Credit: NCI

Each year nearly 150,000 people in the U.S. are diagnosed with colorectal cancer and around 50,000 die from the disease. Studies have shown that when performed every one to two years in people ages 50 to 80, fecal occult blood tests (FOBT) can help reduce the number of deaths from colorectal cancer by 15 to 33 percent. Although various screening methods, including FOBT, have been available for decades and new techniques continue to be developed, colorectal cancer screening rates remain lower than hoped for.

Fecal occult blood tests are the most affordable and least invasive of the various screening tests available for colorectal cancer. Prior to 2001, FOBT was one of the most widely used screening tests for colorectal cancer.  In recent years, FOBT use has been surpassed by colonoscopy.  Reasons for this shift were discussed at a recent NIH State-of-the-Science Conference on Colorectal Cancer Screening.

FOBT tests check for blood in fecal matter by requiring patients to place a small sample of stool on a chemically treated card, pad, or cloth wipe. A positive result leads to a chemical reagent on the material turning blue, indicating that there is blood in the stool sample. Currently, two types of FOBT can be used for detecting occult blood in stool—the guaiac based (chemical test) and an immunochemical test (antibody-based test).

The first, guaiac FOBT, which costs about five dollars, uses the chemical guaiac to detect heme in stool. Heme is the iron-containing component of the blood protein hemoglobin. The second, immunochemical FOBT, also referred to as fecal immunochemical testing (FIT), uses antibodies to detect human hemoglobin protein in stool. Antibodies are proteins generally found in the blood that detect and destroy invaders such as bacteria. The cost of this test is approximately $22. Both tests are commonly completed at home and then submitted to a lab for analysis, with results reported back to the patient and physician within days.

Credit: NCI

In a study conducted in 2007, researchers suggested that the FIT-type of FOBT had a higher ability for detecting left-sided colorectal cancer and that it might be a useful replacement for  guaiac FOBT.   Left-sided tumors tend to encircle the colon thusthey are more likely to obstruct the bowel. Higher sensitivities and specificities imply a greater accuracy for detecting colorectal cancer with FIT than with guaiac-based FOBT.

A technique called the Stool DNA test is another screening option for colorectal cancer. The lining of the colon continually sheds cells and these cells become bound up in the stool as it passes through the colon. Cells from the surface of precancerous polyps and cancerous tumors show recognizable DNA changes and a stool DNA test can identify several of these markers, indicating the presence of precancerous polyps or colon cancer.

In October 2008, a Mayo Clinic study published in the Annals of Internal Medicine found that  first-generation stool DNA tests were better than fecal blood tests for detecting cancer and precancerous polyps of the colon. In a follow-up study in January 2009, published in Gastroenterology, researchers showed technical improvements that nearly doubled the sensitivity of stool DNA testing for detecting premalignant polyps and increased cancer detection accuracy to about 90 percent. Researchers hope that the next generation tests will improve further in accuracy, processing speed, ease of patient use and affordability. However, a gold standard clinical trial comparing the effectiveness of the various tests is the only way to know for certain which test is the best at detecting colon cancer early. Currently, the United States Preventive Services Task Force (USPSTF) concludes that there is insufficient evidence to assess the benefits and harms of stool DNA testing as a screening modality for colorectal cancer.  The Task Force therefore does not recommend use of this test to screen average-risk adults for colorectal cancer.

Cost-effectiveness also is a factor when considering screening mechanisms.  Although not as costly as a colonoscopy , the Stool DNA test—costing $350 to $800—is far more expensive than the FOBT and is not covered by Medicare. At the NIH State-of-the-Science conference on Enhancing Use and Quality of Colorectal Cancer Screening, the independent panel recommended that financial barriers should be eliminated to assure that screening can be accessed by a larger population. Because of its ease of use and cost effectiveness, FOBT may have an important role in improving colorectal cancer screening rates and saving lives.

