T1G3 Non-muscle Invasive Bladder Cancer Research Articles

Blood Extracellular Vesicles Beyond Circulating Tumour Cells: A Valuable Risk Stratification Biomarker in High-Risk Non-Muscle-Invasive Bladder Cancer Patients.

Non-muscle-invasive bladder cancer (NMIBC) prognosis varies significantly due to the biological and clinical heterogeneity. High-risk stage T1-G3, comprising 15-20% of NMIBCs, involves the lamina propria and is associated with higher rates of recurrence, progression, and cancer-specific mortality. In the present study, we have evaluated the enumeration of tumour-derived extracellular vesicles (tdEVs) and circulating tumour cells (CTCs) in high-risk NMIBC patients and their correlation with survival outcomes such as time to progression (TTP), and cancer-specific survival (CSS). Eighty-three high-risk T1-G3 NMIBC patients treated between September 2010 and January 2013 were included. Blood samples were collected before a transurethral resection of the bladder (TURB) and analysed using the CellSearch® system. The presence of at least one CTC was associated with a shorter TTP and CSS. Extending follow-up to 120 months and incorporating automated tdEV evaluation using ACCEPT software demonstrated that tdEV count may additionally stratify patient risk. Combining tdEVs and CTCs improves risk stratification for NMIBC progression, suggesting that tdEVs could be valuable biomarkers for prognosis and disease monitoring. Further research is needed to confirm these findings and establish the clinical significance of tdEVs in early-stage cancers.

Intravesical MgSO4 for the treatment of BCG refractory T1 G3 bladder cancer: Preliminary results on efficacy and safety.

An urgent need of therapy exists for patients with high-risk non-muscle invasive bladder cancer (NMIBC) for whom Bacillus Calmette-Guérin (BCG) refractory treatment has failed. We investigated the role of intravesical magnesium sulfate (MgSO4) therapy in the management of BCG refractory T1 high grade (G3) NMIBC. Between January 2018 and July 2021, we performed a prospective trial enrolling participants with T1 G3 NMIBC refractory in BCG therapy. All patients included were considered ineligible for or have refused to undergo radical cystectomy. Subjects are enrolled into a single treatment group of a fixed dose of intravesical MgSO4. The intravesical solution was given for 3 h bi-weekly × 6 then once per week for 12 months. Cystoscopic surveillance was performed every 3 months. Endoscopic resection was performed if suspicious findings were identified on surveillance cystoscopy to establish pathologic diagnosis. Oncological outcomes and any side effects were reported during follow-up. A total of 8 patients who received intravesical MgSO4 for refractory TG3 tumors were included in our study. The median follow-up time was 29 months (range from 23 to 36). 62.5% of the patients (5/8) achieved a complete response to intravesical MgSO4, while 25% of the patients (2/8) had a partial response and 12.5% (1/8) had persistent disease. None of the patients had disease progression. None of the patients experienced hypermagnesemia. In patients with pTG3 tumors who were refractory to BCG therapy, intravesical MgSO4 was a well-tolerated and potentially effective regimen.

42 - Prognostic role of neutrophil-to-lymphocyte ratio in patients with T1G3 non-muscle invasive bladder cancer

42 - Prognostic role of neutrophil-to-lymphocyte ratio in patients with T1G3 non-muscle invasive bladder cancer

An increased body mass index is associated with a worse prognosis in patients administered BCG immunotherapy for T1 bladder cancer

