Anal Cancer Expanded Information
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1 Anal Cancer Expanded Information What is anal cancer? Cancer describes a set of diseases in which normal cells in the body, through a series of genetic changes, lose their ability to control their growth. As cancers also known as malignancies grow, they may invade the tissues around them (local invasion). They may also spread to other locations in the body via the blood vessels or lymphatic channels where they may implant and grow (metastases). The anus or anal canal is the short passage that is the opening through which stool or feces passes to exit the body at the time of a bowel movement. Anal cancer arises from the cells around the anal opening or in the anal canal just inside the anal opening. Anal cancer is often a type of cancer called squamous cell carcinoma (which includes cancers called basaloid, epidermoid, cloacogenic, or mucoepidermoid all of which are assessed and treated the same way). Other rare types of cancer may also occur in the anal canal (like gastrointestinal stromal tumors or GIST and melanoma to name two), and these require consultation with your physician or surgeon to determine the appropriate evaluation and treatment. Cancer can also develop in the skin in the 5cm, or approximately 2 inches, just outside the anus. This is called perianal or anal margin cancer and is treated more like a skin cancer. Cells that are becoming malignant or premalignant, but have not invaded deeper into the skin are often referred to as high-grade anal intraepithelial neoplasia or HGAIN (previously referred to by a number of different terms, including "high grade dysplasia", "carcinoma-in-situ", anal intra-epithelial neoplasia grade III, high-grade squamous intraepithelial lesion, or "Bowen's disease"). While this condition is likely a precursor to anal cancer, this is not anal cancer and is treated differently than anal cancer. Your physician or colon and rectal surgeon can help clarify the differences. The risk of these types of premalignant cells turning into cancer is unknown, but is thought to be low, especially in patients with a normal immune system. How common is anal cancer? Anal cancer is fairly uncommon, accounting for about 1-2% of all cancers affecting the intestinal tract. Approximately one in 600 men and women will get anal cancer in their lifetime (compared to 1 in 20 men and women who
2 will develop colon and rectal cancer in their lifetime). Almost 6,000 new cases of anal cancer are now diagnosed each year in the U.S., about 2/3rds of the cases in women. Approximately 800 people will die of the disease each year. Who is at risk? A risk factor is something that increases a person's chance of getting a disease. Anal cancer is commonly associated with infection with the human papilloma virus (HPV), the most common sexually transmitted disease. There are a number of different types of HPV, some more likely to be associated with development of cancer than others. The HPV that leads to development of warts in and around the anus as well as genital warts (on the penis in men and the vagina, vulva, or cervix in women), has a low potential of developing cancer. Only about 1% of patients who contract HPV actually develop warts. The types of HPV associated with development of cancer usually lead to long-standing and subclinical infection (one that does not show outside evidence of infection or symptoms/warts) of the tissues in and around the anus as well as in other areas. These types of HPV are associated with the premalignant changes that were described above (high-grade anal intraepithelial neoplasia or HGAIN). These types of HPV are also associated with an increased risk of cervical, vulvar, and vaginal cancer in women, penile cancer in men, as well as with some head and neck cancers in men and women. Having a squamous cell cancer of the genitals, especially cervical or vulvar cancer (or even pre-cancer of the cervix or vulva), can put people at increased risk for anal cancer likely from the association with the cancer-causing types of HPV infection. Interestingly, patients with anal cancer are not at increased risk for colon and rectal cancer or other cancers in the abdominal organs. It should be noted that not all anal cancers are associated with HPV infection. Some develop without a clear reason. Additional risk factors for anal cancer include: Age - While most of the cases of anal cancer develop in people over age 55, over 1/3 rd of the cases occur in patients that are younger than that. In the United States between 2004 and 2008, the numbers of anal cancers diagnosed by age: 0.0% were diagnosed under age 20; 1.1% between 20 and 34; 9.4% between 35 and 44; 24.7% between 45 and 54; 25.0% between 55 and 64; 18.0% between 65 and 74; 15.2% between 75 and 84; and 6.6% 85+ years of age. As noted above, the incidence of anal cancer in younger men, likely related to HIV (human immunodeficiency virus, the virus that leads
