DNA-Methylation Test Shows Promise in Bladder Cancer Detection, Monitoring

By Reuters Staff

September 08, 2020

NEW YORK (Reuters Health) - An assay using methylation markers may offer an alternative to more costly, invasive methods for bladder cancer (BCa) detection and surveillance, according to a new study.

"Urine tumor DNA methylation assessment for early diagnosis, minimal, residual tumor detection and surveillance in bladder cancer is a rapid, high-throughput, non-invasive and promising approach, which may reduce the burden of cystoscopy and blind second surgery," Dr. Tianxin Lin of Sun Yat-sen University in Guangzhou, China, and colleagues write in the Journal of Clinical Investigation.

About three-quarters of patients with BCa have non-muscle-invasive (NMIBC) disease, and most of these will recur, the authors note. Cystoscopy and cytology are the gold standard for monitoring patients, they add, although cytology has low sensitivity, particularly for low-grade disease.

While UroVysion fluorescence in situ hybridization (FISH) is more sensitive, it is also less sensitive for low-grade tumors. For patients with high-grade and T1 disease, repeated transurethral resection of bladder tumor (re-TURBT) is recommended, but there is currently no way to determine which patients have residual disease, according to the authors.

DNA-methylation assays tested in Europe have shown promise for monitoring BCa recurrence, they add, but have not been validated in large Asian cohorts.

The team developed the MassARRAY (utMeMA) using 26 markers identified from bladder tumors and normal tissue from three patient cohorts. Validation identified 25 methylation markers in tumor tissue and matched urine samples, but not in normal tissue, while 23 of the markers in urine were significantly correlated with matched tumor tissue.

The researchers trained and tested their diagnostic model in 313 samples and validated it in 175 samples.

A model with two of the markers had a sensitivity of 88% in the training dataset, 90% in the test dataset, and 92% in the validation dataset, with a specificity of 86%, 84% and 77%, respectively.

Among 251 BCa patients, utMeMA was four times as sensitive as cytology (69.2% vs. 16.0%) and three times more sensitive than FISH (69.2% vs. 22.2%) for detecting low-grade tumors. The model was also more sensitive than cytology or FISH for patients with Ta or T1 disease, high-grade disease or muscle-invasive bladder cancer. Cytology and FISH were more specific than uTMeMA, but not significantly so.

Forty-seven patients in the modeling and validation cohorts underwent re-TURBT, with samples available before surgery. Fifteen had residual tumor, which was correctly diagnosed by utMeMA in 14 patients (93%), versus three of 11 patients with cytology (27%) and nine of 14 with FISH (64%).

"Our approach achieved a great improvement in sensitivity over urine cytology and FISH, especially in the detection of early-stage, minimal, residual and recurrent tumors. Therefore, it is adopted in the optional clinical detection of BCa by more than 10 hospitals in China. A large-scale, multicenter and prospective clinical trial (NCT04314245) is ongoing to validate its clinical applicability in China," the authors write.

The authors report no conflicts of interest and no commercial funding.

Dr. Lin was not available for an interview by press time.

SOURCE: https://bit.ly/3hFdFZQ Journal of Clinical Investigation, online August 20, 2020.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....