European Organization For Research And Treatment Of Cancer Risk Tables Research Articles

[A Randomized Controlled Study of Intravesical Instillation Therapy of Bacillus Calmette-Guérin vs. Epirubicinin Treating Non-muscular Invasive Bladder Cancer].

To explore the best treatment plan of intravesical instillation for patients with non-muscular invasive bladder cancer (NMIBC), to explore recurrence-related clinicopathological factors after intravesical instillation, and to evaluate the value of the prognosis and prediction models currently used for NMIBC patients. Starting from 2016, patients who underwent transurethral resection of bladder tumor (TURBT) in our hospital and who received post-surgery diagnosis of having intermediate or high risks for NMIBC were enrolled in the study. They were randomly assigned to different group sat a ratio of 2∶2∶1 for receiving intravesical instillation therapy of Bacillus Calmette-Guérin (BCG) for 19 times, BCG for 15 times, and epirubicin (EPI) for 18 times. The clinicopathological data of the patients were recorded before, during and after instillation therapy, and survival curves were drawn to evaluate the effects of the three regimens, using recurrence-free survival as the endpoint. Clinicopathological data were analyzed to study the associations between various factors and post-instillation recurrence. The consistency index (c-index) was used to evaluate the predictive accuracy of the scoring model of the Spanish Urological Club for Oncological Treatment (CUETO) and the risk tables of European Organization for Research and Treatment of Cancer (EORTC). A total of 93 NMIBC patients (35 in the 19-time BCG group, 37 in the 15-time BCG group, and 21 in the EPI group) were included, with a median follow-up time of 33.46 months. Twenty-two patients experienced tumor recurrence and eight, tumor progression. The survival curve showed that the BCG group had better recurrence-free survival than the EPI group ( P=0.002), while the difference in recurrence-free survival between 19-time BCG and 15-time BCG groups was not statistically significant. Higher general complication rate was seen in the BCG groups compared with the EPI group (84.7% vs. 61.9%, P=0.022), but there was no grade 3-5 adverse events in any group. The c-index of CUETO scoring model and EORTC risk tables was higher than that of the prediction based solely on T stage, nuclear grade, or EAU risk stratification. In addition, the c-index in the BCG group was higher than that in the whole cohort. Among the subjects of this study, the recurrence rate of bladder cancer in the intravesical BCG instillation groups was lower than that of the epirubicin group. EORTC risk tables and CUETO scoring model exhibited higher predictive accuracies in BCG-treated patients than its performance for the whole NMIBC cohort.

MP72-07 VALIDATION AND MODIFICATION OF THE EORTC RISK TABLES TO PREDICT OUTCOMES IN NON-MUSCLE-INVASIVE BLADDER CANCER IN JAPANESE PATIENTS

You have accessJournal of UrologyBladder Cancer: Non-invasive III (MP72)1 Apr 2020MP72-07 VALIDATION AND MODIFICATION OF THE EORTC RISK TABLES TO PREDICT OUTCOMES IN NON-MUSCLE-INVASIVE BLADDER CANCER IN JAPANESE PATIENTS Hirotake Kodama*, Shingo Hatakeyama, Naoki Fujita, Hayato Yamamoto, Atsushi Imai, Takahiro Yoneyama, Yasuhiro Hashimoto, Kazuaki Yoshikawa, Atsushi Sasaki, and Chikara Ohyama Hirotake Kodama*Hirotake Kodama* More articles by this author , Shingo HatakeyamaShingo Hatakeyama More articles by this author , Naoki FujitaNaoki Fujita More articles by this author , Hayato YamamotoHayato Yamamoto More articles by this author , Atsushi ImaiAtsushi Imai More articles by this author , Takahiro YoneyamaTakahiro Yoneyama More articles by this author , Yasuhiro HashimotoYasuhiro Hashimoto More articles by this author , Kazuaki YoshikawaKazuaki Yoshikawa More articles by this author , Atsushi SasakiAtsushi Sasaki More articles by this author , and Chikara OhyamaChikara Ohyama More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000952.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: To validate the stratification of the European Organization for Research and Treatment of Cancer (EORTC) risk table and to develop the simplified stratification model to improve usefulness and predictive accuracy on oncological outcomes in patients with non-muscle-invasive bladder cancer (NMIBC) who underwent transurethral resection of bladder tumor (TURBT). METHODS: We retrospectively evaluated 433 patients with primary NMIBC who underwent TURBT at from November 1993 to February 2019. We validated the usefulness of EORTC risk table on a risk classification and intravesical recurrence-free survival (RFS). we developed modified stratification based on multivariate analysis for intravesical RFS (lower- and higher-risk). We compared predictive accuracy on oncological outcomes using the receiver operating characteristic curve (ROC) and the area under the curve (AUC) between the EORTC model and the modified model. Then, we validated the modified model using 73 patients with NMIBC who underwent TURBT. RESULTS: Median age and median follow-up periods were 74 years and 29 months. Of 433 patients, 158 (36%) had recurrence after TURBT. A significant difference was observed in number of tumors (multiple) and renal function between the patients with and without recurrences. Of 433, 389 (89%) patients were classified in the high risk group. To improve the risk classification, we developed a modified risk model using number of tumors (multiple), tumor size (> 3cm), category (pT1), high grade, concurrent CIS, and the chronic kidney disease. Each factor was scored as 1 point and patients were classified into low (0-3) and high (4-6) according to total score (0-6). The AUC for recurrence prediction accuracy was significantly higher in the modified model than that in the EORTC model (0.62 vs. 0.57, P = 0.013, respectively). The recurrence free survival was significantly shorter in the patients with modified-high than that in the -low (P = 0.043). In the validation cohort, intravesical PFS was significantly shorter in the patients with the modified-high than that in the -low (P = 0.005) with the c-index of 0.76 (95% CI: 0.634-0.904). CONCLUSIONS: The modified model might be useful to classify the risk of recurrence of bladder cancer than the EORTC risk model. Further large study is necessary to validate our findings. Source of Funding: none © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1076-e1076 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hirotake Kodama* More articles by this author Shingo Hatakeyama More articles by this author Naoki Fujita More articles by this author Hayato Yamamoto More articles by this author Atsushi Imai More articles by this author Takahiro Yoneyama More articles by this author Yasuhiro Hashimoto More articles by this author Kazuaki Yoshikawa More articles by this author Atsushi Sasaki More articles by this author Chikara Ohyama More articles by this author Expand All Advertisement PDF downloadLoading ...

