Q&A: Preventing, Screening, and Treating Colon Cancer

Cancer.Net Q&A Forum
Preventing, Screening, and Treating Colon Cancer with Robert Mayer, MD, of the Dana-Farber Cancer Institute
Questions posted March 1, 2006
Questions posted March 8, 2006
Questions posted March 15, 2006
Questions posted March 22, 2006

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Dr. Mayer is the Vice Chair for Academic Affairs of the Department of Medical Oncology at the Dana-Farber Cancer Institute, a Senior Physician at the Brigham and Women's Hospital, a Physician at the Massachusetts General Hospital, and Professor of Medicine at the Harvard Medical School where he is also Faculty Associate Dean for Admissions. He has directed Dana-Farber Cancer Institute's Medical Oncology Training Program since 1975 and is presently the Director of the Hematology/Oncology Fellowship Program of Dana-Farber/Partners CancerCare. Dr. Mayer's research interests focus on gastrointestinal cancer, a subject about which he has published extensively. Dr. Mayer directs the Center for Gastrointestinal Oncology at the Dana-Farber Cancer Institute and chairs the Gastrointestinal Cancer Committee of the Cancer and Leukemia Group B, a cooperative group sponsored by the National Cancer Institute. He has served as an Associate Editor for the New England Journal of Medicine, is a past President of the American Society of Clinical Oncology (ASCO) and the Association of Subspecialty Professors, and is a former member of the Executive Committee of the American Board of Internal Medicine. Dr. Mayer is a graduate of Williams College and the Harvard Medical School.

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The featured expert is Lodovico Balducci, MD, of the H. Lee Moffitt Cancer Center and Research Institute, University of South Florida.

Questions posted March 1, 2006

Question 1: Are there any specific foods or vitamins I should be eating before, during, or after chemotherapy for colon cancer?

Dr. Mayer:Uncertainty persists about the value of various dietary changes or vitamin supplements as a means of preventing the development of colon cancer. At present, there is general agreement that adequate amounts of folic acid and avoidance of excess amounts of dietary animal fat (such as in red meat) are useful, that regular usage of aspirin is effective, but that neither fiber nor a low fat diet seems to be useful. The benefits of calcium and – particularly – vitamin D supplements are under study.Are these practices similarly valid in individuals in whom colon cancer has already been detected as a means of preventing recurrence or prolonging survival? Nobody knows with certainty but data presented at the 2005 ASCO Annual Meeting suggest that individuals with known colon cancer who utilize aspirin have a more favorable outcome than similar individuals who don't.This preliminary and – as yet – unconfirmed observation should be interpreted with some caution in people who are receiving chemotherapy since aspirin can cause irritation to the stomach (for example gastritis) and possible bleeding which can be exacerbated by the effects of chemotherapy. More important than any specific dietary change or vitamin supplementation in people who have had colon cancer is the use of periodic colonoscopic screening (ideally every three years), performed not to detect recurrent cancer in the bowel (which is quite uncommon after adequate surgery) but to locate and remove newly developed polyps which might lead to further colonic malignancies.

Question 2: My 93 year-old father was diagnosed with colon cancer and had a section of his colon removed. His doctor wants to start him on chemotherapy but my siblings and I are hesitant to put him through treatment at his age. Can you address any special considerations regarding treating elderly patients and what we can expect as the illness develops?

Dr. Mayer: It is clear that the use of prophylactic (adjuvant) chemotherapy can increase the rate of cure in patients who have had complete surgical removal of their tumor – particularly in those people in which cancer cells have spread to localized lymph nodes (such as stage III disease). In the past, understandable concern has been raised by many physicians as well as patients and their families about the safety as well as benefit of offering such treatment to the elderly – particularly patients older than age 80. Several published surveys during the last few years have found similar degrees of anti-tumor efficacy when such adjuvant chemotherapy as the fluorouracil (5-FU)/leucovorin (Wellcovorin) treatment plan has been given to older or younger patients, and a recent presentation at the 2006 Gastrointestinal Cancer Symposium showed a similar age-independent positive outcome when the more contemporary chemotherapy program – FOLFOX (in which oxaliplatin is added to 5-fluorouracil/leucovorin) has been used. These encouraging reports, however, do not justify the use of such treatment in all older individuals. The data suggesting similar outcomes in older versus younger colon cancer patients were generated from the records of individuals who had been registered into clinical trials; undoubtedly, such patients were among the healthier individuals found to have colon cancer. 5-fluorouracil/leucovorin can cause significant diarrhea and would be an unwise treatment option in elderly (and even many younger) people with colitis or other forms of bowel dysfunction. Oxaliplatin (Eloxatin), a major component in the FOLFOX regimen, often leads to peripheral neuropathy and most likely should be avoided in people with neurologic impairment or diabetes. Consequently, there is no reason to deprive a healthy 93-year-old patient of life prolonging chemotherapy but there is also no substitute for medical judgment in determining whether the benefits of such treatment outweigh its risks.

Question 3: There was an article in the New York Times, Washington Post, and the Los Angeles Times on February 14, 2006 about the deaths of seven people with colon cancer who were being treated with bevacizumab (Avastin). What should people currently undergoing this treatment do?