“Studies have shown that patient preferences for colorectal cancer screening tests vary, and many patients prefer FOBT over more invasive tests such as sigmoidoscopy and colonoscopy. Moreover, we have evidence from the Veterans Health Administration and Kaiser Permanente of Northern California that screening rates of 70 percent or higher can be achieved through programs that use FOBT as the primary colorectal cancer screening test,” said Carrie Klabunde, Ph.D., epidemiologist in NCI’s Division of Cancer Control and Population Sciences.

Drinking two cups of strong coffee a day may protect habitual cigarette smokers from developing advanced colon cancer, according to a population-based study of Singapore Chinese, funded by the National Cancer Institute and conducted by researchers from the University of Minnesota. The study was published in the March-April edition of the Nutrition and Cancer journal (U.K.) and appeared online Jan. 26, 2010. This study, however, should not be construed to show that people can continue smoking tobacco and avoid disease if they drink coffee, caution the authors.

“Singapore Chinese prepare coffee in a way that likely preserves the putative chemoprotectants,  cafestol and kahweol, that have been the primary focus of basic science investigations of coffee and cancer prevention,” said Sabrina Peterson, Ph.D., assistant professor of Foods and Health, Department of Food Science and Nutrition, University of Minnesota.

Singaporeans primarily drink coffee made by boiling ground dark roasted coffee beans with water in a pot, letting the grounds settle, and then pouring the liquid through muslin cloth filters to strain. Due to significant trapping of cafestol and kahweol found in the cloth filters, Peterson’s team assumed that these two compounds are present in significant amounts in common Singapore coffee, and may protect frequent coffee drinkers against the development of advanced colorectal cancer.

Colorectal cancer is the third most common malignant cancer worldwide. There has been little improvement in survival for patients with advanced stage disease, despite advances in surgical techniques and therapy. While younger adults can develop colorectal cancer, the chances of developing colorectal cancer increase markedly after age 50. More than 90 percent of people diagnosed with colorectal cancer are older than 50.

Peterson and her colleagues reviewed health information on over 60,000 middle-aged or older Chinese men and women who were enrolled in the Singapore Chinese Health Study. They investigated if coffee consumption was associated with decreased risk of colorectal cancer in frequent cigarette smokers and if the stage of disease was modified by the association.

To achieve their goal, the team assessed baseline dietary exposures through in-person interviews, using a food frequency questionnaire, followed by blood collection and lipid measurement. The relationship between coffee consumption and colorectal cancer risk was assessed through statistical analysis that compared distributions of selected variables across different levels of coffee consumption, as well as factors such as cigarette smoking (never, light, heavy), and the age smokers started.

Of the 60,000 study participants, 961 colorectal cancer cases occurred during the first 12 years of study follow up. Among the 961 colorectal cancer cases, 591 were colon and 370 were rectal cancer cases.

A drawing of a colon with stages 0, I, II, III and IV cancer. The Dukes classification is a staging system used to describe the extent of colorectal cancer. In this study, cancers were grated Dukes A and B (stages I and II) for localized cancer, and Dukes C and D (stages III and IV) for advanced stage cancer, covering metastasis to lymph nodes and to other organs.

The scientists noted that among a subset of ever-smokers (at least one cigarette each day for one year), the consumption of two or more cups of coffee a day was associated with a statistically significant reduction in the risk of advanced colon cancer (Dukes C and D, or stages III and IV), but not for localized cancer (Dukes A and B, or stages I and II), which is usually early stage disease.

A similar analysis for rectal cancer found no association between coffee intake and the risk of rectal cancer in all subjects or those stratified by smoking status. Coffee drinking was not associated with either localized or advanced stages of rectal cancer.

Coffee May Mitigate the Toxicity of Cigarette Smoking

The method of coffee preparation can significantly influence the levels of potentially chemoprotective components in coffee.  Instant, filtered, and percolated coffee have negligible amounts of cafestol and kahweol; whereas espresso has intermediate amounts and Turkish and Scandinavian-type boiled coffee—the the method used by Singaporeans—have large amounts.

