European Organization For Research And Treatment Of Cancer Risk Research Articles

Performance of the EORTC and CUETO Models to Predict Recurrence and Progression in High-risk Non-muscle-invasive Bladder Cancer Patients.

To evaluate the performance of the European Organization for Research and Treatment of Cancer (EORTC) and the Spanish Urological Club for Oncological Treatment (CUETO) risk scoring models in non-muscle-invasive bladder cancer (NMIBC) patients defined as high risk according to European Association of Urology guidelines and managed based on current recommendations. Data from 187 high-risk NMIBC patients treated at a tertiary center between July 2010 and November 2021 were analyzed retrospectively. One- and five-year recurrence- and progression-free survival were assessed for each patient using the EORTC and CUETO risk scores. The patients were divided into four risk groups according to their risk scores as low, medium-low, medium-high and high risk, as indicated in the models. Discriminative ability was evaluated with the Harrell's concordance index (c-index). Both risk scoring models overestimated the risk of recurrence and progression at one and five years. Only the prediction of recurrence at five years in the high risk group according to the CUETO model was compatible with our cohort. CUETO (c-indices for recurrence and progression were 0.802 and 0.834, respectively) exhibited better discrimination than EORTC (0.722 for recurrence and 0.752 for progression) in the prediction of disease recurrence and progression. The CUETO model was superior to the EORTC model in predicting recurrence and progression and stratifying patients with different prognoses in our high-risk NMIBC patient population treated according to current guideline recommendations. However, both models overestimated the probability of disease recurrence and progression. Only the probability of recurrence at five years in the high-risk group of the CUETO model was compatible with our cohort.

HER2 positivity predicts BCG unresponsiveness and adaptive immune cell exhaustion in EORTC risk-stratified cohort of bladder cancer.

Predicting the response to Bacillus Calmette-Guérin (BCG) therapy in high-risk patients with non-muscle invasive bladder cancer (NMIBC) is crucial, as failure may necessitate interventions, such as radical cystectomy or salvage therapy. With the recent classification of genetic class 2a (which has HER2 protein abundance as its signature mutation of ERBB2), evaluating its prognostic role and relationship with BCG response could yield important results. This retrospective study included 160 patients with NMIBC who underwent transurethral resection of bladder tumors at Gangneung Asan Hospital between 2000 and 2013 and were stratified based on the European Organization for Research and Treatment of Cancer (EORTC) risk criteria. In addition, we analyzed a subset of 67 patients who had received BCG induction therapy to identify factors predictive of BCG treatment response. Univariate and multivariate analyses were used to assess the impact of clinicopathological factors, HER2 positivity, and EORTC risk on recurrence, progression, survival, and BCG response. Each variable's prognostic significance was determined using the Kaplan-Meier analysis. The tumor microenvironments (TMEs) were evaluated in relation to HER2 and EORTC risk. Patients with HER2+ had a higher median age, a greater prevalence of high-grade tumors, and more frequent recurrences. The univariate analysis demonstrated that the HER2+, intermediate (vs. low-risk) high (vs. low-risk), and EORTC recurrence risk groups were significantly associated with recurrence. In patients treated with BCG, only the HER2+ status predicted recurrence. In the univariate analysis for progression, age, high EORTC progression risk (vs. low-to-intermediate), HER2+, and programmed death-ligand 1 positive (PD-L1+) were significant factors. In multivariate analyses for progression, age, high EORTC progression risk, and PD-L1+ were significant factors for progression. HER2 expression was associated with the TME, influencing the proportion of PD-L1+ cells, as well as other markers of PD-1, CD8, and Ki67. The HER2+ status may be related to genetic characteristics that appear more frequently in older age, which suggests a potential for predicting the recurrence and response to BCG treatment. Additionally, analyzing TME trends of aggressive adaptive immune response characterized by HER2 expression provides insight into recurrence and BCG response mechanisms.

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.