3 to AIDS) infection, has been increasing in some parts of the world. Anal sex People participating in anal sex, both men and women, are at increased risk. Sexually transmitted diseases Patients with multiple sex partners are at higher risk of getting sexually transmitted diseases like HPV and HIV and are, therefore, at increased risk of developing anal cancer. Smoking - Harmful chemicals from smoking increases the risk of most cancers, including anal cancer. Immunosuppression - People with weakened immune systems, such as transplant patients taking drugs to suppress their immune systems and patients with HIV infection, are at higher risk. Chronic local inflammation - People with long-standing anal fistulas or open wounds in the anal area are at a slightly higher risk of developing cancer in the area of the inflammation. Pelvic radiation - People with previous pelvic radiation therapy for rectal, prostate, bladder or cervical cancer are at increased risk. Can anal cancer be prevented? Few cancers can be totally prevented, but the risk of developing anal cancer may be decreased significantly by avoiding the risk factors listed above and by getting regular checkups. Smoking cessation lowers the risk of many types of cancer, including anal cancer. Avoiding anal sex and infection with HPV and HIV can reduce the risk of developing anal cancer. Using condoms whenever having any kind of intercourse may reduce, but not eliminate, the risk of HPV infection. Condoms do not completely prevent transmission of HPV because the virus is spread by skin-to-skin contact and can live in areas not covered by a condom. Vaccines originally used in clinical trials against the HPV types that have been associated with cervical cancer have also been shown to decrease the risk of developing HGAIN and anal cancer (in men and women), especially in those patients at higher risk (see the risk factors listed above). These vaccines are most effective in people who have not previously been sexually active or have not yet been infected with HPV. People who are at increased risk for anal cancer based on the risk factors listed above should talk to their doctors about consideration for anal cancer
4 screening. This can include anal cytology (study of anal cells under a microscope after using a swab on the anal tissues), also known as Pap tests (much like the Pap tests women undergo for cervical cancer screening). If abnormal cells are found to be present, specialized small, lighted scopes of the anus with high magnification ( high resolution anoscopy or HRA) can be used in the clinic or the operating room to assess for premalignant or malignant changes in the anus. Early identification and treatment of premalignant lesions in the anus may prevent the development of anal cancer. It is unclear how successful these tests, and any subsequent treatments, are at preventing cancers or saving lives from the prevention of anal cancer, but this likelihood is thought to be very similar to the improvements found with the use of cervical cancer screening in women using the pelvic exam Pap test. It is unclear how often the anal Pap tests should be done to successfully identify and prevent anal cancer. If premalignant changes of the anus or HGAIN are identified, they can be treated through a number of methods to hopefully prevent them from developing into anal cancer, although not all of these changes will develop into cancer (the rate of cancer developing in HGAIN is less than 10% in people with a normal immune system). These methods include excision (cutting out the abnormal tissue), using electrocautery (focused application of electricity), laser treatments, phototherapy treatments, radiation treatments, chemotherapy creams (5-fluorouracil or 5-FU), or medications (for example, Imiquimod). None of these treatments have been studied extensively, none of them are effective 100% of the time, and all of them have potential side effects. It is best to consult with your physician or colon and rectal surgeon before considering them. What are the symptoms of anal cancer? While 20% of anal cancer may not present with any symptoms, many cases of anal cancer can be found early because they form in a part of the digestive tract that the doctor can both reach and see easily. Unfortunately, sometimes symptoms don t become evident until the cancer has grown or spread, so it is important to be aware of the symptoms associated with anal cancer so the cancer may be caught early and without delay. Anal cancers often cause symptoms such as: Bleeding from the rectum or anus The feeling of a lump or mass at the anal opening Persistent or recurring pain in the anal area
5 Persistent or recurrent itching Change in bowel habits (having more or fewer bowel movements) or increased straining during a bowel movement Narrowing of the stools Discharge or drainage (mucous or pus) from the anus Swollen lymph nodes (glands) in the anal or groin areas These symptoms can also be caused by less serious conditions such as hemorrhoids, but you should never assume this. More than 50% of anal cancers have a delayed diagnosis or misdiagnosis because of the symptoms being mistaken for some other problem (or because the cancer did not have any symptoms). If you have any of the symptoms listed above, see your doctor or colon and rectal surgeon. How is anal cancer diagnosed? Anal cancer is usually found on examination of the anal canal because of the presence of symptoms like those listed above. It can also be found on routine yearly physical exams by a physician (rectal exam for prostate check or at the time of a pelvic exam), on screening tests such as those recommended for preventing or diagnosing colorectal cancer (for example: colonoscopy or lighted scope exam of the colon and rectum or yearly stool blood tests), or even at the time of other anal surgery (such as removal of a hemorrhoid). There are no blood tests to diagnose anal cancer at this time. Once there is concern that there may be an abnormal mass in the anus, other tests may be performed to try to diagnose what the mass is. Anoscopy, or exam of the anal canal with a small, lighted scope, may be performed to visualize any abnormal findings. If an abnormal area is confirmed, a biopsy may be performed to determine the exact diagnosis. This biopsy may be performed in the clinic with the help of a local anesthetic or may be performed in the operating room with anesthesia. If the diagnosis of anal cancer is confirmed, additional tests to determine the extent of the cancer may be recommended. These tests help to stage the cancer in the anus and, thus, help the physician determine a prognosis. How are anal cancers staged? The stage of a cancer is how advanced the cancer is both in terms of local
