Short-term efficacy and predictive factors of BCG instillation in high risk non-muscle invasive bladder cancer

Abstract

Objective To investigate the short-term efficacy, safety and factors affecting the efficacy of BCG intravesical therapy in high risk non-muscle-invasive bladder cancer (NMIBC) patients. Methods A total of 161 high-risk non-muscle invasive bladder cancer (NMIBC) patients were reviewed in our hospital from March 2014 to December 2017. They were all treated with BCG instillation after transurethral resection of bladder tumor (TURBT). There were 121 males (75.2%) and 40 females (24.8%). Median age was 65 years old, including 17 cases (10.6%) <50 years old, 23 cases (14.3%) within 50-59 years old, 72 cases (44.7%) within 60-69 years old, 49 cases ≥70 years old (30.4%). There were 112 patients (69.6%) with primary bladder cancer and 49 (30.4%) patients with recurrent bladder cancer. 56 cases (34.8%) had single tumor and 105 cases (65.2%) had multiple tumors. The tumors size in 106 cases (65.8%) was less than 3 cm, and tumor size in 55 cases (34.2%) was more than 3 cm. 43 patients (26.7%) suffered carcinoma in situ. 10 patients (6.2%) suffered urothelial carcinoma with variant types. According to the American Joint Commission for Cancer (AJCC) version 7 TNM staging system, 25 cases (15.5%) were classified into Ta stage, 129 cases (80.1%) were classified into T1 stage, and 7 cases (4.3%) were classified into Tis stage. There were 8 cases (5%) with low-grade cancer and 153 cases (95%) with high-grade cancer. 69 patients (42.9%) received chemo-instillation before. 43 cases were directly perfused without re-TURBT and 118 cases were perfused after re-TURBT. They were all treated with BCG instillation after transurethral resection of bladder tumor (TURBT). The 120 mg BCG were dissolved into 50 ml saline for instillation and were kept for 2 hours. Induction scheme of six-weekly and three fortnightly instillations started two weeks after the initial TUR or re-TUR. Maintenance instillations were then be offered in a scheme of ten monthly instillations. During treatment, patients were offered cystoscopy and cytology every three months, while CT and chest radiographs were reviewed every 6-12 months. Recurrence status and adverse effects were recorded. Univariate and multivariate regression analyses were performed to predict risk factors for failure of BCG instillation in bladder cancer. Results A total of 161 patients were followed up. The median follow-up time was 13 months, ranging 7-22 months. The overall recurrence rate was 26.1% (42/161) and the 1-year recurrence-free survival rate was 79.0%. On univariate analysis, recurrence history, history of instillation chemotherapy application and history of re-staging transurethral resection influenced recurrence. Multivariate regression analysis showed recurrence status was an independent prognostic factor regarding recurrence-free survival. The incidence of adverse events in all 161 instillation patients was 40.4% (26/65). Grade 1, grade 2 and grade 3 adverse events accounted for 53.8%(35/65), 40.0%(26/65) and 6.2%(4/65) respectively. 6 cases (3.7%) reduced the dose of BGC and 1 case stop the instillation due to the intolerance of BCG. Conclusion Short-term efficiency and safety were confirmed in BCG-treated high-risk NMIBC patients. And recurrence status was an independent prognostic factor for recurrence-free survival. Key words: Bacillus Calmette-Guerin; Bladder cancer; Intraversical instillation