Further, coffee and its components, specifically cafestol and kahweol, have been found to mitigate the toxicity of heterocyclic aromatic amines (HAA, sometimes referred to as simply heterocyclic amines, HCA), compounds that have been implicated in the development of colorectal cancer in animal studies. Meats cooked at high temperatures are typically considered primary HAA sources, and the main source of HAA exposure in North American or European Whites, according to current epidemiologic data.

But studies by collaborators at the University of Minnesota and New York State Department of Health found that cigarette smoking, not diet, was a major source of HAA exposure in Chinese people.

In light of the predominance of coffee and colorectal cancer data from studies of Caucasians, and identification of cigarette smoking as a major source of HAA in Chinese, the team investigated the coffee and colorectal cancer association of smokers enrolled in the Singapore study.

They found ever-smokers only had a positive association between coffee intake and protection against advanced colon cancer.

Coffee and Colon Cancer Association Strengths and Limitations

There are several strengths to this study, according to the scientists. Information on coffee consumption and other dietary and lifestyle factors were collected prior to cancer diagnosis, thus ruling out the possibility of recall bias and reverse causality, especially when there was a strong coffee and colon cancer association with longer, rather than with shorter, follow-up. Subgroup analyses in ever-smokers were biologically driven given the recent identification of cigarette smoking as a more likely source of HAA than diet in Chinese people. Finally, the study population is genetically homogeneous and free of potential confounders that may be widely studied in various White populations.

One limitation of the study was the relatively small sample sizes in subgroup analysis. Therefore, the findings of this study should be interpreted with caution and need to be confirmed in future studies, according to the scientists.

In addition, future studies that not only assess the amounts of coffee consumed, but also the type of coffee, the method of preparation of the coffee, and contents of cafestol and kahweol are warranted to shed light on the role of coffee in the protection against colon cancer.

Reference: Peterson S et al., Coffee Intake and Risk of Colorectal Cancer Among Chinese in Singapore: The Singapore Chinese Health Study. Nutrition and Cancer, United Kingdom, March-April 2010, DOI: 10.1080/01635580903191528.

Credit: NCI, Bill Branson (Photographer)

Colorectal cancer is the third most frequently diagnosed cancer in both men and women and the second leading cause of cancer-related mortality in the United States.  That said, rates of new cases and rates of death from colorectal cancer have been declining this decade.  According to the Annual Report to the Nation authored by researchers from the National Cancer Institute (NCI), the Centers for Disease Control and Prevention (CDC), the American Cancer Society (ACS), and the North American Association of Central Cancer Registries (NAACCR), if Americans increase use of screening, adopt more favorable health behaviors and pair that with optimal treatment outcomes, overall colorectal cancer mortality rates could decrease by 50 percent by the year 2020.

The importance of colorectal cancer screening has made headlines for many years, raising awareness and leading to higher rates of colonoscopies from 2000 through 2008. This increase in screening levels has played a significant role in decreasing colorectal cancer mortality.  Along with screening, advances in colorectal cancer treatment have played a pivotal role in reducing mortality rates.  Surgery, traditional chemotherapy and newer targeted therapies have been important tools in treating this disease.

Credit: NCI, John Crawford (Photographer)

Surgery continues to be the primary treatment option for colorectal cancer patients and colon/rectal resection has been the standard procedure for cancer primarily contained in the colon/rectum. Studies have shown that laparoscopic surgery has been more successful than traditional open surgery in reducing recovery time for patients, but studies are still underway to determine the overall benefit of one technique over the other. “Specific risk factors and expertise inform a surgeon’s decision of what procedure to perform,” says Jack Welch, M.D., Ph.D, head of GI and Neuroendocrine Cancers Therapeutics in the the Clinical Therapy Evaluation Program (CTEP), within NCI’s Division of Cancer Treatment and Diagnosis.

There are four stages of colorectal cancer, with stage I being the easiest to treat and stage IV being the most difficult.  Stage II and III colorectal cancers offer the greatest challenge in choosing which treatment modalities to use.