Assessing the Impact of the Absence of Detrusor Muscle in Ta Low-grade Urothelial Carcinoma of the Bladder on Recurrence-free Survival

BackgroundObtaining detrusor muscle (DM) in transurethral resection of bladder tumor (TURBt) specimen is considered a surrogate marker of resection quality. However, evidence was principally investigated in high-risk tumors. Therefore, DM sampling for low-grade (LG) urothelial carcinoma (UC) remains poorly investigated and certainly requires further investigation. ObjectiveTo assess whether the absence of DM in TURBt specimen has a negative impact on recurrence-free survival (RFS) in patients with a Ta LG UC. Design, setting, and participantsA multicenter TURBt database was queried for “LG, Ta, UC of the bladder.” All patients treated between 1996 and 2018 with tumor grade assessed according to both 1973 World Health Organization and 2004 WHO/International Society of Urological Pathology grading classifications and with a minimum follow-up of 1 yr were included. Patients with a previous history of high-grade UC, upper urinary tract UC, or bladder tumor differentiations other than UC were excluded. InterventionTURBt. Outcome measurements and statistical analysisBaseline demographic, clinical, and pathologic data were analyzed. The European Organization for Research and Treatment of Cancer (EORTC) risk group was recorded. Kaplan-Meier analysis was performed to assess the predictive role of clinical and pathologic data for RFS. Univariable and multivariable Cox regression analyses were performed to identify the predictors of recurrence. Results and limitationsOverall, 521 patients were included. At Kaplan-Meier analysis, the low-risk cohort displayed significantly higher RFS than the intermediate-risk cohort (1-yr RFS 87% vs 79%; log-rank p = 0.007). At univariable Cox regression analysis, only gender, multiple tumors, tumor diameter ≥3 cm, and EORTC risk group were significant predictors of recurrence. Absence of DM had no impact on RFS. Multivariable Cox regression analysis confirmed gender and EORTC risk group as independent predictors of recurrence. ConclusionsAbsence of DM in TURBt specimen has negligible role in RFS of patients with Ta LG tumors of the bladder. Patient summaryIn this study, we assessed the role that detrusor muscle (DM) in transurethral resection of bladder tumor specimen has in recurrence-free survival, in patients with a Ta low-grade urothelial carcinoma of the bladder. Absence of DM has no impact on tumor recurrence; therefore, it does not require additional attention.

Therapeutic Options in High-Risk Nonmuscle Invasive Bladder Cancer During the Shortage of Bacillus Calmette-Guérin

Bladder cancer is the second most common malignant tumor of the urinary tract and is the seventh most common cancer among men worldwide and 17th among women. Seventy to eighty percent of bladder cancers are nonmuscle invasive bladder cancer (NMIBC) at the first diagnosis, and about 20%–25% of patients progress to invasive bladder cancer. According to the EORTC (European Organisation for Research and Treatment of Cancer) risk classification study, patients with high-risk NMIBC (T1, high grade/G3, carcinoma in situ) have a 5-year recur risk of up to 80% and a 50% chance of advance. Treatment options for high-risk NMIBC recommend Bacillus Calmette-Guérin (BCG) intrabladder infusion therapy after transurethral resection of bladder tumor, and intrathecal bladder chemotherapy such as mitomycin C or epirubicin, or early radical bladder resection may also be considered in recurrent high-risk patients. Among them, BCG intrathecal bladder infusion therapy has been demonstrated to reduce progression to mycoinvasive disease and has been used as a primary treatment for high risk NMIBC patients. BCG intrathecal infusion therapy reported that less than 10%–20% of patients in the responding group developed myoinvasive disease, while 66% of the patients in the poor response group developed myoinvasive disease. However, because BCG is made from Mycobacterium bovis, mass production is difficult due to a number of factors, such as the strength, quality, purity, and potency of BCG vaccines that pharmaceutical companies need to control. Most of all, BCG vaccines are prone to bacterial contamination due to long incubation periods and expensive specialized equipment. These factors eventually led to the closure of the Sanofi Institute for BCG vaccines in 2012, which continues the difficulties Merck has faced due to the lack of BCG supplies. Because BCG is a generic drug, the 2003 Medicare Modernization Act limited costs by up to 6% above the Medicare average selling price. Therefore, in 2016, Sanofi did not find any party to continue BCG's manufacturing technology and acquire the company, as a result, it announced that it will stop production in the United States, Canada, the United Kingdom, and France. In this article, we will discuss how to treat high-risk NMIBC patients under these BCG deficiencies, along with some of the treatment options that can be implemented in cases of drug shortage. Key Words: BCG vaccine; Urinary bladder neoplasms; Intravesical administration.

