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

Abstract

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.

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

“…Although some earlier Caucasus studies claimed significant differences in RFS rates between different risk groups [21][22], other studies (Asian or American), including ours ( Fig. 2A, 2C and 2E), found that prediction of recurrence was poorly related to the EORTC [10][11][12]. Also in another Chinese study [17], no significant difference in the RFS rates was found.…”

“…In this study, 77.6% of patients (287 patients in the testing group; 189 patients in the validation group; 123 patients in the external validation group) were classified into the intermediate-risk group according to EORTC. Xu et al [17], Ieda et al [10] and Sakano et al [18] displayed similar results with 78.0%, 87.8% and 92.5% of NMIBC cases classified as intermediate-risk, respectively. The low frequency of low-risk cases could possibly because of the lower ratio of G1 tumors in our current study (18.6% in the testing group; 20.0% in the validation group; 22.9% in the external validation group) compared with the EORTC trials (43.2%) [8].…”

“…The low frequency of low-risk cases could possibly because of the lower ratio of G1 tumors in our current study (18.6% in the testing group; 20.0% in the validation group; 22.9% in the external validation group) compared with the EORTC trials (43.2%) [8]. Since the other Asian studies including Japanese [10,[18][19] and Korean [20] populations also found a low incidence of G1, there might be racial difference in grade distribution of NMIBC between Asian and Caucasian populations.…”

“…EORTC risk stratification divides NMIBC patients into low-risk, intermediate-risk, and high-risk recurrence groups, and then develops different treatment options through these groups [8]. However, there are certain restrictions on the EORTC, including the following aspects [10][11][12]: (1) The calculation steps of the EORTC are cumbersome; (2) No tumor heterogeneity was considered; (3) There is no evidence that EORTC can improve patient survival; (4) During the EORTC building process, TURBT did not receive intravesical instillation chemotherapy in 22% of patients, and only 6% of patients received postoperative intravesical Bacillus Calmette-Guerin (BCG) immunotherapy. Moreover, the effect of BCG instillation or intravesical instillation chemotherapy on recurrence was not considered; (5) Less than one-third of patients received immediate intravesical instillation after surgery, and fluorescent cystoscopy was not available at the time.…”

Infiltrative lamina propria invasion pattern as an independent predictor for cancer‐specific and overall survival of instillation treatment‐naïve stage T1 high‐grade urothelial bladder cancer

“…23 A very recent study of two Japanese NMIBC cohorts of 1497 patients by Ieda et al, including 490 T1 BC and 52 pure CIS patients, revealed bladder instillation treatment with various compounds in just 38% of the total cohort. 24 This indicates that our rate of instillation treatment of 57% more or less match with these "real world data." Because of this nearly 1:1 situation of patients after instillation treatment and instillation-na€ ıve patients, we were able to make an analysis of these subcohorts.…”