Tackling Testing

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CUREColorectal Cancer Special Issue
Volume 9
Issue 0

Screening has improved the prevention and early detection of colorectal cancer, but how can it reach more people?

Screening for colorectal cancer can save lives in the best possible ways—by preventing some people from ever getting the disease, and by finding it early in others.

But those outcomes aren’t likely unless people agree to get tested. And that can pose a problem when the test is a colonoscopy, the most frequently recommended screen for the disease.

“Thousands of people die each year because they find the idea of a colonoscopy repulsive and intimidating. We need to get doctors pushing them harder to do the right thing at the right time,” says Alan P. Venook, a colorectal cancer expert at the University of California, San Francisco’s Helen Diller Family Comprehensive Cancer Center, where he heads up the gastrointestinal oncology program.

That reluctance is at the heart of concern over how best to prevent colorectal cancer, or diagnose it as early as possible.

The disease tends to be asymptomatic until it reaches advanced stages, so diagnosing patients before symptoms appear is an important way to avoid harsh treatment regimens and a worse prognosis. Due to the push to begin routine screening at age 50, there was a nearly 30 percent reduction in deaths from colorectal cancer between 2000 and 2010. Yet experts say the number of lives saved could be much higher if more of those who are eligible complied.

There’s talk about increasing the focus on other available screening methods, which don’t offer all the advantages of colonoscopy but are roughly equivalent in terms of reducing colorectal cancer deaths—and may be more palatable to those targeted for the tests.

At the same time, there’s concern about a rise in the rate of colorectal cancer among younger adults, who are not in the right age group to receive routine screening. Would it make sense to routinely screen people younger than 50, and at what age should that start?

According to George J. Chang, of MD Anderson Cancer Center, in Houston, it’s too soon to make such a change to national screening guidelines.

But the time is right for a concerted increase in public education about that trend and the disease itself, as well as prevention efforts, says Chang, associate professor of surgical oncology, health services researcher and associate medical director of the Colorectal Center at MD Anderson.

COLORECTAL CANCER: JUST THE FACTS

The term “colorectal cancer” encompasses two similar diseases, colon cancer and rectal cancer, which each originate in the portion of the large intestine for which they are named.

The two diseases are similar enough that they are often considered as one type of cancer that, in any given year, will affect roughly 137,000 Americans, with 50,000 of those cases ultimately being fatal.

About 4.7 percent of Americans will be diagnosed with the disease at some point in their lives, researchers estimate, and more than 1 million of them are living with it today. Diagnoses are about 30 percent more common in men than in women and approximately 40 percent more common in African Americans than in either Asians or Hispanics. Non-Hispanic whites fall in the middle. (These numbers have led the American College of Gastroenterology [ACG] to recommend that African Americans begin routine screening at age 45.)

Five-year survival rates rose from 48.6 percent in 1975 to 66.4 percent in 2002 and then plateaued. The sharp drop in colorectal cancer deaths since then stems almost entirely from the increased detection (and quick removal) of cancer precursors and diagnosis at earlier stages.

The five-year survival rate for people diagnosed with localized disease that does not penetrate the colon or involve lymph nodes is nearly 90 percent. For patients diagnosed with distant disease, however, the five-year survival rate is just 13 percent.

Disease subtypes that are known to be hereditary, such as familial adenomatous polyposis (FAP) and Lynch syndrome, account for 5 to 10 percent of colorectal cancers. The rest seem to arise from some combination of genetics and environmental factors.

Known risk factors include tobacco use, heavy alcohol use, diabetes, Crohn’s disease, obesity, a sedentary lifestyle and a diet rich in red meat, processed meat or any meat cooked at very high temperatures.

These factors can help explain differing colorectal cancer rates among large groups, but they’re not correlated with the disease strongly enough to predict individual risk.

The only truly predictive risk factor, beyond a family history of the disease, is age. Colorectal cancer, despite the steady decline of cases among older patients and the steady rise of cases among younger ones, is still a disease of age. Only about 20 percent of all new cases are diagnosed in people younger than 55.

THE GREAT SCREENING DEBATE

Typical screening guidelines call for colonoscopies every 10 years starting at age 50, in people with no family history of colorectal cancer and no symptoms.

A New York Times analysis of data from the Centers for Disease Control (CDC) suggests that about 10 million Americans undergo colonoscopies each year, at a total cost of around $10 billion. In a 2011 review of 55 studies of the cost-effectiveness of various methods of screening for colorectal cancer, “All studies found that colorectal cancer screening was cost-effective or even cost-saving compared with no screening,” the investigators wrote.

In fact, 60 percent of deaths from colorectal cancer could be avoided if everyone eligible chose to get screened, experts say. But to achieve that, the health care community will need to screen a larger percentage of the over-50 cohort with greater regularity—at least until researchers discover more effective ways to target screening efforts specifically to those who need them most.