Utility of the EORTC risk tables and CUETO scoring model for predicting recurrence and progression in non-muscle-invasive bladder cancer patients treated with routine second transurethral resection.

Routine second transurethral resection (TUR) for non-muscle-invasive bladder cancer (NMIBC) is common practice in Germany. Applicability of European Organization for Research and Treatment of Cancer (EORTC) and Spanish Urological Club for Oncological Treatment (CUETO) models in NMIBC patients is still controversial. Aim of the study was to assess the performance of EORTC and CUETO predictive models in NMIBC patients treated with second TUR. 479 NMIBC patients with routine second TUR were analyzed retrospectively between 2003 and 2011, and investigated with clinical and pathological variables in regard to tumor recurrence and progression. Furthermore, recurrencefree survival (RFS) and progression-free survival (PFS) were evaluated according to EORTC and CUETO, and the discrimination of the models assessed. With a median follow-up of 60months, prior recurrence rate, grade, and second TUR pathology were independent prognostic factors for the risk of disease recurrence and progression. The concordance index of the EORTC and the CUETO model was 0.563 and 0.516 for recurrence and 0.681 and 0.702 for progression, respectively. The positive pathology after second TUR was significantly associated with risk of disease recurrence and progression. EORTC and CUETO risk models estimated progression better than recurrence, especially with higherscore groups. Improved predictive tools should be developed for optimal treatment selection.

EORTC risk tables are more suitable for Chinese patients with nonmuscle-invasive bladder cancer than AUA risk stratification

Background:Patients with non-muscle-invasive bladder cancer (NMIBC) need accurate estimations of the risk of recurrence and progression. Physicians can offer individualized therapy after identifying high-risk tumors. In our study, we compared the applicability of European Organization for Research and Treatment of Cancer (EORTC) risk tables and American Urological Association (AUA) risk stratification in Chinese patients with NMIBC.Methods:We retrospectively studied 301 patients with NMIBC who underwent transurethral resection of bladder tumor (TURBT) between October 2000 and July 2009 at Huashan Hospital of Fudan University and analyzed their parameters. The recurrence and progression rates at 1 and 5 years postoperatively were calculated along with 95% confidence intervals. We compared them with results obtained from the EORTC risk tables and AUA risk stratification. P values <.05 were considered statistically significant.Results:The median patient age was 67 years (21–92 years) and the median follow-up duration was 46 months (2–151 months). We used EORTC risk tables to classify patients into 3 groups, depending on whether they suffered recurrence or progression after TURBT. Kaplan–Meier curves showed significant differences among the 3 recurrence-free survival (RFS) levels (P < .0001, log-rank test) and among the 3 progression-free survival (PFS) levels (P < .0001, log-rank test). AUA risk stratification showed the same results. Both classifications were suitable to predict recurrence and progression in Chinese patients. However, for high-risk patients in both series, Kaplan–Meier curves showed significant differences between RFS levels (P < .0001, log-rank test) and between PFS levels (P < .0001, log-rank test). EORTC risk tables were stricter and AUA was more sensitive in assigning patients to a high-risk group.Conclusion:EORTC risk tables are better than AUA risk stratification for predicting recurrence and progression in Chinese patients with NMIBC, especially among high-risk patients.