Dr. Mayer:Enormous excitement has emerged from the introduction of molecularly targeted forms of treatment in the management of human cancer. One of such newly developed therapies is bevacizumab, known commercially as Avastin, which is thought to retard the development of new blood vessels surrounding tumors, potentially "starving" such cancers, and making bevacizumab a form of anti-angiogenic treatment. Bevacizumab was shown to be effective in the treatment of colon cancer in a large randomized placebo-controlled trial, initially presented at the 2003 ASCO Annual Meeting and then published in The New England Journal of Medicine in 2004. Bevacizumab seems to be far more effective when administered in combination with chemotherapy and seems to prolong the survival in patients with widespread metastatic disease by at least several months. Clinical trials are ongoing in the United States and in Europe to determine whether a similar benefit – possible leading to greater likelihood of cure – can be achieved when bevacizumab is added to adjuvant chemotherapy.

While many have considered bevacizumab to be a "magic bullet," realistically, as with any form of anti-cancer treatment, its use is associated with various side effects. Patients treated for several months with bevacizumab frequently experience hypertension, are at greater risk for thrombosis, and also have enhanced difficulty with wound healing if a surgical procedure is performed within a few days of its administration. Additionally, the use of bevacizumab has occasionally been associated with perforation of the bowel – a life-threatening emergency requiring immediate surgery, or with bleeding into the lungs if pulmonary spread of tumor has occurred. It is conceivable that if unusually severe toxicity might occur from accompanying chemotherapy, the serious side effects from bevacizumab may occur more frequently and be even more severe.

It remains unclear what the causes of death were in the colon cancer patients in Europe who were receiving bevacizumab along with oxaliplatin and an oral form of 5-fluorouracil (i.e. capecitabine [Xeloda]) in a combination known as Xelox. To maintain the integrity of large, randomized clinical trials while offering study patients continued protection, cancer specialists who are not participants in the clinical trial, serve on what are known as Data Safety Monitoring Boards; these individuals, along with the study statistician, are the only ones who have access to the actual study outcome while the clinical trial is proceeding; it is the task of such individuals to scrutinize the available information and to declare a moratorium on the study should unexpected events such as the deaths in the recent European trial become apparent.

Bevacizumab has been used safely in North America in the treatment of colon cancer when combined with various forms of chemotherapy but not, up to this point, with "Xelox." There is no reason not to continue receiving bevacizumab in combination with chemotherapy if the treatment is being directed by an experienced oncologist who is knowledgeable about both the potential benefits and side effect that this intriguing new molecule can bring.

Question 4: I have heard about virtual colonoscopies being studied in clinical trials. Are these effective for patients?

Dr. Mayer:In 2006, the "gold standard" for colon cancer screening is widely thought to be endoscopic colonoscopy. Such a test requires cleansing the large bowel (i.e. colon and rectum) of stool through the use of cathartics and then inserting a flexible tube into the rectum in which fiber optic visualization is possible and advancing the tube through the entire large bowel to identify cancers or premalignant polyps. Most people who have undergone this 30-minute procedure find that the "preparation" of cathartic purging of the bowel to be far more unpleasant than the examination itself. Many individuals have been reluctant to undergo such cancer screening because of the unpleasant nature of the preparation and the unpleasant thought of the insertion of the colonoscopic tube.

To make screening of the entire large bowel a more acceptable and available option, a technique known as virtual colonoscopy (or – more precisely – virtual colonography) has been developed in which the bowel is visualized radiographically through a CT-scan rather than through the insertion of a tube through the rectum. When performed by expert radiologists, it appears that virtual colonography is almost as effective a means of screening for colon cancer as is endoscopic colonoscopy. However, when performed by radiologists who lack this particular expertise, at present, virtual colonography has been found in comparative studies to be only 50% to 60% as accurate as endoscopic colonoscopy. Additionally, an adequate virtual colonographic examination requires the same preparation of cathartic purging as is necessary for endoscopic colonoscopy, making the "preparation" for either screening technique equally unpleasant. Lastly, virtual colonography is solely a diagnostic test, meaning that it can identify abnormalities in the bowel; if such abnormalities are detected, endoscopic colonoscopy is required so that a biopsy or the removal of polyps can be achieved. Endoscopic colonoscopy, therefore, is both diagnostic and therapeutic.

The optimal technique for colon cancer screening is still evolving. In the absence of rare familial syndromes, such screening should begin at age 50. Until quite recently, less than 40% of such appropriate middle-aged individuals availed themselves of any form of screening. Through public education and – particularly – the efforts of a variety of celebrities, the percentage of suitable Americans undergoing colon cancer screening have been increased. While endoscopy does remain the "gold standard" today, attempts are ongoing to examine DNA extracted from stool for the presence of unique mutations as a means of screening. Additionally, attempts are ongoing to devise computer software to distinguish fecal material from colonic tissue, so that virtual colonography can be performed without the unpleasant cathartic preparation. What is most important today is to remember that any form of screening is better than no screening at all and that periodic screening for colon cancer should be as routine a part of medical care as mammography, pap smears, or elevations in blood pressure or cholesterol.

Question 5:For whom would you recommend genetic testing for colorectal cancer?

