Club Urológico Español De Tratamiento Oncológico Research Articles

Prognostic Significance of the Neutrophil-to-Lymphocyte Ratio in Patients with Non-Muscle Invasive Bladder Cancer treated with Intravesical Bacillus Calmette-Guérin and the Relationship with the CUETO Scoring Model.

In this study, we evaluated the predictability of a modified Club Urológico Español de Tratamiento Oncológico (CUETO) scoring model and preoperative neutrophil-to-lymphocyte ratio (NLR) in patients with non-muscle invasive bladder cancer (NMIBC). From August 2005 to May 2016, a total of 281 patients received intravesical bacillus Calmette-Guérin therapy after transurethral resection of a bladder tumor. The pathologic stage of all patients was Ta or T1. Of 281 patients, 84 (29.9%) experienced recurrence and 14 (5.0%) developed progression. The mean follow-up period was 46 months. The cut-off value for NLRs was 2.29. One hundred-eight patients (38.4%) displayed a high NLR (> 2.29). In Kaplan-Meier curve analysis, a high NLR was associated with lower recurrence-free survival (RFS) (P < .001) and progression-free survival (PFS) (P = .002). CUETO scores were associated with RFS (P < .001), but not with PFS (P = .423). A combination of NLRs and the CUETO risk model correlated with RFS (P < .001) and PFS (P = .002). In multivariate analysis, female gender, concomitant carcinoma in situ (CIS), tumor number >3, recurrent tumors, and a high NLR were independent factors predicting recurrence (all P < .05). Concomitant CIS, recurrent tumors, and a high NLR were independent factors for predicting progression (all P < .05). In patients with NMIBC, an NLR >2.29 was identified as a significant factor for predicting tumor recurrence and progression. Inclusion of preoperative NLR enhanced the accuracy of the CUETO model to predict disease progression.

Clinicopathological Criteria Predictive of Recurrence Following Bacillus Calmette-Guérin Therapy Initiation in Non-Muscle-Invasive Bladder Cancer: Retrospective Cohort Study.

BackgroundBacillus Calmette-Guérin (BCG) is currently the most clinically effective intravesical treatment for non–muscle-invasive bladder cancer (NMIBC), particularly for patients with high-risk NMIBC such as those with carcinoma in situ. BCG treatments could be optimized to improve patient safety and conserve supply by predicting BCG efficacy based on tumor characteristics or clinicopathological criteria.ObjectiveThe aim of this study is to assess the ability of specific clinicopathological criteria to predict tumor recurrence in patients with NMIBC who received BCG therapy along various treatment timelines.MethodsA total of 1331 patients (stage Ta, T1, or carcinoma in situ) who underwent transurethral resection of a bladder tumor between 2006 and 2017 were included. Univariate analysis, including laboratory tests (eg, complete blood panels, creatinine levels, and hemoglobin A1c levels) within 180 days of BCG therapy initiation, medications, and clinical and demographic variables to assess their ability to predict NMIBC recurrence, was completed. This was followed by multivariate regression that included the elements of the Club Urológico Español de Tratamiento Oncológico (CUETO) scoring model and variables that were significant predictors of recurrence in univariate analysis.ResultsBCG was administered to 183 patients classified as intermediate or high risk, and 76 (41.5%) experienced disease recurrence. An abnormal neutrophil-to-lymphocyte ratio measured within 180 days of induction BCG therapy was a significant predictor (P=.047) of future cancer recurrence and was a stronger predictor than the CUETO score or the individual variables included in the CUETO scoring model through multivariate analysis.ConclusionsAn abnormal neutrophil-to-lymphocyte ratio within 180 days of BCG therapy initiation is predictive of recurrence and could be suggestive of additional or alternative interventions.