Risk factor assessment in high-risk, bacillus Calmette-Guérin-treated, non-muscle-invasive bladder cancer.

ObjectiveTo assess the risk factors associated with recurrence, progression and survival in high-risk non-muscle-invasive bladder cancer (NMIBC) patients treated with bacillus Calmette–Guérin (BCG) and validate the European Organization for Research and Treatment of Cancer (EORTC) and Spanish Urological Club for Oncological Treatment (CUETO) scores.Patients and methodsWe retrospectively analyzed all BCG-treated NMIBC patients from 1998 to 2012. Multiple variables were tested as risk factors for recurrence-free survival and progression-free survival (PFS). Variables included age, sex, grade, stage, tumor size, number of tumors, carcinoma in situ (CIS), recurrence status, BCG strain used, smoking status, use of re-staging transurethral resection and use of single immediate postoperative instillation. We also tested the accuracy of EORTC and CUETO scores in predicting recurrence and progression.ResultsOverall, 123 patients were analyzed. Median (interquartile range) follow-up was 49 months. The 5-year overall survival, cancer-specific survival, recurrence-free survival and PFS were 75.0%, 89.3%, 59.4% and 79.2%, respectively. On univariate analysis, multiple tumors (≥3), concomitant CIS and smoking influenced recurrence. Regarding progression, multiple tumors, concomitant CIS and Connaught strain (vs Tice) negatively influenced PFS on univariate and multivariate analyses were independent prognostic factors. CUETO scores were accurate, with a slight overestimation, while EORTC score was not predictive of recurrence or progression.ConclusionIn this study, CIS and tumor multiplicity were unfavorable predictors of recurrence and progression in patients with NMIBC receiving BCG. CUETO model was superior to EORTC risk tables in predicting recurrence and progression in our BCG-treated patient population. Nonetheless, both scores overestimated recurrence and progression rates. Prospective trials are needed to validate our findings.

Preditores de recorrência e progressão do câncer de bexiga: validação externa do escore de risco EORTC e a Classificação do Instituto do Câncer do Estado de São Paulo

Introdução: Classificações de risco baseadas em fatores preditivos de recorrência e progressão são essenciais para condutas no câncer de bexiga. Tabelas de risco combinam essas variáveis para uso clínico. As tabelas de risco da Organização Europeia para Pesquisa e Tratamento do Câncer (EORTC) são aceitas para esse propósito, mas nunca foram validadas no Brasil. Objetivos: Validar as tabelas de risco EORTC e criar uma classificação de risco baseada na população de pacientes acompanhados em um centro terciário de câncer. Métodos: Estudo retrospectivo de 561 pacientes submetidos a ressecção transuretral (RTU) de câncer de bexiga superficial de fevereiro de 2005 a junho de 2011. As variáveis analisadas foram as mesmas das tabelas de risco EORTC. A regressão logística foi realizada usando SPSS. A análise da curva COR determinou o limite de tamanho do tumor. Resultados: As tabelas de risco EORTC não conseguiram prever recorrência nem progressão. Na análise para prever recorrência isoladamente, estadio T e tamanho do tumor previram o desfecho. O limite de tamanho do tumor foi definido em &lt;4cm vs ≥4cm (AUC=0,61; p=0,001). Criamos uma classificação: Ta/CIS=0 pontos, T1=4 pontos, tamanho do tumor=0 ou 3 pontos. A classificação de risco foi obtida somando os pontos. A taxa de recorrência em 2 anos foi: escore 0=11,2%; escore 3=20,7%; escore 4=29,2%; escore 7=37,9%. Para prever recorrência e progressão, estadio T e tamanho do tumor previram significativamente o desfecho. A classificação em escores foi: Ta/CIS=0 pontos, T1=2 pontos, tamanho do tumor = 0 ou 2 pontos. A classificação de risco foi obtida somando os pontos. A taxa de recorrência em 2 anos foi: escore 0=17%; escore 2=28,6%; escore 4=40,7%. Conclusões: Constatamos que as tabelas de risco EORTC não conseguiram prever recorrência ou progressão do câncer de bexiga na nossa população. Portanto, desenvolvemos uma classificação de risco para auxiliar urologistas a individualizar as condutas por paciente.

Applicability of the EORTC risk tables to predict outcomes in non-muscle-invasive bladder cancer in Turkish patients.

