Colon Cancer Update -- Robert J. Mayer, MD -- 3/4/2004

By Robert Mayer
WebMD Live Events Transcript

Colon cancer is diagnosed in 130,000 Americans every year, but it is highly treatable. And the newly approved drug Avastin offers even greater hope. In honor of National Colorectal Cancer Awareness Month, we discussed diagnosis, prevention, and treatment with gastrointestinal cancer expert Robert J. Mayer, MD.

The opinions expressed herein are the guest's alone and have not been reviewed by a WebMD physician. If you have questions about your health, you should consult your personal physician. This event is meant for informational purposes only.

Moderator: Welcome to WebMD Live, Dr. Mayer. What's your take on the recent FDA approval of Avastin? Is it a big step forward in cancer treatment?

Mayer: Avastin represents a new and welcome tool for the treatment of colon cancer. The study that led to the approval by the FDA demonstrated that adding Avastin to at least one combination chemotherapy program prolonged the survival of people who received this innovative compound compared to a similar group who were given the chemotherapy with a placebo.

How effective Avastin will turn out to be, combined with other forms of chemotherapy, and how certain any of us can be of its mechanism of action in the inhibition of new blood vessel formation (what is called angiogenesis) all remains to be determined. Nonetheless, I certainly agree it merited approval by the FDA.

Member question: Is a virtual colonoscopy as good as the real thing for detecting colon cancer? Is it OK to do as a first step, to wait to have a real colonoscopy only if the virtual one finds a problem?

Mayer: That's an excellent question, and one for which we all would like to have a better answer than is available at the moment. The advantages of a virtual colonoscopy are:

It does not require patients to undergo the insertion of a lengthy tube into their rectum. It usually can be performed without sedation.

It doesn't require the services of an expert gastroenterologist or a surgeon specially trained to perform this procedure.

On the other hand, it represents a diagnostic test, meaning that if something is found by the X-ray test, no intervention, such as removal or biopsy, is possible, and a colonoscopy with the insertion of a tube will be required in a subsequent procedure.

Equally important is the fact that at present both the virtual colonoscopy (the X-ray test) and the endoscopic colonoscopy, meaning with the insertion of the tube, require the same preparation with cathartics (laxatives) to cleanse the bowel of fecal material, and for many patients this is the single greatest impediment for undergoing definitive colorectal cancer screening.

Studies are underway to try to develop computerized mechanisms to maintain the accuracy of the virtual colonoscopy without the need for this cathartic preparation, and if this turns out to be possible I would hope that compliance for such screening would increase.

As to the bottom line question of whether the data are as good with virtual colonoscopy as with endoscopic colonoscopy, the early returns suggest similarity, but more experience will be required, particularly as virtual colonoscopy becomes available to a wider community of radiologists who may not have the particular expertise of those who were involved in the development of the test.

Member question: Occasionally my stool is bloody, I feel tired all the time, and I get nauseated for no apparent reason. On this site all of these symptoms are linked to colorectal cancer. I was wondering if my condition could be colorectal cancer or not.

Mayer: I suppose it could, but the odds would favor that it is not. However, passage of blood in the stool, fatigue, which may be an indication of anemia, and abdominal symptoms would encourage me to recommend that a colonoscopy be carried out as part of a medical evaluation.

The symptoms that lead people to seek medical attention in the setting of a colorectal cancer vary according to the anatomic location of the tumor within the large bowel, that is the colorectum. The colon begins in the right lower part of the abdomen, adjacent to the appendix, and the colon itself is a rather stupid organ, because it has only one function, that being the re-absorption of water from the fecal material that has passed into the colon from the small bowel. It is within the small bowel that nutrients, protein, fat, and other important molecules and compounds are absorbed.

If the colon does not function in its normal manner, either because there is an inherent defect in its ability to reabsorb water or because there is such excess intestinal gas that is propelling the fecal material at a more rapid than normal rate through the large bowel, this is what we experience as diarrhea.

When a cancer develops in the right side of the abdomen close to the appendix (an area that we call the secum, or the right colon) or even sometimes the ascending colon, even though that growth can become rather large and can significantly narrow the opening in the tube that represents the colon, because the stool is liquid it is unusual for patients to complain of pain or cramping.