6 growth (size of the tumor and whether it has grown into other important structures) and distant spread ( metastasis or spread into lymph nodes or other structures in the body). Once the cancer is diagnosed, the physician may perform a number of tests to determine the stage of the cancer. Staging helps determine what the likelihood is that a person may survive from the cancer and helps to determine what treatments should be recommended. When anal cancer spreads, it tends to spread to groin lymph nodes or lymph nodes in the abdomen, or to other organs like the liver, lungs, and bones. Approximately 15% of patients who are diagnosed with anal cancer will already have spread of the cancer to the lymph nodes and 10-17% will have spread to other organs. The cancer is first staged by physical exam when the doctor examines the anal canal to assess the size of the tumor and where it is growing. They also check to see if they can feel any abnormally large lymph nodes in the groins or elsewhere around the body, and may even use a small needle to biopsy any abnormal nodes (called an FNA or fine needle aspiration). A pelvic exam should be performed in all women with anal cancer due to the association with cervical and vaginal cancers. Another test may include an ultrasound of the tumor (endorectal or endoanal ultrasound) to assess its size, growth into other structures, and whether the nodes around it look enlarged. X-ray tests like a chest X-ray and/or CT (computed tomography) scans of the pelvis, abdomen, and/or chest may be used to look for cancer spread in the body. Finally, some patients may undergo a PET (positron emission tomography) scan to look for cancer spread elsewhere in the body, especially if there are unclear areas of concern on the CT. How are anal cancers treated? Treatment for most cases of anal cancer is very effective in curing the cancer. There are 3 types of treatment used for anal cancer: Surgery: This is when an operation is performed to remove the cancer. Occasionally a very small or early tumor may be removed surgically (local excision) without the need for further treatment and with minimal damage to the anal sphincter muscles that are important for bowel control. Sometimes more major surgery to remove the anal cancer is needed, and this requires removal of the anus and rectum and the creation of a permanent colostomy (where the large bowel or colon is brought out to the skin on the belly wall and a bag is then attached with adhesive to the skin to collect the fecal matter). This is called an abdominoperineal resection or APR, and it used to be the main treatment for anal cancer until the 1970s when radiation and
7 chemotherapy were found to be successful in treating anal cancer. APR is still used when other treatments fail and the cancer persists (still present locally in the anus within 6 months of completing treatments) or recurs (cancer develops again locally in the anus over 6 months after having appeared to have been successfully treated), or when patients are not a candidate for other treatment options. Complication risks after an APR are higher, especially problems with incisional healing, after patients have had their anal cancer treated with chemotherapy and radiation. Surgery can sometimes be used to remove areas of anal cancer spread, including in groin lymph nodes and other organs, but the success of this type of surgery in curing anal cancer is not as good. Not all patients are candidates for undergoing an operation, especially if other health conditions make surgery unsafe. Radiation therapy: This is when high-dose X-rays are used to kill the cancer cells. Anal cancer is a type of cancer that is very sensitive to radiation, which means it responds well to this type of treatment (especially when chemotherapy is used in addition to the radiation). Usually the cancer is treated as well as the groin areas to try to treat any possible cancer cells that may have spread to the lymph nodes in that region. Complications from radiation may include skin damage, narrowing of the anal canal from scarring, anal or rectal ulcers, diarrhea, urgency to have bowel movements or even incontinence (inability to control the bowels), bladder inflammation (radiation cystitis), or small bowel blockages from radiation damage (radiation enteropathy or enteritis). Chemotherapy: This is when medications are given, usually intravenously (directly into a vein) in the case of anal cancer, to kill cancer cells. These treatments were found to provide an added benefit to the use of radiation and improve the likelihood of avoiding the need for surgery for anal cancer. Drugs that are commonly used for anal cancer include 5-fluorouracil or 5-FU, mitomycin C, and cisplatin. These medications have some common side effects that include nausea, vomiting, diarrhea, hair loss, decrease of the bone marrow to produce immune and blood cells, lung inflammation (pneumonitis) or lung scarring (fibrosis), or changes in nerve function of the hands and feet (peripheral neuropathy). Even death can occur from the use of these medications, but this is rare (less than 5%) and usually occurs in patients with other health conditions prior to treatment.