“We have made great strides in the past 15 years. In some regions of the country, the percentage of people who get screened at least once after their 50th birthday has basically tripled to around the two-thirds mark. That said, we can do dramatically better,” says Chang.

A coalition led by the American Cancer Society (ACS) and the CDC has vowed to increase that percentage to 80 percent of people aged 50 and over by the year 2018.

But encouraging compliance can be a challenge due to the reluctance of some to undergo a colonoscopy.

The screen is certainly a commitment: It requires the test taker to spend a day on a liquid diet, take colon-clearing laxatives and possibly undergo an enema. During the test, a tube is inserted through the rectum so that the colon can be examined and the doctor can ensnare and remove any suspicious tissue for testing.

Elaine Newcomb complied with recommended screening colonoscopies, so she was shocked when she learned, between tests, that she had developed the disease.

Elaine Newcomb was shocked to learn she had developed colorectal cancer between regular screening colonoscopies.

With a year to go before she was due for her second colonoscopy, gallbladder pain sent her to the local emergency room.

Testing there revealed she had lesions on her liver that had originated in her colon and spread through her lymph nodes. An oncologist diagnosed her with stage 4 disease and told her to get her affairs in order.

“I was gobsmacked,” says Newcomb, of Wyoming, who is alive six years later because her tumor responded remarkably well to surgery followed by chemotherapy. “The whole point of having the colonoscopy at 10-year intervals was to make it nearly impossible for the disease to get beyond an early stage.”

It’s true that screening colonoscopy is an imperfect technique, just like any screening method for any cancer. Still, studies show it’s effective enough to make a big difference in outcomes, especially when expertly applied.

One recent study looked at the effectiveness of individual doctors in using colonoscopy to find adenomas—polyps that can turn cancerous if left unchecked. Specifically, the study looked at the proportion of screening colonoscopies each doctor performed that detected an adenoma. That’s known as an adenoma detection rate, and it’s an important gauge of the efficacy of colonoscopies. To establish a reasonable likelihood that patients will not develop cancers between screenings, professional societies prefer that doctors have an adenoma detection rate of at least 15 percent for female patients and at least 25 percent for male patients.

In the study, doctors’ adenoma detection rates ranged from 7.4 percent to 52.5 percent. Not surprisingly, patients of doctors with the highest adenoma detection rates were found to be half as likely to develop colorectal cancer between screenings as patients of doctors with the lowest detection rates.

Even with that disparity among adenoma detection rates, colonoscopy results tend to be accurate enough overall to justify the recommended schedule of screening at 10-year intervals.

One study showed that repeating colonoscopies in 1,256 patients after just five years did not lead to the discovery of fast-growing cancers that would otherwise have gone undetected. The colonoscopies, conducted in patients whose last tests had been clean, reported zero malignancies. Only 1.3 percent of the patients had even developed advanced adenomas, the sort of polyps that would present a serious threat of future cancer.

From many a doctor’s viewpoint, the biggest problem with colonoscopy is simply timid patients.

“The big hurdle is getting patients to agree to that first colonoscopy,” Venook says. “Once they submit to the first one, they’ll come back in 10 years for the next one.”

CONSIDERING THE ALTERNATIVES

Some experts believe that screening compliance would jump (and colorectal cancer rates would drop) if doctors advocated gentler screening techniques, at least for those patients who resist colonoscopy.

One is the virtual colonoscopy, which entails a CT (computed tomography) scan of the abdomen and pelvis, creating 3-D pictures that can identify polyps or other abnormal tissue. The test still involves the insertion of a tube—albeit a shorter one—into the rectum and colon, but is less likely to cause complications such as bleeding or tearing. It also offers the advantage of being able to identify problems not just inside, but outside the colon. However, the test emits radiation, and patients must still prepare with laxatives. Also, the test is not yet widely available.

Another alternative is a sigmoidoscopy, which is like colonoscopy- lite. A physician guides a tube through the bowel and the straight portion of the colon directly above the anus, but not past the sharp turns that hide the rest of the colon. Patients sacrifice information about the far half of their colons and face screenings every five years. In exchange, they get a cheaper, quicker test without anesthesia that involves a bit less preparation to clear the rectum. Depending on the doctor ordering the test, patients might be asked to adhere to a daylong liquid diet, take a strong laxative and possibly undergo an enema—as they would for a colonoscopy—or instead might simply be instructed to undergo an enema with no additional preparation.

And then there are stool tests, which are even less invasive.

