Screening for cancer: Colon, lung, and skin cancers

Content provided by the Faculty of the Harvard Medical School

Screening for cancer: Colon, lung, and skin cancers

One of modern medicine's proudest achievements is its ever-improving ability to detect disease early. The rationale is obvious: Early diagnosis leads to early treatment and a better outcome. When it comes to a disease like cancer, early diagnosis is particularly important, even urgent.

There are many ways to facilitate early detection. People should learn to recognize warning symptoms and call them to a doctor's attention. Physicians should perform careful exams and follow up on any abnormalities they find. And testing should be used to root out disease even before it shows up on a doctor's exam or causes any symptoms at all.

Screening tests are procedures performed on a routine basis when people feel well and neither patients nor their doctors have any specific cause for concern. Screening tests have been spectacularly successful in detecting cardiovascular risk factors. Routine blood pressure checks and cholesterol tests are the best examples. Both can detect abnormalities long before they cause any symptoms, and both can lead to safe and effective lifestyle and medical treatments. Screening for high blood pressure and increased cholesterol levels gets much of the credit for the 56% decrease in deaths from heart disease and the 70% decline in stroke deaths that Americans have enjoyed over the past 50 years.

Heart disease and stroke are the first and third leading causes of death in the United States. Since cancer is in second place, taking more than 570,000 lives each year, screening is every bit as important. In fact, the first medical screening test that produced major benefits was a cancer test: In the 1930s, Dr. George Papanicolaou introduced the simple screening test that bears his name. As a result of the Pap test, deaths from cervical cancer have declined by more than 85% — and most of the 4,100 American women who die from the disease each year could have been saved if they had had their recommended Pap smears.

The Pap test has set a high standard for cancer screening. Unfortunately, no other test can match it. But if screening mammograms are not as effective as Pap tests, most authorities still believe they are very beneficial. At present, the only cancer screening procedures of proven value for men are the tests for colorectal cancer — and even here, experts debate the best use of the various tests. Still, the choice a man has to make about colon cancer screening seems easy compared with his decision about prostate cancer screening, the most controversial issue of all.

What makes a good screening test, and what should men do to detect cancer in its earliest stages?

Screening the tests

Before a test becomes part of routine medical care, it should meet several standards. To be useful, a test should have a high sensitivity: It should be able to detect a large percentage of cases, with few false-negative results. It should also have a high specificity: It will not produce many false-positive results, diagnosing disease when none is present. A good test should be reliable and reproducible, so a patient can expect the same results wherever he is tested. The test should be convenient and comfortable enough to gain wide acceptance and inexpensive enough to be affordable. Needless to say, tests that are performed on people who feel perfectly well should be extremely safe. Above all, perhaps, good tests should lead to an effective treatment that will improve a person's outcome.

In a word, a test should do more good than harm.

Testing the tests

Early diagnosis is always scored as a success for the scientists who developed the tests, but it's not necessarily a success for the patient. The measure of a test's value is not its ability to find a disease but its ability to improve the quality and duration of life.

A randomized clinical trial is the best way to evaluate a test. Volunteers are randomly divided into two groups, one of which gets the test while the other does not. Because the assignment is by lot, the two groups will have an identical mix of risk factors, and the two should receive identical medical care and follow-up treatment during the trial. At the end of the study, the researchers evaluate the groups to see if the test has led to a better outcome.

Randomized clinical trials require large numbers of patients and many years of follow-up. As an example, scientists calculate that a study designed to detect a 25% decline in deaths from testicular cancer would require 6.5 million volunteers and take many years.

Randomized clinical trials are slow and expensive. They are also very complex, which is why there has been some debate about the various mammogram trials that have been completed to date. The only cancer screening test for men that has run the gauntlet of a randomized clinical trial is the fecal occult blood test for colon cancer. It passed — but other procedures, such as colonoscopy and sigmoidoscopy, which have not been evaluated as stringently, are likely to be substantially better.

In the real world, we don't have the luxury of a full answer to many important medical questions. Lacking proof, we have to make decisions based on the best available evidence.

Should you be tested?

Cancer triggers so much anxiety, and early diagnosis is so logical, that many people choose to be tested even if proof of benefit is lacking. In many cases it's a reasonable choice, but before a man rolls up his sleeve or pulls down his pants for a test, he should understand the potential drawbacks.