To evaluate the consistency of the results of patients who were treated for non-muscle-invasive bladder cancer (NMIBC) in our clinic with the European Organization for Research and Treatment of Cancer (EORTC) risk table. Data were retrospectively analyzed from 452 patients who had undergone transurethral resection of bladder tumor (TUR-BT) between the years 2002, and 2010 for primary or recurrent NMIBC. Our study had a retrospective design but based on prospective cohort study. Patients were staged according to the 2002 Tumor Node Metastasis (TNM) classification and the 1973 World Health Organization grading system. Recurrence was defined as non-muscle-invasive or muscle-invasive and progression as muscle-invasive tumor determined based on following cystoscopy and TUR-BT results, and confirmed by histopathologic analysis. Patients in the current study were classified into four groups according to the EORTC risk tables. Time to first recurrence and progression was determined for each risk group. Of the 452 patients, 348 were enrolled in this study. The overall mean follow-up period was 55.25 months of all patients. Of 348 patients, 130 (37.4%) and 258 patients (74.1%) had recurrence after treatment at the 1 and 5 year follow-up period, respectively. While 35 (10.1%) and 99 patients (28.4%) progressed to muscle-invasive cancer at the 1 and 5 year follow-up period, respectively. In the multivariate analysis, grade, number, size of the tumor size, and concomitant carcinoma in situ were found to be statistically significant for disease progression and recurrence. When EORTC risk tables were comparatively evaluated in our patient population, we can say that EORTC tables predict nearly accurately the clinical course of patients with NMIBC.

Predicting recurrence of non-muscle-invasive bladder cancer after transurethral resection.

To determine clinical prognostic factors and their impact on the risk of recurrence of newly discovered non-muscle-invasive bladder cancer. The study included 120 patients of both sexes aged 45-80 years with newly discovered non-muscle-invasive bladder cancer. All the patients were treated surgically by transurethral electro resection (TUER). The outcome of patients with and without recurrence was followed at intervals of three months after surgery, the total of two years. For monitoring the probability of early recurrence the criteria of the European Organization for Research and Treatment of Cancer (EORTC) were used. The average age of the patients was 65.9 years, 79 (79.2%) males and 21 (20.8%) females. The total of 67 (55.8%) patients had a recurrence during the period of monitoring. The average time to the first and fourth recurrence was 15.4 and 23.9 months, respectively. Numbers of tumors and a degree of invasion had a significant prognostic impact on the risk of recurrence. The EORTC score was a highly significant predictor of recurrence (OR=1.237; p < 0.001). Based on available clinical and pathological prognostic factors and by stratification of patients into three disease risk groups it is possible to predict the possibility of disease. Individual approach and recommendations for the treatment using EORTC risk tables should improve the quality of treatment.

EORTC Risk Model to Predict Progression in Patients With Non–Muscle-Invasive Bladder Cancer: Is It Safe to Use in Clinical Practice?

PurposeTo evaluate the validation of European Organization for Research and Treatment of Cancer (EORTC) risk tables to predict progression in Brazilian patients with non–muscle-invasive bladder cancer (NMIBC). Patients and MethodsTwo hundred five consecutively and prospectively selected patients with NMIBC who underwent transurethral resection were analyzed during 12 years. Six parameters were analyzed: tumor grade, size, and number, pT stage, previous recurrence rate, and carcinoma-in-situ. Time to progression, risk score, and progression probabilities were calculated and compared to probabilities obtained from the EORTC model. The C index was calculated, and accuracy was analyzed for external validation. ResultsA total of 152 patients had complete follow-up data, 36 died, and 17 were lost to follow-up. One hundred thirty-seven patients had primary tumors and 68 had recurrent tumors. Progression to muscle-invasive disease occurred in 42 patients (20.5%). Significant characteristics related to progression were male gender, pT1 stage, lesion size ≥ 3 cm, high grade of disease, and no combined intravesical therapy. Mean time to progression was 26.9 months; the 1-year progression rate was 3.4% and the 5-year rate was 19.1%. The C index was 0.86 at 1 year and 0.78 at 5 years. For calibration, 1- and 5-year progression rates were lower than the values predicted by EORTC risk tables, mainly in high-risk groups. Although the EORTC model overestimated the short- and long-term risk of progression, an overlapping of the confidence intervals between both populations was detected. ConclusionThe EORTC model successfully stratified progression risks in a Brazilian cohort, although it overestimated progression rates. This scoring system is useful in predicting progression of NMIBC; however, updating new risk markers is essential to improve risk classification and prediction of progression.

