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Fighting a resilient form of cancer // Effective tests and treatments for bladder cancer have eluded doctors, but there are hopeful signs.
( Minneapolis Star Tribune )

Four years ago, a longtime smoker from Cambridge, Mass., got a most unwelcome surprise. Ellen Pinzur had gone to her gynecologist for a routine exam, and he suspected that she had a fibroid, a benign growth in the uterus. He sent her for an ultrasound. Sure enough, she did have a fibroid. But that was the good news. The test also showed that Pinzur, now 52, had bladder polyps. She had them removed, then several months later had a cystoscopy, in which a urologist inserts a lighted tube through the urethra to see inside the bladder while the patient is under local anesthesia.

The polyps were gone, but they had "seeded" her bladder with tumors. In hopes of boosting the odds of beating the cancer, Pinzur joined a study in which tuberculosis bacteria were squirted into the bladder, along with an immune-boosting drug called interferon. The idea was to cause an immune response to kill cancer cells.

"You hold it for two hours," Pinzur says. "It's seriously irritating. All you do is think about peeing." But Pinzur has been cancer-free now for two years. The therapy she had is one of several new techniques to improve treatment and diagnosis of bladder cancer, which will strike 54,200 Americans this year - most of them smokers like Pinzur - and kill 12,100. If the disease is caught early, its five-year survival rate is 95 percent. For cancers that have spread, it's 50 to 60 percent. But the most striking thing about bladder cancer is that it recurs in 70 percent of cases, no matter what doctors do. For the 500,000 Americans who have it, this means a lifetime of monitoring - including cystoscopy every three to 12 months. This is not only unpleasant, but expensive, says Dr. Ihor Sawczuk, vice chairman of urology at Columbia University's College of Physicians and Surgeons. However, nearly a dozen new tests now on the market or under development could lighten this burden. The goal of the tests is "to make cystoscopy unnecessary," says Dr. Kevin Loughlin, a urologist at Boston's Brigham and Women's Hospital. So far, he cautions, none is "good enough to replace cytology done by a well-trained pathologist." Cytology is a noninvasive exam in which a pathologist looks through a microscope at cells shed from the bladder into the urine. If any suspicious cells are seen, the patient must then undergo cystoscopy. But cytology is not a perfect test. In fact, it picks up only about 40 percent of cancers, and it's worst at spotting the most common, early-stage bladder cancers. The hope is that the new tests can do much better. On Dec. 13, Matritech Inc. of Newton, Mass., asked the U.S. Food and Drug Administration to expand approval of the company's NMP22 test, used to monitor those with cancer. It wants doctors to use the urine test to test those who have symptoms such as blood in the urine. In Japan, the test is already approved for wider screening. The NMP22 test measures a protein made in the nucleus of cells. High levels indicate high turnover of cells, a sign of cancer. Overall, the test finds 70 percent of tumors at all stages of cancer combined. That, of course, means it misses 30 percent, but that's better than cytology. Even so, the rate is underwhelming to some urologists.

"I did a six-month pilot trial at our institution and abandoned it," says Dr. Michael O'Donnell, director of the bladder cancer center at Beth Israel Deaconess Medical Center in Boston. The test often said patients had cancer when they didn't and missed those who did have it. Even if it were 80 percent sensitive, "that just isn't good enough in my mind," said Brigham's Loughlin. In one Italian study published last year, however, NMP22 was a better cancer detector than a marker called BTA. Another 1998 study found NMP22 just as sensitive as a marker called telomerase. A Cleveland Clinic study in January showed the test to be 100 percent sensitive. And a Spanish study published this month suggested that NMP22 combined with another marker can help reveal whether cystoscopy is needed. Ultimately, it's not just better detection but better treatment that's needed. At Beth Israel, O'Donnell is expanding the trial that Pinzur participated in, to 70 centers. It's already been shown that treating bladder cancer patients with TB seems to prevent recurrence in about 60 percent of cases. O'Donnell hopes that adding alpha interferon will improve those odds. But the best treatment probably will be gene therapy to correct messages from bad genes on chromosomes 9 and 17. Scientists believe that bladder cancer begins when genes on these chromosomes are damaged by tobacco and other carcinogens. So far, says Loughlin, that research is young. But "this is where the real, major advance is going to be.".- Judy Foreman is health columnist for the Boston Globe..Risk factors and signs You may be at risk for bladder cancer if you are over 50, male or smoke. In fact, men's risk is four times that of women's, probably because, historically, men were likelier to smoke. Men also tend to urinate less frequently than women, which means that whatever toxins or carcinogens are in the urine stay in the bladder longer. Smoking causes nearly half of bladder cancer deaths in men and more than a third in women. Those at risk include those who are exposed to chemicals called aromatic amines. Painters, as well as people who work in the leather, rubber, dye and aluminum industries, often use such compounds. In recent years, the incidence of bladder cancer has been rising slowly, for unclear reasons. One sign of bladder cancer is blood in the urine, either enough to be visible or in traces detected through urine testing. It doesn't always indicate cancer. In fact, it's usually a sign of infection or inflammation in the urinary tract, prostate problems or a kidney stone. Still, if you have blood in your urine, you should call your doctor.

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