Deep Learning-based Recalibration of the CUETO and EORTC Prediction Tools for Recurrence and Progression of Non–muscle-invasive Bladder Cancer

Despite being standard tools for decision-making, the European Organisation for Research and Treatment of Cancer (EORTC), European Association of Urology (EAU), and Club Urologico Espanol de Tratamiento Oncologico (CUETO) risk groups provide moderate performance in predicting recurrence-free survival (RFS) and progression-free survival (PFS) in non–muscle-invasive bladder cancer (NMIBC). In this retrospective combined-cohort data-mining study, the training group consisted of 3570 patients with de novo diagnosed NMIBC. Predictors included gender, age, T stage, histopathological grading, tumor burden and diameter, EORTC and CUETO scores, and type of intravesical treatment. The models developed were externally validated using an independent cohort of 322 patients. Models were trained using Cox proportional-hazards deep neural networks (deep learning; DeepSurv) with a proprietary grid search of hyperparameters. For patients treated with surgery and bacillus Calmette-Guérin-treated patients, the models achieved a c index of 0.650 (95% confidence interval [CI] 0.649–0.650) for RFS and 0.878 (95% CI 0.873–0.874) for PFS in the training group. In the validation group, the c index was 0.651 (95% CI 0.648–0.654) for RFS and 0.881 (95% CI 0.878–0.885) for PFS. After inclusion of patients treated with mitomycin C, the c index for RFS models was 0.6415 (95% CI 0.6412–0.6417) for the training group and 0.660 (95% CI 0.657–0.664) for the validation group. Models for PFS achieved a c index of 0.885 (95% CI 0.885–0.885) for the training set and 0.876 (95% CI 0.873–0.880) for the validation set. Our tool outperformed standard-of-care risk stratification tools and showed no evidence of overfitting. The application is open source and available at https://biostat.umed.pl/deepNMIBC/. Patient summaryWe created and validated a new tool to predict recurrence and progression of early-stage bladder cancer. The application uses advanced artificial intelligence to combine state-of-the-art scales, outperforms these scales for prediction, and is freely available online.

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.

Validation of the CUETO scoring model for predicting recurrence and progression in T1G3 urothelial carcinoma of the bladder

Introduction and objectivesVarious studies tried to validate Club Urológico Español de Tratamiento Oncológico (CUETO) tables, yet, none of this papers focused on the high and very high risk bladder cancers. The aim of the study was to externally validate the CUETO model for predicting disease recurrence and progression in group of T1G3 tumours treated with BCG immunotherapy. Patients or materials and methodsData from 414 patients with primary T1G3 bladder cancer were analyzed. To evaluate the model discrimination, Cox proportional hazard regression models were created and concordance indexes were calculated. ResultsThe median follow-up was 68 months. The recurrence was observed in 212 (51.2%) and 64 patients (15.5%) experienced the recurrence more than once during the study follow-up. Progression of the cancer was observed in 106 patients (25.6%). Radical cystectomy was performed in 115 patients (27.8%) and there were 64 (15.5%) cancer specific deaths. For recurrence and progression probability, the concordance index of the CUETO models was 0.633 and 0.697 respectively. CUETO tables underestimated significantly the risk of recurrence and marginally the risk of progression in the first year of observation. For 5 years of observation, the trend for the recurrence was much less clear. On the contrary, there was slight overestimation in the risk of progression. The study is limited by retrospective nature. ConclusionsIt was shown that the CUETO risk tables exhibit a fair discrimination for both disease recurrence and progression in T1G3 patients treated with BCG. CUETO scoring model underestimates the risk of tumour recurrence, but predicts well risk of progression.

Validación de las tablas del grupo CUETO para predecir la recurrencia y progresión del carcinoma urotelial de vejiga T1G3

Introduction and objectivesVarious studies tried to validate Club Urológico Español de Tratamiento Oncológico (CUETO) tables, yet, none of this papers focused on the high and very high risk bladder cancers. The aim of the study was to externally validate the CUETO model for predicting disease recurrence and progression in group of T1G3 tumors treated with BCG immunotherapy. Patients or materials and methodsData from 414 patients with primary T1G3 bladder cancer were analysed. To evaluate the model discrimination, Cox proportional hazard regression models were created and concordance indexes were calculated. ResultsThe median follow-up was 68 months. The recurrence was observed in 212 (51.2%) and 64 patients (15.5%) experienced the recurrence more than once during the study follow-up. Progression of the cancer was observed in 106 patients (25.6%). Radical cystectomy was performed in 115 patients (27.8%) and there were 64 (15.5%) cancer specific deaths. For recurrence and progression probability, the concordance index of the CUETO models was 0.633 and 0.697 respectively. CUETO tables underestimated significantly the risk of recurrence and marginally the risk of progression in the first year of observation. For 5 years of observation, the trend for the recurrence was much less clear. On the contrary, there was slight overestimation in the risk of progression. The study is limited by retrospective nature. ConclusionsIt was shown that the CUETO risk tables exhibit a fair discrimination for both disease recurrence and progression in T1G3 patients treated with BCG. CUETO scoring model underestimates the risk of tumor recurrence, but predicts well risk of progression.