Comparison of expected treatment outcomes, obtained using risk models and international guidelines, with observed treatment outcomes in a Dutch cohort of patients with non-muscle-invasive bladder cancer treated with intravesical chemotherapy

To compare the risks according to the American Urological Association (AUA), EAU, European Organization for Research and Treatment of Cancer (EORTC) and Club Urológico Español de Tratamiento Oncologico (CUETO) classifications with real outcomes in a cohort of patients in the Netherlands, and to confirm that patients who were undertreated according to these risk models have worse outcomes than adequately treated patients. Patients treated with complete transurethral resection of bladder tumour and intravesical chemotherapy were included. Not all patients would have received intravesical chemotherapy had they been treated to current standards, and thus comparison of the observed outcomes in our Dutch cohort vs expected outcomes based on the EORTC risk tables and CUETO scoring model was possible. The cohort was reclassified according to the definitions of five index patients (IPs), as defined by the AUA guidelines, and three risk groups, defined according to the EAU guidelines, to compare the outcomes of undertreated patients with those of adequately treated patients. A total of 1001 patients were available for comparison with the AUA definitions and 728 patients were available for comparison with the EORTC and CUETO models. There was a large overlap between the observed outcomes and expected recurrence and progression probabilities when comparison was made using the EORTC risk tables. The observed recurrence outcomes were in general higher than the expected probabilities according to the CUETO risk classification, especially in the long term. No differences in progression were found when comparing these two models to the Dutch cohort. Patients who were undertreated according to the guidelines showed, in general, a higher risk of developing recurrence and progression. Limitations are i.a. its retrospective nature and the differences in grading system. Comparisons between the observed outcomes in our Dutch cohort and the expected outcomes based on EAU and CUETO risk models and the EORTC and AUA guidelines showed that lack of adherence to existing guidelines translates into worse outcomes.

Accuracy of the EORTC risk tables and of the CUETO scoring model to predict outcomes in non-muscle-invasive urothelial carcinoma of the bladder

Background:The European Organization for Research and Treatment of Cancer (EORTC) risk tables and the Spanish Urological Club for Oncological Treatment (CUETO) scoring model are the two best-established predictive tools to help decision making for patients with non-muscle-invasive bladder cancer (NMIBC). The aim of the current study was to assess the performance of these predictive tools in a large multicentre cohort of NMIBC patients.Methods:We performed a retrospective analysis of 4689 patients with NMIBC. To evaluate the discrimination of the models, we created Cox proportional hazard regression models for time to disease recurrence and progression. We incorporated the patients calculated risk score as a predictor into both of these models and then calculated their discrimination (concordance indexes). We compared the concordance index of our models with the concordance index reported for the models.Results:With a median follow-up of 57 months, 2110 patients experienced disease recurrence and 591 patients experienced disease progression. Both tools exhibited a poor discrimination for disease recurrence and progression (0.597 and 0.662, and 0.523 and 0.616, respectively, for the EORTC and CUETO models). The EORTC tables overestimated the risk of disease recurrence and progression in high-risk patients. The discrimination of the EORTC tables was even lower in the subgroup of patients treated with BCG (0.554 and 0.576 for disease recurrence and progression, respectively). Conversely, the discrimination of the CUETO model increased in BCG-treated patients (0.597 and 0.645 for disease recurrence and progression, respectively). However, both models overestimated the risk of disease progression in high-risk patients.Conclusion:The EORTC risk tables and the CUETO scoring system exhibit a poor discrimination for both disease recurrence and progression in NMIBC patients. These models overestimated the risk of disease recurrence and progression in high-risk patients. These overestimations remained in BCG-treated patients, especially for the EORTC tables. These results underline the need for improving our current predictive tools. However, our study is limited by its retrospective and multi-institutional design.

1701 ACCURACY OF THE EORTC RISK TABLES AND OF THE CUETO SCORING MODEL TO PREDICT OUTCOMES IN NON MUSCLE-INVASIVE UROTHELIAL CARCINOMA OF THE BLADDER

Background: The European Organization for Research and Treatment of Cancer (EORTC) risk tables and the Spanish Urological Club for Oncological Treatment (CUETO) scoring model are the two best-established predictive tools to help decision making for patients with non-muscle-invasive bladder cancer (NMIBC). The aim of the current study was to assess the performance of these predictive tools in a large multicentre cohort of NMIBC patients. Methods: We performed a retrospective analysis of 4689 patients with NMIBC. To evaluate the discrimination of the models, we created Cox proportional hazard regression models for time to disease recurrence and progression. We incorporated the patients calculated risk score as a predictor into both of these models and then calculated their discrimination (concordance indexes). We compared the concordance index of our models with the concordance index reported for the models. Results: With a median follow-up of 57 months, 2110 patients experienced disease recurrence and 591 patients experienced disease progression. Both tools exhibited a poor discrimination for disease recurrence and progression (0.597 and 0.662, and 0.523 and 0.616, respectively, for the EORTC and CUETO models). The EORTC tables overestimated the risk of disease recurrence and progression in high-risk patients. The discrimination of the EORTC tables was even lower in the subgroup of patients treated with BCG (0.554 and 0.576 for disease recurrence and progression, respectively). Conversely, the discrimination of the CUETO model increased in BCG-treated patients (0.597 and 0.645 for disease recurrence and progression, respectively). However, both models overestimated the risk of disease progression in high-risk patients. Conclusion: The EORTC risk tables and the CUETO scoring system exhibit a poor discrimination for both disease recurrence and progression in NMIBC patients. These models overestimated the risk of disease recurrence and progression in high-risk patients. These overestimations remained in BCG-treated patients, especially for the EORTC tables. These results underline the need for improving our current predictive tools. However, our study is limited by its retrospective and multi-institutional design.