The body mass index (BMI) may be associated with an increased incidence and aggressiveness of urological cancers. In this study, we aimed to evaluate the impact of the BMI on survival in patients with T1G3 non-muscle-invasive bladder cancer (NMIBC). A total of 1155 T1G3 NMIBC patients from 13 academic institutions were retrospectively reviewed and patients administered adjuvant intravesical Bacillus Calmette-Guérin (BCG) immunotherapy with maintenance were included. Multivariable Cox regression analysis was performed to identify factors predictive of recurrence and progression. After re-TURBT, 288 patients (27.53%) showed residual high-grade NMIBC, while 867 (82.89%) were negative. During follow-up, 678 (64.82%) suffered recurrence, and 303 (30%) progression, 150 (14.34%) died of all causes, and 77 (7.36%) died of bladder cancer. At multivariate analysis, tumor size (hazard ratio [HR]:1.3; p = 0.001), and multifocality (HR:1.24; p = 0.004) were significantly associated with recurrence (c-index for the model:55.98). Overweight (HR: 4; p < 0.001) and obesity (HR:5.33 p < 0.001) were significantly associated with an increased risk of recurrence. Addition of the BMI to a model that included standard clinicopathological factors increased the C-index by 9.9. For progression, we found that tumor size (HR:1.63; p < 0.001), multifocality (HR:1.31; p = 0.01) and concomitant CIS (HR: 2.07; p < 0.001) were significant prognostic factors at multivariate analysis (C-index 63.8). Overweight (HR: 2.52; p < 0.001) and obesity (HR: 2.521 p < 0.001) were significantly associated with an increased risk of progression. Addition of the BMI to a model that included standard clinicopathological factors increased the C-index by 1.9. The BMI could have a relevant role in the clinical management of T1G3 NMIBC, if associated with bladder cancer recurrence and progression. In particular, this anthropometric factor should be taken into account at initial diagnosis and in therapeutic strategy decision making.

The long-term prognostic value of survivin expressing circulating tumor cells in patients with high-risk non-muscle invasive bladder cancer (NMIBC).

Long-term follow-up study to evaluate the impact on disease-free survival and cancer-specific survival of survivin expression in tissue and CTCs from T1G3 bladder cancer patients. The study was conducted using tumor tissue and blood samples from 54 patients with a primary diagnosis of T1G3 NMIBC. Survivin was evaluated by reverse transcription-polymerase chain reaction in tumor tissues. CTCs were isolated from blood by CELLection™ Dynabeads (Invitrogen, Carlsbad, CA, USA). Cells were lysed and cDNA was synthesized and analysed for the expression of CD45, CK8 and survivin. The endpoints of this long-termanalysis were disease-free survival, DFS and cancer-specific survival, CSS. Here, we report that, at 9years of median follow-up, disease-free survival and cancer-specific survival are both significantly influenced by the expression of survivin in tumor tissue (p=0.006), by the presence of CTCs (p<0.0001) and by the expression of survivin in CTCs (p<0.0001). The statistically significant impact of survivin expressing CTCs on cancer-specific survival that we observed might be interpreted as the result of the persistence of a subpopulation of highlander cells in the blood of T1G3 bladder patients over time.

391 - Potential utility of apparent diffusion coefficient (ADC) value as a biomarker to predict the difference between T1G3 non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC)

391 - Potential utility of apparent diffusion coefficient (ADC) value as a biomarker to predict the difference between T1G3 non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC)

Retrospective study of various conservative treatment options with bacille Calmette-Guérin in bladder urothelial carcinoma T1G3: Maintenance therapy