Advances in chemotherapy over the past decade have lead to a change in treatment practice standards for colorectal cancer, increasing the cure rate and prolonging survival rates for patients with advanced disease.  For several decades, chemotherapy regimens based on the drug fluorouracil (5-FU) have been part of the treatment for stage III colon cancer.  Adding other agents to a backbone of 5-FU has further advanced treatment in both the adjuvant and advanced setting. FOLFOX, a combined chemotherapy regimen, which includes 5-FU, leucovorin and oxaliplatin (other chemotherapy drugs) is a classic example.  FOLFOX produced higher response rates in patients and also demonstrated superior clinical benefit in patients with advanced colorectal cancer when compared to 5-FU plus leucovorin alone or 5-FU plus oxaliplatin alone.

Chemotherapy is not typically recommended in the treatment of stage II colorectal cancer because the side effects from treatment outweigh the benefit derived for most patients. However, some clinical studies are underway with the aim of identifying stage II patients who are at particularly high risk for recurrence of their disease, and giving them treatment to prevent the cancer from coming back.

Targeted therapies also offer great promise in the fight against colorectal cancer. In 2004, the FDA approved bevacizumab (Avastin®, Genentech, Inc.) as a first-line treatment or initial treatment for patients with metastatic colorectal cancer. Then in 2006, the FDA granted approval as a second-line treatment as well. This meant that bevacizumab could be used if the current first-line treatment was not successful. These recommendations were based on findings that showed better overall survival in patients receiving bevacizumab plus FOLFOX when compared to receiving FOLFOX alone.  Bevacizumab is an antiangiogenic agent; it inhibits tumor growth by blocking the formation of new blood vessels.  According to Welch, “clinical trials have shown that bevacizumab improves outcome in metastatic disease, but in a recent phase III study of adjuvant colon cancer, the addition of bevacizumab to standard therapy did not increase disease free survival.” Therefore, while targeted therapies have shown promise, there is no guarantee that they will work in every treatment setting, highlighting the need for clinical trials to prove benefit.

“Similarly, patients with [some types of] advanced colorectal tumors have benefitted from cetuximab or panitumumab (two other types of targeted therapies). These targeted agents typically have toxicities that do not strongly overlap those of traditional chemotherapy, which opens up new ways to combine these agents with existing chemotherapy,” Welch says.

Improving treatment and its dissemination will most likely have the earliest impact on colorectal cancer mortality. “Finding the right combination therapy for the right patient and tailoring treatment to individuals with a specific genetic background or to specific types of tumors will help improve treatment outcomes in the future,” says Welch. “Biomarkers are things that we can measure from blood or tissue samples. We hope that by studying biomarkers in individual patients, we will be able to predict how that person will respond to a specific type of treatment and then tailor the therapy accordingly.”   Moreover, “improvements in imaging technology and methods will allow us to determine earlier if our treatment is being effective. Biomarkers and imaging will help us make decisions more quickly, more accurately, and on an individual-by-individual level.”

Currently, the National Cancer Institute is sponsoring 357 clinical trials addressing colorectal cancer treatment and prognosis.  Many of these trials now include targeted agents as part of the treatment regimen. For more information please visit http://www.cancer.gov/clinicaltrials.

Virtual Colonoscopy

Even though it is estimated that over 90 percent of patients with colorectal cancer could be cured if detected at an early stage, colorectal cancer remains the second leading cause of cancer death in the nation. This is believed to be due to the fact that the screening rate for the disease lags far behind that of other cancers, with only 30 to 40 percent of people over 50 years old actually being screened for colorectal cancer.

One highly publicized screening method for colorectal cancer is colonoscopy–a method that involves the insertion of a six-foot long flexible endoscope into the colon of a sedated patient. Despite the probable effectiveness of colonoscopy and its highly accurate results, it has not been implemented on a large-scale nationwide. Resistance to the test is partly due to its highly invasive nature and the fact that sedatives administered during the exam require recovery time and leave the patient groggy and unable to drive home on their own. It is hoped that the development of a more convenient and non-invasive colorectal cancer screening test might increase compliance and ultimately reduce the mortality rates of the disease.

