• 12/4/2004
  • Amy Dockser Marcus
  • The Wall St. Journal

Cancer screening is getting easier, with new tests available — and many more in the works — that can detect the disease even in tiny amounts, when it still is in its earliest stages. Some of the new tests use just a small amount of saliva or urine to search for molecular changes in cells that indicate the cancer process is under way. Others use high-speed computers to identify genetic signatures of cancer in the blood. Advanced imaging machines are becoming more widely available that enable doctors to spot cancers smaller than the size of a period at the end of a sentence.

But the debate over who should take advantage of the newer screens, and even some of the older ones, is intense. While cells may look abnormal under a microscope, they may never grow into something that harms the patient.

“We are beginning to understand that there are some cancers that are better for people not to know about,” says H. Gilbert Welch, a senior research associate with the Department of Veterans Affairs in White River Junction, Vt.

At the same time, some cancers are so aggressive or unpredictable that knowing about them early may be of little use. Barnett Kramer, associate director for disease prevention at the National Institutes of Health, says finding a cancer early is sometimes like being tied down to a railroad track and being given a pair of binoculars: “You can see the train coming from further away, but you haven’t done anything to change when the train is going to hit you.”

For patients, deciding when to take a new screen can be difficult. Many reject as paternalistic the notion that no one should use a screen until it is proven to reduce the risk of dying from a particular cancer — a process that can take as long as 10 years. But that instinct isn’t always right, especially for people who are only at average risk of getting cancer.

The American Cancer Society and the U.S. Preventive Services Task Force offer general guidelines online about which tests to take and which to talk about with your doctor. But often the decision is a personal one based on factors such as your family history, your general health and what you are exposed to at work or at home. Someone who has seen a loved one die of cancer also may choose to take a risk on newer screens.

“People are going to have to start making choices, because there are a plethora of possible things to be tested for,” says Dr. Welch, a prominent researcher on cancer screening who recently published a book questioning the wisdom of some screens.

“If you have a strong family history of cancer, you will benefit, but if you have a strong family history of heart disease, maybe you should focus on that.”

Below is a look at recent developments in cancer screening and at the latest, best thinking on when to get tested.

Breast cancer

Mammography has been one of the most successful cancer-screening tests and is widely accepted based on studies showing it saves lives. The American Cancer Society also lists more than 20 imaging technologies that now can be used for breast-cancer detection, such as sonograms, which often are combined with mammography.

Mammography still isn’t as good as doctors want it to be. Current guidelines recommend that women of average risk start mammography at age 40, in part because mammography doesn’t work very well on denser breasts, which are more common in younger women.

Mammography also misses a lot of cancers in older women. A study published last month found that almost 40 percent of women with late-stage breast cancer had a negative mammogram one to three years prior to their diagnosis.

There is some hope that so-called digital mammography, which uses detectors similar to those found in digital cameras, will be able to detect breast cancer better than the standard screen-film mammography. The technology is available at some medical centers, and a large trial on the subject is expected to publish results next year.

MRIs, or magnetic resonance imaging, have been shown to detect more tumors than mammograms, but also come with a high false-positive rate; they are recommended only for women who are at high risk because of a family or personal history of breast cancer.

One new test generating excitement is a more precise mammogram called tomosynthesis breast imaging. The tomosynthesis machine takes more pictures of the breast, from many more angles and much more quickly, than a conventional mammogram.

Pilot studies conducted at Massachusetts General Hospital in Boston indicate the test sees abnormalities more clearly than the standard mammogram, even in younger women. The hospital still has more research to conduct before the test can be made widely available.

Other tests, such as positron emission tomography (PET) scans, X-ray computer tomography (CT), and novel ultrasound methods such as 3D and Doppler, have shown some promise and are available at many hospitals and clinics. More research needs to be done before they could be recommended for widespread screening.

Bottom line: Until more trial results are published and more work is done on tomosynthesis, most women of average risk of getting breast cancer are advised to get standard mammograms.