Tests may be frightening, time-consuming, inconvenient, or uncomfortable. These drawbacks are easy to understand. It's also easy to realize that invasive tests may have side effects that can be serious. Less obvious is the fact that a test that's safe and simple can lead to treatments that are not. In some cases, the treatment is worse than the disease, in which case the test that starts the ball rolling ends up doing more harm than good. And testing is expensive, particularly if a false-positive test leads to additional procedures. In the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, for example, 43% of participants received at least one false-positive result. On average, each person received about $1,100 in extra medical care in the year following the false alarm.

Touting the tests

"Who shall decide," asked Alexander Pope, "when doctors disagree?" It's a good question. In the case of cancer screening, smart, well-intentioned scientists can come up with different conclusions and recommendations. In general, advocacy groups, such as the American Cancer Society, and associations of medical specialists who perform tests and treatments, such as the American Urological Association, are more aggressive about testing than academic panels, such as the U.S. Preventive Services Task Force, and government agencies, such as the National Cancer Institute. And the problem of competing guidelines has become more acute since commercial interests have entered the arena, offering body scans and other tests to the public through direct advertising, often very forcefully.

Your call

In the last analysis, each man must decide for himself. Talk with your doctor and ask what a test will cost in terms of time and discomfort, as well as dollars. Ask if there are side effects. Try to determine your risk for the particular cancer; in general, men at high risk tend to benefit from testing much more than men at low risk. And although it can be hard to think about the consequences of a cancer diagnosis, ask what's likely to happen if you find you have the disease and if treatment is apt to change that result.

In a nationwide survey, 87% of people believed that routine cancer screening is almost always a good idea and that it saves lives — even though more than a third of them had experienced a false-positive result. Is screening right for you? Here is a rundown of some common cancer screening tests to help you decide.

Colorectal cancer

About 29,000 American men die from colorectal cancer each year. That puts the disease far behind lung cancer and slightly behind prostate cancer on the hit list. Even so, screening for colorectal cancer is more important than screening for the other two because it really can save lives. Testing can detect prostate cancer at an early stage, and new technology may do the same for lung cancer, but doctors don't yet know if early diagnosis will translate into longer survival. Surprisingly, perhaps, only 48% of American men over 50 have had up-to-date colon cancer screening, whereas about 75% have been screened for prostate cancer at least once and 54% report regular screenings.

Colon cancer is an ideal target for screening because it develops slowly in a predictable pattern and because early detection is highly effective but late treatment is not. In nearly all cases, the first abnormality is a benign adenomatous polyp (see figure below). About 99% of polyps remain harmless, but some become cancerous. Even then, the disease progresses predictably, spreading from the polyp into the wall of the colon, then into other tissues at a measured pace. If doctors remove polyps while they are benign, they can actually prevent colon cancer. And by removing cancers that are diagnosed early, doctors can cure more than 90% of patients, a figure that drops precipitously if the disease is diagnosed at a later stage.

Colonoscopy. (Left) This screening exam is similar to sigmoidoscopy with one big advantage: The doctor can check for polyps throughout the entire length of the colon. Removal of polyp. (Right) If a stalked polyp is sighted, the doctor uses a wire snare threaded through the colonoscope to remove it.

The trick is early detection. Four tests have been approved for colon cancer screening (see Table 1).

The simplest is fecal occult blood testing (FOBT), which takes advantage of the fact that polyps and cancers are more likely to bleed than normal tissues. In most cases, the blood is too scant to be visible, but it can be detected by a sensitive chemical test. The theory is simple, but like most easy answers, it has flaws. Many polyps and cancers don't bleed or bleed only intermittently, so FOBTs are often falsely negative (i.e., they have a low sensitivity). On the other hand, benign abnormalities, ranging from gastritis to hemorrhoids, can bleed; as a result, FOBTs are often falsely positive (i.e., they have a low specificity). Despite the test's low cost, wide availability, ease, and safety, the problem of false negatives and positives would seem to rule it out as a screening test but for one fact: It works. Five randomized clinical trials show that people who submit three stool specimens a year (or even every other year) and follow up a positive result with a colonoscopy are 15%–34% less likely to die from colon cancer than people who are not screened at all. That's a high yield from an easy test. Remember, though, that a digital rectal exam with a single FOBT in a doctor's office is not a useful test for colon cancer.

