Patients with rectal cancer could be spared the brutal consequences of radiation

Rectal cancer researchers have made a huge achievement by showing in a large clinical trial that patients do just as well without radiation therapy as they do with radiation.

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, each year could give more than 10,000 patients in the United States the option of foregoing 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 other questions,” he said. “Instead of asking how cancer therapy can be intensified, they are asking if there are elements of successful treatments that can be eliminated to provide patients with a better quality of life.”

That is why researchers looked again at the standard treatment of rectal cancer.

For decades it was common to use pelvic irradiation. But the radiation puts women in immediate menopause and damages sexual function in men and women. It can also damage the gut and cause problems such as chronic diarrhea. Patients risk pelvic fractures and the radiation can cause additional cancers.

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

For colon and rectal cancer specialists, the results could be life-changing for their patients, said Dr. Kimmie Ng, co-director of the Dana-Farber Cancer Institute’s Colon and Rectal Cancer Center, who was not an author on the study.

“Now, especially with patients getting younger and younger, do they actually need radiation?” she asked. “Can we choose which patients get away without this highly 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 he added that he would like to see the patients followed for a longer period of time before concluding that the results are consistent with the two treatment options were equivalent.

The trial focused on patients whose tumors had spread to lymph nodes or tissues around the gut, but not to other organs. That subgroup of patients, whose cancer is considered locally advanced, makes up about half of the 800,000 newly diagnosed rectal cancer patients worldwide.

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

The other group received the experimental treatment, which consisted of chemotherapy first, followed by surgery. At the discretion of their doctor, another round of chemotherapy may be given. These patients received radiation only if the first chemotherapy failed to shrink their tumors — which happened in only 9 percent of cases.

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 — that’s too risky,'” said Dr. Deborah Schrag of Memorial Sloan Kettering Cancer Center, who led the trial. Those patients received standard radiation treatment.

Dr. Schrag and Dr. Ethan Basch of the University of North Carolina at Chapel Hill also took the extra step by asking patients to report on their quality of life: How much pain were they in? How tired were they? How much diarrhea? Did they have neuropathy – hands and feet that tingle and lose feeling? How was their sex life? Have the symptoms disappeared? How long did it take for the symptoms to subside?

“If 80 percent of patients are alive after five years, we want to say they are living well,” said Dr. Trestle.

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

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

“Patients now trying to decide whether to have radiation or chemotherapy can see how the subjects fared and decide which symptoms are most important to them,” said Dr. Basic.

These kinds of clinical trials are very challenging. It’s known as a de-escalation trial because it takes away standard treatment to see if it’s needed. No company will pay for such a trial. And, as the rectal cancer researchers found, even the National Institutes of Health was hesitant to support their study, arguing that the researchers could never convince enough doctors to enroll patients and that even if they did, too few patients would agree to participate, fearing it would endanger their health.

Although the NIH eventually agreed to sponsor the study, its reservations were justified — it took the researchers eight years to enroll 1,194 patients at 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 took “incredibly courageous patients” and physicians convinced that the study was ethical.

“You’re living on your conscience with this,” said Dr. Trestle.

Radiation has long been used as a way to prevent the recurrence of rectal cancer. Chemotherapy and surgery often controlled the disease, but all too often cancer in the pelvis resurfaced. Horrific effects can follow – tumors affecting the bladder, uterus, vagina.

The addition of radiation treated recurrence in the pelvis, but created its own set of problems.

As the years passed, some researchers began to question whether radiation was still necessary. Chemotherapy, surgery and medical imaging had improved and patients were diagnosed earlier, before their cancer had progressed that far.

Dr. Schrag and her colleagues decided to test the idea of ​​eliminating radiation with a pilot study involving what they called “30 courageous patients.” The results were encouraging enough to call for a wider investigation.

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

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

So for the study to succeed, he added, “surgeons, oncologists and radiation oncologists must accept the protocol.”

And, of course, so did 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 participate in the trial because, she said, “I was motivated by the hope” that she could avoid radiation and be cured.

Her hopes were fulfilled: 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. “That gave me strength,” said Ms. Peña, who is now cancer-free.

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