Colorectal cancer

Effective screening tests already exist for colorectal cancer. Unlike virtually every other area of screening, patients have a range of choices that are endorsed by the American Cancer Society.

The society recommends annual fecal occult blood tests; flexible sigmoidoscopy every five years; annual FOBT plus flexible sigmoidoscopy every five years; double contrast barium enema every five years; or colonoscopy every 10 years.

Fewer than half of those recommended for regular screening — men and women over 50 — do so. That is partly out of an aversion to the various procedures, which can involve enemas, anesthesia and handling of stool samples.

CT colonography, also known as virtual colonoscopy, has received a fair amount of attention of late; early tests indicate the test may be more effective in picking up certain lesions than standard colonoscopies.

There is hope that people will be more willing to use it since it is faster and less uncomfortable than a standard colonoscopy and doesn’t require anesthesia.

Downsides: It still requires bowel preparation and, if any polyps are found, a follow-up standard colonoscopy to remove them. While the test still isn’t widely recommended, that could change with results from a major trial set to begin next year.

In addition, private companies are creating tests that are far less invasive. International Medical Innovations Inc. has developed ColorectAlert, a low-cost screening test that identifies the presence of sugars in a sample of rectal mucus that can be associated with cancer. Because the sugars can be associated with benign conditions as well, the test isn’t used to replace a colonoscopy but to signal who should go for further testing.

Exact Sciences of Marlborough, Mass., has developed a test that screens DNA extracted from a stool sample for gene alterations that can suggest cancer. The company sells the test for $795.

Bottom line: The cancer society and U.S. Preventive Services Task Force both have called virtual colonoscopy promising but don’t recommend it for general screening, saying there isn’t enough evidence yet for it, or for DNA stool tests.

For patients who do choose the virtual route, it is important to ask what kind of machine is involved, since not all procedures are equal. A 2003 study in the New England Journal of Medicine found that a 3D version of the machine — which isn’t the same as that used in hundreds of screening venues — worked just as well as regular colonoscopy.

Lung cancer

Lung cancer frequently doesn’t have any symptoms until it is advanced and difficult to treat. The traditional way to detect it has been with an X-ray.

Now, there is a test — spiral CT scan — that seems to find the cancer much earlier, when surgery still is an option. The screen is controversial, both because it is expensive and because the machines are so powerful they often pick up nodules that aren’t cancer at all.

Patients can get a spiral CT at various sites, including some malls. The cost is around $300, and insurance generally doesn’t cover it.

In a study at the Mayo Clinic in Rochester, Minn., 50 percent of heavy, long-term smokers over 50 who were given spiral CT scans were found to have at least one nodule. In most cases, however, doctors couldn’t tell if the nodule was malignant or benign.

Among the lung operations done as a result of those scans, 17 percent turned up benign conditions, meaning these people unnecessarily faced the risks of major complications such as a collapsed lung or death.

Other studies have demonstrated the effectiveness of spiral CT in finding lung cancer earlier. This month researchers at Weill Cornell Medical Center in New York will report early results of a large study suggesting lung-cancer screening with CT scans saves lives and should be common for people at high risk for the disease.

Bottom line: While it probably will be five years before learning the outcome of a large 50,000-person trial comparing spiral CT and chest X-rays, the American Cancer Society acknowledges that early studies look promising. Patients are advised to first discuss the test with a doctor, and if taking the test, to do it in an experienced center capable of diagnosis and follow-up.

Oral cancer

Oral cancer kills more than 8,000 people a year and is the sixth-leading form of cancer death, but it often isn’t detected before it is plainly visible to the naked eye. “Oral-cancer screening is at a barbaric stage,” says Dr. Douglas Burkett, chairman, chief executive and president of Zila Inc., a Phoenix company working on new screening devices.

Even visual screens aren’t performed as often as they should be; people over 40, and anyone who smokes or drinks more than one drink a day may be at greater risk for the disease.

Zila has a product on the market called ViziLite, a $20 lightstick that illuminates abnormalities in someone’s mouth after the patient rinses with a special solution. Dentists charge around $45 for the exam, Dr. Burkett says. ViziLite does turns up a large number of benign conditions that can resemble cancer. A second product in the works called OraTest shows promise for a higher accuracy rate, Burkett says.

