DNA Test Can Help Predict Bladder Cancer Recurrence

By Jo Cavallo
Posted: 4/1/2014 12:16:28 PM
Last Updated: 4/1/2014 12:16:28 PM

Key Points:

A DNA methylation marker test performed on patients with noninvasive urothelial carcinoma can predict tumor recurrence with high sensitivity and specificity and may help eliminate costly and unnecessary invasive exams to monitor bladder cancer recurrence.
A combination of three DNA methylation markers, SOX1, IRAK3, and L1-MET, provides better resolution than cytology and cystoscopy in the detection of early bladder cancer recurrence.

A DNA methylation marker test performed on patients with noninvasive urothelial carcinoma can predict tumor recurrence with high sensitivity and specificity, according to a study by Su et al. The findings may help eliminate costly and unnecessary invasive exams and reveals the importance of DNA methylation in bladder tumorigenesis. The study is published in Clinical Cancer Research.

The researchers analyzed the DNA methylation levels of six markers in 368 urine sediment samples collected over 7 years from 90 patients with non–muscle-invasive bladder cancer (Tis, Ta, and T1). The patients’ ages ranged from 41 to 96 years, with a median age of 69 years. The patients were under surveillance for tumor recurrence.

The optimum marker combination was identified using logistic regression with fivefold cross-validation and validated in separate samples.

Study Findings

A panel of three markers—SOX1, IRAK3, and L1-MET—discriminated between patients with and without recurrence with the area under the curve of 0.90 (95% confidence interval [CI] = 0.86–0.92) and 0.95 (95% CI = 0.90–1.00). The test had a sensitivity and specificity of 86% and 89% (95% CI = 74%–99% and 81%–97%) and 80% and 97% (95% CI = 60%–96% and 91%–100%) in the testing and validation sets, respectively.

The researchers found that 80% of the patients whose urine tests were positive for the markers subsequently developed non–muscle-invasive bladder cancer recurrence. Current standard methods of monitoring—cytology and cystoscopy—were able to detect tumor recurrence in only 35% and 15% of these patients, respectively. Seventy-four percent of the patients whose urine tests were negative for the markers did not experience tumor recurrence.

“[Non–muscle-invasive bladder cancer] accounts for 80% of all bladder cancer cases and is characterized by a high rate of recurrence, which leads to a high cost in treatment and management,”Gangning Liang, PhD, a coauthor of the study and an Associate Professor in the Department of Urology at USC Norris Comprehensive Cancer Center in Los Angeles, said in a statement. “The current standards for monitoring of bladder cancer recurrence are either unreliable or invasive. We wanted to find reliable biomarkers to monitor recurrence of [non–muscle-invasive bladder cancer] using a noninvasive assay.”

The study authors concluded, “Our study provides new insights into the value of a combination of hypermethylated and hypomethylated tumor-specific markers to screen urine sediments from patients following bladder tumor resections. This study provides evidence that a marker panel may help minimize the frequency of cystoscopy for patients with a negative score. We suggest that patients with a positive urinary methylation test, but no clinical evidence of bladder cancer disease should still be closely monitored because they carry a high risk of recurrence.”

Dr. Liang and Kimberly D. Siegmund, PhD, of USC Norris Comprehensive Cancer Center are the corresponding authors for the Clinical Cancer Research article.

The study was supported by a grant from the National Cancer Institute. Study author Peter A. Jones, PhD, DSc, is a consultant/advisory board member of Astex, Lilly, and Zymo.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.