ObjectiveTo compare various conservative treatment options for high-grade T1 nonmuscle-invasive bladder cancer (NMIBC). Bacille Calmette-Guérin (BCG) is the preferred intravesical treatment for high-grade T1 tumors; however, a number of experts still question the need for maintenance BCG. Material and methodsWe retrospectively analyzed data from 1039 patients with primary and recurrent T1G3 NMIBC. All patients underwent complete transurethral resection of the bladder tumor (TURBT), with muscle in the sample and multiple bladder biopsies. The patients were treated with the following: only one initial TURBT (n=108), re-TURBT (n=153), induction with 27mg of BCG (Connaught strain) (n=87), induction with 81mg of BCG (n=489) or induction with 81mg of BCG+maintenance (n=202). The time to first recurrence, progression (to T2 or greater or to metastatic disease) and specific mortality of the disease was assessed using the Kaplan–Meier survival function and were compared using the log-rank test and the Cox multivariate regression model of proportional risks. ResultsThe mean follow-up was 62±39 months. The risk of recurrence was significantly lower for the patients treated with maintenance therapy of 81mg of BCG than in the other treatment groups (p<0.001). The risk of tumor progression was also significantly lower for the patients treated with maintenance BCG than for the patients treated only with one TURBT, re-TURBT and with induction therapy with 27mg of BCG (p=0.0003). The specific disease mortality was significantly lower with BCG maintenance (9.4%) than with only one TURBT (27.8%; p=0.003). ConclusionsIn the case of T1G3 NMIBC, a complete dose of BCG with maintenance is associated with better recurrence results than are other conservative treatment modalities. The results of progression and survival specific to the disease were also better with induction BCG, with or without maintenance.

Non-muscle invasive high grade urothelial carcinoma of the bladder. Which factors can influence understaging at the time of radical cystectomy?

To evaluate the main factors which influence understaging in patients with T1G3 non-muscle invasive bladder cancer (NMIBC). 109 patients with T1/G3 underwent transurethral resection of bladder tumor (TURBT) and then radical cystectomy (RC) with pelvic lymph nodes dissection. A number of variables were considered when evaluating the detection of understaging. We considered the patients age and gender, as well as the size, number, location and morphology of their tumor. We also considered coexistence of bladder carcinoma in situ (CIS), microscopic vascular invasion and deep lamina propria invasion. The level of experience of the surgeon was also analyzed. in RC samples muscle invasion, that is understaging, was detected in 74 (67.9%) patients, while 35 (32.1%) patients were appropriately staged. In these cohort of patients with high grade tumors, understaging was associated with deep lamina propria and microscopic vascular invasion, multiple tumors, tumor size &gt; 6 cm, tumor location (trigone and dome), presence of residual tumor; age, gender, tumor morphology, CIS associated, and experience of urological surgeon were not associated with clinical understaging. in our study, evaluating patients with high grade NMIBC at first TURBT, we identified some risk factors that need to be considered and that are able to increase the risk of understaging: deep lamina propria and microscopic vascular invasion, multiple tumors, tumor size &gt; 6 cm, tumor location (trigone and dome), presence of residual tumor. When these risk factors are present, performing an early cystectomy, and not a re-TURBT, could lower the risk of worse pathological finding due to rapid disease progression of the high grade tumors, and can prolong survival.

MP01-10 POTENTIAL UTILITY OF APPARENT DIFFUSION COEFFICIENT (ADC) VALUE AS A BIOMARKER TO PREDICT THE DIFFERENCE BETWEEN T1G3 NON-MUSCLE INVASIVE BLADDER CANCER (NMIBC) AND MUSCLE INVASIVE BLADDER CANCER (MIBC)