Dr. Mayer:Approximately 25% of colorectal cancers arise in families whose members develop the disease more frequently than observed in the general population. Such a likelihood of hereditary disease occurs more frequently if a given patient has two first-degree relatives who have had colon cancer, one first-degree relative who developed the disease prior to age 50 or the patient in question developed the disease before age 50. Obtaining an accurate family history is unquestionably the most important step in determining whether it is likely that a given patient's condition has a hereditary basis. Unfortunately, at the present time, techniques for genetic testing are available for only two identifiable syndromes. Familial adenomatous polyposis, known more colloquially as "FAP," is characterized by the development of literally thousands of polyps throughout the entire large bowel by age 20 with more than 90% of afflicted individuals developing a cancer by age 30 unless prophylactic surgery is performed, removing the entire large bowel. Patients with this condition have a mutation in a specific chromosome (5q) which is identifiable in every cell in the body ("germline mutation"); a blood test is commercially available in which DNA is extracted from peripheral blood cells and is tested for the presence of this chromosomal abnormality. If such a test gives a positive result, first-degree relatives should be similarly tested as should children and if the mutation is identified, particularly if multiple polyps are visualized, prophylactic surgery performed. Another 5% of colon cancer cases appear to be related to another familial condition known as hereditary non-polyposis colorectal cancer ("HNPCC")which was initially described by Dr. Henry Lynch and is sometimes also known as "Lynch Syndrome." Individuals with this condition have a significantly higher likelihood of developing large bowel cancers during their 30's and 40's, particularly on the right side of the colon near the appendix. Women with this condition are also at increased risk for cancer of the ovary and of the endometrium (uterus). Tumor tissue from the vast majority of patients with HNPCC can be shown to demonstrate what is known as "microsatellite instability" – a term referring to an inability of the chromosomes for correcting minute errors in replication – much like a "spell checker" would do for a typist. Not all patients whose colon tumors demonstrate microsatellite instability will have HNPCC but sophisticated, expense genetic testing should only be performed if microsatellite instability can be established. Once this has occurred, a peripheral blood sample can be obtained, assessments for one of several potential germline mutations made, and the diagnosis confirmed. Once again, if a diagnosis of HNPCC has been established, first-degree relatives should be tested for the presence or absence of that specific mutation. Healthy, asymptomatic individuals found to carry the HNPCC mutation should undergo colonoscopy far more frequently than the general population (probably annually) and if these individuals are women, careful assessments of the ovaries and uterus should be made as well.FAP and HNPCC comprise only 20% of familial colorectal cancer. Regardless of whether FAP or HNPCC can be confirmed, if large bowel cancer is occurring frequently in a given family – particularly in younger individuals, colonoscopic surveillance should begin by age 30, 20 years earlier than usual, and be repeated on a regular basis.

Question 6: My father, who has colon cancer, has developed constipation. Are there any ways to relieve him of the constipation?

Dr. Mayer: Bowel function frequently deteriorates as we age, and as the colon loses its elasticity. Older individuals frequently experience spontaneous bowel movements on an irregular schedule, often believing themselves to be constipated, while alternatively having episodes of flatus and soilage. Such bowel irregularity may be related to medications which have been prescribed for other purposes. A variety of remedies exist, including the enhancement of fiber in the diet, stool softeners, and mild laxatives. However, if constipation is a significant issue, a medical evaluation with one's primary care physician should be scheduled before adopting any of these treatment options.

Questions posted March 8, 2006

Question 7: My grandmother, who has colorectal cancer, is nearing the end of her life. What can I do to help her during these last days and weeks?

Dr. Mayer: The terminal phase of any chronic illness is often a trying as well as sad experience for families. It is, however, also an opportunity to bring family members together and to reminisce about happy memories with the loved one. The goal of management in such circumstances should focus on the relief of any symptoms. For many such elderly people, merely knowing that a sibling, a child, or a grandchild is present is highly reassuring. Often such reassurance can be achieved in a non-verbal manner, particularly if the patient has trouble maintaining a conversation. Often, a devoted spouse may become exhausted in trying to provide care; much benefit can be achieved by offering the spouse a respite or simply helping with meals or shopping.

Question 8: Please discuss complementary and alternative therapies for the treatment and prevention of colorectal cancer.

Dr. Mayer: We all want to believe that there is something we can do through lifestyle changes that can reduce our odds of developing colorectal cancer or improving the chance that we will benefit from treatment. Many unorthodox approaches have been put forth to achieve this goal ranging from high doses of vitamins, unusual diets, cathartics, and the like. The Internet is filled with such candidate "cures," most of which have never been scrutinized for their efficacy in a rigorous scientific manner and some of which offer their developers considerable financial rewards. My own philosophy is that if such a treatment or lifestyle change is not harmful and provides satisfaction to a patient and their family, I encourage its use. As such, I endorse the notion of "complementary" rather than "alternative" treatments.

Question 9: I am 36 years old and have been diagnosed with colon cancer. My husband and I were hoping to start a family soon. What sort of side effects can chemotherapy and colon cancer have on fertility and the health of a baby?

Dr. Mayer: I assume that your question refers to the safety of prophylactic chemotherapy after an operation has removed all detectable colon cancer. In the past, such prophylactic ("adjuvant") chemotherapy would have consisted of two drugs — 5-fluorouracil and leucovorin — given for six months. Such treatment may lead to temporary diarrhea and low blood counts but has no effect on fertility or the potential health of any child that might be conceived and then born following such treatment. More recently, an additional chemotherapeutic drug — oxaliplatin — has been added to the 5-fluorouracil and leucovorin; the emerging results of two large clinical trials suggest that this newer combination of drugs is more effective in reducing the likelihood of cancer recurrence. While there are no definitive data regarding the effect of this new oxaliplatin-containing combination on subsequent fertility, oxaliplatin does belong to a class of drugs that are known to reduce the number of eggs in the ovary and sperm in the testes, potentially making subsequent conception more difficult. This issue is easier dealt with in men where "banking" of sperm prior to the use of chemotherapy can be easily accomplished. Storage of human eggs ("ova") is a more cumbersome and time-consuming process. It would seem useful for you to speak with your oncologist, weighing the potential likelihood for cancer recurrence (based on the number of involved regional lymph nodes, the appearance of the tumor under the microscope, etc.) to determine whether adding the oxaliplatin will be in your best interest.

