Molecular followup of newly diagnosed bladder cancer using urine samples

Patients with superficial bladder cancer can be treated with transurethral resection. However, 50% to 70% of them have intravesical recurrence after transurethral resection and muscle invasive disease develops in 10% to 20%, which is eventually indicated for radical cystectomy. Therefore, reliable predictors of intravesical recurrence are required for management of superficial bladder cancer. We investigated whether detection of the loss of heterozygosity in urine samples would be available as a sensitive diagnostic modality for recurrence of bladder cancer.

Urine samples, cancer tissue and peripheral blood lymphocytes were obtained from 37 patients with newly diagnosed bladder cancer, and analyzed for the loss of heterozygosity on chromosomes 9 and 17p by single strand DNA conformation polymorphism analysis.

Chromosomal loss was detected on 24 (65%) cancer tissues and 26 (70%) urine samples. The loss of heterozygosity on chromosome 17p was detected in 19 (51%) urine samples, mostly in cancers with higher grades and/or stages. During postoperative followup of 24 patients with superficial bladder cancer who had undergone transurethral resection, intravesical recurrence did not develop in 9 of 10 without chromosomal aberrations in urine samples. In contrast, intravesical recurrence developed in 11 of 14 patients who had a loss of heterozygosity in urine samples. This loss showed a significant correlation with the intravesical disease-free period (p = 0.004). Multivariate analysis revealed that the loss of heterozygosity in urine samples was a significant predictor of intravesical recurrence.

Detection of the loss of heterozygosity in urine samples is available as a sensitive marker for predicting intravesical recurrence of superficial bladder cancer.