Failure to achieve a complete response to induction BCG therapy is associated with increased risk of disease worsening and death in patients with high risk non-muscle invasive bladder cancer

Abstract

Purpose-The Southwest Oncology Group conducted a randomized trial of induction BCG with or without maintenance BCG. In these additional retrospective analyses, our goal was to evaluate the association of a complete response (CR) or remaining with no evidence of disease (NED) versus no CR during induction therapy with subsequent survival after adjusting for other potential confounders. Among all patients randomized to maintenance treatment, we also wanted to identify combinations of baseline covariates in order to define prognostic groups for subsequent worseningfree survival.Methods-Outcome measures of worsening-free and overall survival were assessed using Kaplan Meier estimates and proportional hazards regression models. For the Classification and Regression Tree (CART) analysis, 434 patients randomized to maintenance vs. no therapy with complete covariate information were included.Results-Of the 593 evaluable patients, 341 were not randomized to maintenance BCG. Patients who achieved a prior complete response during induction BCG had a 5-year survival probability of 77% compared to 62% for patients who did not [Hazard ratio (HR) 0.60; 95% confidence interval (CI) 0.44, 0.81; p= 0.0008]. Prior CR retained significance when adjusted for age, gender, prior intravesical chemotherapy, and papillary disease versus CIS (HR=0.63; 95% CI: .46, .86; p=0.003). CART analysis identified 4 prognostic groups. Older patients (≥ 62 years old) previously treated with intravesical chemotherapy who failed to achieve a CR had a 5-fold higher risk of a worsening event relative to those who are younger (< 67 years old) and achieve a CR (HR=5.09; 95% CI: 3.37, 7.68; p<0.0001). Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Conclusion-Failure to achieve a complete response after induction BCG is associated with a significant risk of a worsening event and death for patients with CIS or Ta or T1 bladder cancer at increased risk of recurrence. NIH Public Access

Papillary Recurrence of Bladder Cancer at First Evaluation after Induction Bacillus Calmette-Guérin Therapy: Implication for Clinical Trial Design

“…Recurrence with papillary tumor(s) by 3 mo after induction of BCG is a poor prognostic indicator in patients with high-risk nonmuscle invasive bladder cancer [5,6], with a progression rate of 47% in those with clinical T1 (cT1) disease [7]. However, the impact of a clinical Ta (cTa) papillary recurrence at 3 mo after BCG is often debated.…”

Sequential Intravesical Mitomycin plus Bacillus Calmette–Guérin for Non–Muscle-Invasive Urothelial Bladder Carcinoma: Translational and Phase I Clinical Trial

“…Intravesical BCG provides a significant improvement in recurrence-free survival and consistently affords an improvement over intravesical chemotherapy. Unfortunately, up to 70% of patients with high-risk NMIBC will eventually recur despite intravesical BCG and some recurrent tumors will progress to higher stage (3, 4). …”

Prostate-Sparing Radical Cystectomy for Selected Patients with Bladder Cancer

“…RC also seems to be one of the options for selected patients with a diagnosis of high-risk non-muscle-invasive bladder cancer because it was shown that it brings significant survival benefit when compared with patients having RC at the time of progression into muscle-invasive disease [3,4,5,6]. It may be even more important in some patients with previous bacillus Calmette-Guérin treatment failure; it was shown that in general this group of patients is at increased risk of death from disease progression [7]. Nevertheless, early RC is performed in only 4.7-8% of patients with high-risk non-muscle-invasive bladder cancer as it carries non-negligible risks of surgical complications and a major impact on quality of life (QoL) following surgery, depending on the type of urinary diversion [3,8].…”