Another commonly used screening tool, the Fecal Occult Blood Test (FOBT), is a non-invasive and relatively inexpensive colorectal cancer screening tool that looks for traces of blood in the stool. This test, however, is not highly sensitive or specific–that is, it fails to identify colorectal lesions (polyps or cancers) that do not produce blood in the stool, and it also generates false-positive results from blood being present in the stool due to other diseases or disorders.

However, a new noninvasive method that is in the early stages of development may offer better sensitivity and specificity than an FOBT. The Multitarget Assay Panel (MTAP) test looks specifically for mutations in DNA found in the stool that are indicative of colorectal cancer. In this test, the presence of any of 21 specific DNA mutations known to be present in colorectal cancer, as well as changes in DNA structure, are used to diagnose colorectal cancer. Benefits of this test include the fact that it requires neither a prior bowel-cleansing regimen (as in colonoscopy or virtual colonoscopy) nor the use of any sedatives.

In a study published last year, Dr. Kuldeep Tagore and colleagues used the MTAP test in order to attempt to distinguish between healthy patients and those with colorectal cancer. The researchers looked at 80 patients with verified colorectal cancer and 212 control patients. The MTAP test correctly identified over 60 percent of the patients with colorectal cancer as having the disease, while only about four percent of control group patients were improperly diagnosed as having cancer. These numbers compare favorably to similar studies testing the effectiveness of FOBT that resulted in only about 35 percent of cancer patients being correctly diagnosed and about 6 percent of patients incorrectly identified as having cancer.

“Compared with historic FOBT results,” says Tagore, “the detection of DNA abnormalities in stool appears to be substantially more sensitive [for colorectal cancer], with comparable specificity. The MTAP as a noninvasive screening option may be useful in bringing a larger segment of the population into screening and help patients who can benefit most from colonoscopy.”

Virtual Colonoscopy

To commemorate March as National Colon Cancer Prevention month, this edition of BenchMarks focuses on potential new screening methodologies for the early detection of colorectal cancers. An interview with Ernest Hawk, M.D., chief of Gastrointestinal and Other Cancers Research Group at the National Cancer Institute (NCI), covers colorectal cancer screening tools and compares and contrasts colonoscopy (or optical colonoscopy) with virtual colonoscopy.

Colorectal cancer is the second leading cancer killer in the United States. It is estimated that 146,940 people in this country will be diagnosed with colorectal cancer and 56,730 people will die of the disease. Experts believe that over 90% of all colorectal cancers can be cured through early detection and treatment.

Who should be screened for colorectal cancer and how often?

Currently, it’s recommended that Americans 50 years and older should be screened for colorectal cancer. If there’s a tendency towards colon cancer in the family, as evidenced by a close relative with either adenomas or cancer, it’s advised to start 10 years earlier and to use a more sensitive and specific technique. But for the general population, it’s 50 years and older.

How many people over the age of 50 actually get screened by the current processes?

The unfortunate thing is colorectal cancer should largely be a preventable illness, but in the United States at the moment only 30 to 40 percent of people who should be screened have actually been screened. That leaves us a lot of ground to make up.

It seems clear, then, that there is a pressing need for additional screening technologies. What are the available screening methods for detection of colon cancer?

While there is always room for technological improvements, we need to do a better job of using the current screening technologies. Because, despite their limitations, they have been proven effective in reducing the burden of disease. There are five regimens that are currently recommended, providing practitioners and patients with a menu of screening options. They include annual fecal occult blood testing (FOBT) – that is, looking for blood in the stool; flexible sigmoidoscopy every five years; colonoscopy every 10 years; air-contrast barium enema every five years; and a combination of FOBT with flexible sigmoidoscopy, each at their usual intervals.

Each of these tests have various advantages and disadvantages; for example, they vary in sensitivity and specificity — that is, how well they detect colon cancer or polyps when they’re present and reassure us when they’re absent. Colon cancer is the end-result of a prolonged process during which changes in genes in the cells lining the intestine accumulate, resulting in abnormal growths called polyps. If polyps accumulate additional genetic changes, a fraction of them may become cancerous. We tend to worry about polyps becoming cancerous as they grow; for example, polyps greater than one centimeter in diameter are usually removed because they present a high cancer risk.