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 ...

Validation of EORTC, CUETO, and EAU risk stratification in prediction of recurrence, progression, and death of patients with initially non-muscle-invasive bladder cancer (NMIBC): A cohort analysis.

Brief Description: The results demonstrate that the European Organisation for Research and Treatment of Cancer (EORTC) scale provides the best recurrence and progression prediction in comparison with European Association of Urology (EAU) and Club Urologico Espanol de Tratamiento Oncologico (CUETO) risk scores among a mixed population of patients with non–muscle‐invasive bladder who were treated with, or without, Bacillus Calmette‐Guerin (BCG) and without any immediate postoperative chemotherapy. The study highlights the role of tumor diameter and extent in transition prediction.This retrospective cohort analysis of 322 patients with newly diagnosed non–muscle‐invasive bladder cancer (NMIBC) assesses the concordance and accuracy of predicting recurrence and progression by EAU‐recommended tools (EAU risk groups, EORTC, and CUETO). One‐year and five‐year c‐indices ranged from 0.55 to 0.66 for recurrence and from 0.72 to 0.82 for progression. AUCROC of predictions ranged from 0.46 for 1‐year recurrence risk based on CUETO groups, to 0.82 for 1‐year progression risk based on EAU risk groups. Diameter (HR: 1.91; 95% CI: 1.39‐2.61) and tumor extent (HR: 1.21; 95% CI: 1.01‐1.46 for recurrence; HR: 3.1; 95% CI: 1.40‐6.87 for progression) were shown to be significant predictors in multistate analysis. Lower accuracy of prediction was observed for patients treated with BCG maintenance immunotherapy. The EORTC model (overall c‐index c = 0.64; 95% CI: 0.61‐0.68) was superior to the EAU (P = .035; .62; 95% CI: 0.59‐0.66) and CUETO (P < .001; c = 0.53; 95% CI: 0.50‐0.56) models in predicting recurrence. The EORTC model (c = 0.82; 95% CI: 0.77‐0.86) also performed better than CUETO (P = .008; c = 0.73; 95% CI: 0.66‐0.81) but there was no sufficient evidence that it performed better than EAU (P = .572; c = 0.81; 95% CI: 0.77‐0.84) for predicting progression. EORTC and CUETO gave similar predictions for progression in BCG‐treated EAU high‐risk patients (P = .48). We share anonymized individual patient data. In conclusion, despite moderate accuracy, EORTC provided the best recurrence and progression prediction for a mixed population of patients treated with, or without BCG, and without immediate postoperative chemotherapy.

Development and Validation of a Novel Recurrence Risk Stratification for Initial Non-Muscle Invasive Bladder Cancer in the Han Chinese Population.

Background: Some classification models for determining the risk of recurrence after transurethral resection of bladder tumor (TURBT) in patients with non-muscle invasive bladder cancer (NMIBC) had some shortcomings in clinical applications. This study aimed to investigate whether the European Organization for Research and Treatment of Cancer (EORTC) risk stratification was useful to predict the recurrence of NMIBC in the Han Chinese population. In addition, we developed and validated a novel risk stratification method for recurrence prediction of NMIBC.Methods: Excluding cases who do not meet the inclusion criteria, 606 patients with NMIBC from the First Affiliated Hospital of Zhengzhou University were included in the testing and validation groups. The recurrence-free survival (RFS) curve according to the EORTC risk classifications was calculated by the Kaplan-Meier and the log-rank test methods. Receiver operating characteristic (ROC) curve analysis was used to estimate the diagnosis value for recurrence. We built a logistic regression model for recurrence in NMIBC patients combining the independent recurrence prognostic factors. One external validation group including 166 patients with NMIBC from the Zhongnan Hospital of Wuhan University was also used to assess the logistic regression model.Results: There was no significant difference in RFS rates between the groups grouped according to EORTC. We constructed a novel risk model to predict recurrence by classifying patients into two groups using ten independent prognostic factors [bladder cancer-specific nuclear matrix protein 4 (BLCA-4), bladder tumour antigen (BTA), nuclear matrix protein 22 (NMP22), carcinoembryonic antigen (CEA), body mass index, smoking, family history of bladder cancer, occupational exposure to aromatic amine chemicals, number of tumours, bladder instillation of chemotherapeutic agents] to predict tumour recurrence based on logistic regression analyses (testing group). According to the novel recurrence risk classification, there was a significant difference in 5-year RFS rates between the low-risk group and the high-risk group (Validation group and the external validation group).Conclusions: Our novel classification model can be a useful tool to predict recurrence risk in the Han Chinese population with NMIBC.

