Maintenance bacillus Calmette‐Guérin in high‐risk nonmuscle‐invasive bladder cancer

Abstract

BACKGROUND. Intravesical bacillus Calmette‐Guérin (BCG) immunotherapy is effective in preventing recurrence and progression in nonmuscle‐invasive bladder cancer but the dosing schedule and duration of treatment remain empirical. The outcome of BCG therapy was prospectively evaluated on patients according to the number of maintenance cycles received. METHODS. Between 1997 and 2002, 111 patients with nonmuscle‐invasive bladder cancer at high risk of recurrence and progression underwent transurethral resection followed by intravesical instillations of BCG. After an induction treatment of 6 weekly instillations, patients were scheduled to receive a 3‐weekly maintenance treatment at the 3rd, 6th, 12th, 18th, 24th, 30th, and 36th month. At each visit a clinical assessment was obtained. RESULTS. Over a median clinical follow‐up of 31 months, 43% of patients experienced recurrence and 8.1% progressed to muscle‐invasive disease or metastasis. Only 1 patient received all scheduled instillations. Patients who received at least 3 maintenance BCG cycles had a significantly reduced risk of recurrence (hazard ratio [HR] = 0.23, P = .0064, adjusted for gender, age, and stage) compared with patients receiving only induction BCG. Twelve months after the end of maintenance, the estimated Kaplan‐Meier recurrence‐free survival was 89% for patients who received at least 3 maintenance BCG cycles, 67% for those who received 2 maintenance BCG cycles, and 41% for those who received only the induction BCG or 1 maintenance cycle (P = .0003). CONCLUSIONS. The results of this study suggest that a minimum of 3 cycles of maintenance BCG is required to significantly reduce the recurrence rate. It also suggests that more cycles may result in further improvements but the benefits may be outweighed by increasing side effects in some patients. Cancer 2008. © 2008 American Cancer Society.

Expression Signature Defined byFOXM1–CCNB1Activation Predicts Disease Recurrence in Non–Muscle-Invasive Bladder Cancer

“…Intravesical therapy (IVT) of Bacillus Calmette-Gu erin (BCG) combined with transurethral resection (TUR) of bladder cancer is recognized as the best treatment option for the prevention or delay of recurrence or progression in high-risk NMIBC (2)(3)(4). However, many patients fail to respond to BCG therapy and are at a high risk of disease recurrence and progression (3)(4)(5).…”

Phase II Drug-Metabolizing Polymorphisms and Smoking Predict Recurrence of Non–Muscle-Invasive Bladder Cancer: A Gene–Smoking Interaction

“…Details regarding eligibility were reported previously (21,22) and all patients had provided an informed written consent. Demographics, smoking history, presentation, and clinicopathologic data as well as time to recurrence, progression of disease, and death were available for the 189 patients.…”

“…A total of 131 patients with high-risk NMIBC from eight institutions in Canada were offered participation in a prospective study, and all of them received BCG therapy. Inclusion and exclusion criteria were described in a previous publication (21). Of the 131 patients, we had blood samples from the 58 patients from our institution, obtained at time of preoperative evaluation.…”

“…In this study, we tested whether the patient's smoking status as well as two of the most common and functional genetic variations in GSTM1 (deletion status), and UGT1A1 rs8175347 (low-activity promoter variant) predict the risk of bladder cancer recurrence in patients with NMIBC (21,22). No study has addressed the link between these functional germline variations with bladder cancer recurrence.…”

The management of BCG failure in non-muscle-invasive bladder cancer: an update

“…The absence of long-lasting immune activation after a single 6-week course of BCG could be related to the increased clinical efficacy observed with BCG maintenance instillations. 12,13,14 Inadequate immune response. There is strong evidence that the success of BCG therapy might be due to a preferential induction of a TH-1 response (detected in the urine by analysis of relevant cytokines).…”