Rather, in such a setting there is frequently the occult loss of blood into the stool -- not of a sufficient amount to discolor the fecal material or to make, as in the case of the questioner, the stool bloody, but enough to result in anemia of an iron deficiency type. This may lead to weakness and fatigue. It can also lead to symptoms related to low oxygen carrying capacity, which in an individual, say, with coronary artery disease might lead to angina.

None of these people have symptoms focusing on the site of the tumor, and even when such cancers are present examination of the stool for the presence of blood may frequently be negative since the bleeding occurs only intermittently.

As one progresses up the colon now from the lower right abdomen to the bottom of the rib cage, where the colon then makes a turn and crosses the upper abdomen (what is called the transverse colon) the stool now becomes more formed, because liquid water has been reabsorbed, and when a narrowing occurs in the bowel because of a cancer, patients feel pain and cramping and may experience an actual blockage, an obstruction, due to this narrowing. In such circumstances the symptoms are quite specific and there rarely is any uncertainty or ambiguity as to what sort of medical evaluation is necessary.

Now to the left side of the abdomen, where the colon makes another abrupt turn in the left abdomen (the so-called descending or left colon) to the lower abdomen, where the colon then makes an S-turn in a portion known as the sigmoid and then enters an exit chute into the pelvis into a storage area called the rectum. Now the stool is formed. But a narrowing of the bowel often does not produce the same symptoms as in the transverse colon, because the bowel can expand as a storage area, without which we would be moving our bowels far more frequently than we normally do.

In such circumstances, when cancers develop, people complain of a sensation of straining, of a sensation of being unable to completely empty their bowels, and often the appearance of the fecal material may change, becoming more narrow and even having a groove that can visibly be seen, corresponding to a growth that is in the bowel over which the exiting stool has passed.

Many times such tumors are also associated with the passage of bright red blood surrounding the stool, which may at times be mistakenly thought to represent hemorrhoids. Interestingly, such bright red blood in the stool, in the setting of a cancer, usually is not accompanied by anemia, so the presence of a normal blood count does not represent a guarantee that the blood in the stool has a benign cause. People who experience the passage of blood in the stool or any of these symptoms merit an examination of the bowel.

Getting back to the question, colon cancer occurs predominantly in individuals over age 50, the average age being in the mid 60s. If you are in your 20s or 30s and do not have a family history for colorectal cancer it would be more likely that your constellation of symptoms may be due to what is known as irritable bowel syndrome. However, nobody should be guessing about such an important issue, and strong consideration should be given to a colonoscopy, regardless of the age.

Member question: My husband has his last chemo treatment Monday. What do you suggest as a follow up?

Mayer: I assume what is meant is the last treatment in a course of prophylactic chemotherapy following an operation, at which time a colon cancer was removed. When such cancers have spread to adjacent lymph nodes -- what is known as stage III disease -- and even in certain higher-risk individuals who do not have lymph node involvement but may have had a perforation (a popping of the tumor due to a blockage), six months of chemotherapy is usually recommended and has been shown repeatedly to significantly reduce the likelihood of disease recurrence and to improve the probability for cure.

Once such treatment has been completed, which usually occurs seven to nine months after the original operation, it would seem appropriate to repeat the colonoscopy to be certain that no additional abnormalities, such as polyps that might have been overlooked at the time the original cancer was identified, might still be present. I generally re-evaluate people every three months for the first five years after they have undergone their surgery, during which time blood studies, including a so-called tumor marker known as the CEA test, standing for the carcinoembryonic antigen, is measured.

There does not appear to be any long-term benefit, in terms of further improvement in the likelihood for cure, for performing additional CT scans, chest X-rays, or the like. The CEA test, that blood tumor marker, is perhaps more sensitive than any other method presently available for identifying possible recurrent disease long before it becomes clinically apparent. And were the CEA test to show a progressive increase from a previously normal value, CT scans and even the most recently developed diagnostic test -- a PET/CT scan -- should be considered, because if a single isolated site of recurrent disease can be identified at an early point, further surgery can be curative.

