Can we offer additional BCG therapy for three-month BCG refractory high grade/T1, Tis bladder cancer patients?

Background: We lack tools to predict treatment and survival outcomes in patients receiving additional BCG therapy as a bladder-preserving therapy in high grade/T1, Tis NMIBC patients who showed persistent/recurrent tumors at three-month follow-up.

Objectives: To assess the predictors of additional BCG response in patients who experienced persistent/recurrent tumors at three-month follow-up after BCG induction.

Patients and methods: We retrospectively analyzed database for NMIBC. Between 2000 and 2019, 231 patients with high-grade T1/Tis NMIBC showed persistent/recurrent tumors at 3-month after BCG-induction, refused or were unfit to radical cystectomy (RC) and were offered additional intravesical BCG as bladder-preserving treatment. Predictors of the outcome after additional BCG were studied using univariate and multivariate logistic regression analysis. Kaplan Meier curve was utilized to estimate the recurrence-free survival (RFS) and progression-free survival (PFS). COX regression analysis was performed to identify independent predictors or RFS and PFS.

Results: During a median (range) of 148 (24-224) months, poor response to additional BCG (tumor recurrence and/or progression) was noted in 112 (48.5%) patients. On multivariate logistic regression analysis, 3-month tumor features (persistent T stage, persistent grade and persistent/new CIS) significantly predicted poor response to additional BCG (OR: 3.4, 95%CI: 1.3-10.8, p = 0.021, OR: 2.1, 95%CI: 1.1-4.1, p = 0.02 and OR: 16.6, 95%CI: 4.5-109, p=<0.001, respectively). The mean RFS was 26 (9-152) months with identified 3-month tumor features (persistent T stage and persistent/new CIS) as independent predictors of RFS (HR = 11.5, 95%CI = 2.7-48.3, p = 0.001 and HR = 2.5, 95%CI = 1.5-4.1, p=<0.001, respectively) on multivariate COX regression analysis. In addition, 3-month tumor features (persistent/new CIS, non-papillary shape and bladder neck involvement) were identified to significantly predict PFS (HR = 6.2, 95%CI = 3.4-11.5, p=<0.001 and HR = 2.3, 95%CI = 1.3-4.3 p = 0.001 and HR = 2.1, 95%CI = 1.2-3.8, p=<0.005, respectively).

Conclusions: Three-month tumor features could be utilized as a tool to predict treatment outcomes and survival benefits when additional intravesical BCG is utilized as a bladder-preserving treatment in patients with recurrent/persistent tumors at three-month follow-up.