Time interval from transurethral resection of bladder tumour to bacille Calmette-Guérin induction does not impact therapeutic response.

OBJECTIVES: To investigate bacille Calmette-Guérin (BCG) tolerability and response with respect to the timing of BCG administration after transurethral resection of bladder tumour (TURBT) in patients with non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: A review of patients with NMIBC at our institution managed with at least 'adequate BCG' (defined by the United States Food and Drug Administration as at least five of six induction instillations, with two additional instillations comprising either maintenance or repeat induction) at our institution from 2000 to 2018 was performed. Time from TURBT to first instillation of induction BCG was stratified by quartile and analysed as a continuous variable. Kaplan-Meier and log-rank tests analysed differences in recurrence-free (RFS) and progression-free survival (PFS). Cox proportional hazards regression models identified associations between risk factors and survival outcomes. RESULTS: A total of 518 patients received adequate BCG at a median (range) of 26 (6-188) days from TURBT. Overall, 45 patients (9%) developed BCG intolerance at a median (range) 12 (7-33) instillations. When time from TURBT to BCG was stratified into quartiles, there was no difference with respect BCG intolerance (P = 0.966), RFS (P = 0.632) or PFS (P = 0.789). On both uni- and multivariate regression analysis for RFS and PFS, time from TURBT to BCG was not a significant predictor when analysed by quartile or as a continuous variable (the hazard ratio for RFS was 1.00, 95% confidence interval [CI] 0.99-1.00, P = 0.449; and for PFS was 0.99, 95% CI 0.98-1.00, P = 0.074). CONCLUSION: The rates of tolerability and response to adequate BCG are not predicated by the timing of induction BCG instillation after TURBT. Early administration in properly selected patients is safe and delays do not affect therapeutic response.

Evidence for alternative candidate genes near RB1 involved in clonal expansion of in situ urothelial neoplasia.

In this paper, we present whole-organ histologic and genetic mapping studies using hypervariable DNA markers on chromosome 13 and then integrate the recombination- and single-nucleotide polymorphic sites (SNPs)-based deletion maps with the annotated genome sequence. Using bladders resected from patients with invasive urothelial carcinoma, we studied allelic patterns of 40 microsatellite markers mapping to all regions of chromosome 13 and 79 SNPs located within the 13q14 region containing the RB1 gene. A whole-organ histologic and genetic mapping strategy was used to identify the evolution of allelic losses on chromosome 13 during the progression of bladder neoplasia. Markers mapping to chromosomal regions involved in clonal expansion of preneoplastic intraurothelial lesions were subsequently tested in 25 tumors and 21 voided urine samples of patients with bladder cancer. Four clusters of allelic losses mapping to distinct regions of chromosome 13 were identified. Markers mapping to the 13q14 region that is flanked by D13S263 and D13S276, which contains the RB1 gene, showed allelic losses associated with early clonal expansion of intraurothelial neoplasia. Such losses could be identified in approximately 32% bladder tumor tissue samples and 38% of voided urines from patients with bladder cancer. The integration of distribution patterns of clonal allelic losses revealed by the microsatellite markers with those obtained by genotyping of SNPs disclosed that the loss within an approximately 4-Mb segment centered around RB1 may represent an incipient event in bladder neoplasia. However, the inactivation of RB1 occurred later and was associated with the onset of severe dysplasia/carcinoma in situ. Our studies provide evidence for the presence of critical alternative candidate genes mapping to the 13q14 region that are involved in clonal expansion of neoplasia within the bladder antecedent to the inactivation of the RB1 gene.