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.

Comparison of the EORTC tables and the EAU categories for risk stratification of patients with nonmuscle-invasive bladder cancer

PurposeTo characterize outcomes of patients with TaT1 urothelial carcinoma of the bladder stratified by the European Association of Urology (EAU) categories and to compare them with European Organization for Research and Treatment of Cancer (EORTC) risk groups to assess the rate and effect of reclassification. Patients and methodsA multi-institutional database of 5,122 patients with TaT1 urothelial carcinoma of the bladder who underwent transurethral resection of the bladder with or without adjuvant therapy at 8 institutions between 1996 and 2007. Multivariable Cox-regression analyses addressed factors associated with disease recurrence and progression. The net reclassification index was used to compare the performance of the EAU categories with the EORTC scoring system. ResultsOf 5,122 patients, 632 (12.3%), 2,302 (45.0%), and 2,188 (42.7%) were assigned to the low-, intermediate-, and high-risk EAU category, respectively. Within a median follow-up of 62 months (interquartile range: 27–97), 2,365 (46.2%) and 516 (10.1%) patients experienced disease recurrence and progression, respectively. In multivariable Cox-regression analyses, EAU intermediate- and high-risk categories were associated with a higher risk of disease recurrence (P<0.001) and progression (P<0.001) compared to low-risk patients. Application of the EAU categories reclassified 1,940 (37.9%) patients into a higher risk group for recurrence. Likewise, 602 (11.8%) patients were reclassified to a higher and 278 (5.4%) to a lower risk group for progression. The net reclassification index of the EAU risk stratification was 0.1% (95% CI: −3.1% to 3.2%) for recurrence and 10.1% (95% CI: −8.0% to 12.0%) for progression, respectively. ConclusionsCompared to EORTC risk stratification, the EAU categories reclassifies 37.9% patients into a higher risk group of recurrence and 11.8% into a higher risk of progression. However, the novel risk stratification assigns most patients to the same treatment as the more complex EORTC tables and can be regarded as an alternative tool for treatment decision-making.

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.

Cell-cycle markers do not improve discrimination of EORTC and CUETO risk models in predicting recurrence and progression of non–muscle-invasive high-grade bladder cancer

PurposeTo assess if a panel of cell-cycle markers could improve the discrimination of European Organization for Research and Treatment of Cancer (EORTC) and Spanish Urological Club for Oncological Treatment (CUETO) models in predicting recurrence and progression of high-grade non–muscle-invasive bladder cancer (NMIBC). Materials and methodsBetween January 2007 and January 2012, every patient with high-grade NMIBC treated with transurethral resection of bladder underwent immunohistochemical staining for 5 biomarkers (p21, p27, p53, KI-67, and cyclin E1). We excluded patients who had muscle-insvasive disease, underwent early cystectomy, and those with incomplete follow-up. Kaplan-Meier curves assessed recurrence and progression-free survival. Univariate and multivariate Cox regression analysis assessed the predictive ability of markers after correcting for EORTC or CUETO risk scores. Harrel concordance index assessed for discrimination. ResultsThere were 131 patients with a median follow-up of 31.1 months. Stage was Ta (50%), T1 (44%), and Tis (8%). For 95 patients this was the primary tumor. Intravesical therapy was used in 76% of cases of which 45% had maintenance. Recurrence-free survival rates at 6, 12, and 24 months were 68.9%, 52.1%, and 33.2%, respectively, whereas progression-free survival rate at 6, 12, and 24 months were 93.8%, 88%, and 84.3%, respectively. No differences in survival based on number of altered markers were noted. Biomarker status was neither a significant predictor of recurrence nor progression. Marker alterations marginally improved discrimination of EORTC and CUETO models, which were confirmed to be mediocre. ConclusionsMarkers were not significant predictors of recurrence nor progression in patients with high-grade NMIBC and their addition to prediction models is of little benefit.

