Advances in the management of colorectal cancer
By Eleanor Mayfield
Laura Hauser was 34, a busy mom of a five-year-old and a seven-year-old, with a full-time job and a business on the side.
“When I saw my OBGYN for my annual checkup, I mentioned that I’d noticed blood in my stool,” she recalls. “She pushed me to get a colonoscopy, just for peace of mind. So I did, and after I woke up the doctor came in and said, ‘We found something—we think it’s cancer.’”
Worse news arrived just days before she was scheduled to have surgery: the cancer had spread to her liver.
Laura, of Wesley Chapel, Florida, near Tampa, is an atypical colorectal cancer patient. Of the more than 132,000 people in the United States whom the American Cancer Society estimates will receive a diagnosis of colorectal cancer (CRC) in 2015, nine out of 10 will be 50 or older. But while rates of CRC have been steadily declining in that age group—most likely because of effective screening— for reasons that aren’t clear, more people ages 20 to 49 are being diagnosed with the disease.1,2
In another sense, Laura may represent a new face of advanced CRC— that of a chronic condition that many people live with for years. Six years after her diagnosis, after multiple surgeries and rounds of chemotherapy, a stint in a clinical trial, and more chemotherapy, Laura is not letting the disease slow her down—and she is not alone. “I’ve met people who are 12 years out from a Stage IV CRC diagnosis,” she says.
Advances such as new medications, minimally invasive surgical techniques, and personalized treatment regimens are helping CRC survivors live longer and better.
“The era of one-size-fits-all care for CRC is over,” says Steven Nurkin, MD, assistant professor of oncology at Roswell Park Cancer Institute in Buffalo, New York. “No two patients are the same, and every patient should expect to be offered treatment options appropriate to the characteristics of their disease.”
Dr. Nurkin specializes in CRC surgery using small instruments and incisions that, he says, result in less pain and a faster recovery without tradeoffs in survival or risk of cancer recurrence. Moreover, with advances in techniques such as sphincter-preserving surgery, says Dr. Nurkin, most patients should not need a permanent colostomy.
New drugs and new understanding of how to target treatment to specific features of patients’ tumors are transforming chemotherapy for CRC, says Wells Messersmith, MD, associate professor of medical oncology at the University of Colorado Cancer Center in Aurora.
“Usually, we give a drug to 100 people, knowing it will help at most 10 or 20 of them,” says Dr. Messersmith. “Now, at least with some drugs, we can identify the 10 or 20 patients most likely to benefit from treatment based on their tumors’ molecular and genetic characteristics.”
Powerful new tests that scan tumor samples for the presence of hundreds of molecular or genetic changes help doctors match patients with treatments more likely to work and avoid those that probably will not (see sidebar “Resources, page 42”).
Taken together these advances provide reasons for hope for those facing a CRC diagnosis.
When Laura’s tumor showed signs of growth after several months in a clinical trial (TAS-102 trial), her doctor switched her to a standard chemotherapy regimen plus a recently approved drug, Zaltrap® (ziv-aflibercept). Her children, now 11 and 13, and her husband, Richard, keep her going, she says. In early 2015, hooked up to her chemo pump, she celebrated her fortieth birthday at a party with family and friends.
“I wasn’t happy about being on chemo at my birthday party,” she says, “but I also felt so grateful to have made it to that milestone.”
Colorectal Cancer Treatment Primer
Treatment advances are encouraging, but the volume of information about tests, treatments, and trials can be overwhelming. Here is what you should know if you or someone you love is facing CRC today.
Alphabet Soup: Abbreviations You Need To Know
CAPIRI or XELIRI
A combination of the drugs Xeloda® (capecitabine) and Camptosar® (irinotecan), used to treat advanced colorectal cancer
CAPOX or XELOX
A combination of the drugs Xeloda (capecitabine) and Eloxatin® (oxaliplatin), used to treat advanced colorectal cancer
A substance in cells that passes genetic information from parents to children
A protein on the surface of some cells that stimulates the cells to divide. Many cancer cells have too much EGFR, which fuels their growth. Drugs such as Erbitux® (cetuximab) and Vectibix® (panitumumab) try to stop cancer cell growth by blocking EGFR.
A combination of folinic acid (or leucovorin), fluorouracil, and irinotecan, used to treat advanced colorectal cancer
A combination of folinic acid (or leucovorin), fluorouracil, and oxaliplatin, used to treat advanced colorectal cancer
A gene that may cause cancer when mutated. It makes the KRAS protein, which among other functions helps cells grow. A normal (not mutated) KRAS gene is called “wild type.” Research has shown that the EGFR-blocking drugs Erbitux and Vectibix do not work for colorectal cancer patients whose tumors have a KRAS mutation.3
A gene similar to KRAS. A recent study found that Erbitux and Vectibix are ineffective against tumors that have a normal KRAS gene but a mutation in NRAS4
A protein that stimulates blood vessels to form. Tumors need blood vessels to grow. Some drugs try to stop cancer cell growth by blocking VEGF.
New Drugs for Advanced CRC
Newly Diagnosed: Questions to Ask Your Doctor
Cancer Clinical Trials: Separating Fact from Myth
Without clinical trials there would be no advances in cancer treatment. Yet, according to the National Cancer Institute, for every 100 patients with cancer who could enroll in a clinical trial, only about three do so.9
Many people have misconceptions about cancer clinical trials. Here are the facts.
Are clinical trials a last resort?
Clinical trials are an option for advanced cancer when standard treatments have not worked, but they are offered for every stage of cancer as well as for cancer prevention.