What prevents people from going in to get screened?

There are a wide variety of reasons why people aren’t screened. A lot of it has to do with whether they recognize that they should be screened. Do they know the current screening guidelines? If not, has colorectal cancer screening been recommended to them by their health care provider? Unfortunately, some recent surveys suggest that colorectal cancer screening is not routinely recommended by health care providers, despite evidence of its benefit. After overcoming that challenge, other issues like convenience, cost, availability, and embarrassment represent significant barriers for some patients. Fortunately, colon cancer screening – even colonoscopy – is now paid for by Medicare, so cost is not as big a barrier as it has been in the past.

What is it about optical colonoscopy that is considered the “gold standard” for colorectal cancer screening?

Colonoscopy is considered the gold standard for colorectal cancer screening by some groups but not by others. The American College of Gastroentology recommends colonoscopy as a preferred approach to colorectal screening. By contrast, the Centers for Disease Control and Prevention recommend colonoscopy as one of the five acceptable colorectal cancer screening options outlined above. However, optical colonoscopy is considered the gold standard by some professionals because it allows complete and direct visualization of the entire colon, thereby providing the opportunity to identify precancerous polyps and cancer, and then to do diagnostic biopsies or therapeutic removal of these lesions, all in one setting.

What is virtual colonoscopy?

Virtual colonoscopy is a new technique that uses X-rays delivered through a CT scanner to take cross-sectional views through the abdomen, and then reconstruct those views in a special way using computer software. The result is a set of images that provide a radiologist with essentially the same sort of view of the colon as a gastroenterologist would have by doing an optical colonoscopy with a tube inserted into the colon. The advantages really have to do with the fact that the technique is relatively quick, fairly sensitive, and only minimally invasive.

How is a virtual colonoscopy performed?

A patient undergoes a routine bowel preparation at home the night before the exam by taking laxatives to purge the colon of waste matter. Then, on the day of the exam, a small amount of air is introduced into the colon via the rectum. The introduction of air is the only invasive component of the exam. The exam itself consists of lying on a table to have a series of very fast X-rays taken. It only takes a few minutes to complete, as opposed to optical colonoscopy, which can take a half hour or more. The big drawback at the moment is that virtual colonoscopy is not widely available and not yet definitively tested.

What are the benefits of a virtual colonoscopy over an optical colonoscopy?

The speed, relatively low level of invasiveness, and potential for broad availability are virtual colonoscopy’s major advantages at the moment.

A virtual colonoscopy only takes on the order of a few minutes to actually do the exam, and probably 15 minutes to 30 minutes more to read the exam.

Why does an optical colonoscopy take so much longer?

Optical colonoscopy takes a longer period of time because the procedure itself takes more time than a virtual colonoscopy exam and because sedatives are used — medicines to dull the patient’s senses so that they’re not fully aware of what’s going on. So, the exam usually takes a half hour or so and then there’s the additional time to administer and recover from the sedatives. Finally, it is important to have someone available to drive the patient home because the effects of the sedative can last a couple of hours. Virtual colonoscopy gets around some of these aspects of convenience and cost.

What are the disadvantages of a virtual colonoscopy compared to an optical colonoscopy?

The biggest limitation of virtual colonoscopy at the moment is that patients still need to go through the same bowel preparatory regime; patients really don’t like that. In addition, there is still the need for some instrumentation to put air into the colon. Other big drawbacks at the moment are its limited availability and lack of definitive testing or validation. These are the key issues holding virtual colonoscopy back from being widely appreciated and implemented.

What is your opinion on studies demonstrating the effectiveness of virtual colonoscopy?

