Liquid biopsies may aid diagnosis, treatment of bladder, nerve tumors

Sept. 3, 2021

Blood and urine tests could lead to faster and less invasive methods to diagnose and monitor various types of tumors, new research indicates. Two studies led by Washington University School of Medicine in St. Louis describe the potential of liquid biopsies to identify and track tumor growth in two very different cancers: bladder cancer and peripheral nerve tumors.

Despite the differences between these cancers and their associated biopsies, the studies demonstrate the possible benefits of this relatively new tool in the fight against cancer.

Both studies appear in PLOS Medicine in a special issue of the journal dedicated to liquid biopsies.

One study reports on the development of a urine biopsy to monitor bladder cancer. With an easy to collect urine sample, doctors could determine whether the initial treatment eradicated the cancer or left some remnants of disease behind. That knowledge could lead to fewer patients undergoing unnecessary surgeries. The second study describes a blood biopsy to diagnose a tumor of the sheath — or lining — that covers peripheral nerves. This rare cancer is caused by an inherited genetic disorder called neurofibromatosis type 1 (NF1). In patients with NF1, it is difficult to determine whether tumors developing in the nerve sheath are benign or malignant.

“For bladder cancer, if a urine biopsy can detect whether the early chemotherapy totally eradicated the tumor, it could help some patients avoid major surgery to remove the bladder,” said Aadel A. Chaudhuri, MD, PhD, Assistant Professor of Radiation Oncology and the senior author of both papers. “And for NF1, if we can distinguish between tumors that are cancerous versus precancerous, we open the door to early cancer detection in hereditary conditions that predispose people to developing cancer.”

Patients with bladder cancer that has invaded the underlying muscle typically undergo chemotherapy to shrink the tumor, followed by surgery to remove the bladder. Bladder removal, which also can include removal of the prostate and seminal vesicles for men, and removal of the uterus, ovaries and part of the vagina for women, reduces the risk of the cancer returning. But some patients may respond well to the initial chemotherapy and not need to have the bladder or nearby organs removed. Unfortunately, there is no way today to identify which patients may not need to undergo bladder removal, a procedure that has a major impact on quality of life. The urine biopsy that Chaudhuri and his colleagues have implemented could, in the future, be a way to determine which patients may safely avoid bladder removal.

In the study, the researchers analyzed the DNA found in the urine of healthy people and patients with bladder cancer treated with chemotherapy. After chemotherapy but before surgery to remove the bladder, the scientists were able to identify, in cancer patients’ urine, residual tumor DNA that otherwise would go undetected. All patients underwent surgery to remove the bladder. The researchers found tumor DNA in the urine of patients whose bladders later were found to still show remaining tumor, even after chemotherapy. In contrast, those patients who had so-called complete responses to the chemotherapy — no evidence of tumors remaining in the bladder after it was surgically removed — also showed no tumor DNA in their urine prior to surgery.

While the test is not yet sensitive enough to guide treatment decisions, Chaudhuri said the study paves the way for further refinement of the test toward the goal of identifying patients who can keep their bladders after chemotherapy.

Patients with NF1 are predisposed to developing cancer, and peripheral nerve sheath tumors are the most common cause of death for such patients. These cancers usually stem from benign tumors, and it’s often difficult to distinguish between the benign and malignant forms of these tumors.

The researchers developed a method to analyze the DNA in a blood sample that can distinguish between healthy individuals, NF1 patients with benign tumors and NF1 patients with malignant peripheral nerve sheath tumors. The DNA analysis also correlated with how well the patients responded to treatment.

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