Loss of Heterozygosis on IFN-α Locus is a Prognostic Indicator of Bacillus Calmette-Guerin Response for Nonmuscle Invasive Bladder Cancer

PurposeWe evaluated the role of loss of heterozygosity on the interferon-α locus to predict the response to bacillus Calmette-Guerin therapy in patients with nonmuscle invasive bladder cancer.Materials and MethodsA total of 117 consecutive patients were selected, including 77 with nonmuscle invasive bladder cancer and 40 controls. Loss of heterozygosity on the interferon-α locus (chromosome 9p21) was assessed in blood and urine samples before transurethral resection. All patients underwent transurethral resection and then 6 weekly bacillus Calmette-Guerin instillations. Those with nonmuscle invasive bladder cancer were assigned to groups 1 and 2 with and without loss of heterozygosity on the interferon-α locus, respectively.ResultsOf the 77 patients with nonmuscle invasive bladder cancer 39 (50.6%) had loss of heterozygosity on the interferon-α locus (group 1) and 38 (49.4%) had no alteration (group 2). Only 1 of 40 controls showed loss of heterozygosity on the interferon-α locus. At the end of followup 13 patients in group 1 and 27 in group 2 were alive without recurrence. We noted a significant difference between loss of heterozygosity on interferon-α and followup status (dF 01, LR 11.252, p = 0.003). Kaplan-Meier analysis revealed a significant difference in recurrence probability (response to bacillus Calmette-Guerin) and loss of heterozygosity on interferon-α (p <0.0001). On multivariate analysis loss of heterozygosity (HR 4.09, 95% CI 2.59–6.28, p = 0.002), grade (grade 3 HR 3.31, 95% CI 1.38–3.35, p = 0.03) and the number of lesions (3 or greater HR 2.31, 95% CI 1.38–3.25, p = 0.03) were independent predictors of the bacillus Calmette-Guerin response.ConclusionsThis study highlights the predictive value of loss of heterozygosity analysis on interferon-α in patients with nonmuscle invasive bladder cancer treated with bacillus Calmette-Guerin.