There have been three or four large trials conducted over the past five years comparing virtual colonoscopy to optical colonoscopy. The key comparisons involve the testing of relative sensitivity – that is, determining whether virtual colonoscopy is as good as optical colonoscopy is at identifying adenomatous polyps or cancers. The first two or three of those studies showed virtual colonoscopy had significant limitations, in that it was not able to identify polyps — in particular smaller polyps — as reliably as optical colonoscopy.

However, there was a major report published by Dr. Perry Pickard and colleagues in the Dec. 4, 2003, issue of the New England Journal of Medicine. That study reported that virtual colonoscopy was quite comparable to optical colonoscopy in terms of the lesions it could identify. The study stimulated new interest in the technique among researchers and, to some extent, among the public at large.

Of course, that was only one study. Typically in medicine, we like to have a couple of studies to confirm a result before we really believe it. At the moment, additional work is needed to validate these findings and to see if the very promising sensitivity and specificity of virtual colonoscopy in that particular study will hold when the technique is applied in the broader medical community.

What else needs to happen in order for this technique to be ready for widespread patient usage?

What really needs to happen at this point is for the New England Journal of Medicine study to be re-evaluated in a much broader study. That study, conducted in Bethesda, was unique in several ways. First of all, it was one of the first times we looked at a true screening population – that is, in patients at average risk for colorectal cancer. Most prior studies had looked at a different population of patients – those with prior adenomas or cancers. This is important because the results in one group may not reflect those seen in another. In addition, Dr. Pickard’s study involved only three centers and used state-of-the-art techniques — they had multi-detector scanners, which improve the sensitivity of this technology; they used a stool and fecal water tagging procedure (to aid the physician in correctly identifying polyps) that hadn’t been done in the same way previously; they used software to reconstruct images in a specific way, which hadn’t been used previously. And finally, they used a limited number of radiologists who had been specifically trained in the virtual colonoscopy technique. For these four reasons, the study was quite unique. Now this finding needs to be replicated more broadly in more centers across the country to see if these excellent results hold up or not.

How long do you think this validation process could take?

There are a couple of studies being proposed to try to validate and build on the results from Dr. Pickard’s group. I’m aware of one study in particular, proposed by a national network of NCI-funded radiologists, that we’re hoping to see initiated within the next year. We anticipate that it would take a couple years for results from these trials, so I would say we may be three years or so away from having the best evidence to say whether this screening technique will provide a compelling new option.

In your opinion, do you think virtual colonoscopy will ever render optical colonoscopy obsolete?

I guess the answer to that question depends on what aspects of virtual colonoscopy and optical colonoscopy you’re asking about. If you’re talking about virtual colonoscopy versus optical colonoscopy for first-line colorectal cancer screening, I would say that, yes, virtual colonoscopy may very well supplant much of the screening currently done by optical colonoscopy. But even if that occurs, it will never make optical colonoscopy obsolete, per se, because there will probably always be patients that prefer the “one-stop shopping” approach offered by optical colonoscopy. That is, the opportunities to screen, diagnose, and treat colorectal polyps and small cancers in one procedure. In addition, it cannot replace the usefulness of optical colonoscopy for subsequent diagnosis and treatment. Indeed, virtual colonoscopy is probably most efficient and acceptable to patients when it is accompanied by the “real-time” availability of subsequent optical colonoscopy for those with a lesion. Without that sort of immediate access to optical colonoscopy, patients with lesions would have to go through another preparative regimen and colonoscopic exam at a later date, thus diminishing whatever convenience and cost advantage virtual colonoscopy may offer.

In any case, there’s a lot more work that needs to be done before we have good data to answer that question with more than speculation.

What other new colorectal cancer screening technologies are being investigated?

There are several attempts to improve upon old technologies, like ways to improve the sensitivity of assays that identify blood in the stool – improved fecal occult blood tests.

But perhaps the most promising new strategy is the one that’s designed to identify mutations or signatures of colon cancer in stool specimens. This procedure is called an MTAP, or multi-targeted assay panel. There are a few different groups working on it, and one major company has invested in it. The idea is to screen not for blood in the colon, which can be derived from cancers or other lesions, but rather to screen more specifically for the molecular determinants of cancer – that is, their molecular “signatures” in the stool. It’s been shown to be highly sensitive for identifying large polyps and cancer in the colorectum (that is, lesions one centimeter and larger) in preliminary studies, but the definitive phase III trials are ongoing now. It’ll be several years yet until we know whether it’s really going to be effective or not.

