Treatments for late-stage colorectal cancer patients are a case in point of how new, targeted therapies help people live longer.
The changing treatments offered to patients with stage 4 colorectal cancer — the third most common type of cancer in the United States — paint a picture of how advances in cancer medicine affect patients with deadly cancers.
People with stage 4 colorectal cancer have a primary tumor in their colon or rectum as well as metastatic cancer growths elsewhere, most often on the liver. Previously, the standard treatment was to remove the primary tumor before administering chemotherapy. (It’s rare that all of the cancer could be removed surgically by the time the disease has progressed to stage 4.)
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From a patient’s viewpoint, this approach made sense.
“There are some patients, when faced with the diagnosis, their first response is, ‘Get it out,’” said Dr. George Chang, chief colorectal oncological surgeon at the University of Texas MD Anderson Cancer Center in Houston.
But as new, targeted medications have become available, doctors are increasingly leaving the primary tumors and beginning treatment with chemotherapy. This approach first started in 2004 when bevacizumab (Avastin) entered the market.
According to a study Chang published this week in JAMA Surgery, this new approach has led to higher survival rates: In 2000, just 12 percent survived a year. Now 17 percent survive one year and 12 percent survive at least five years.
At first glance, the statistics suggest that the surgery was a bad idea. But that’s not the real story, according to Chang and to Dr. Mark Welton, professor and colorectal surgeon at Stanford University School of Medicine.
Rather, the surgery was being overused. As long as the primary colorectal tumors aren’t causing bleeding or digestive blockages, they aren’t responsible for a patient’s death. Death from stage 4 colorectal cancer happens when the cancer spreads to the liver or lungs.
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From a medical perspective, it never made much sense to remove most tumors first. Surgery takes a big toll on a person’s immune system and delays the start of chemotherapy by weeks or months as patients recover, Welton told Healthline.
“The reason that the surgery was done so often is that you had nothing else to do; the chemo didn’t work. You take a 40 year-old guy with two kids at home, and you go, ‘All we can do is take it out and hope that you’re one of the guys who will live,’” he said.
With better drugs, doctors can now treat the deadly metastatic cancer first; and then, if things go well, remove the primary tumor.
In 2001, almost 70 percent of patients had their primary tumors removed. This includes those with blockages and bleeding and those without. In 2010, just 57 percent did, Chang’s analysis shows.
“Because the other treatments are good, doctors felt more comfortable not to operate,” Chang said.
Chang thinks that only about 30 percent of patients really need to have surgery before chemotherapy, so some are still likely being overtreated.
His analysis of more than 60,000 patients from 1998 to 2010 reveals that doctors are more likely to remove a primary tumor when the surgery is technically easier to perform. For example, women, who have a more surgically accessible pelvic area, are more likely to undergo surgery than men. If the choice were based entirely on who needs the surgery most, this kind of bias wouldn’t show up in the numbers.
Opting for chemotherapy first has become the standard approach at major cancer centers Welton said. But “it takes a long time for what’s known in specialty centers to disseminate out to the average population,” he added.
The rise of personalized and targeted cancer treatments has made it possible to see surgeries for colorectal cancer as overtreatment and to spur doctors to stop using this old-fashioned method.
“The inflexion point in the trend is in 2001. And what happened in 2001 was that Avastin became available,” said Welton, pointing to the crisscrossed lines of declining surgeries and increasing survival rates in Chang’s study. Avastin hadn’t yet gained approval from the Food and Drug Administration in 2001, but it was getting attention for promising results in clinical trials.
With Avastin came two similar drugs: cetuximab (Erbitux) and panitumumab (Vectibix). The drugs all mimic the activity of immune antibodies by attacking a specific receptor on tumor cells. Avastin goes after vascular endothelial growth factor while cetuximab and panitumumab go after epidermal growth factor.
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Just today, a study released from Dana-Farber Cancer Institute argued that vitamin D can also boost the body’s immune response against cancer.
Immunotherapy drugs have risen hand-in-hand with screening methods that let doctors determine in advance which patients’ tumors have the receptors. Patients who respond well to chemotherapy regimens then become candidates for surgery, because they might actually survive their cancers. Patients who are unlikely to respond well to the targeted drugs don’t get them.
Putting chemotherapy first allows it to serve as a kind of screening process to find out which patients may benefit most from surgery.
“We can see how they respond and select out who’s a good candidate for surgery,” Welton said. “We’re able to tailor our surgeries.”
For patients, cancer research on new genetic markers or drugs that target very specific types of tumors can seem overly abstract. But the way they’re playing out in colorectal cancer shows that these advances are leading to longer life expectancies for people with advanced cancers.