Question 10: I am 25 years old, have been diagnosed with colon cancer, and am 12 weeks pregnant. What are the side effects of chemotherapy during a pregnancy and is it considered safe to undergo chemotherapy? What other options do I have?

Dr. Mayer: It is unclear, from your question, whether you have a localized cancer that can be surgically removed or whether you have been found to have a cancer that has spread to other parts of your body. Regardless, with you still being in your first trimester of pregnancy, and at least four if not five months away from any attempt at an early delivery, the primary focus of your care, at least in my opinion, should lie with treating your cancer. It would be extremely unwise to delay the start of cancer therapy for four months — particularly if such treatment might prove to be curative. Much of the chemotherapy that is used in the treatment of colorectal cancer — particularly 5-fluorouracil and leucovorin — can be safely administered during the first trimester of pregnancy. Little information is available about the use of such additional forms of therapy such as oxaliplatin or irinotecan. There is little likelihood that their inclusion in your treatment would lead to a deformity in the baby, but it is possible that they might precipitate a miscarriage. I would avoid such molecularly targeted forms of treatment such as Avastin or Erbitux during pregnancy.

Question 11: What role does chemoprevention play in colorectal cancer?

Dr. Mayer: The term "chemoprevention" describes a strategy where the use of oral medication may prevent the development of colon cancer. Such medications are directed at reducing the appearance of polyps which occur several years before cancers develop. It is generally acknowledged that the most effective form of chemoprevention for colon cancer is aspirin — taken on a regular basis for many years. Aspirin is also known to reduce the likelihood of coronary artery disease and studies in which individuals who were randomly assigned to receive aspirin or a placebo showed not only a reduction in the amount of heart disease but also a decrease in the appearance of colon cancer. Aspirin is thought to inhibit an enzyme — cyclo-oxygenase 2 (also known as COX-2) — which is present in the lining cells of the normal bowel; this enzyme is instrumental in a pathway that leads such lining cells to divide and proliferate, sometimes forming polyps and subsequently cancers. Available data suggest that the use of a regular aspirin several times each week is optimal; furthermore, the chemopreventative benefit from the aspirin does not become apparent until the drug has been used for 10 years or longer. It has been speculated that medications related to aspirin — so called "non-steroidal anti-inflammatory drugs" (NSAID's) — such as ibuprofen (Motrin, Advil, etc.) or naprosyn (Aleve) may be equally as effective. Both aspirin and NSAID's can cause irritation to the stomach and occasional bleeding, which led chemists to develop more specific forms of such compounds which has less likelihood for bleeding. These carefully designed drugs — Celebrex and Vioxx — are under study for their ability to reduce the recurrence of polyps in people who have previously had such polyps removed. However, as has been well publicized, both Celebrex and Vioxx appear to be toxic to the heart in a small number of patients and should not be used for chemoprevention of colon cancer.

Other forms of chemoprevention for colon cancer that have been explored including increased concentrations of dietary folic acid (a vitamin), increased concentrations of dietary calcium, and increased concentrations of vitamin D. The folic acid and calcium levels that are thought necessary can be found in most multivitamins. Ongoing efforts are underway to better study how best to enhance vitamin D levels for this purpose.

Question 12: I have colon cancer and my physician wants to treat it with surgery to remove the tumor and 26 rounds of chemotherapy. I am not sure I want that much chemotherapy and wanted to know the risks of not completing the 26 treatments.

Dr. Mayer: You have apparently undergone a complete removal of a colon cancer and your physician would like you to receive prophylactic ("adjuvant") chemotherapy. Such treatment is generally given for six months (26 weeks) based on the results of clinical trials that have shown that six months of treatment is equivalent in benefit to 12 months (one year). Whether the same value could be achieved giving your therapy for only three or four months rather than six months is unknown. While, ultimately, it is your decision whether to receive a full six months of adjuvant therapy, what has been recommended to you is standard practice in 2006.

Questions posted March 15, 2006

Question 13: I am 51 years old and am being treated for cancer of the colon, liver and lungs. I have lost a great deal of weight due to the radiation therapy and chemotherapy. What sort of things can I include in my diet to gain some of the weight back?

Dr. Mayer: Being treated with radiation therapy and chemotherapy is an ordeal, leading to fatigue, loss of appetite, and weight loss. While these symptoms gradually resolve once treatment has been completed, there are some practical interventions that can be useful to help regain strength and weight more rapidly. Most of us normally focus our diet on three daily meals supplemented with one or two snacks. Radiation therapy and chemotherapy make it difficult to ingest a normal meal; quite often, people who have been so treated get a sense of being "filled-up" after only a few mouthfuls of food. Additionally, the thought of a multi-course meal becomes "distasteful." What is helpful in such circumstances – the opposite of what is advised for dieters – is to become a "grazer," eating small feedings every two hours or so. Such small feedings can include a small dish of apple sauce, a bit of custard, a couple of soft boiled eggs, a small dish of ice cream, a small serving of meatloaf – soft, caloric, relatively bland foods that are easily digestible. Shakes - either commercially or personally prepared, are also quite useful. Knowing that only small volumes of food are tolerable, it is important to focus on high caloric feedings and not to fill up with water, tea, Jell-O, and the like. These dietary hints, coupled with successful treatment of your colon cancer, will hopefully resolve your weight loss.

