Rectal cancer patients may not need radiation therapy, study finds

Rectal cancer researchers have achieved a daunting feat, demonstrating in a large clinical trial that patients do just as well without radiation therapy as they do with it.

The results, revealed Sunday at the annual meeting of the American Society of Clinical Oncology and in a paper in the New England Journal of Medicine, could give more than 10,000 patients each year in the United States the chance to forgo cancer treatment that can have serious side effects.

The study is part of a new direction for cancer 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. “Instead of asking how cancer treatment can be intensified, they ask if there are elements of effective treatments that can be eliminated to provide patients with a better quality of life.”

That’s why researchers have re-examined the standard treatment for rectal cancer.

For decades, it was common to use pelvic radiation therapy. But radiation puts women into immediate menopause and damages sexual function in both men and women. It can also injure the gut, causing problems like chronic diarrhea. Patients risk pelvic fractures and radiation can cause other cancers.

Still, radiation therapy, according to the study, did not improve outcomes. After a median follow-up of five years, there was no difference in key measures – time to survival without signs of cancer recurrence and overall survival – between the group that received the treatment and the group that did not. had not done. And, after 18 months, there was no difference between the two groups in terms of quality of life.

For colon and rectal cancer specialists, the results can be life-changing for their patients, said Dr. Kimmie Ng, co-director of the colon and rectal cancer center at the Dana-Farber Cancer Institute, who was not one of the authors of the study.

“Now, especially, with patients getting younger and younger, do they really need radiation therapy?” she asked. “Can we choose which patients can get away with this extremely toxic treatment that can lead to lifelong consequences, such as infertility and sexual dysfunction?”

Dr. John Plastaras, a radiation oncologist at Penn Medicine Abramson Cancer Center, said the results “are certainly interesting,” but added that he would like to see patients followed longer before concluding that results with both options of treatment were equivalent.

The trial involved patients whose tumors had spread to lymph nodes or tissue around the intestine, but not to other organs. This subset of patients, whose cancer is considered locally advanced, constitutes approximately half of the 800,000 patients with newly diagnosed rectal cancer worldwide.

In the study, 1,194 patients were randomly assigned to one of two groups. One group received the standard treatment, a long and arduous ordeal that began with radiation therapy, followed by surgery and then, once the patients recovered from surgery, chemotherapy at their doctor’s discretion.

The other group received the experimental treatment, which consisted first of chemotherapy, followed by surgery. At their doctor’s discretion, another round of chemotherapy may be given. These patients only received radiation therapy if the initial chemotherapy failed to shrink their tumors, which happened only 9% of the time.

Not all patients were eligible for the trial. The researchers excluded those whose tumors seemed too dangerous for chemotherapy and surgery alone.

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

Dr. Schrag and Dr. Ethan Basch of the University of North Carolina at Chapel Hill also took it a step further by asking patients to report on their quality of life: how much pain did they suffer? How tired were they? How much diarrhea? Did they suffer from neuropathy – hands and feet that tingled and lost all sensation? How were their sex lives? Have the symptoms disappeared? How long did it take for the symptoms to go away?

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

Both groups had different symptoms at different times. But after two years, there was a trend toward better quality of life in the group that received chemotherapy. And on one measure – male and female sexual function – the chemotherapy group clearly fared better.

At first, those who received chemotherapy without radiation therapy had more nausea, vomiting and fatigue. A year later, Dr. Basch said, the radiation therapy group suffered more, with fatigue, impaired sexual function and neuropathy.

“Now patients trying to decide whether they want radiation or chemotherapy can see how trial participants behaved and decide which symptoms are most important to them,” Dr. Basch said.

This type of clinical trial is very difficult. This is a de-escalation study because it removes standard treatment to see if it is needed. No company will pay for such a lawsuit. And, as rectal cancer researchers found, even the National Institutes of Health were hesitant to support their study, arguing that investigators would never persuade enough doctors to enroll patients and that even if they did, too few patients would agree to join, fearing it would put their health at risk.

While the NIH eventually agreed to sponsor the study, its reluctance was justified — it took researchers eight years to recruit 1,194 patients from 200 medical centers.

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

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

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

Radiation therapy has long been used as a way to prevent the recurrence of rectal cancer. Chemotherapy and surgery often brought the disease under control, but all too often the cancer returned in the pelvis. Horrific effects could ensue – tumors that erode the bladder, uterus, vagina.

Adding radiation treated the recurrence in the pelvis but caused its own set of problems.

Over the years, some researchers began to wonder if radiation was still necessary. Chemotherapy, surgery and medical imaging had improved and patients were being diagnosed earlier, before their cancer was so advanced.

Dr. Schrag and her colleagues decided to test the idea of ​​eliminating radiation with a pilot study with what she called “30 brave patients.” The results were encouraging enough to argue for a larger study.

Dr Venook said the study was a triumph in more ways than one.

“In rectal cancer, there are schools of thought,” he said. “People think they know what the right answer is.”

So, for the study to be successful, he added, “surgeons, oncologists and radiation oncologists must all adhere to the protocol.”

And the same goes, of course, for patients like Awilda Peña, 43, who lives in Boston. She found out she had rectal cancer when she was 38.

“I couldn’t believe it,” she said.

She agreed to take part in the trial because, she says, “I was motivated by the hope” that she could avoid radiation and be cured.

Her hope came true: she was randomized to the group that had no radiation and was reassured when the researchers told her they would be watching her closely for five years. “It gave me strength,” said Ms Peña, who is now cured of cancer.

“You’re not just doing this for yourself,” she said. “You help the best scientists and researchers. You take a risk but you bring something.