A Kinder, Gentler Bladder Cancer Test

Medically Reviewed by Gary D. Vogin, MD
From the WebMD Archives

Jan. 16, 2001 -- A simple, painless urine test may soon help doctors tell which patients with bladder cancer are at risk for having the disease recur. That's important because such cancer reappears about 80% of the time, say researchers from Yale University, and the current method used to test for it -- which involves inserting a scope through the urethra into the bladder -- is quite uncomfortable for patients.

That method, called a cystoscopy, might become just an unpleasant memory if the Yale team's urine test continues to prove effective. The new test looks for the presence of something called survivin in the urine, says Dario Altieri, MD, professor of pathology at the Yale School of Medicine in New Haven, Conn.

Altieri explains that survivin is a natural substance that hinders "apoptosis," the body's built-in system of killing off unnecessary cells. "For this reason, survivin is very important during fetal development," Altieri says. "By inhibiting apoptosis, it helps keep cells alive."

In the case of cancer cells, which are multiplying out of control, it is not surprising that there is an excess of survivin. "The molecule helps preserve the viability of cancer cells and makes them more resistant to chemotherapy," Altieri says.

In collaboration with physicians from Yale's department of surgery, Altieri devised a strategy for exploiting this phenomenon to determine if a patient with a history of bladder cancer is at risk for having the cancer come back.

"The assumption is that if there were a tumor in the bladder, the tumor cells, which would be released in the urine, would contain the survivin molecule," he says. "We reasoned that we might be able to detect it with a simple urine test."

Their hunch appears to be borne out.

Altieri and colleagues surveyed urine samples from various groups of individuals: healthy volunteers, patients with noncancerous urinary tract disease, patients with genitourinary cancer, and patients with bladder cancer. They found that survivin was detected in the urine samples of all of the patients with new or recurrent bladder cancer, but was not found in healthy volunteers or in patients with prostate, kidney, vaginal, or cervical cancer.

The results indicate a high degree of test sensitivity, Altieri says, meaning the presence of the molecule is a strong signal a tumor is present. At the same time, however, he notes that three of the patients with noncancerous urinary tract disease, and one patient with increased prostate specific-antigen, also tested positive for survivin.

This indicates the test may not be perfectly specific for bladder cancer and could therefore lead to false-positive results.

"Clearly, this study needs to be expanded in a much larger population," Altieri cautions. "We are following the three individuals who had a false-positive test and have found after six months had elapsed, that one of them did develop bladder cancer."

While more research is necessary, and approval by the FDA is required before the test can become routinely available, Altieri says the technology for performing the test already is available and could be performed by doctors at low cost.

Ultimately, if proven successful in future research, the test may be best used in combination with other diagnostic tests.

The survivin study is particularly promising because of the invasive and uncomfortable nature of cystoscopy, says Sudhir Srivastava, PhD, MPH, chief of the cancer biomarkers research group at the National Cancer Institute.

The effort to use survivin to detect bladder cancer recurrence is part of a broad scientific effort to develop biomarkers for a variety of diseases, Srivastava tells WebMD. But the problem of false-positives is one that plagues many of these efforts, some of which have been highly touted by commercial companies without appropriate scientific validation, he says.

"For many years, we have been discovering biomarkers and leaving it there, without taking it further along to prove whether they are clinically applicable," he says. "Validation studies are not very glamorous and do not get the same kind of funding and attention that discovery does."

For that reason, the NCI has developed an Early Detection Research Network to shepherd research on biomarkers from discovery to validation. And he says that the NCI is likely to instigate large-scale trials of survivin to validate the results found by Altieri and colleagues.

"Anyone who has a cancer is looking for the light at the end of the tunnel," he says. "Naturally, they hope to be the first one to use it. We owe it to them to have something that has been proven."

The study by Altieri and colleagues appears in the Jan. 17 edition of the Journal of the American Medical Association.