Question 14: I was treated for colon cancer and recently finished six months of chemotherapy treatment that included methotrexate (Folfox), bevacizumab (Avastin), and oxaliplatin (Eloxatin). My joints have stiffened throughout my body and my hands are numb, stiff and deformed. What can I do to improve my condition and how long do these side effects usually last?

Dr. Mayer: I assume you were treated with six months of FOLFOX (5-fluorouracil, leucovorin [Folinic Acid], oxaliplatin) and bevacizumab (Avastin) as prophylactic (adjuvant) treatment following the surgical removal of a colon cancer; most likely, you did not receive methotrexate. The numbness and joint stiffening that you have experienced most likely represents a side effect caused by the oxaliplatin (a component of the FOLFOX chemotherapy combination); this side effect, technically termed peripheral neuropathy, causes a sensation of "pins and needles" in the fingers and toes; these symptoms are often made a bit worse upon exposure to cold temperatures. Most often, the peripheral neuropathy associated with oxaliplatin diminishes greatly within six months after the completion of treatment; about 10% of treated patients appear to experience long-term symptoms. Efforts are underway to identify medications to be taken along with the oxaliplatin to reduce the degree of neuropathy. For now, it would seem helpful to keep your hands and feet warm (use gloves and thick socks in wintry weather) and avoid reaching into a freezer to grasp a particularly cold item. With the passage of time, your symptoms should recede.

Question 15: I have heard mixed reports about the use of aspirin to prevent colorectal cancer—what do you recommend to your patients?

Dr. Mayer: Aspirin is a drug that is thought to reduce the rate of cellular division in the lining cells (mucosa) of the intestines; in doing so, it is thought to reduce the likelihood for the development of polyps which are the benign precursors of colon cancer. To be a bit more technical, aspirin inhibits an enzyme (cyclo-oxygenase-2 [also known as COX-2]) that stimulates the synthesis of a chemical (prostaglandins) that leads to the cell division. The ability of aspirin to reduce the risk for colon cancer has been shown in multiple population-based studies, but does not become apparent until the drug has been used regularly for at least 10 years. The use of a baby aspirin three times a week, which has been found effective in reducing cardiac events in individuals with coronary artery disease (by preventing clot formation), is sufficient to reduce the risk for colon cancer as well. However, recent reports suggest that taking one adult aspirin per day represents a superior strategy. Aspirin belongs to a class of drugs known as non-steroidal anti-inflammatory agents which also include ibuprofen (Motrin, Advil, etc.), naprosyn (Aleve), and celecoxib (Celebrex). While experience with these compounds for colon cancer prevention is not as mature as that for aspirin, they all seem to offer benefit. Lastly, data reported last year suggest that the use of aspirin in patients who have undergone a successful operation to remove a colon cancer who use aspirin on a regular basis have less likelihood of experiencing recurrence of their malignancy.

Question 16: What is the rate of cancer recurrence for colon and rectal cancers? How can I prevent recurrence? What does follow-up care after treatment include?

Dr. Mayer: The likelihood of recurrence after the surgical removal of a colon or rectal cancer is dependent on the stage of the tumor. Tumor stage is determined by three factors; the depth of penetration of the tumor into the lining of the bowel (T), the presence or absence of tumor spread to adjacent lymph nodes (N) and if such spread is present, the number of nodes that are involved; and the presence or absence of tumor spread to other organs in the body (M). Individuals with stage I tumors – those having infiltrated relatively slightly into the lining of the bowel without spread to any lymph nodes or other organs – have a 90% to 95% likelihood of being cured with surgery. In those patients with stage II tumors – which have penetrated more deeply into the lining of the bowel but also have not spread to adjacent lymph nodes or distant organs, the likelihood of cure following surgery alone is in the range of 75% to 85%; controversy exists as to whether the use of post-operative prophylactic (adjuvant) chemotherapy can significantly improve this outcome. Stage III tumors of the colon and of the rectum are those in which cancer cells have spread to adjacent lymph nodes but not to distant sites in the body; surgery alone results in a 45% to 60% percent likelihood of cure with the variability based on the number of involved lymph nodes.

There is general agreement that post-operative chemotherapy can significantly improve the cure rate achieved with surgery alone. Radiation therapy is usually added to chemotherapy as a form of adjuvant treatment following the removal of stage II and stage III rectal cancers and more recently has been utilized as the initial type of treatment – even before surgery (induction or neoadjuvant therapy). There is general agreement that patients who have undergone the removal of a colon or a rectal cancer should undergo periodic follow-up for approximately five years since if a recurrence is destined to develop, it will nearly always have appeared by that time. There is also general agreement that such follow-up should include a colonoscopy approximately one year after the original operation and then every three years thereafter; the purpose of the colonoscopy is not to identify recurrences at the anatomic site where the bowel was sewn together at the time of the operation (such suture-line recurrences are extremely uncommon) but rather to search for and then remove newly developed polyps which could be the source of future cancers. Most, but not all, cancer specialists recommend that a blood test called the carcino-embryonic antigen (CEA) be performed every three months during these post-operative five years; the CEA is a protein shed into the blood by tumor cells (but also inflamed lining cells of the bowel or the bronchus) which, if the value continues to rise on sequential testing, can predict the presence of a recurrence long before any symptoms develop or even before radiographic studies can identify any abnormality. Most such cancer specialists also recommend that routine blood tests be performed twice yearly after the colon or rectal cancer has been removed.