Who needs numbers more: patients or doctors?

One of the most burning problems of modern urology still remains the treatment of bladder cancer, which has the highest recurrence rate of any malignancy. Depending on a patient's individual characteristics, the probability of recurrence of non–muscle invasive bladder cancer (NMIBC) at one–year ranges from about 20% to 72% and the probability of progression at five years ranges from about 5% to 45%. In 2006, Sylvester et al. published a paper based on data from 2,596 patients with NMIBC included in seven trials conducted by European Organization for Research and Treatment of Cancer (EORTC) [1]. Their aim was to provide a simple scoring system based on universally assessed clinical pathological factors, which might allow urologists to easily calculate the risk of recurrence and progression after transurethral resection of the bladder tumor (TURBT). Many authors verified the value of this calculator whether it may be replicated and adopted into every day practice. The results were divergent, mostly due to smaller number of cases than those impressively collected by Sylvester. Altieri et al. and Fernandez–Gomez et al., after analysis of 259 and 1,062 cases of NMIBC respectively, found them useful for stratification of recurrence and progression in their cohorts, and suggested the introduction EORTC risk tables into clinical practice [2, 3]. However, a multicenter Spanish team concluded that the discriminative ability of the EORTC tables decreased in patients with BCG progression and overestimated the risk of recurrence in this subgroup of patients [3]. In other words, it makes these tables less useful in high–risk patients. The practical proposal from these and some other studies may be expressed by generally stating that patients from groups stratified as high–risk need more frequent and careful follow–up [4]. The authors of the paper published in this issue of CEJU performed another external validation of EORTC tables in the group of 91 patients with NMIBC [5]. However, this paper concerns clinically important problems, but while both the incidence of bladder cancer is high and EORTC tables still need to be validated in contemporary series of patients, in my opinion, the authors leave us with some unaddressed and unexplained issues. First of all, I feel the lack of clear definition of progression used by the authors. If it was proven by pathological examination, what was the protocol and classification used? Time to progression as defined by EORTC is the time from randomization to the date of first increase to T2 or higher stage [1]. In most of patients this results with withdrawal from further follow–up and the decision about cystectomy. On the other hand, patients with low–risk cancers would benefit from less intensive therapy and surveillance. As authors admit the poor reproducibility of pathologic stage and grade is a well and widely recognized problem. A clear definition must be established in order to standardize the results of different studies and because of the important impact of the clinical decisions about adjuvant therapy, that may be taken based on the nomograms. Even more vital for the individual patients may be the decision about abandoning a bladder preservation approach. The crucial factor, which determines the risk of recurrence, is the quality of primary performed TURBT procedure, as we know that the tumor on a reTURBT in high–risk patients is present in up to half of cases. This high quality is expressed by the most reliable oncological radicalness, personal surgical integrity, and dealing according to the most up–to date clinical and pathological protocols. All this can only be achieved by years of training in high–volume centers. As the authors stated, among other things, tumor recurrence can be attributed to a combination of missed lesions and not complete initial resection, I suppose they are appreciative of well–performed TURBT. As the presence of CIS is considered a strong prognostic factor, both for recurrence and progression, the number of patients with accompanying presence of intraepithelial neoplasia may strongly interfere with the results obtained. In the EORTC, CUETO and UK groups the percentage of CIS–positive cases were 4.4, 7.5, and 8.3% respectively [1, 2, 6]. The authors’ data are roughly the same. Ufortunately, they do not provide the information about the method of diagnosis of CIS (NBI, PDD, biopsy taken?). I would be grateful for the explanation because, in my center, the diagnosis of CIS is a bird of big rarity. Currently, prognostication of patients with all forms of bladder cancer is hampered owing to the inadequacy of clinicopathological risk factors to accurately predict individual treatment outcomes. Therefore, there is definitely an urgent need for having reliable genetic or molecular markers of bladder cancer. There are many of them studied currently and in the past, also by the authors [7–10]. On one hand, I regret that they did not use their investigational experience to combine clinical, pathological, and molecular variables in order to identify a powerful and objective tool to be used in daily practice. On the other hand, I would be happy to congratulate the authors for creating such a tool in the future. There is no clear answer to the question presented in the title. It seems that patients need small number of oriented and well educated urologists who might use big numbers for the their best interests at heart and mind. This is what EORTC tables were created for.

