Detecting, treating bladder cancer early

Four years ago, Ellen Pinzur, a Cambridge woman who had been a lifetime smoker, got a most unwelcome surprise.

When she went to her gynecologist for a routine exam, he suspected 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 checkup by 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 cancerous tumors. Unlike many people who get bladder cancer, Pinzur did not have the telltale sign of blood in her urine.

In hopes of boosting the odds of beating her cancer, Pinzur joined a study in which tuberculosis bacteria, of all things, are squirted into the bladder to trigger an influx of white blood cells that attack both the TB and cancer cells. (The risk of TB spreading to other parts of the body is low.)

Perhaps because of this unusual therapy, Pinzur has been cancer-free now for two years.

The therapy she had is but one of a number of new techniques that scientists are working on to improve both treatment and diagnosis of bladder cancer, which will strike 54,200 Americans this year and kill 12,100. Men are four times more likely to get bladder cancer than women because smoking is a major trigger for the cancer, and historically, men have smoked more than women.

If caught early, while the cancer is a shallow spot in the lining of the bladder, the 5-year survival rate is 95 percent; for cancers that have invaded muscle tissue and spread throughout the body, 5-year survival is 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, it’s expensive – much more so than caring for someone with breast or prostate cancer, notes Dr. Ihor Sawczuk, vice chairman of urology at Columbia University’s College of Physicians and Surgeons.

But nearly a dozen new tests now on the market or under development could lighten this burden.

The goal of all these tests is “to make cystoscopy unnecessary,” says Dr. Kevin R. Loughlin, a urologist at Brigham and Women’s Hospital. So far, he cautions, none of the tests has replaced cytology – a noninvasive exam in which a pathologist looks through a microscope at cells shed from the bladder into the urine. If he or she sees any suspicious cells, the patient must then undergo cystoscopy, the more invasive test.

But cytology, the current “gold standard,” is not a perfect test. In fact, it picks up only about 40 percent of cancers, and is worst at spotting the most common, early stage bladder cancers.

The hope is the new tests can do much better.

Today , for instance, Matritech, Inc. of Newton will present its case to the US Food and Drug Administration, arguing for expanded approval of its already-marketed test, NMP22, which measures a protein made in the nucleus of cells in urine. High levels of NMP22 indicate high turnover of cells, a sign of cancer. The company wants doctors to use the test not just to monitor people who have cancer, as is now the case, but to test those who merely show symptoms, like having blood in the urine. In Japan, the NMP22 test is already approved for wider screening.

Overall, the test is 70 percent sensitive, which means it finds 70 percent of tumors at all stages of cancer combined.

That also means it misses 30 percent. And while that’s better than cytology, it’s still underwhelming to some urologists.

“It’s not the greatest test in the world,” says Dr. Michael O’Donnell, director of the bladder cancer center at Beth Israel Deaconess Medical Center. “I did a 6-month pilot trial at our institution and abandoned it.” The test often said patients had cancer when they didn’t and missed it in those who did have it.

Even if it were 80 percent sensitive, “that just isn’t good enough in my mind,” adds Loughlin of the Brigham.

Still, in one Italian study published last year, NMP22 was a better cancer detector than a marker called BTA. Another 1998 study found NMP22 was just as sensitive as a marker called telomerase, and that both were more sensitive than BTA. A Cleveland Clinic study published in January, showed the test was 100 percent sensitive. And a Spanish study, published this month suggested that NMP22 combined with another marker, CYFRA 21-1, can help reveal whether cystoscopy is needed.

For instance, if a patient scores low on the NMP22 test, it may be safe to postpone the invasive exam for a few months or do it under local anesthesia in the doctor’s office. If a patient scores high, it suggests the procedure should be done in a hospital under anesthesia, so that if the urologist does see cancer, he or she can remove it right then and there.

The NMP22 test may also tip the balance when other tests are ambiguous, notes Dr. Eric J. Sacknoff, a urologist at Cambridge Urological Associates. If the NMP22 score is high and a bladder X-ray is negative, for instance, that may indicate there is indeed a cancer, but higher up in the urinary system.

Ultimately, it’s not just better detection but better treatment that’s needed to turn the tide in bladder cancer.

At the Beth Israel, for instance, urologist O’Donnell is expanding the trial that Pinzur participated in to 70 centers nationwide. 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 may improve those odds. So far, though, his study hasn’t followed patients long enough to tell.

Ultimately, says Loughlin of the Brigham, the best treatment for bladder cancer will probably be gene therapy to correct messages from errant genes on chromosomes 9 and 17. And the best way to prevent it is not to smoke. Scientists believe that bladder cancer begins when genes on one or both of these chromosomes are damaged by tobacco and other carcinogens.

So far, he says, that research is still in its infancy. But “this is where the real, major advance is going to be.”< SIDEBAR

SMOKERS AT HIGHER RISK YOU MAY BE AT RISK FOR BLADDER CANCER IF YOU ARE OVER 50, MALE OR SMOKE. IN FACT, MEN ARE FOUR TIMES MORE LIKELY THAN WOMEN TO GET BLADDER CANCER, PROBABLY BECAUSE, HISTORICALLY, THEY’VE BEEN MORE LIKELY 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. Others 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 these compounds.

In recent years, the incidence of bladder cancer has been rising slowly, for unclear reasons.

One sign of possible bladder cancer is blood in the urine, either enough to see with the naked eye, or traces detected through urine testing. But this doesn’t always indicate cancer. It can also be – in fact, it usually is – a sign of infection or inflammation anywhere in the urinary tract, prostate problems, or a kidney stone. Or sometimes, simply having eaten beets can give the urine a reddish hue.

Still, if you have blood in your urine, you should call your doctor.