Controversy exists regarding the value of annual or biannual chest x-rays, CT-scans, or even newly introduced PET scanning. These radiographic studies are expensive and – up to the present time – have not been shown in the properly designed clinical studies in which they have been examined, to lead to a greater likelihood of prolonging survival. Merely detecting an incurable recurrence a few months earlier, many experts argue, does not justify the widespread use of such technology. Nonetheless, many cancer specialists do recommend such scans yearly for the first two or three years after a colon or rectal cancer has been removed.

Question 17: It is possible that my grandfather will need to undergo a colostomy procedure for the treatment of colorectal cancer. How can our family ease his fears of the procedure and help him overcome the physical changes that are happening to his body?

Dr. Mayer: The need for a colostomy is, for most people, an extremely upsetting if not frightening event.Younger individuals understandably worry about their self-image and social attractiveness while more elderly patients frequently find the technical aspect of colostomy care difficult to master. Such a procedure has undoubtedly been recommended to your grandfather because he has a cancer at the very end of the rectum, adjacent to the muscle (sphincter) which controls the anus and the only way that the tumor can be removed and the disease potentially cured is if the anal sphincter is included in the portion of the bowel that requires operative removal. First and foremost, your grandfather should be reminded and reassured that the goal of his treatment is to prolong his survival and that learning how to care for a colostomy is “better than the alternative!” Presumably, your grandfather has been or will be introduced by his surgeon to a nurse who specializes in the care of ostomies, who can provide many tips as to how to change the bag, avoid leakage, adjust diet, provide care for the skin around the ostomy opening (stoma), and suggest types of clothing that will be most comfortable covering this new appliance. Many individuals who require a colostomy initially think that it will be, almost by definition, malodorous and that fecal soilage will be inevitable. At first, the accidents resulting in such episodes may take place but most individuals – even the elderly – become quite adept at caring for the appliance. It might be helpful, perhaps with the assistance of a social worker, for close family members to meet as a group with your grandfather to talk openly about the colostomy, to reassure him that this will not limit his social activities, and to indicate how family members will be willing to learn to provide him added assistance if he should need it.

Questions posted March 22, 2006

Question 18: I just read the article on the website called Chemotherapy Given Directly to the Liver Improves Survival for Patients with Colorectal Cancer That Has Spread to the Liver." Can you discuss other new treatments for advanced colon cancer?

Dr. Mayer: Until about 10 years ago, a single chemotherapy drug, fluorouracil (5-FU), which blocks the action of an enzyme necessary for cells to divide, represented the only known form of effective treatment for individuals with advanced (metastatic) colon cancer. Only a minority of treated patients benefited from such therapy. The liver, which acts as a filter for the blood flow and lymphatic drainage from the abdomen (where colon cancer develops) is the most common initial site of metastatic spread. Knowing that 5-FU, when administered into a peripheral blood vessel (usually in the arm or hand) did not benefit the majority of patients with tumor spread to the liver, cancer researchers began to explore the notion of infusing the drug directly into the liver through the hepatic artery more than 40 years ago with the thought that if higher concentrations of the chemotherapy compound could be achieved in the liver, the likelihood for benefit would be greater.

This notion of "regional chemotherapy" was greatly advanced around 1980 by the development of a surgically implanted pump, placed directly under the skin of the abdomen and connected by a tube into the artery that flows into the liver. Such a pump could be "loaded" with chemotherapy periodically and drug flow into the liver could be maintained for days if not weeks on end, on an outpatient basis. Enthusiastic reports emerged from institutions where such a treatment approach was utilized, claiming a greater likelihood of disease shrinkage, and possibly, a prolonged time for survival.Skeptics noted that such therapy was toxic and expensive and wondered whether the patients included in such enthusiastic reports were different (for example, not ideally representative) of the vast majority of patients with this condition.

During the last month, the results of a randomized clinical trial, sponsored by the National Cancer Institute, including patients from multiple institutions, was reported in ASCO's Journal of Clinical Oncology. In this experiment, patients with colorectal cancer with spread to the liver (but no other sites) who had received no prior therapy for their disease, were randomly allocated, after giving consent, to receive 5-FU chemotherapy directly into the liver or into a peripheral vein. The study conclusively demonstrated that the regional chemotherapy approach led to a greater likelihood of disease shrinkage and control of the liver metastases than did similar chemotherapy administered to a peripheral vein, leading to a somewhat longer survival, with an enhanced quality of life, but that the patients who received regional chemotherapy also had a greater likelihood of experiencing the development of metastatic disease in organs such as the lung where the liver-directed chemotherapy did not appear to provide adequate efficacy. While regional chemotherapy in this well conducted study did not cure patients with metastatic colon cancer to the liver, it was shown to be effective and tolerable. Despite this result, however, only a limited number of cancer centers continue to embrace the use of regional chemotherapy since this study, designed more than 10 years ago, was developed before such newer treatments for colon cancer such as irinotecan and oxaliplatin (forms of chemotherapy) or cetuximab (Erbitux) and bevacizumab (Avastin) (forms of molecularly targeted treatment) had been introduced. The outcomes of patients treated with these new drugs and molecularly targeted molecules surpasses the results achieved with 5-FU based regional therapy. Whether combining these two strategies will provide synergy remains to be determined.

Question 19: My mom was diagnosed with Stage IV colon cancer about 16 months ago and has undergone two rounds of chemotherapy with no positive results. Recently, a relative suggested that my mom take advantage of hospice care. Does placing my mom in hospice care change the approach of how the doctors will treat her condition?