Sigmoidoscopy allows doctors to see polyps and cancers in the lower third of the colon. A patient prepares for the test by taking a laxative and/or enema at home and skipping breakfast. The doctor passes a fiberoptic tube through the rectum and advances it about 25 inches upward. If he spots a polyp, he can biopsy or remove it through the scope. The test takes about 15 minutes and is mildly uncomfortable.

A sigmoidoscopy is highly accurate as far as it goes, but it only goes a third of the way up the colon. A colonoscopy goes the distance, making it the best way to detect polyps and early colon cancers. Unfortunately, it will miss 5% of polyps. It's also the most arduous test. Colonoscopy requires a much more vigorous cleansing preparation than sigmoidoscopy, and it also requires a sedative. Although the preparation is unpleasant, sedation minimizes any discomfort from the test itself. A colonoscopy takes 30–40 minutes, but it takes several hours for the sedation to wear off. President George W. Bush was out jogging a few hours after his colonoscopy, but for most people, the test will disrupt normal activities for the better part of a day. At present, colonoscopy is the "gold standard" in screening for colon cancer.

A double-contrast barium enema relies on x-rays to detect polyps and cancers. An enema is used to fill the colon partially with barium. Next, the colon is inflated with air and x-rays are obtained. The preparation is similar to that for a sigmoidoscopy, and the test takes about 30 minutes. Barium enemas cannot distinguish between polyps and cancers, so patients with abnormalities require colonoscopies. The test can miss small polyps and cancers.

Which test is best for you? It depends on your risk factors and personal choice (see Table 2).

Men at high risk may be candidates for genetic testing and require frequent colonoscopies, sometimes beginning at a young age. Men at moderate risk should choose a colonoscopy when they turn 50; even if the test is negative, it should be repeated every 5–10 years. Men at average risk can choose a colonoscopy every 10 years, a sigmoidoscopy every 5 years (preferably with annual FOBT), or annual FOBT; colonoscopy offers the best protection (but is the most arduous). A barium enema every 5–10 years is also an approved option but seems less desirable. One report suggests that African Americans may be wise to begin screening at the age of 45.

New tests for colon cancer are being developed. The most promising is a stool test for cancer genes, but it is at least a few years away from clinical use. Virtual colonoscopy, which uses computed tomography (CT scanning) to visualize the colon, is also being studied; early results have varied, and most experts agree it's not ready for prime time. More progress will follow, but it's a great mistake to put off colon cancer screening with the excuse that a better test is on the way. Evaluate your risk, talk with your doctor, then pick a test and do it. And while you're at it, think about lifestyle changes that may reduce your risk of colon cancer; exercising regularly, staying lean, shunning tobacco, taking a daily multivitamin, eating a diet high in fruits, vegetables, and calcium but low in red meat, and the long-term use of anti-inflammatory drugs are on the list of hopeful possibilities.

Lung cancer

It's a dreadful disease. With 93,010 new cases diagnosed in American men in 2005, lung cancer is common, and with 90,490 deaths, it is highly lethal. And the real tragedy of lung cancer is that it is largely preventable. The key is to avoid exposure to tobacco in all its forms, including secondhand smoke; reducing radiation exposure, including residential radon, will also help.

In 1974, the American Cancer Society (ACS) endorsed lung cancer screening with annual chest x-rays. It was a well-intentioned and logical recommendation, and it was widely accepted by the medical community and the general public. But as the results of four large randomized trials were known, it became clear that annual chest x-rays don't reduce deaths from lung cancer, and the ACS reversed itself in 1980.

Screening chest x-rays don't save lives because by the time a lung cancer is large enough to show up, it is likely to have already spread, making surgical cure unlikely. But a new radiology procedure, low-dose high-resolution spiral computed tomography (spiral CT) can pick up cancers that are much smaller, when they may still be cured. The problem is that spiral CTs also detect many tiny nodules that are not malignant. As a result, patients are faced with the worry and expense of repeat spiral CTs every three or four months, or with the risks of surgery.

Spiral CTs are being promoted as an effective screening test for lung cancer. They may turn out to meet that goal, but they may not — and because an abnormal spiral CT often leads to lung surgery, they could even do more harm than good. The only way to find out is with randomized clinical trials, which are in progress.