You have accessJournal of UrologyBladder Cancer: Epidemiology & Evaluation I1 Apr 2016MP01-10 POTENTIAL UTILITY OF APPARENT DIFFUSION COEFFICIENT (ADC) VALUE AS A BIOMARKER TO PREDICT THE DIFFERENCE BETWEEN T1G3 NON-MUSCLE INVASIVE BLADDER CANCER (NMIBC) AND MUSCLE INVASIVE BLADDER CANCER (MIBC) Masaaki Fujimura, Shinichi Sakamoto, Nobuyuki Sekita, Hiroaki Sato, Hiroyoshi Kono, Nobuyoshi Takeuchi, Rika Nishikawa, Masashi Yano, Naoki Nihei, Hiroyoshi Suzuki, Kazuo Mikami, and Tomohiko Ichikawa Masaaki FujimuraMasaaki Fujimura More articles by this author , Shinichi SakamotoShinichi Sakamoto More articles by this author , Nobuyuki SekitaNobuyuki Sekita More articles by this author , Hiroaki SatoHiroaki Sato More articles by this author , Hiroyoshi KonoHiroyoshi Kono More articles by this author , Nobuyoshi TakeuchiNobuyoshi Takeuchi More articles by this author , Rika NishikawaRika Nishikawa More articles by this author , Masashi YanoMasashi Yano More articles by this author , Naoki NiheiNaoki Nihei More articles by this author , Hiroyoshi SuzukiHiroyoshi Suzuki More articles by this author , Kazuo MikamiKazuo Mikami More articles by this author , and Tomohiko IchikawaTomohiko Ichikawa More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1840AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Recently the usefulness of apparent diffusion coefficient (ADC) for characterizing tumor grade and T stage have been suggested. MIBC needs more invasive treatment including total cystectomy, radiation and chemotherapy, whereas T1G3 NMIBC has less invasive treatment options including re-TURBT or BCG instillation as bladder preservation therapy. Between these two tumor's groups the treatment selection is drastically changed, however, the relationship between these groups and ADC value has not yet been clearly identified. We investigated the difference between T1G3 NMIBC and MIBC by evaluating ADC value measured from DWI. METHODS Diffusion-weighted MRI (DW-MRI) at 1.5 Tesla using b-values of 0, 1000 s/mm2 was taken before transurethral resection or total cystectomy by 156 bladder urothelial tumor patients in our hospital. ADC value was measured and its relationship with clinico-pathological factors were analyzed. Fisher's exact test, receiver operating characteristic (ROC) curve analysis and logistic regression analysis were performed for data analysis. RESULTS Among 156 cases of bladder urothelial tumor, 34 and 42 cases were diagnosed as T1G3 NMIBC and MIBC, respectively. Area under the ROC curve for differentiating between T1G3 NMIBC and MIBC by using ADC value was 0.701, with optimal thereshold of 0.91x10-3mm/s2, which was associated with a sensitivity of 50.0%, specificity of 88.1%. Multivariate analysis showed that ADC value less than 0.91x10-3mm/s2(OR: 0.148, p=0.035) and lymphatic invasion (ly) (OR: 10.540, p=0.006) were significant predictive factors for distinguishing between T1G3 NMIBC and MIBC. CONCLUSIONS This is the first report which indicated that ADC value was significant predictive biomarker differentiating between T1G3 NMIBC and MIBC, which would be useful prior to treatment for patient counseling and treatment selection, especially about bladder preservation. Consequently it may provide more accurate diagnosis between these two groups, which leads to avoid unnecessary invasive treatment. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e4-e5 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Masaaki Fujimura More articles by this author Shinichi Sakamoto More articles by this author Nobuyuki Sekita More articles by this author Hiroaki Sato More articles by this author Hiroyoshi Kono More articles by this author Nobuyoshi Takeuchi More articles by this author Rika Nishikawa More articles by this author Masashi Yano More articles by this author Naoki Nihei More articles by this author Hiroyoshi Suzuki More articles by this author Kazuo Mikami More articles by this author Tomohiko Ichikawa More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Estudio retrospectivo de diferentes opciones de tratamiento conservador con Bacilo de Calmette-Guèrin en el carcinoma urotelial vesical T1G3: terapia de mantenimiento

