ABSTRACT
PURPOSE: Bacillus Calmette-Guerin is the most effective therapy for nonmuscle invasive bladder cancer. Recently to calculate the risks of recurrence and progression based on data from 7 European Organisation for Research and Treatment of Cancer trials a scoring system was reported. However, in that series only 171 patients were treated with bacillus Calmette-Guerin. We developed a risk stratification model to provide accurate estimates of recurrence and progression probability after bacillus Calmette-Guerin. MATERIALS AND METHODS: Data were analyzed on 1,062 patients treated with bacillus Calmette-Guerin and included in 4 Spanish Urological Club for Oncological Treatment trials. Stepwise multivariate Cox models were used to determine the effect of prognostic factors. In each patient the weight of all factors was summed to a total score. Patients were then divided into groups, and cumulative recurrence and progression rates were calculated. RESULTS: A scoring system was calculated with a score of 0 to 16 for recurrence and 0 to 14 for progression. Patients were categorized into 4 groups by score, and recurrence and progression probabilities were calculated in each group. For recurrence the variables were gender, age, grade, tumor status, multiplicity and associated Tis. For progression the variables were age, grade, tumor status, T category, multiplicity and associated Tis. For recurrence calculated risks using Spanish Urological Club for Oncological Treatment tables were lower than those obtained with Sylvester tables. For progression probabilities were lower in our model only in patients with high risk tumors. CONCLUSIONS: We propose a scoring model to stratify the risk of recurrence and progression in patients treated with bacillus Calmette-Guerin.
Subject(s)
Adjuvants, Immunologic/therapeutic use , BCG Vaccine/therapeutic use , Neoplasm Recurrence, Local/epidemiology , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/epidemiology , Aged , Aged, 80 and over , Disease Progression , Female , Humans , Male , Middle Aged , Models, Statistical , Neoplasm Invasiveness , Prognosis , Urinary Bladder Neoplasms/pathologyABSTRACT
BACKGROUND: European Organization for Research and Treatment of Cancer (EORTC) risk tables only included 171 patients treated with bacillus Calmette-Guérin (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.
Subject(s)
Adjuvants, Immunologic/administration & dosage , BCG Vaccine/administration & dosage , Neoplasm Recurrence, Local , Urinary Bladder Neoplasms/therapy , Administration, Intravesical , Aged , Aged, 80 and over , Discriminant Analysis , Disease Progression , Humans , Kaplan-Meier Estimate , Middle Aged , Neoplasm Invasiveness , Randomized Controlled Trials as Topic , Reproducibility of Results , Risk Assessment , Risk Factors , Spain , Time Factors , Treatment Outcome , Urinary Bladder Neoplasms/immunology , Urinary Bladder Neoplasms/pathologyABSTRACT
OBJECTIVES: To evaluate the prognostic factors of recurrence and progression after intravesical adjuvant bacillus Calmette-Guérin (BCG) immunotherapy in patients with non-muscle-invasive bladder tumors. METHODS: From 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. RESULTS: Multivariate 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. CONCLUSION: Significant 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.