Animation/Video

Dr. Ernest Hawk of the National Cancer Institute’s Cancer Prevention Division describes the tests that are used to detect colon cancer beginning at age 50.

View Video Clip on NIHSeniorHealth.gov

This movie requires the QuickTime plug-in. If you do not have the plugin, please click here to install.

Text Transcript

The following clip is a ‘virtual’ tour of the colon. The left side of the screen is an exterior representation of the colon and the right side of the screen is a tour of the inside of the colon.

The image presented is a computer generated ‘virtual’ tour of the colon and rectum. It starts at the rectum and descends through the colon, winding through reddish tissue in a twisting tour of the tunnel that comprises the colon, passing polyps and other growths that could be cause for further evaluation.

Audio Clips

1. Dr. Ernest Hawk of the National Cancer Institute’s Cancer Prevention Division describes the tests that are used to detect colon cancer beginning at age 50.

      ( Audio – Length: 3:14 )

   Text Transcript

   Dr. Ernest Hawk of the National Cancer Institute’s Cancer Prevention Division describes the tests that are used to detect colon cancer beginning at age 50.

   Narrator: Most cancers in their early, most treatable stages don’t exhibit any symptoms. Colon cancer might be prevented if polyps that lead to the cancer are detected and removed.

   Dr. Ernest Hawk of the National Cancer Institute’s Cancer Prevention Division describes the tests that are used to detect colon cancer beginning at age 50.

   Dr. Ernest Hawk: The first of them is probably the most well-proven and that’s fecal occult blood testing, or looking for blood in the stool. Both polyps, as well as cancers, can bleed and you can identify that by doing a special test that’s done at home. The results are given to your physician and we know that the use of that test can result in about a 30% reduction in colon cancer deaths. So that test is relatively convenient — that is, it doesn’t require any special procedures — but some people are not particularly attracted to the methods that are involved.

   Narrator: Another test is a flexible sigmoidoscopy which is an examination of the rectum and lower colon using a lighted instrument.

   Dr. Ernest Hawk: And they look at the last part of the colon. Can go in about 50 centimeters — about a couple of feet — and look at the lining, look for polyps, as well as cancer. That’s another very effective method. So it requires going into a doctor’s office, doesn’t require any sort of anesthesia, but it takes 15 minutes or so.

   The third option is a barium enema. That’s an x-ray examination of the colon where you go into a hospital, typically, have an enema to clear out the colon. Subsequently, a radiologist takes you into the x-ray room, puts a dye into the colon and then takes x-ray pictures. That, again, takes half an hour or so. It has slightly less sensitivity — it can’t find polyps quite as well as some of the other tests — but it’s perfectly acceptable, as well as one of the several methods.

   And lastly, there’s colonoscopy where a physician takes a lighted tube and looks at the entire lining of the colon, several feet long. That procedure typically requires some amount of anesthesia so a doctor gives you medicine — makes you a little bit drowsy. It takes about 15 minutes to half an hour. And that procedure — its benefits really are that it can both identify cancers and polyps, but also treat those that are not complicated. So if a small, pre-cancerous growth polyp is identified, it can be removed in the same setting.

   Narrator: Dr. Hawk says whatever test you and your doctor determine is right for you — fecal occult blood test, sigmoidoscopy, barium enema, colonoscopy, or a combination of some of these — if you are 50 or over, the important thing is to get tested.

   Dr. Ernest Hawk: I think the big message is that people need to be screened. For any one of — for any individual, each of those tests have plusses and minuses that are best decided in the context of the patient and the physician making the decision that’s best for them. So I don’t know that there’s any one test that’s better for seniors versus another. The important message is that you need to avail yourself of at least one of them.

Photos/Stills