Bottom line: Even though there is the risk of false positives with emerging oral-cancer screens, the ramifications are less serious than with some other cancers. Biopsies for oral cancer are noninvasive, involving a swipe of cells from inside the mouth.

Prostate cancer

When it comes to controversies about screening tests, one of the loudest and longest has been over the PSA, or prostate specific antigen, blood test. Used widely since the 1980s, it looks for elevated levels of certain substances that could indicate early cancer.

More and more experts lately are arguing against it, contending it doesn’t reliably indicate how much cancer someone has or how serious it may be. Many men would prefer not to have an uncomfortable biopsy without greater assurance that it is called for.

Even a biopsy may not accurately assess the cancer, because there is no guidance from a PSA test on precisely where to look. Severity of the cancer is an important consideration, since patients who opt for treatment face the risk of side effects including impotence and urinary and bowel problems. Also, there are no large clinical trials that conclusively demonstrate that having a PSA test helps reduce a man’s chances of dying from cancer.

There have been some efforts to refine the PSA, and there are at least six different variations of the test now available that aim to be more accurate, including free PSA, which measures the percentage of PSA that isn’t bound to proteins in the blood, and PSA velocity, which looks for change in several readings rather than a single PSA test.

Some groups around the country are searching for markers in blood, saliva and urine that might indicate when prostate cancer is present. Efforts are under way to improve imaging of the prostate using MRIs, ultrasound and other technologies.

These methods “are not ready for prime time yet,” says Philip Kantoff, director of the prostate-cancer program at Dana-Farber Cancer Institute in Boston. “I wouldn’t throw out the PSA test yet.”

Bottom line: The consensus on whether to take the PSA — or one of the variations of it — is to discuss the potential benefits and possible drawbacks with a doctor before deciding. Personal choice, family history and an individual’s risk factors will play a big role. The American Cancer Society also says men should be offered the option of a digital rectal exam, which can help detect cancer.

OCF Note: The foundation disagrees with the comments by Dr. Burkett of Zila Pharmaceuticals. Oral cancer screening being characterized as “at a barbaric stage,” is a gross misstatement of the situation. In actuality oral cancer screenings, when they are opportunistically conducted by members of the dental or medical professions are highly effective. They are no different than the screenings which women undergo annually for cervical cancer. Those screenings are directly responsible for the dramatic drop in death rates in women from cervical cancer in the 1950’s. The parallels between oral and cervical cancers are many. First, the cancer which is primarily involved in both situations, is the identical disease, squamous cell carcinoma. Then there is the examination itself, which in both cases is visual, tactile, and if a suspicious area is detected, it is then sampled through a brush biopsy procedure. This procedure, if it is returned as positive, is followed up by an incisional biopsy for finite diagnosis of malignancy. If the examination was conducted as frequently in the dental environment or in the primary medical care practice, as the annual screening for cervical cancer currently is, we would see similar drops in the rates of both morbidity and death associated with oral cancer as we have seen in cervical cancers. While Zila has obtained the rights to, and sells, a chemolucent light which aids in the visual part of the examination, it is not a quantum leap in the discovery process related to the visual identification of suspect tissues which may need further examination or biopsy. Those dramatic death rate reductions that have taken place in the cervical arena have taken place without the need for any type of discovery assistance light. The issue in oral cancer is not the availability of new diagnostic devices, but rather the lack of mass implementation of the simple 3-5 minute screening itself. The evidence for this exists in several places. First a cancer which is not hidden deep within the body requiring any invasive procedure to discover it, but is easily visible with the naked eye (oral cancer), is found routinely as a late stage 3 or 4 disease 66% of the time. Given the ease of discovery and its location, this is an indication of lack of opportunistic screenings taking place. Second, Zila has not made significant market penetration with their disposable screening light after several years of effort, not because the light does not function as described, but because the actual screenings in the dental and general medical practices are not routinely taking place.