Dr. Mayer: It appears that your mother has not benefited from two different chemotherapy programs which have been administered to her since her metastatic colon cancer was diagnosed 16 months ago. Undoubtedly she and your family are disappointed if not frustrated by this lack of benefit – particularly since she most likely has had to endure a variety of often painful side effects in association with her treatment. The question now at hand is whether it is more appropriate to continue fighting her cancer by identifying a third (and – in the future – possibly a fourth) form of anticancer therapy for her to try, or to acknowledge the slim likelihood of such additional and potentially toxic treatment providing her benefit, and focusing her medical management on symptom control (palliative care) which is increasingly performed at home with the assistance of a hospice group.

Making the decision to shift one's primary goal from fighting the cancer to fighting cancer symptoms is often difficult and is usually best achieved with the guidance of a sensitive cancer specialist – be it a physician, a nurse, or social worker. Hospice organizations usually provide round the clock responsiveness to the needs of patients, and are often better trained in controlling pain, nausea, constipation, and the other symptoms which affect patients with advanced colon cancer. Because the mechanism for reimbursement for hospice units is different from that for traditional cancer clinics, patients and their families often have to choose between one care strategy versus the other. Personally, I am an enormous advocate of the hospice movement and maintain the care of my patients as they transition into such a palliative care setting. Whether this is the correct choice for your mother at this time depends on her overall physical condition, her personal preference, her relationship with her health care providers, and the extent of symptoms she is presently experiencing. A family meeting with the health care providers might be an effective setting in which to help make this important decision.

Question 20: How are tumor markers used to screen, detect, or monitor colorectal cancer?

Dr. Mayer: The term tumor markers is used to describe the measurement of a substance (usually a protein) in the blood whose presence correlates with the development of a cancer, and where the level of that protein in the blood would correlate with the extent of the tumor in a given patient. If such a tumor marker were totally specific for a given cancer, meaning that it would never be present in normal individuals, it could be used to screen, detect, and monitor a malignant condition. Unfortunately, with the possible exception of what is known as human chorionic gonadotrophin (which is the protein that is measured in pregnancy tests but also links with an unusual cancer called a choriocarcinoma [appearing in women in the placenta and in men in the testes]), such ideal tumor markers have not been identified. Those that are utilized may be falsely elevated in benign conditions, often do not increase in concentration until metastatic cancer is present, and do not correlate in their concentration in the blood with the extent of disease that may be evident.

The tumor marker utilized most frequently in the setting of colon cancer is known as the carcinoembryonic antigen CEA. This is a protein that is normally found in low concentrations in the lining cells of the bowel but also in the bronchi of the lungs and the ducts in the breasts. When these tissues become inflamed – in the setting of colitis or bronchitis – the CEA levels may increase. Most (but not all) colon cancers contain the CEA protein which is not surprising since colon cancer arises from the lining of the bowel. However, most patients with colon cancers that can be cured with surgery have normal CEA levels before their operation, even though they have a colon cancer. Having an elevated CEA level before such an operation has been shown to be an ominous prognostic sign, even if the CEA level falls to normal after the tumor has been removed. CEA levels rise most frequently when colon cancer spreads to the liver; interestingly, such elevations are not as uniform when the disease spreads to such other organs as the lungs.

Cancer specialists often measure CEA levels every 3 or 4 months during the first several years after a colon cancer has been removed since a rising pattern in the CEA level over time is often the first indication of recurrent disease in asymptomatic patients in whom other blood tests are normal and even CT scans remain normal. In such circumstances, a PET scan, which is now becoming more widely available, is likely to show an otherwise undetectable small area of disease which occasionally may be surgically removed, leading to potential cure. In the setting of metastatic colon cancer, CEA levels are frequently elevated and usually return to more normal values if the chemotherapy and/or radiation treatment that has been offered as management is effective, or continue to rise if a patient's disease does not respond to such anticancer management.

The identification of molecular abnormalities in colon cancer cells, associated with changes (mutations) in certain chromosomes in tumor cells, has recently led some investigators to obtain stool samples from patients at risk for colon cancer, extract the desired genetic material (DNA) from these cells, and analyze the DNA for certain specific mutations. If this strategy proves to be successful, a new form of a tumor marker that could be highly useful in cancer screening might become available. It is too soon to know how effective this approach will turn out to be.

Question 21: My mother had breast cancer four years ago, participated in a clinical trial for her treatment, and so far is disease free. Now my Dad has been diagnosed with colon cancer and we are trying to decide on the best course of treatment for him. We have heard that the "standard" treatment for early-stage colon cancer is very good. What are your thoughts on going the standard treatment route versus a clinical trial?

Dr. Mayer: Many people have been led to believe that participation in a clinical trial, almost by definition, guarantees a better outcome than being treated in a standard manner. A clinical trial represents, in essence, an experiment in human beings in which patients, through their participation, are volunteering to be treated in a relatively standardized manner – often (but not always) with newer forms of treatment, and in doing so, giving their physicians permission to report in detail the success and tolerability of the therapy into a data collection center that includes similar information from other identically treated people. Individuals participating in a clinical trial are usually (but not always) managed by cancer specialists perhaps a bit more expert in the type of cancer being treated, frequently will be asked to have more office or clinic visits and more blood tests and scans than they would otherwise receive, and occasionally (but – again – not always) may have access to newer forms of treatment that would not otherwise be available.

