LIQUID BIOPSY IN BLADDER CANCER

NEW YORK (Reuters Health) - Measuring tumor DNA in "liquid biopsies" may help diagnose residual bladder cancer or discover aggressive forms of bladder cancer early, new research suggests.

"In our study to determine if circulating tumor DNA (in blood or cell-free urine) is associated with disease aggressiveness, genomic alterations disappeared from blood and urine in disease-free patients," principal study investigator Dr. Lars Dyrskjot told Reuters Health by email.

"It was surprising to observe high levels of tumor DNA in cell-free urine samples. This may pave the way for future use of noninvasive urine-based tests during surveillance to monitor disease aggressiveness in bladder cancer patients," said Dr. Dyrskjot, a professor in the Department of Molecular Medicine of Aarhus University Hospital in Denmark.

The authors noted in an article online January 21 in European Urology that at least half of patients with non-muscle-invasive bladder cancer experience recurrence, and in approximately 15% of them, the tumor invades muscle or becomes metastatic.

In their retrospective pilot study, Dr. Dyrskjot and colleagues analyzed 377 samples collected from 12 patients with recurrent or progressive/metastatic disease between 1994 to 2015.

Patients in the study were followed for up to 20 years.

The researchers applied three next-generation sequencing methods and monitored somatic variants in DNA from tumor, plasma, and urine by personalized assays using droplet digital polymerase chain reaction.

They developed one to six personalized assays per patient and measured the progression to muscle-invasive or metastatic bladder cancer.

Patients with muscle-invasive disease had significantly higher tumor DNA levels in plasma and urine before disease progression by t-test, compared with patients with recurrent disease (p=0.032 and 0.0000013, respectively). Tumor DNA was not detected in disease-free patients.

A significant level of heterogeneity was found in each patient, which the authors speculated could be due to tumor heterogeneity or assay performance.

Considering future study, Dr. Dyrskjot said his research team is building on the results of their pilot study. "We are currently analyzing samples from additional patients to determine the robustness of the results," he added.

Dr. Sumanta Kumar Pal, co-director of the Kidney Cancer Program at City of Hope National Medical Center in Duarte, California, told Reuters Health by email, "These findings are interesting. The small number of patients who were assessed limits the clinical application of these findings. However, as we start to integrate cell-free DNA assays in the clinic to look for druggable mutations, this study informs the feasibility of those assays."

"An emerging body of evidence is looking at mutations in cell-free DNA. This particular study suggests that the amount of cell-free DNA may increase as localized bladder cancer progresses," said Dr. Pal, who was not involved in the study.

"Cell-free DNA assays have a substantial advantage over DNA assays using tumor tissue and we may increasingly be using cell-free DNA to characterize mutations in patients with bladder cancer," he added.

The study was supported by the Danish Cancer Society, the John and Birthe Meyer Foundation, the Danish Council for Independent Research, the Lundbeck Foundation, and the Danish Cancer Biobank. The authors and Dr. Pal declared no conflicts of interest.

SOURCE: http://bit.ly/1Ko96ks

Eur Urol 2016.