Tuesday, August 12, 2008

Early Test for Cancer Isn’t Always Best Course

August 12, 2008
Well

Sometimes what you don’t know might end up being better for you.

For years patients have been told that early cancer detection saves lives. Find the cancer before the symptoms appear, the thinking goes, and you’ve got a better chance of beating the disease.

So it might have seemed surprising last week when a panel of leading medical experts offered exactly the opposite advice. They urged doctors to stop screening older men for prostate cancer, which will kill an estimated 28,600 men in the United States this year.

Their advice offered a look at the potential downside of cancer screening and our seemingly endless quest to detect cancer early in otherwise healthy people. In this case, for men 75 and older, the United States Preventive Services Task Force concluded that screening for prostate cancer does more harm than good.

“We’ve done a great job in public health convincing people that cancer screening tests work,” said Peter B. Bach, a pulmonologist and epidemiologist at Memorial Sloan-Kettering Cancer Center in New York City. “We’re uncomfortable with the notion that some screening tests work and others don’t. That seems mystifying to people.”

But the reality is that while some cancer screening tests — like the Pap smear for cervical cancer or mammography for breast cancer — clearly save lives, the benefits of other screening tests are less clear.

Studies of lung cancer screening, for instance, have failed to prove that it prolongs life. A mass screening for neuroblastoma in Japanese infants was halted after it became clear that the effort wasn’t saving children and worse, led to risky treatments of tumors that weren’t life threatening.

The case seemed stronger for screening for prostate cancer. By some measures, death rates from the disease in the United States have plummeted since the introduction of the screening test for prostate specific antigen, which detects levels of a protein that can signal prostate cancer.

The data, in fact, are highly misleading. The introduction of screening can trigger big statistical fluctuations that can be difficult to interpret. But if you look at prostate cancer statistics in the 1970s, long before screening was introduced, death rates have dropped only slightly since then. The small decline seems largely because of improvements in treatment, many experts say, though others point to early detection as the reason.

Whether there really is a measurable benefit from PSA screening for younger men won’t be known for a few more years, after data from two major clinical trials studying the test are reported.

How can it be that finding prostate cancer early doesn’t help save lives? For starters, a large percentage of prostate cancers aren’t deadly. They are slow growing and unlikely to result in any symptoms before the end of a man’s natural life expectancy. By some estimates, as many as 44 percent of the men who are treated for prostate cancer as a result of PSA testing didn’t need to be. Had they been left alone, they would have died of something else and never known they had cancer.

“Screening tests don’t only pick up life-threatening cancers, they pick up tumors that look identical to traditional tumors, but they don’t have the same biologic behavior,” said Dr. Barry Kramer, associate director for disease prevention at the National Institutes of Health. “Some are so slow growing they never would have caused medical problems in the person’s natural life span.”

In the case of PSA testing, the Preventive Services Task Force, an expert panel that makes recommendations about preventive care for healthy people, said there was not enough evidence to recommend for or against screening of younger men, although they urged doctors to advise men of all the risks and benefits of screening. But they did conclude that 75 is the age at which the risks clearly begin to outweigh the benefits, and the disease, if detected, would most likely not have a meaningful effect on life expectancy.

Another problem with determining the value of screening is that it results in “lead time bias.” For instance, someone diagnosed with lung cancer at the age of 65 may die at 67 and be remembered as a two-year survivor. If the same man had been diagnosed at 57 through screening and died at the age of 67, he would be known as a 10-year survivor. That sounds a lot better, but the reality is that diagnosis and treatment didn’t prolong his life. He died at 67 either way.

“Even a harmful screening test could appear on the surface as a helpful test,” Dr. Kramer said. “Because you measure survival from the date of diagnosis, even if the person dies of the same cause on the same day they would have without screening, it looks like survival was longer.”

Any screening test can lead to false positives, followed by invasive and risky tests. Large numbers of people often end up being poked, prodded and tested only to discover they’re fine.

Biopsies to detect prostate cancer get mixed reviews. Some men find them to be a minor discomfort; others say they were left in debilitating pain. Once cancer is found, surgery, radiation or hormone therapy, or “watchful waiting,” may be advised.

Treatments for prostate cancer can cause significant harm, rendering men incontinent or impotent, or with other urethral, bowel or bladder problems. Hormone treatments can cause weight gain, hot flashes, loss of muscle tone and osteoporosis.

“It’s just a needle stick, but the cascade of events that follows are fairly serious,” Dr. Bach said. “I think the burden is on medicine to try and generate some evidence that the net benefits are there before drawing that tube of blood.”

The problem with prostate screening is that some men are very likely to have been saved by early detection. But how many have been hurt?

“I’m a little worried we may look back on the prostate cancer screening era, after we learn results of clinical trials, and see that we’ve harmed a lot of people without doing them good,” said Dr. David Ransohoff, a professor of medicine and cancer screening researcher at the University of North Carolina at Chapel Hill. “By being so aggressive with so many people, did we do the right thing? I don’t know that it’s going to turn out that way.”