As a clinical investigator, I very much try to encourage my patients to take part in clinical trials since the information from these studies leads to new advances, progress, and changes in standard care. As a cancer physician, however, my primary responsibility is to the well-being and satisfaction of my patients and if such individuals decline to participate in a clinical trial, I manage them in the standard manner. However, it should be acknowledged that what we define as standard care today only became standard because it was shown to be effective in a previous clinical trial in which patients faced with the same decision had the courage to participate. It is through clinical trials that progress has been made.

Question 22: My good friend has been diagnosed with Stage I colorectal cancer. Her oncologist has said that with chemotherapy and radiation treatment there would be a 90% to 95% success rate of getting rid of the cancer. However, her oncologist also said that a colostomy would give her a 100% success rate. Can you please discuss the quality of life people have when living with a pouch? Thank you.

Dr. Mayer: By the nature of your question, I assume that your friend had a stage I rectal cancer with a tumor arising at the very end of the rectum, extremely close to the muscle which is necessary for adequate anal function, the sphincter. Since chemotherapy and radiation therapy have been recommended as an alternative to a radical operation requiring a permanent colostomy, I would assume that the tumor invaded through the first layer of the lining (submucosa) of the rectum into but not through the muscle layer just below the submucosa (muscularis). Such tumors are classified as being T₂ lesions. If the tumor had been restricted to the submucosa (T₁), no chemotherapy or radiation therapy would likely have been suggested. Because of the location of your friend's T₂ rectal cancer, a definitive operation cannot be performed without sacrificing the anal sphincter and, as an alternative, the primary tumor most likely was removed by her surgeon directly from the lining of the rectum without making any incision into the abdomen. In the hands of an expert colorectal surgeon, such procedures can be safely performed, retaining the anal sphincter and avoiding the need for a colostomy and controlling the tumor in the majority of patients.

However, based on the results from the few clinical trials that directly addressed this issue, the 90% to 95% percent success rate which you quote may be a bit high; even though all tumor may have been removed, if tumor cells entered lymphatics (lymphovascular invasion) or the space around nerves (perineural invasion), the likelihood of recurrence increases. If either of these pathologic characteristics are identified, I would favor surgical removal of the rectum and the construction of a permanent colostomy.

A colostomy represents the surgical diversion of the end of the bowel to the surface of the abdominal wall with fecal material passing through that opening (ostomy) rather than through the anus which has been removed. Understandably, adjusting to the presence of colostomy represents a social as well as a physical challenge which can be surmounted with proper instruction and encouragement in the vast majority of patients. Individuals need to be reminded that the reason a colostomy has been placed has been to cure an otherwise potentially lethal cancer. Most patients become quite adept at caring for ostomies, making certain that the surrounding skin does not become irritated, changing the collection bag on a regular basis, and learning how to irrigate the opening periodically so as to better control the passage of fecal material. Surgical departments in most medical centers have specialized nurses who focus their efforts on the care of ostomies and can provide highly useful tips to make the adjustment as easy as possible. On rare occasions, an ostomy bag can become dislodged and accidents can happen, but similar accidents may take place through the anus if bowel function becomes irregular. It has been amazing for me to see how complete the lives have remained – socially, sexually, as well as physically, for most patients of mine who have had to have a (submucosa) created because of rectal cancer.

Question 23: What age is best to start colorectal cancer screening? What tests are necessary and how often?

Dr. Mayer: The median age for the development of colon cancer in individuals who do not have a strong family history for the disease is at approximately 67. The development of colon cancer before age 50 is relatively uncommon. Consequently, guidelines from multiple organizations have uniformly recommended that screening for colorectal cancer begin at age 50. In the past, such screening involved repeated assessments of stool for the presence of blood (so-called guaiac or Hemoccult testing); however, the accuracy of such a strategy has been proved to be inadequate since it is based on the premise that colorectal cancers uniformly bleed. In truth, such bleeding, if it occurs, may be intermittent so the test may be falsely negative; more importantly, the vast majority of blood that might be occultly present in stool is not a reflection of colon cancer, making such testing falsely positive.

More recently, attention has focused on visualizing the lining of the bowel, searching for either cancers or benign polyps which may eventually develop into cancers. The results of screening studies have shown that identifying and removing polyps through a sigmoidoscope (a tube that extends through the part of the large bowel closest to the rectum) or colonoscope (a longer tube through which the entire colon and rectum can be visualized) significantly reduces the risk for developing colon cancer. At present, it has been proposed that adequate screening for colon cancer, beginning at age 50, might include a sigmoidoscopy every five years along with an examination of stool for the occult presence of blood, or – preferably, a colonoscopy every 10 years. If polyps are identified through these examinations, which will be the case in approximately 40% to 50% percent of middle aged to elderly individuals, colonoscopy should be repeated every 3 or 4 years.

These screening recommendations have been formulated for individuals with either no family history for colorectal cancer, or perhaps, a rare relative with the disease in which the malignancy was diagnosed at an elderly age. If colorectal cancer has been found in a first-degree relative younger than age 50 or two first-degree relatives before age 60, screening should begin at age 40. Individuals with even stronger histories of colorectal cancer (such as the hereditary non-polyposis syndrome) or inflammatory bowel disease (ulcerative colitis or Crohn's disease), require different screening recommendations and should consult their personal physicians.

Please check back next week for more answered questions. In addition, feel free to post a question.

More Information

Guide to Colorectal Cancer

JCO Cancer Advances: Chemotherapy Given Directly to the Liver Improves Survival For Patients With Colorectal Cancer That Has Spread to the Liver

ASCO Virtual Meeting: 2006 Gastrointestinal Cancers Symposium

Last Updated: March 01, 2006