In the setting of colorectal cancer the five-year anniversary of the original surgery can be fairly well considered a benchmark for declaring victory, since more than 90% of any patients destined to experience disease recurrence will have had such a recurrence by that point in time.

After that five-year anniversary periodic colonoscopies should continue every four to five years, because people who have had one colon cancer and the polyp formation that predates the development of the cancer are far more likely to experience the development of additional polyps, whose removal through colonoscopy can prevent the development of additional malignancies.

Member question: Under what conditions should Avastin be considered for a stage IV colorectal cancer patient?

Mayer: The only data available now have shown that adding Avastin to a chemotherapy program that includes a drug called Irinotecan, in patients who have never received prior chemotherapy, will prolong survival. This has only been examined up to now in individuals with stage IV disease. We do not yet know whether adding Avastin to other forms of chemotherapy will be similarly beneficial, or whether adding Avastin to chemotherapy given prophylactically after a complete surgical removal of a colorectal cancer will further enhance the likelihood for cure.

Avastin given by itself does not seem to provide antitumor effect, which is not all together surprising, since it's assumed antiangiogenic mechanism would be most efficacious if it were given along with chemotherapy, thereby making the chemotherapy work even better. So, as of now, the indications for Avastin remain somewhat limited, but stay tuned!

Member question: My father has had a colonoscopy, but my mother has not because she believes colon cancer is not a major issue for women. Is this true?

Mayer: Regrettably what your mother has told you is what all too many women believe. Men in our society seem far more agreeable to undergoing cancer screening than do women, particularly colorectal cancer screening. The facts are:

  • There is no difference in the likelihood of developing colon cancer when men and women are compared.
  • The likelihood of screening benefiting men and women is equal.
  • The likelihood of colorectal cancer leading to death, when men and women are matched according to the extent or stage of their disease, is similar.

I hope you will be able to convince your mother to come to her senses.

Member question: Can an aspirin a day help prevent colon cancer the way it does heart attacks? How does that work?

Mayer: Good question. Does an aspirin a day keep the doctor away? It turns out that aspirin and aspirin-like drugs, such as ibuprofen, are effective in blocking the action of an enzyme, cyclo-oxygenase, which is present in increased concentrations in the lining cells of the bowel, the colon, and rectum, and which seems to be increased in concentration when cancers or polyps develop. Aspirin and ibuprofen use over a prolonged period of time -- probably 10 years -- seems, through inhibition of this enzyme, to reduce the developments of polyps and cancers.

Such a "chemoprevention" strategy has now been recommended since such drugs are, as you rightly imply, also useful as means of minimizing heart attacks, and also the likelihood of developing colorectal cancer.
At present, utilizing a baby aspirin three or four times a week seems to be efficient to achieve this effect. Additionally, there are data that increased amounts of folate, a vitamin, and calcium in the diet can be beneficial in preventing colon cancer, and such folate and calcium supplements are readily available through commercially distributed multi-vitamin tablets.

One further way to lessen the risk of developing colon cancer is to avoid obesity through exercise and sparing inclusion of cholesterol-laden red meat in one's diet. Despite the beliefs of some, there is no evidence at present that antioxidants, vitamin C, or even high concentrations of fiber in the diet offer similar benefit.

Member question: I'm turning 50 next month and my sister, who is a nurse, was teasing me that she was going to get me a "Couric" exam for my birthday. Is 50 the age when I should start getting checked for this? What are the risk factors besides age?

Mayer: Clearly your sister thinks a lot of you! Fifty years of age is, indeed, the time in our lives when the likelihood for developing colorectal cancer seems to increase. Unless one has a strong family history for the development of colorectal cancer or has specific symptoms there does not appear to be any evidence that beginning screening maneuvers before age 50 is beneficial.

After 50 years of age, several different strategies for screening have been proposed, which include:

  • Annual assessments of stool for the presence of blood
  • A flexible sigmoidoscopy every five years
  • A colonoscopy every 10 years, or maybe now, maybe in the future a virtual colonoscopy every 10 years

Essentially, the only people who develop colon cancer are those who are found to have benign polyps in their bowel, and it has been estimated that the time duration for the normal lining of the bowel to become a benign polyp, which in turn can become a cancer, actually is more than 5 years. That's why periodic screening does not have to occur annually.