ObjectiveTo compare various conservative treatment options for high-grade T1 nonmuscle-invasive bladder cancer (NMIBC). Bacille Calmette-Guérin (BCG) is the preferred intravesical treatment for high-grade T1 tumours; however, a number of experts still question the need for maintenance BCG. Material and methodsWe retrospectively analysed data from 1039 patients with primary and recurrent T1G3 NMIBC. All patients underwent complete transurethral resection of the bladder tumour (TURBT), with muscle in the sample and multiple bladder biopsies. The patients were treated with the following: only one initial TURBT (n=108), re-TURBT (n=153), induction with 27mg of BCG (Connaught strain) (n=87), induction with 81mg of BCG (n=489) or induction with 81mg of BCG+maintenance (n=202). The time to first recurrence, progression (to T2 or greater or to metastatic disease) and specific mortality of the disease was assessed using the Kaplan-Meier survival function and were compared using the log-rank test and the Cox multivariate regression model of proportional risks. ResultsThe mean follow-up was 62±39 months. The risk of recurrence was significantly lower for the patients treated with maintenance therapy of 81mg of BCG than in the other treatment groups (P<.001). The risk of tumour progression was also significantly lower for the patients treated with maintenance BCG than for the patients treated only with one TURBT, re-TURBT and with induction therapy with 27mg of BCG (P=.0003). The specific disease mortality was significantly lower with BCG maintenance (9.4%) than with only one TURBT (27.8%; P=.003). ConclusionsIn the case of T1G3 NMIBC, a complete dose of BCG with maintenance is associated with better recurrence results than are other conservative treatment modalities. The results of progression and survival specific to the disease were also better with induction BCG, with or without maintenance.

Female Gender and Carcinoma In Situ in the Prostatic Urethra Are Prognostic Factors for Recurrence, Progression, and Disease-Specific Mortality in T1G3 Bladder Cancer Patients Treated With Bacillus Calmette-Guérin

BackgroundControversy exists over the most important prognostic factors in T1 high-grade non–muscle-invasive bladder cancer (NMIBC) patients treated with bacillus Calmette-Guérin (BCG). ObjectiveEvaluate prognostic factors for recurrence, progression, and disease-specific mortality after adjuvant intravesical BCG immunotherapy in patients with T1G3 NMIBC and long-term follow-up. Design, setting, and participantsA single-institution retrospective analysis of 146 patients with primary stage T1G3 NMIBC. InterventionAll patients were treated with complete transurethral resection (TUR) plus multiple bladder biopsies that included the prostatic urethra. No second TUR was done. Patients underwent an induction course of intravesical BCG (Connaught strain, 81mg) without maintenance therapy. MeasurementsThe variables analysed for time to recurrence, progression, and death due to bladder cancer (BCa) were gender, age, tumour multiplicity, diameter, aspect, substaging, concomitant carcinoma in situ (CIS), and CIS in the prostatic urethra. Cox regression models were used to assess the univariate and multivariate prognostic importance of these factors and estimate hazard ratios (HRs). Time-to-event distributions were estimated using cumulative incidence functions. Results and limitationsThe median follow-up was 8.7 yr. Sixty-five patients (44.5%) had recurrence, 25 patients (17.1%) had progression, and 18 patients (12.3%) died because of BCa. Female gender and presence of CIS in the prostatic urethra were associated with an increased risk of recurrence (p=0.0003, HR: 2.53), progression (p=0.001, HR: 3.59), and death due to BCa (p=0.004, HR: 3.53). ConclusionsIn primary T1G3 bladder tumours treated with induction BCG, female gender or having CIS in the prostatic urethra were the only prognostic factors for time to recurrence, progression, and disease-related mortality. It is very important to perform a biopsy of the prostatic urethra in patients with primary high-grade NMIBC as a first step to obtain this prognostic information.

UP-01.067 How Do Tumour Characteristics Influence Outcome Regarding Different Conservative Treatment Options for Non-Muscle Invasive Bladder Cancer T1G3?

Management of T1G3 non-muscle invasive bladder cancer (NMIBC) has evolved during the last 20 years but recurrence and progression remain the main concerns in these patients. The introduction of intravesical Bacillus Calmette-Guerin (BCG) with maintenance has changed the perspective in conservative approach. There are several clinical prognostic factors that influence recurrence and progression: gender, age, association to CIS, tumour size, multifocality and primary or recurrent tumour. To evaluate, in a large retrospective series of patients, the differences in recurrence, progression to invasive disease and cancer specific survival according to the characteristics of the tumours related to the treatment received.