Prediction tools in non-muscle invasive bladder cancer.

Non-muscle invasive bladder cancer (BCa) is the second most common genitourinary malignancy, burdened by high rates of recurrence and progression. Urologist are encouraged to stratify patients on the bases of recurrence and progression risks in order to define the best therapeutic approach and follow-up scheme. For these reasons, the aim of the present non-systematic review was to assess the literature on prediction tools in non-muscle invasive BCa. Currently, the most widely used tools remain the European Organization for Research and Treatment of Cancer (EORTC) and the Club Urologico Espanol de Tratamiento Oncologico (CUETO) risk tables, which are based on clinicopathologic features. Recent external validations, therefore, reported their low accuracy, probably related to the lack of the role of re-transurethral resection (TURBT), early instillations, chemotherapy and complete BCG schedules in the studies included to asses these scores. More recently several immunological, biochemical and genetics biomarkers have been tested by themselves and in combination with clinicopathologic features, and many of them resulted related with risk of recurrence and progression. Future perspectives will presumably include the update of EORTC and CUETO scores with newest guidelines’ recommendations and their integration with biomarkers.

Predicting Nonmuscle Invasive Bladder Cancer Recurrence and Progression in a United States Population

We assessed the performance of the EORTC (European Organisation for Research and Treatment of Cancer) and CUETO (Club Urológico Español de Tratamiento Oncológico) nonmuscle invasive bladder cancer predictive models compared to current United States NCCN Guidelines® in an American population. We retrospectively analyzed the electronic medical records of patients with nonmuscle invasive bladder cancer in a multicenter population in the United States. We evaluated recurrence-free and progression-free survival according to EORTC and CUETO, and assessed discriminative performance with the c-index at 1 and 5 years. We then compared the discrimination of EORTC and CUETO to the discrimination of the 4 nonmuscle invasive bladder cancer treatment groups described in NCCN Guidelines. We identified 1,333 patients with nonmuscle invasive bladder cancer and a median followup of 37 months. At 5 years the recurrence c-index of EORTC and CUETO was 0.59 and 0.56 while for progression it was higher at 0.74 and 0.72, respectively. NCCN Guidelines demonstrated a similar c-index of 0.56 and 0.75, respectively. The discrimination of all 3 risk models decreased in patients who received bacillus Calmette-Guérin. EORTC was better able to identify patients at low risk for recurrence or progression but it overestimated the 5-year risk of progression in patients at high risk. This study was limited by its retrospective design. Our work illustrates the need for improved predictive tools for clinicians who treat patients with nonmuscle invasive bladder cancer. However, until new tools are developed NCCN Guidelines are a simple option for clinicians who treat patients with nonmuscle invasive bladder cancer. Those guidelines provide predictive power comparable to that of the EORTC and CUETO models.

Non-muscle invasive bladder cancer risk stratification.