Multicenter Validation of Cyclin D1, MCM7, TRIM29, and UBE2C as Prognostic Protein Markers in Non-Muscle–Invasive Bladder Cancer

Transcripts from the four genes encoding cyclin D1, MCM7, TRIM29, and UBE2C have previously been included in gene expression signatures for outcome prediction in stage Ta/T1 urothelial carcinomas. We investigated the prognostic value of the protein expressions in Ta/T1 urothelial carcinomas patients. We used four different tissue microarrays (TMAs) with a total of 859 Ta/T1 urothelial carcinomas from Danish, Swedish, Spanish, and Taiwanese patient cohorts with long-term follow-up. Protein expression was measured by IHC, and antibody specificity was validated by Western blotting. We found the expression of cyclin D1, MCM7, TRIM29, and UBE2C to be significantly associated with progression to muscle-invasive bladder cancer (log-rank test; P < 0.001) in the Danish training cohort (n = 283). Multivariate Cox regression analysis identified cyclin D1 (P = 0.003), TRIM29 (P = 0.001), and UBE2C (P < 0.001) as independent prognostic markers. The prognostic value of the four proteins was validated in a joint validation cohort from Sweden, Spain, and Taiwan (n = 576). Computer-assisted image analysis of the prognostic markers produced results comparable to those obtained by manual scoring. Finally, a four-protein maximum-likelihood classifier was trained on the Danish training cohort and applied to the validation cohort. The four protein markers may help optimize treatment of patients with Ta/T1 bladder cancer. Additional prospective studies are needed for further validation of their clinical relevance.

Efficacy of European Organization for Research and Treatment of Cancer (EORTC) risk tables for the prediction of recurrence and progression of non-muscle invasive bladder cancer after intravesical pirarubicin instillation

To analyze the influence of intravesical Pirarubicin (THP) instillation on the prediction results of European Organization for Research and Treatment of Cancer (EORTC) risk tables and to discuss the efficacy of EORTC risk tables in clinical application. We retrospectively reviewed the clinical data of 389 patients with non-muscle invasive bladder cancer after TURBT treated with intravesical pirarubicin instillation. According to the EORTC Scoring System, all the cases were divided into low risk group, intermediate risk group and high risk group. The 1-year and 5-year recurrence and progression rates of each group were calculated and compared with the prediction results of the EORTC risk tables. The 1-year recurrence and progression rates of the low risk group were 8.0% and 0, those of the intermediate risk group were 31.0% and 2.8%, and those of the high risk group were 52.5% and 18.6%, respectively. The 5-year recurrence and progression rates of low risk group were 16.0% and 5.3%, those of the intermediate risk group were 42.6% and 10.7%, and those of the high risk group were 63.9% and 41.9%, respectively. The prediction results of progression rate were similar to that of the EORTC risk tables while the overall recurrence rate was lower. The EORTC risk tables can be effectively used to predict the recurrence rate and progression rate of non-muscle invasive bladder cancer. However, the EORTC risk tables have a tendency to overestimate the recurrence rate. Intravesical pirarubicin instillation is helpful to reduce the recurrence rate, yet has no obvious influence on the tumor progression.

Recurrence and Progression in Non-Muscle-Invasive Bladder Cancer Using EORTC Risk Tables

Objectives: It was the aim of this study to evaluate the recurrence and progression at 1, 3 and 5 years in patients with non-muscle-invasive bladder cancer (NMIBC) who underwent a transurethral resection of bladder cancer following intravesical adjuvant chemotherapy or immunotherapy if indicated and to compare them with the European Organization for Research and Treatment of Cancer (EORTC) risk tables. Patients and Methods: Between 2002 and 2011, a total of 259 patients with NMIBC were treated with transurethral resection of bladder cancer. According to the clinical and pathological factors used by the EORTC scoring system, the patients were divided into four groups, and for each group, the probabilities of recurrence and progression were calculated. Results: The recurrence and progression rates of NMIBC of our patients were similar to those in the EORTC risk score system. Moreover, in our sample group, we found a minimally significant reduction in the recurrence rate in the intermediate- and high-risk groups. Conclusion: From the results obtained, we considered it essential to introduce the use of EORTC risk tables into our clinical practice to determine the recurrence and progression of NMIBC.

The EORTC tables overestimate the risk of recurrence and progression in patients with non-muscle-invasive bladder cancer treated with bacillus Calmette-Guérin: external validation of the EORTC risk tables