An annual guaiac-based fecal occult blood test (gFOBT) looks for blood in stool that might indicate the presence of polyps or cancer. It requires patients to avoid certain meats, fruits and vegetables for several days before bringing in a stool sample for analysis. Research indicates that the latest gFOBTs catch up to three-quarters of all tumors and up to a quarter of advanced adenomas. Those numbers pale in comparison to colonoscopy figures, but annual testing compounds the power of individual tests. And the test is lower in cost than other screening methods for colorectal cancer.

Newer stool tests, including the fecal immunochemical test (FIT), which also detects the presence of blood and is a lower-cost test, appear more effective. In fact, last year, the U.S. Food and Drug Administration approved Cologuard, a stool test that detects red blood cells and DNA abnormalities that may indicate the presence of colorectal cancer or precancerous polyps.

The clinical trial that led to Cologuard’s approval found that the test accurately detected cancers and advanced adenomas more often than did FIT. Cologuard detected colorectal cancers at a rate of 92 percent and detected advanced adenomas at a rate of 42 percent, while FIT detected 74 percent of colorectal cancers and 24 percent of advanced adenomas. However, Cologuard was less accurate than FIT at determining which of the people tested were negative for colorectal cancer or advanced adenomas (87 percent correct versus 95 percent correct).

A caveat with any of these screens—from virtual colonoscopy to stool tests—is that, if the tests come back positive or inconclusive, the patient still must undergo a colonoscopy to confirm and remove any polyps.

So, how do all these tests compare with colonoscopies when it comes to protecting patients?

Research has yet to provide definitive answers (and the rapid evolution of newer tests would quickly render any answers obsolete), so experts disagree, often heatedly. Some say that recommending universal colonoscopies for people aged 50 and older is not economically feasible when much cheaper alternative screening methods are available. Yet others in the oncology community have likened the effectiveness of sigmoidoscopies to that of “single-breast mammograms,” and have argued that it will be years before fecal analysis is as effective as colonoscopy.

Even official guidelines disagree. The ACG lists colonoscopy at 10-year intervals as its preferred screening tool. The CDC gives equal preference to 10-year colonoscopy, five-year sigmoidoscopy or annual gFOBT. The ACS relegates all the stool tests to its list of less-preferred techniques on the grounds that they catch too few pre-cancerous polyps to be effective cancer-prevention tools.

All of them agree, however, on the need to detect tumors by means of routine screening rather than screening that takes place in response to common symptoms such as diarrhea, constipation, persistent abdominal pain, weakness and unexplained weight loss.

“People who do suffer from any of the symptoms need to seek medical help and keep after it until they get satisfactory answers,” says Josh Wimberly, a social worker who was diagnosed with stage 3b rectal cancer three years ago, at age 30.

Diagnosed with stage 3b colon cancer at age 30, Josh Wimberly was thrilled to have a child after being warned that treatment might leave him sterile. He is pictured with his wife, Kimberly, and son, Bryan, age 3.

Not only was Wimberly too young to be routinely screened, he found that doctors were reluctant to test him, even in the face of symptoms.

“I went to the hospital with significant, sustained bleeding, and I was actually told it was probably just stress. I had to lie about having a close relative with polyps to convince them to do the colonoscopy that was very obviously the only test that would explain the problem,” he says. “If I hadn’t made a nuisance of myself, I’d have been diagnosed weeks or months later.”

Given the current screening recommendations and the lack of a more specific way to identify those most likely to benefit, there is little chance for early detection in people who develop colorectal cancer as young as Wimberly did.

If, as Chang asserts, it’s too soon to change the screening age nationwide, can anything else be done to help protect this population?

Chang and his fellow investigators encourage younger adults to help prevent colorectal cancer by eating fewer processed and fast foods and adding more fruits and vegetables to their menus. On the flip side of the coin, Christina Bailey, who co-authored a study with Chang on the rise in the disease among younger adults, urges doctors not to dismiss symptoms in that population that could signal colorectal cancer.

Younger adults have the option of screening themselves by buying over-the-counter gFOBT kits for use at home to check for blood in their stool, although there is some risk of false positives, which is minimized by avoiding certain foods for three days prior to testing. Anyone who does test positive for blood in the stool will need to visit a doctor for further tests.

Of course, on the other end of the spectrum, there is a dramatic opportunity for earlier detection and outright prevention now in older Americans, and that opportunity will only grow as screening methods improve.

“Colonoscopy has been the gold standard for a long time, but the understandable desire for less invasive, more economic screening measures has attracted considerable research and development efforts,” says Al B. Benson, III, a professor at Northwestern University’s medical school and the associate director for clinical investigations at the school’s cancer center.

“We are nowhere near the point of abandoning routine colonoscopies, but the research clearly shows repeated improvement in newer techniques like stool DNA analysis,” he says. “There is legitimate hope that at least one of these cheaper and easier diagnostics will eventually match the performance of the colonoscopy and remove a major barrier to both early tumor detection and prevention.”

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