1740 RETROSPECTIVE STUDY OF DIFFERENT OPTIONS IN THE MANAGEMENT OF NON-MUSCLE INVASIVE BLADDER CANCER T1G3: MAINTENANCE BCG IS HERE TO STAY

You have accessJournal of UrologyBladder Cancer: Superficial1 Apr 20111740 RETROSPECTIVE STUDY OF DIFFERENT OPTIONS IN THE MANAGEMENT OF NON-MUSCLE INVASIVE BLADDER CANCER T1G3: MAINTENANCE BCG IS HERE TO STAY Juan Palou, Eduardo Solsona, J. Angulo, Jesús María Fernández, Miguel Unda, and L.M. Piñeiro Juan PalouJuan Palou Barcelona, Spain More articles by this author , Eduardo SolsonaEduardo Solsona Valencia, Spain More articles by this author , J. AnguloJ. Angulo Madrid, Spain More articles by this author , Jesús María FernándezJesús María Fernández Madrid, Spain More articles by this author , Miguel UndaMiguel Unda Madrid, Spain More articles by this author , and L.M. PiñeiroL.M. Piñeiro Madrid, Spain More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.2067AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The management of T1G3 non-muscle invasive bladder cancer (NMIBC) has evolved during the last 20 years but recurrence and progression remain the main concerns. The introduction of intravesical Bacillus Calmette-Guerin (BCG) with different doses and number of doses is still under debate. Good first TUR and Re-TUR has become standart of care in high grade NMIBC in order to improve clinical staging and otucomes by decreasing understaging and residual disease. To evaluate, in a large retrospective series of patients, the differences in recurrence, progression to invasive disease and cancer specific survival according to the different treatments received in the different periods before and after the introduction of BCG. METHODS This is a retrospective analysis of 1039 patients with primary and recurrent stage T1G3 NMIBC including 945 males (mean age of 66.5, b9.8 years, range 21–89). All underwent a complete TUR with multiple bladder biopsies, with muscle present in the specimen. All of them were treated conservatively as follows: 1) no BCG, 2) Re-TUR only, 3) BCG Connaught 27 mgrs induction course, 4) BCG Connaught 81 mgrs induction course, 5) BCG Connaught 81 mgrs induction course + maintenance. There were no differences on the distribution in the groups except that patients with CIS and recurrent tumours were treated more frequently with BCG (p<0.001). We evaluate the time to first recurrence, progression to a higher stage (T2 or greater, or metastatic disease), disease specific mortality. Time to event was estimated with Kaplan Meier and then compared using the logrank test and the multivariate Cox proportional hazards regression model. RESULTS The following results were observed with a median followup of 62±39 months. CONCLUSIONS BCG treatment with maintenance offers the best results in recurrence, progression and disease specific survival in patients with stage T1G3 bladder cancer. Full dose BCG is better than one third dose related to the same parameters. There is an important difference in recurrence rate between the patients treated with or wihout BCG. Full dose BCG treatment reduces progression to invasive disease. Disease specific mortality is better in those patients treated with BCG. Despite being a retrospective study, the large number of patients offers an overview of the impact of the different conservative modalities in patients with T1G3 NMIBC. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e698-e699 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Juan Palou Barcelona, Spain More articles by this author Eduardo Solsona Valencia, Spain More articles by this author J. Angulo Madrid, Spain More articles by this author Jesús María Fernández Madrid, Spain More articles by this author Miguel Unda Madrid, Spain More articles by this author L.M. Piñeiro Madrid, Spain More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Abstract 4673: Myopodin methylation is a prognostic marker in patients with T1G3 bladder cancer

