAVESICAL IMMUNOTHERAPY WITH BACILLUS CALMETTE-GUERIN

We prospectively examined the incidence of recurrence and progression in patients with stage pT1, grade 3 carcinoma of the bladder following complete transurethral resection of the bladder tumor and adjuvant immunotherapy with bacillus Calmette-Guerin (BCG). Between July 1987 and March 1999, 123 patients presenting to our clinic with superficial urothelial carcinoma (stage pT1, grades 1 to 3) received adjuvant intravesical immunotherapy with BCG after histologically confirmed complete transurethral tumor resection. Disease was stage pT1, grade 3 in 44 patients (36%). Median followup was 28 months (mean 43, range 5 to 141). Of the patients 36 (82%) with bladder preservation remained tumor-free during followup after 1 or 2 cycles of BCG. Superficial tumor recurred in 5 patients (11%) and muscle invasive progression was noted in 7 (16%). Radical cystectomy was performed in 4 cases (9%). Of the patients 5 (11%) died of cancer. Tumor-free survival for all patients was 89% (39 of 44). Adjuvant immunotherapy with BCG after complete transurethral resection of bladder tumor represents a highly effective primary treatment of stage pT1, grade 3 carcinoma of the bladder. Immediate radical cystectomy does not appear necessary.

Long-term results of intravesical bacillus calmette-guérin therapy for stage T1 superficial bladder cancer

Objectives. To examine in a prospective study the incidence of recurrence and progression in patients with Stage T1 bladder carcinoma after complete transurethral resection of the bladder tumor and adjuvant immunotherapy with bacillus Calmette-Guérin (BCG). Methods. Between July 1987 and April 1999, 126 patients presenting to our clinic with a superficial urothelial carcinoma of the bladder (Stage pT1, grade 1-3) received adjuvant intravesical immunotherapy with BCG after complete transurethral resection of the bladder tumor. In the case of recurrence of superficial tumor (pTa, pT1, or carcinoma in situ), patients received a second cycle of BCG. For muscle-invasive tumor progression (pT2, pT3, or pT4), radical cystectomy was recommended. Six of the patients (5%) presented with Stage pT1,G1 tumor, 74 (59%) with Stage pT1,G2 tumor, and 46 patients (36%) with Stage pT1,G3 tumor. Median follow-up was 53 months (range 3 to 144). Results. One hundred eight patients (86%) remained tumor-free with a retained bladder during the follow-up after one or two 6-week cycles of BCG. Twenty-four patients (19%) had a recurrence of superficial tumor, 13 (10%) had muscle-invasive progression after the first BCG cycle, and an additional 4 (3%) had progression after the second BCG cycle. Six patients (5%) underwent radical cystectomy, and 9 patients (7%) died as a result of tumor progression. The tumor-free survival rate of all patients was 89% (112 of 126). Conclusions. Adjuvant immunotherapy with BCG after complete transurethral resection of the bladder tumor represents a highly effective primary treatment for Stage T1 carcinoma of the bladder. Even in Stage pT1,G3 tumor, immediate radical cystectomy does not appear necessary.