If one has no family history for colon cancer, has a normal colonoscopy during his or her 50s and perhaps another normal colonoscopy during his or her 60s, it is highly unlikely they will ever develop a colorectal cancer. However, 50% of us will be found to have polyps in our bowel by the time we reach age 65 to 70, and those of us with the polyps are those of us prone to develop cancer and should undergo screening.

As for you, I would accept your sister's birthday gift, as I'm sure Katie Couric would, cheering from the sidelines.

Moderator: Having elevated concentrations of C-reactive protein (CRP) in the blood is linked to an increased risk for developing colon cancer, according to a study in the February 4 issue of The Journal of the American Medical Association (JAMA). Does this mean we will be seeing a test developed for colon cancer, looking for this marker?

Mayer: The C-reactive protein is a measure of inflammation and is relatively nonspecific. Elevations in the C-reactive proteins have been associated with a greater likelihood of developing heart disease, arthritis, or any other form of inflammation. In a sense, polyps and cancers may have inflammatory components. I do not believe that the C-reactive protein will serve to be a useful mechanism for providing any of us sufficient additional information to make it a helpful means of screening for colon cancer.

Member question: Have there been any studies on people who have had gastric bypass and their chances of developing colorectal cancer?

Mayer: Interesting question, for which I believe there are no sufficient data at present. Obese individuals have a higher likelihood of developing colorectal cancer, and it has been postulated this occurs because of an increased concentration in the blood of a protein called the insulin growth factor receptor, which can act as a stimulator of the lining of the bowel, meaning, that it can cause polyps or cancers.

Elevated levels of this protein are also linked with the development of adult-type diabetes, and individuals with such a form of glucose intolerance may sometimes be at a higher risk for colon cancer, as well.

One could postulate that overcoming obesity through gastric bypass procedures might avoid this possible form of cancer development, but this is only a hypothesis, and I am unaware of any facts to support it.

Member question: I had what they considered between B1 and B2 colon cancer with clear margins, no lymph node involvement, and low CEA. I had colon resection and a panel of doctors in Atlanta could see no benefit for chemo at this time. What I want to know is what can I do to fight this disease the best way I can?

Mayer: Certainly the results of your operation are encouraging, and the likelihood is very high that your disease has been cured. I agree with the doctors from Atlanta that there is no reason to subject you to chemotherapy at this time. Exercise, baby aspirin several times a week, a multivitamin daily, colonoscopy every three to four years, and regular medical evaluations for the next five years would seem to be appropriate. Most importantly, you have crossed the biggest hurdle, which is the operation itself, and the outcome is most encouraging.

Moderator: Do you have any final words for us, Dr. Mayer?

Mayer: March is colon cancer awareness month, and it is so important that we all do become aware of this malignant condition, which now represents the second-most common cause of cancer death in the United States. Only lung cancer kills more people than colon cancer, and if we stop smoking, colon cancer might well be equal in this statistical comparison. Yet just as lung cancer can be prevented by a good ashtray, colon cancer can be prevented by regular screening procedures. The presence of polyps, which develop long before the cancers, offer the windows of opportunity for all of us to undergo the proper examinations and removal of the polyps to prevent cancers from occurring.

While I am extremely excited about the new forms of chemotherapy and so-called targeted treatments such as Erbitux and Avastin that have become available to treat patients and prolong survival of individuals with advanced disease, the best treatment for colon cancer is prevention, and we really have no excuse not to undergo such preventative examinations. Both Medicare and Medicaid, as well as essentially all private insurers within the U.S. provide coverage for a colonoscopy every 10 years. Let's not miss this opportunity!

Moderator: Thanks to Robert J. Mayer, MD, director of the Center for Gastrointestinal Oncology at the Dana-Farber Cancer Institute, for sharing his expertise with us today. For more information on colon cancer, be sure to head for the WebMD message boards, including the Colorectal Cancer Support Group, where you can post questions and get advice and support from fellow WebMD members.



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