8 Combination therapy including radiation and chemotherapy is now considered the standard treatment for most anal cancers. This combination has shown the best long-term survival from anal cancer of up to 70-90% of patients still alive and cancer free at 5 years after completing treatments. If the cancer recurs or persists, however, surgery such as an APR can still potentially cure the cancer but not as successfully (studies show anywhere from 24% to almost 50% of patients cancer-free and alive at 5 years from salvage surgery after failed chemotherapy and radiation). The majority of patients with anal cancer are able to avoid the need for a permanent colostomy. What happens after treatment for anal cancer? Follow-up care to assess the results of treatment and to check for recurrence is very important. Most anal cancers are cured with combination therapy and/or surgery. In addition, many tumors that recur may be successfully treated with surgery if they are caught early, so patients are encouraged to report any concerning symptoms to their treating physicians right away. A careful examination of the anus with finger exam and (if needed) anoscopy by an experienced physician or colon and rectal surgeon at regular intervals is the most important method of follow-up. These exams are recommended every 3 months for the first 2 years after the diagnosis, then every 6 months for up to 5 years. Additional studies may also be recommended including CT scans, MRI scans, chest X-rays or PET scans, especially if there is concern for cancer recurrence. Some physicians use endorectal ultrasound to assess for recurrence in and around the anal canal. Conclusion Anal cancers are unusual tumors arising from the skin or lining of the anal canal. As with most cancers, early detection is associated with excellent survival. Most tumors are well-treated with combination chemotherapy and radiation. Recurrences may be treated successfully with surgery. Follow the recommended screening examinations for anal and colorectal cancer and consult your doctor or colon and rectal surgeon early when any concerning symptoms occur. What is a colon and rectal surgeon? Colon and rectal surgeons are experts in the surgical and non-surgical treatment of diseases of the colon, rectum and anus. They have completed advanced surgical training in the treatment of these diseases as well as full general surgical training. Board-certified colon and rectal surgeons
9 complete residencies in general surgery and colon and rectal surgery, and pass intensive examinations conducted by the American Board of Surgery and the American Board of Colon and Rectal Surgery. They are wellversed in the treatment of both benign and malignant diseases of the colon, rectum and anus and are able to perform routine screening examinations and surgically treat conditions if indicated to do so. Disclaimer The American Society of Colon and Rectal Surgeons is dedicated to ensuring high-quality patient care by advancing the science, prevention, and management of disorders and diseases of the colon, rectum, and anus. These brochures are inclusive, and not prescriptive. Their purpose is to provide information on diseases processes, rather than dictate a specific form of treatment. They are intended for the use of all practitioners, health care workers, and patients who desire information about the management of the conditions addressed by the topics covered in these brochures. It should be recognized that these brochures should not be deemed inclusive of all proper methods of care or exclusive of methods of care reasonably directed to obtaining the same results. The ultimate judgment regarding the propriety of any specific procedure must be made by the physician in light of all the circumstances presented by the individual patient. Citations and Selected Readings Welton ML and Raju N. Chapter 20, Anal Cancer. Chapter in Beck DE, Roberts PL, Saclarides TJ, Senagore AJ, Stamos MJ, Wexner SD, Eds. ASCRS Textbook of Colon and Rectal Surgery, 2nd edition. Springer, New York, NY; ASCRS website, 2008 Core Subjects; Dunn, KB Anal Tumors : s/ Fleshner PR, Chalasani S, Chang GJ, Levien DH, Hyman NH, Buie WD; Standards Practice Task Force, American Society of Colon and Rectal Surgeons. Practice Parameters for Anal Squamous Neoplasms. Dis Colon Rectum Jan;51(1):2-9. National Institutes of Health Surveillance Epidemiology and End Results website: American Cancer Society website:
10 author: Paul E. Wise, MD, FACS, FASCRS, on behalf of the ASCRS Public Relations Committee
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