Until results are available, neither Medicare nor private insurance carriers will pay for screening CTs. A man at high risk because of many years of heavy smoking might reasonably choose to pay for a scan himself, but he should understand that the test's benefits and risks are not known. The same is true for an even newer test, positron emission tomography (PET scanning).

Despite mounting publicity for testing, the ACS and other medical groups do not recommend screening for lung cancer, even in smokers. Needless to say, however, they all recommend that people stop smoking and avoid secondhand smoke.

Whole body scans

The fear of cancer is understandable and legitimate, but turning fear into profit is reprehensible. Because spiral CTs can detect small nodules in the abdomen as well as the chest, whole-body scans to detect cancer are being marketed directly to the public, often with come-ons such as "Father's Day specials." As a result, a 2004 survey found that 73% of respondents would choose a whole-body CT over $1,000 in cash.

While preliminary evidence raises the possibility that spiral CTs may be able to detect lung cancer in smokers, there are no data to support whole-body scans, which may do more harm than good, both from false-positive results that lead to anxiety and unnecessary treatment and from radiation exposure. Whole-body scans are not recommended, and they are not covered by insurance. Critics who call them "whole-body scams" may be right.

Skin cancer

Basal cell and squamous cell skin cancers are very common but rarely serious. Malignant melanomas are much less common but much more serious; about 33,500 cases are diagnosed in American men each year, and 4,900 will be lethal.

Because melanomas are visible to the naked eye, screening involves little more than a careful look. Systematic screening has not been validated by randomized trials, but it's logical, easy, safe, and inexpensive. Here's how to go about it on your own.

First, make a schedule that will remind you to check yourself at least three or four times over the course of a year. Pick the first day of each season, important family anniversaries, birthdays, or major holidays. If that's hard to remember, use the first day of each month and inspect yourself a bit more often.

Next, establish a routine to bring your whole body under scrutiny. For example, you can start with your head and move down. Don't be complacent about protected areas such as the skin between your fingers and toes and your thighs and genitals. When it comes to your back and the back of your legs, you'll need help from your spouse or you'll need to stand with your back to a full-length mirror holding a hand mirror in front of you. The hand mirror will also help you view the soles of your feet. Needless to say, good lighting is essential.

Finally, you'll need to learn the warn­ing signs of melanomas, which can be sum­marized with the letters A, B, C, D, E:

Asymmetry. Most melanomas have an irregular shape; benign moles tend to be symmetrical and regular.

Border. Most melanomas have borders that are scalloped, notched, or blurry and indented; moles are usually defined by a smooth, regular margin.

Color. Melanomas tend to be multicolored, with hues ranging from black to brown to red or even white or blue. Most moles are uniformly tan or dark brown.

Diameter. Melanomas are usually larger than 6 mm across (about the diameter of a pencil eraser) at the time of diagnosis.

Evolution. Skin lesions that are enlarging or changing in color, texture, or shape are more worrisome than stable lesions.

While it's important to master your A, B, C, D, and E, you should also be prepared to recognize other warning signs. Moles that become elevated or bleed without being scratched call for medical attention. Even itching can sometimes be a sign of trouble.

Although you should be your own early warning system, your doctor can also help by systematically inspecting your skin at your annual check-ups. People at risk should consider seeing a dermatologist as well; risk factors include having had two or more blistering sunburns in childhood, having a fair complexion with light hair and eyes, having lots of moles or freckles, and having a parent or sibling with a history of melanoma.

Screening is important, prevention even better. Excessive sun exposure explains the melanoma epidemic, which has produced a twenty-fold increase in the disease over the past 75 years. To protect yourself, avoid direct sun exposure, especially between 10 a.m. and 2 p.m. Whenever possible, wear a wide-brimmed hat and light-colored, long-sleeved shirts and full-length pants. And use a broad-spectrum sunscreen with an SPF of 15–30, applying it liberally before and during outdoor activities.

Research has uncovered a genetic mutation in the so-called BRAF gene that appears responsible for 70% of all malignant melanomas. That discovery may someday improve diagnosis and treatment — but until scientists shed more light on the subject, you should shun sunlight, but use a bright incandescent light to screen your skin for melanomas.

Last updated:	September 05, 2008