Colorectal cancer: patients can avoid radiation – 06/11/2023 – Health

Researchers studying colorectal cancer have just accomplished a remarkable feat, demonstrating in a large clinical trial that patients do just as well without radiotherapy as they do with it.

Revealed Sunday at the annual meeting of the American Society of Clinical Oncology and in an article published in the New England Journal of Medicine, the results could give more than 10,000 patients a year in the United States the option of giving up a cancer treatment that can have serious side effects.

The study is part of a new direction being taken by oncology researchers, said Dr. Eric Winer, who is president of the oncology organization but was not involved in the trial.

“Now that cancer treatments have improved, researchers are starting to ask different questions,” he said. “Rather than asking how cancer therapy can be scaled up, they are asking whether there are elements of successful treatments that can be eliminated to provide a better quality of life for patients.”

That’s why the researchers took another look at standard treatment for colorectal cancer, which affects 47,500 people a year in the United States (but the class of disease analyzed in the study affects 25,000 Americans a year).

For decades, the practice involved the use of pelvic radiation. But radiation puts women into immediate menopause and impairs sexual function in both men and women. It can also cause intestinal damage, causing problems such as chronic diarrhea. Patients are at risk for pelvic fractures, and radiation can cause additional cancers.

However, as the study found, radiotherapy did not produce better results. After a median follow-up of five years, there was no difference in the main measures — the time spent surviving without signs of cancer returning and overall survival — between the group that received treatment and the group that did not. And, after 18 months, there was no difference between the two groups’ quality of life.

For colon and colorectal cancer specialists, the results could be life-changing for patients, said Kimmie Ng, co-director of the colon and colorectal cancer center at the Dana-Farber Cancer Institute. She is not one of the study’s authors.

“Especially today, when patients are getting younger and younger, do they really need radiotherapy?” she asked. “Can we choose which patients can recover without this highly toxic treatment, which can cause lifelong consequences like infertility and sexual dysfunction?”

John Plastaras, an oncologist at Penn Medicine Abramson Cancer Center who uses radiotherapy, called the results “certainly interesting” but said he would like to see patients followed longer before concluding that the results with the two treatment options are equivalent.

The trial focused on patients whose tumors had spread to lymph nodes or the tissues around the intestines, but not to other organs. This subset of patients, whose cancer is considered locally advanced, constitutes about half of the 800,000 patients worldwide with newly diagnosed colorectal cancer.

In the study, 1,194 patients were randomly divided into two groups. One received standard care, a long and arduous process that begins with radiotherapy, followed by surgery, and then, after recovery from surgery, chemotherapy, at the doctor’s discretion.

The other group received the experimental treatment, which consisted of chemotherapy first, followed by surgery. Another round of chemotherapy could be given after surgery, at the doctor’s discretion. These patients only received radiotherapy if the initial chemotherapy had not caused the tumors to shrink, something that only happened in 9% of cases.

Not all patients were able to participate in the trial. The researchers excluded those whose tumors seemed too dangerous to be treated with chemotherapy and surgery alone.

“We said ‘no, it’s too risky,'” said Deborah Schrag of Memorial Sloan Kettering Cancer Center, who led the trial. These patients received radiotherapy, according to the standard practice.

Schrag and Ethan Basch of the University of North Carolina at Chapel Hill also asked patients to report their quality of life. How much pain were they suffering? How much fatigue? How much diarrhea? Did they have neuropathy—tingling and numbness in the feet and hands? How was your sex life? Did the symptoms resolve? How long did it take for the symptoms to subside?

“When 80% of patients are alive after five years, we mean they are living well,” said Schrag.

The two groups showed different symptoms at different times. But after two years, there was a trend towards a better quality of life in the chemotherapy group. And on one thing—male and female sexual function—the chemotherapy group did clearly better.

At first, patients who received chemotherapy without radiation had more nausea, vomiting and fatigue. A year later, Basch said, the group that had radiotherapy was suffering more, with fatigue, impaired sexual function and neuropathy.

“Now patients trying to decide whether they want radiotherapy or chemotherapy can see how the patients who participated in the trial did and decide which symptoms bother them the most,” said Basch.

This type of clinical trial is challenging. It’s known as a de-escalation study because it pulls out a standard treatment to see if it’s needed. No company will pay for an essay like this. And, as the colorectal cancer researchers discovered, even the National Institutes of Health (NIH) was hesitant to support their study, arguing that the researchers could never persuade enough doctors to enroll their patients and that even If doctors did, few patients would agree to participate, for fear of putting their health at risk.

When the NIH finally agreed to sponsor the study, their fears proved justified: It took researchers eight years to enlist 1,194 patients from 200 medical centers.

“It was very difficult,” said Alan Venook of the University of California San Francisco, who helped design the study.

Schrag noted that it took “incredibly brave patients” and doctors who sincerely believed the study was ethical.

“You live with that on your conscience,” Schrag said.

For Venook, the study was a victory in more ways than one.

“There are different schools of thought regarding colorectal cancer,” he said. “People think they know what the correct answer is.”

Thus, for the study to be successful, “surgeons, oncologists and radiology oncology practitioners had to adhere to the protocol”.

And it also required compliance from patients, like Awilda Peña, 43, of Boston. She found out she had colorectal cancer when she was 38.

“I didn’t believe it,” she commented.

Peña agreed to participate in the trial “motivated by the hope” that she would be able to heal without radiotherapy.

Her hope came true: she was randomly placed in the group that didn’t have radiotherapy and was reassured when the researchers told her they would monitor her closely for five years. “It gave me strength,” said Peña, who is now cancer-free.

“You’re not just doing this for yourself. You’re helping the best scientists and researchers. You’re taking a risk, but you’re contributing to something.”

^{Translated by Clara Allain}