Abstract Background European Organization for Research and Treatment of Cancer (EORTC) risk tables only included 171 patients treated with bacillus Calmette-Guerin (BCG) for non–muscle-invasive bladder cancer (NMIBC). Objective To evaluate the external validity of the EORTC tables in patients with NMIBC treated with BCG over 5–6 mo. Design, setting, and participants Data on 1062 patients treated with BCG were analyzed. Measurements Discrimination was assessed using the concordance index (c-index) and the prognostic separation index (PSEP). For calibration, probabilities of recurrence and progression obtained with the EORTC risk tables in our series were compared with those reported by the EORTC. Results and limitations With respect to the discriminative ability of the EORTC model, c-index was similar to those reported in the EORTC series for recurrence. However, c-indices for progression in our series were lower than c-indices reported by Sylvester et al. [1]. Although PSEP in our series was lower than in the EORTC series for recurrence at 1 yr, similar results were found at 5 yr. Regarding progression, PSEP in our series was lower than in the EORTC series. Whilst a successful stratification of recurrence and progression probability at 1 and 5 yr was achieved using the EORTC tables in our series, model calibration showed lower risks of recurrence than those reported by Sylvester et al. [1] in all groups. For progression, lower risks were found in higher-risk groups. There are some limitations in the present study. A different distribution of patients was found, with higher proportions of primary grade 3 T1 tumors and tumors in situ than in the EORTC series. An additional limitation is that prior recurrence of the EORTC table was not included in our parameters. Consequently, two separate analyses were performed for recurrence. Conclusions The EORTC model successfully stratified recurrence and progression risks in our cohort. However, the discriminative ability of the EORTC tables decreased in our patients for progression. Moreover, these tables overestimated risks of recurrence and progression after BCG therapy.

Clinical evaluation of European Organization for Research and Treatment of Cancer risk tables in non-muscle invasive bladder cancer

Objective To evaluate the feasibility of European Organization for Research and Treatment of Cancer (EORTC) risk tables in non-muscle invasive bladder cancer in Chinese patients.Methods A retrospective analysis was performed on the data from 185 patients with non-muscle invaaive urothelial bladder cancer from January 2003 to February 2009. Among the 185 patients, 128 patients were stage Ta compared with 57 patients who were stage T1. There were 87, 53 and 45 patients with grade G1, G2 and G3 respectively. Transurethral resection of the bladder tumor was performed on all the patients and all the patients received routine post-operative intravesical instillation. A telephone interview follow-up was conducted on all the patients, and the average follow-up period was 36 months. EORTC risk tables were used to calculate risk scores for recurrence and progression for each patient. The recurrence and progression rates of different risk groups were recorded and compared with the estimated rates by EORTC risk table. Statistical analysis was used for comparison. ResultsTotal 1-year recurrence rate and progression rate for these patients were 25.9% and 3.8% respectively. According to calculated values of the patients, the 1-year recurrence rates of Group 0, Group 1-4, Group 5-9, Group 10-17 were 10.4%(5/48), 21. 5%(14/65), 35. 2% (19/54), 55.6%(10/18), respectively. The 1-year progression rates of Group 0, Group 2-6, Group 7-13, Group 14-23 were 0% (0/43), 1.5% (1/67), 6. 7% (4/60), 13. 3% (2/15). There was no significant difference between the real rates and estimated rates of the EORTC risk tables (P＞0. 05). However,the 1-year recurrence and progression rates between the low risk group, the medium risk group and the high risk group showed significant differences respectively (P ＜ 0. 05 ). Conclusions The EORTC risk tables are feasible to evaluate the recurrence and progression risk of non-muscle invasive bladder cancer in the present cohort. Nevertheless, the long term value and feasibility need more research to confirm. Key words: Urinary bladder neoplasms;  Carcinoma;  Non muscle-invasive bladder cancer; European Organization for Research and Treatment of Cancer risk tables;  Prognosis

The Efficacy of the EORTC Scoring System and Risk Tables for the Prediction of Recurrence and Progression of Non-Muscle-Invasive Bladder Cancer after Intravesical Bacillus Calmette-Guerin Instillation

PurposeThe European Organization for Research and Treatment of Cancer (EORTC) scoring system and risk table were introduced in the 2008 European Association of Urology guidelines on TaT1 bladder cancer. We compared the recurrence and progression rate between EORTC risk tables and author's patients who underwent transurethral resection of bladder cancer (TURB) following intravesical Bacillus Calmette-Guerin (BCG) instillation.Materials and MethodsThe medical records of 251 patients who underwent TURB and were diagnosed with non-muscle-invasive bladder cancer from l993 to 2007 were analyzed. The patients were divided into 2 groups: the recurrence group and the progression group. According to the EORTC scoring system, the patients in each group were categorized in terms of number of tumors, tumor size, prior recurrence rate, T category, carcinoma in situ, and pathologic grade and the scores were summed. According to the summed scores, the recurrence group and the progression group were divided into 3 subgroups: low, intermediate, and high risk, respectively. The recurrence rate and progression rate of each group were compared with the EORTC risk tables.ResultsThe recurrence rate and progression rate were almost similar to the EORTC risk tables. However, the recurrence rate was low in the intermediate-risk group.ConclusionsClinical utilization of the EORTC scoring system and risk tables is very effective in predicting the recurrence and progression of non-muscle-invasive bladder cancer and in selecting treatment.