Are the treatments offered in clinical trials unproven?
All new treatments are unproven before they are tested in clinical trials. Every potential new treatment goes through extensive lab testing before being tried in people. Every trial follows a detailed plan, and doctors watch participants closely for adverse effects.
Are patients in clinical trials “guinea pigs”?
The “informed consent” process explains the reasons for the trial, the potential risks and benefits, and your rights. The medical team will keep you informed about what happens during the trial. In one survey 97 percent of clinical trial participants said the care they received was very good and they were treated with dignity and respect.10
Can I leave a trial if I change my mind?
You can change your mind and leave a trial at any time. Your doctor will continue to treat you with the best available standard treatment.
Will I get a sugar pill or no treatment?
In most trials you will receive either the best standard treatment or a new treatment that might be better. Sometimes you may receive standard treatment plus a new treatment. Placebos may be used when no standard treatment exists or in cases of advanced cancer when all standard treatments have failed.
Will my insurance cover it?
Many states require health insurers to cover the costs of treatment in clinical trials. Medicare has covered these costs since 2000. Certain conditions usually apply. Learn more at cancer.gov/clinicaltrials/learningabout/payingfor/insurancecoverage.
Will I have to travel far from home?
In many clinical trials, you can receive treatment at your local hospital or your doctor’s office.
“I Consider Myself Very Lucky.”
Emily Gruttadauria was newly married and about to leave on her honeymoon when she noticed blood in her stool. At first she blamed a recurrence of hemorrhoids, but when the problem persisted, she saw her doctor, who recommended a colonoscopy.
The colonoscopy found a polyp so large only part of it could be removed. “They told me the biopsy showed cancerous cells,” Emily recalls. She was 27 years old.
At Roswell Park Cancer Institute in Buffalo, near Emily’s home in Cheektowaga, New York, a second biopsy showed a Stage 0 rectal cancer—the earliest stage, when the tumor is confined to the inner layer of the rectum.
After surgery to remove the rest of the polyp, Emily underwent genetic testing that showed she has Lynch syndrome, a condition that runs in families and elevates the risk of developing colorectal and other cancers early in life. Subsequent testing revealed that her father, brother, and paternal grandmother also have the syndrome.
“We all need to have regular colonoscopies to ensure that any polyps we get don’t develop into cancer,” says Emily, who is now 29 and planning to start a family with her husband, Brandon. Once they have had children, she can opt for surgery to remove her ovaries to reduce her risk of ovarian cancer, also associated with Lynch syndrome.
Screening for Colorectal Cancer: What You Need To Know
CRC “is probably the only cancer for which we have a screening test that not only catches the disease early but can potentially prevent it,” says Deborah Fisher, MD, a gastroenterologist and associate professor of medicine at Duke University School of Medicine in Durham, North Carolina.
She is talking about colonoscopy, considered the gold standard screening test for CRC. In addition to detecting CRC at an early stage, when about 90 percent of cases are curable, a colonoscopy also finds polyps—growths that could develop into cancer. Abnormalities found during a colonoscopy can usually be removed then and there.
Who should be screened for colorectal cancer?
All healthy adults ages 50 to 75 who do not have symptoms or a family history of CRC should be screened. If you have a family history, talk with your doctor about when to start screening—it might be earlier than age 50.
If you have symptoms—such as visible blood in your stool, unintended weight loss, diarrhea that lasts longer than a few days—see your doctor right away. You need diagnostic testing, not screening.
Do I have to have a colonoscopy?
No, there are several effective screening tests for CRC. For some you see a doctor; others you do at home. The bad news is that all tests have a “yuck” factor; and if a non-colonoscopy test finds anything abnormal, you’ll need a colonoscopy to check it out.
Can I wait until there is a blood test?
Researchers are working on a blood test for CRC, but it is unlikely that one will be on the market anytime soon. A blood test will need to be at least as good as existing tests, which—despite the yuck factor— work pretty well.
Which test is right for me?
The right test for you is the one you will actually get done. And remember, no CRC screening test is “one and done.” You need to be retested at recommended intervals, which vary depending on the test.
What else can I do to prevent CRC?
Eat your vegetables, maintain a healthy weight, get regular exercise, and don’t smoke. Consider eating more fish and less meat. In a recent study, people who ate fish at least once per month and meat less than once per month reduced their risk of CRC by about 40 percent.11
If you take aspirin to help reduce your risk of heart attack or stroke, it will also reduce your risk of CRC, although you will still need a CRC screening test. Taking aspirin solely to reduce CRC risk is not recommended because aspirin heightens the risk of bleeding. Some studies suggest that high blood levels of vitamin D may reduce CRC risk, but the evidence is not clear enough to recommend taking vitamin D supplements to prevent CRC.
What are the pros and cons of CRC screening tests?
See the following chart.
|Tests Done by a Doctor|
|“Virtual Colonoscopy”(also called CT colonography)How Often?
|Flexible SigmoidoscopyHow Often?
|Tests You Do At Home|
|Fecal Occult Blood Test(also called Guaiac [“gwy-ack”] test)How Often?
|Fecal Immunochemical TestHow Often?
|Stool DNA TestHow Often?
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Colon Cancer Alliance
Patient advocacy organization
Toll-free helpline: (877) 422-2030
Detailed guide from the American Cancer Society
Colorectal Cancer Risk Assessment Tool
Online tool that helps estimate the risk of developing CRC
CRC screening choices explained in plain English
Supported by the American Society for Gastrointestinal Endoscopy
Genetic Testing For Cancer: What You Need To Know
Information from the American Cancer Society about testing for inherited cancer risk