Development and Validation of a Novel Recurrence Risk Stratification for Initial Non-muscle Invasive Bladder Cancer in Asia

BackgroundSome risk classifications to determine prognosis of patients with non-muscle invasive bladder cancer (NMIBC) have disadvantages in the clinical setting. We investigated whether the EORTC (European Organization for Research and Treatment of Cancer) risk stratification is useful to predict recurrence and progression in Japanese patients with NMIBC. In addition, we developed and validated a novel, and simple risk classification of recurrence. MethodsThe analysis was based on 1085 patients with NMIBC at six hospitals. Excluding recurrent cases, we included 856 patients with initial NMIBC for the analysis. The Kaplan–Meier method with the log-rank test were used to calculate recurrence-free survival (RFS) rate and progression-free survival (PFS) rate according to the EORTC risk classifications. We developed a novel risk classification system for recurrence in NMIBC patients using the independent recurrence prognostic factors based on Cox proportional hazards regression analysis. External validation was done on an external data set of 641 patients from Kyorin University Hospital. FindingsThere were no significant differences in RFS and PFS rates between the groups according to EORTC risk classification. We constructed a novel risk model predicting recurrence that classified patients into three groups using four independent prognostic factors to predict tumour recurrence based on Cox proportional hazards regression analysis. According to the novel recurrence risk classification, there was a significant difference in 5-year RFS rate between the low (68.4%), intermediate (45.8%) and high (33.7%) risk groups (P<0.001). InterpretationAs the EORTC risk group stratification may not be applicable to Asian patients with NMIBC, our novel classification model can be a simple and useful prognostic tool to stratify recurrence risk in patients with NMIBC. FundingNone.

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.

Value of detection of preoperative urinary soluble Fas expression in predicting the recurrence of non-muscle invasive bladder cancer

To investigate the clinical value of detection of preoperative urinary soluble Fas (sFas) expression in predicting the recurrence of non-muscle invasive bladder cancer (NMIBC). We performed a prospective research, which included 128 cases with NMIBC from January 2008 to April 2011. Expression levels of sFas in urine, which was saved at the first morning from preoperative NMIBC patients, were analyzed by ELISA. Clinical and pathological data, European Organization for Research and Treatment of Cancer (EORTC) risk group category, follow-up data and urinary sFas values were collected from each patient, and each prognostic outcome was evaluated by statistical analysis of non-parametric test. Urinary sFas values and recurrence-free probabilities were estimated by the Kaplan-Meier method and compared by the log rank test. Cox proportional hazards regression models were performed to determine the independent predictors of NMIBC recurrence. The prognosis index (PI) was established. The urinary sFas level was significantly elevated in the NMIBC cases with a higher stage or grade or high-risk EORTC group category than in those with a lower stage or grade or low-risk EORTC group category (each P<0.05), regardless of age or gender (P>0.05). Kaplan-Meier analysis revealed a significant increase in incidence of recurrence in the NMIBC patients with high sFas levels in the urine (P<0.001). According to Cox regression analysis, the urinary sFas level and EORTC risk group category (each P<0.05) were the independent predictors of NMIBC recurrence. Based on the outcome of Cox regression, the formula of PI=(0.004×sFas value+1.179×EORTC score) was established. Our study indicates that urinary sFas test may help to identify NMIBC patients at risk of tumor recurrence and it deserves further research.

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.

Bladder cancer: ESMO Practice Guidelines for diagnosis, treatment and follow-up

Bladder cancer: ESMO Practice Guidelines for diagnosis, treatment and follow-up