Multimodality Approach Delivers Effective Treatment for Colorectal Cancer
Of all the cancers treated at the Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, colorectal cancer presents the greatest paradox. Despite being highly preventable and usually curable when caught early, colon and rectal cancer caused an estimated 56,000 deaths last year, according to the American Cancer Society.
“The psychosocial issues associated with colorectal cancer are different from other cancers because it involves body parts and functions people don’t really want to talk about,” says Stephen Ristvedt, PhD, an assistant professor in the psychiatry department at Washington University School of Medicine. “Embarrassment is a real impediment to people getting screenings or seeing their doctor when they have symptoms.”
As one of the top colorectal cancer programs in the country, the Siteman Cancer Center is working to change the statistics associated with the disease. Siteman, which averages 350 new colon and rectal patients a year, stresses a multimodality approach.
“We have a weekly multidisciplinary conference during which difficult cases are presented by our surgeons and discussed with radiologists, pathologists, medical oncologists, radiation oncologists and gastroenterologists,” says James Fleshman Jr., MD, professor of surgery and chief of the section of colon and rectal surgery. “Within 15 minutes, we have input from 10 experts that helps us determine the right course of treatment for each patient.”
The effectiveness of this multidisciplinary strategy is seen in results such as this: Fewer than 5 percent of the rectal cancer patients who receive multimodality therapy at Siteman have local recurrence of their cancer – compared to an average of 10 percent to 15 percent throughout the rest of the country.
Leading the way in laparoscopic surgeryAnother major strength of Siteman’s colorectal cancer program is the expertise of its surgeons, including Fleshman; associate professor Elisa Birnbaum, MD; assistant professor David Dietz, MD; Solon and Bettie Gershman Professor of Surgery Ira Kodner, MD; assistant professor Jennifer Lowney, MD; and assistant professor Matthew Mutch, MD.
Surgery serves as the backbone for treating colorectal cancer, and five of Siteman’s six colon and rectal surgeons are trained in laparoscopic surgery techniques to treat the disease. Fleshman was one of the investigators in a national study designed to develop a protocol for laparoscopic colectomy for cancer, and Washington University was the second-largest contributor to the study. At its completion last spring, the study showed minimally invasive surgery is as safe and effective as standard open surgery for most patients with cancer confined to the colon. Its advantages for patients include less pain and a shorter recovery time at home.
“We initiated the cadaver courses now used to teach fellows in training for the American Society of Colorectal Surgeons (ASCRS),” Fleshman says. “We teach laparoscopic colectomy techniques to fellows at other programs around the country and to surgeons already in practice. In addition, three of us are on the national faculties for the American College of Surgeons and the ASCRS. If you want to know what is being taught and who is performing this surgery in a particular way, we can tell you.”
The surgeons also are experts in sphincter-sparing surgical techniques that allow most patients with rectal cancer to be treated successfully without a colostomy. For patients with metastatic cancer, they have particular expertise in pelvic reoperation and work with Siteman physicians who specialize in hepatobiliary and pancreatic surgery to treat liver disease.
Chemotherapy, radiation improve outcomesIn addition to surgery, both chemotherapy and radiation therapy play vital roles in treating patients with colorectal cancer. “Data going back nearly 15 years show that chemotherapy after surgery improves the survival rate of patients with colorectal cancer by about 30 percent,” says Joel Picus, MD, associate professor of medicine. “For patients with metastatic disease, there’s abundant evidence that we can improve their survival rate and the quality of their lives.”
Over the past five years, several new drugs have increased the arsenal of chemotherapy agents available to treat patients with colorectal cancer. Picus and his colleagues are conducting a number of clinical studies to discover what combinations of these treatments have the most impact.
“These studies range from seeing if we can improve the cure rate of patients receiving chemotherapy after surgery to determining whether large tumors can be reduced in size so a surgical cure is possible,” he says. “The advances achieved over the last several years can be attributed to the willingness of patients to participate in clinical studies. For that reason, we enroll many of our patients in one or more studies so that we can learn as much as possible and so they can benefit from the latest treatment modalities.”
Chemotherapy also can make other treatments – such as concurrent radiation therapy – more effective. Although radiation therapy sometimes is used for colon cancer, its more common application is for rectal cancer.
“The rectum’s location in a narrow compartment close to large blood vessels and bones limits surgeons’ ability to take out enough tissue surrounding a tumor to ensure all of the cancer is removed,” explains Robert Myerson, MD, PhD, professor of radiation oncology. “Radiation therapy attacks any small extensions of cancer going into the side walls of the pelvis. Today, most patients with rectal cancer receive preoperative radiation with concurrent chemotherapy and then additional chemotherapy after surgery.”
One group of patients, usually those with early stage, small tumors, may receive endocavitary radiation, in which radiation is delivered directly to the tumor through a scope inserted into the rectum.
Clinical studies using positron emission tomography (PET) scans show promise for both diagnosing and treating colorectal cancer. The scans may be useful in identifying hypoxic areas of tumors, which resist chemotherapy and radiation, and in identifying rapidly growing parts of cancers.
“We’re also in an era of developing new ways to deliver radiation with greater precision,” Myerson says. “Three-dimensional treatment planning and intensity-modulated radiotherapy are two methods that will allow us to deliver higher doses to certain areas of a tumor, rather than basing dosage on a representative cross-section of the tumor.”
Genetics: Refining treatments, defining risksOther researchers at the Siteman Cancer Center are striving to improve the precision of treatment in a different arena – pharmacogenetics, the study of interactions between drug treatments and an individual’s genetic makeup. Howard McLeod, PharmD, associate professor of medicine, specializes in the burgeoning field. Along with colleagues at Washington University and Barnes-Jewish Hospital, he put together a study that uses patients’ genetic information to determine their treatments. Now about halfway completed, the study focuses on a gene that appears to be linked to how well colorectal cancer patients respond to chemotherapy and radiation. Patients with a form of the gene that decreases their chances of having a good response are given added chemotherapy.
“More than one gene is known to contribute to colorectal cancer, so a thorough pharmacogenetic approach to managing treatment will inevitably have to consider several different genes’ potential effects on treatment,” McLeod says. “Understanding the effects of these genes and other variables in patient responses to treatment is essential as new drugs become available. We have to find out information from our patients and their DNA to determine which drug will most likely give them the best results.”
Another way Siteman addresses the importance of genetics for patients with colorectal cancer is through its Hereditary Cancer Program, which offers cancer risk assessment and education to those with a family history of the disease.
“It’s vital that these families are identified because their risk of getting colorectal cancer is so high,” says Jennifer Ivanovich, MS, research instructor in surgery. “For instance, those with hereditary nonpolyposis colon cancer (HNPCC) have a risk of developing the disease that approaches 80 percent. For those with familial adenomatous polyposis (FAP), that risk is closer to 100 percent.”
Once a hereditary risk is identified, Siteman’s genetic counselors can recommend ways for families to modify their medical care. For example, members of families with FAP should start getting colonoscopies in their teens, rather than at age 50 like the majority of the population.
Counselors also can recommend further cancer screening. “People often aren’t aware other cancers are associated with the same gene mutation that causes these colorectal cancer syndromes,” Ivanovich says. “Take HNPCC — the second most common cancer associated with this syndrome is endometrial cancer. In addition to this type of education, we are able to provide patients with up-to-date information as new genes and their complications are discovered.”