Introduction:Non-muscle invasive bladder cancer (NMIBC) comprises about 70% of all newly diagnosed bladder cancer, and includes tumors with stage Ta, T1 and carcinoma in situ (CIS.) Since, NMIBC patients with progression to muscle-invasive disease tend to have worse prognosis than with patients with primary muscle-invasive disease, there is a need to significantly improve risk stratification and earlier definitive treatment for high-risk NMIBC.Materials and Methods:A detailed Medline search was performed to identify all publications on the topic of prognostic factors and risk predictions for superficial bladder cancer/NMIBC. The manuscripts were reviewed to identify variables that could predict recurrence and progression.Results:The most important prognostic factor for progression is grade of tumor. T category, tumor size, number of tumors, concurrent CIS, intravesical therapy, response to bacillus Calmette–Guerin at 3- or 6-month follow-up, prior recurrence rate, age, gender, lymphovascular invasion and depth of lamina propria invasion are other important clinical and pathological parameters to predict recurrence and progression in patients with NMIBC. The European Organization for Research and Treatment of Cancer (EORTC) and the Spanish Club UrológicoEspañol de Tratamiento Oncológico (CUETO) risk tables are the two best-established predictive models for recurrence and progression risk calculation, although they tend to overestimate risk and have poor discrimination for prognostic outcomes in external validation. Molecular biomarkers such as Ki-67, FGFR3 and p53 appear to be promising in predicting recurrence and progression but need further validation prior to using them in clinical practice.Conclusion:EORTC and CUETO risk tables are the two best-established models to predict recurrence and progression in patients with NMIBC though they tend to overestimate risk and have poor discrimination for prognostic outcomes in external validation. Future research should focus on enhancing the predictive accuracy of risk assessment tools by incorporating additional prognostic factors such as depth of lamina propria invasion and molecular biomarkers after rigorous validation in multi-institutional cohorts.

Are we undertreating invasive bladder cancer? Optimizing outcomes in a high-risk disease

To highlight the important issues that may improve patient outcomes in the setting of invasive bladder cancer. Although approximately 80% of patients with bladder cancer present with disease confined to the mucosa which can be treated locally, progression to muscle-invasive bladder carcinoma (MIBC) is associated with adverse outcomes. Stage and grade have traditionally been used to predict progression. European Organization for Research and Treatment of Cancer (EORTC) and Club Urológico Español de Tratamiento Oncológico (CUETO) have designed prognostic models that further refine risk assessment. Recent attempts to integrate molecular biomarkers may further improve these models. Treating appropriate patients earlier with radical cystectomy offers the hope of decreasing the extent of disease at the time of surgery. In patients with MIBC, neoadjuvant chemotherapy has been shown to improve patient outcome. Selecting appropriate patients remains a challenge. Preoperative models to predict risk of lymph node-positive disease and preoperative imaging with fluorodeoxyglucose positron emission tomography or MRI have been shown to be useful in that regard. Multidisciplinary care offers better patient support and collaboration during the treatment phase and improves quality of life. Improved outcomes in localized bladder cancer requires an integrated approach including better identification of high-risk disease, earlier use of cystectomy, broader use of chemotherapy and the availability of a dedicated multidisciplinary team.

Prognostic Factors in Patients with Non–Muscle-Invasive Bladder Cancer Treated with Bacillus Calmette-Guérin: Multivariate Analysis of Data from Four Randomized CUETO Trials

ObjectivesTo evaluate the prognostic factors of recurrence and progression after intravesical adjuvant bacillus Calmette-Guérin (BCG) immunotherapy in patients with non–muscle-invasive bladder tumors. MethodsFrom February 1990 to May 1999, the Spanish Club Urológico Español de Tratamiento Oncológico (CUETO) group has performed four randomized phase 3 studies comparing different intravesical treatments in patients with noninvasive bladder cancer. Data from 1062 evaluable patients treated only with BCG were analyzed. Most patients received BCG once weekly for 6 consecutive weeks and a short-term BCG maintenance (once every 2 wk 6 times more). Associated tumor in situ (TIS) was found in 7.5% (n=80) of cases. There were 22.1% (n=235) patients with T1G3 tumors, 22.9% of whom (n=54) were associated with TIS. Stepwise multivariate Cox regression models with stratification by study and dose were used to assess the independent effect of predictive factors and hazard ratios (HRs) were estimated from the Cox model. ResultsMultivariate analysis demonstrated that female gender (HR=1.71) compared to male gender, recurrent tumors (HR=1.9) compared to primary tumors, multiplicity, and presence of associated TIS (HR=1.54) increased the risk of recurrence. Recurrent tumors (HR=1.62) compared to primary tumors, high-grade tumors (HR=5.64) compared to G1 tumors, T1 tumors (HR=2.15) compared to Ta tumors, and recurrence at 3-mo cystoscopy (HR=4.6) increased the risk of progression. ConclusionSignificant independent predictors for recurrence were female gender, history of recurrence, multiplicity, and presence of associated TIS. Age, history of recurrence, high grade, T1 stage, and recurrence at first cystoscopy were independent predictors of progression by multivariate Cox analysis.