Abstract BACKGROUND: Urothelial carcinomas presenting T1G3 non muscle-invasive lesions are high-risk tumors because of the high recurrence and progression to muscle invasive disease rates. The Bacillus of Calmette-Guérin (BCG) is a standard treatment to reduce tumor recurrence and delay progression of high-risk non-muscle invasive bladder tumors. However, it is not clear yet which T1G3 patients are more prone to display a more aggressive clinical behavior or be susceptible to respond to BCG. OBJECTIVE: The aim of this study was to evaluate the role of myopodin methylation as a clinical outcome prognosticator and predictive biomarker for BCG response in patients with T1G3 bladder tumors. DESIGN, SETTING, AND PARTICIPANTS: The methylation status of myopodin was analyzed on tumor specimens belonging to 170 patients with T1G3 non-muscle invasive bladder cancer, being a subset of them undergoing BCG treatment (n=108). MEASUREMENTS: Myopodin methylation was assessed by methylation-specific polymerase chain reactions. Recurrence, progression into muscle invasive tumors and disease-specific overall survival rates were analyzed using competing risks regression analysis. RESULTS: Among the 170 cases analyzed, 72 of them recurred (42.4%), 36 progressed (21.2%), and 24 died of the disease (14.1%). Univariate and multivariate survival analyses revealed that myopodin methylation was significantly associated with an increased recurrence rate (p=0.004), progression (p=0.002), and shorter disease-specific overall survival (p=0.020). Interestingly, in a subset of cases treated with BCG, myopodin methylation was also related to an increased recurrence rate (p=0.011), progression (p=0.030), and a shorter disease-specific overall survival (p=0.028). CONCLUSIONS: Epigenetic analyses revealed that myopodin methylation was associated with the clinical outcome of patients with T1G3 tumors. Myopodin methylation was related to tumor aggressiveness in patients with T1G3 disease undergoing BCG treatment. Myopodin methylation distinguished patients responding to BCG from those who may require a more aggressive therapeutic approach. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4673.

Intravesical mitomycin C combined with hyperthermia for patients with T1G3 transitional cell carcinoma of the bladder

Objectives Non-muscle invasive bladder cancer (NMIBC) classified as T1G3 represents one of the most challenging issues in urologic oncology. Although it is still considered a lesion amenable for conservative management, the risk for recurrence and progression remains high. The aim of this study was to define both recurrence and progression rate in patients with T1G3 UCC treated by complete transurethral resection (TURT) and adjuvant thermochemotherapy approach. Materials and methods We retrospectively evaluated the clinical data of patients with T1G3 NMIBC who underwent TURT followed by thermochemotherapy (TCT) treatment. Data recorded included age, gender, previous resections, previous intravesical treatment, time to tumor recurrence, and progression. TCT was given once weekly for 6 consecutive weeks, followed by 6 maintenance sessions at 4 to 6 weeks intervals. During each treatment session, 40 mg of mitomycin C (MMC) was instilled into the bladder in combination with bladder wall hyperthermia of 42 ± 2°C for 60 minutes. Follow-up cystoscopy and urinary cytology were performed every 3 months for the first 2 years and than biannually. Results A total of 56 T1G3 patients were treated with adjuvant TCT treatment at 7 urologic centers. Mean age was 68 years (range 35–91), 10 were females and 46 were males. Twenty-six patients failed on at least 1 previous intravesical treatment. Five patients who dropped out due to adverse events before reaching the first outcome evaluation cystoscopy were referred to another intravesical therapy, and were therefore excluded from the current analysis. A total 51 patients were available for analysis. Median follow-up time of tumor-free patients was 18 months (average 20, range 2–49 months). Seventeen patients (33.3%) had tumor recurrence and 4 of them progressed to muscle invasive disease. The median time to recurrence was 9 months (average 11, range 2–31 months). The Kaplan-Meier estimated recurrence rate for this group is: 42.9% at 2 years, 51.0% at 4 years. Conclusions TCT can be an effective adjuvant treatment option after TURT to prevent recurrence in patients with T1G3 NMIBC. Progression rate after this treatment was low (7.9%). TCT treatment was documented to be effective also in those who failed previous intravesical BCG. Treatment was confirmed to be safe and well tolerated.