Rectal cancer researchers have pulled off a daunting feat, demonstrating in a large clinical trial that patients do just as well without radiation therapy as 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 every year in the United States the option to forgo a 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 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 was why researchers took another look at the standard treatment for rectal cancer, which affects 47,500 people per year in the United States (although the class of the disease in the study affects about 25,000 Americans annually).
For decades, it was typical to use pelvic radiation. But the radiation puts women into immediate menopause and damages sexual function in men and women. It also can injure the bowel, causing issues like chronic diarrhea. Patients risk pelvic fractures, and the radiation can cause additional cancers.
Yet radiation treatment, the study found, did not improve outcomes. After a median follow-up of five years, there was no difference in key measures — the length of survival with no signs that the cancer has returned, and overall survival — between the group that had received the treatment and the group that had not. And, after 18 months, there was no difference between the two groups in quality of life.
For colon and rectal cancer specialists, the results can transform their patients’ lives, said Dr. Kimmie Ng, a co-director of the colon and rectal cancer center at the Dana-Farber Cancer Institute, who was not an author of the study.
“Now, especially, with patients skewing younger and younger, do they actually need radiation?” she asked. “Can we choose which patients can get away without this extremely toxic treatment that can lead to lifelong consequences, such as infertility and sexual dysfunction?”
Dr. John Plastaras, a radiation oncologist at the Penn Medicine Abramson Cancer Center, said the results “certainly are interesting,” but he added that he would like to see the patients followed for a longer time before concluding that outcomes with the two treatment options were equivalent.
The trial focused on patients whose tumors had spread to lymph nodes or tissues around the bowel, but not to other organs. That subset of patients, whose cancer is deemed locally advanced, constitutes 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 the standard treatment, a long and arduous ordeal that began with radiation, followed by surgery, and then, after the patients recovered from surgery, chemotherapy at their doctor’s discretion.
The other group received the experimental treatment, which consisted of chemotherapy first, followed by surgery. At their doctor’s discretion, another round of chemotherapy could be given. These patients had radiation only if the initial chemotherapy failed to shrink their tumors — which happened just 9 percent of the time.
Not all patients were eligible for the trial. The researchers excluded those whose tumors seemed too dangerous for only chemotherapy and surgery.
“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 the standard radiation treatment.
Dr. Schrag and Dr. Ethan Basch of the University of North Carolina at Chapel Hill also took the extra step of asking patients to report on their quality of life: How much pain were they in? How much fatigue did they have? How much diarrhea? Did they have neuropathy — hands and feet that tingle and lose feeling? How were their sex lives? Did symptoms resolve? How long did it take for symptoms to wane?
“When 80 percent of patients are alive after five years, we want to say they are living well,” Dr. Schrag said.
The two groups had different symptoms at different times. But after two years, there was a trend toward a 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.
Early on, those who had chemotherapy without radiation had more nausea, vomiting and fatigue. A year later, Dr. Basch said, the radiation group was suffering more, with fatigue, impaired sexual function and neuropathy.
“Now patients trying to decide if they want radiation or chemotherapy can see how those in the trial fared and decide which symptoms matter most to them,” Dr. Basch said.
This sort of clinical trial is very challenging. It is known as a de-escalation study because it takes away a standard treatment to see if it’s needed. No company will pay for such a trial. And, as the rectal cancer researchers discovered, even the National Institutes of Health was hesitant to support their study, arguing that the 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 risk their health.
While the N.I.H. eventually agreed to sponsor the study, its misgivings 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 required “unbelievably courageous patients” and doctors who were confident that the study was ethical.
“You live with this on your conscience,” Dr. Schrag said.
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 emerged again in the pelvis. Horrific effects could follow — tumors that eroded the bladder, the uterus, the vagina.
The addition of radiation addressed recurrence in the pelvis but caused its own set of problems.
As years went by, 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 as advanced.
Dr. Schrag and her colleagues decided to test the idea of eliminating radiation with a pilot study with what she called “30 courageous patients.” The results were encouraging enough to make the case for a broader 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 succeed, he added, “surgeons, oncologists and radiation oncologists all have to buy into the protocol.”
And so, of course, did patients like Awilda Peña, 43, who lives in Boston. She found out she had rectal cancer when she was 38.
“I could not believe it,” she said.
She agreed to participate in the trial because, she said, “I was motivated by hope” that she could avoid radiation and be cured.
Her hope was fulfilled: She was randomized to the group that did not have radiation and was reassured when the researchers told her they would be monitoring her closely for five years. “That gave me strength,” said Ms. Peña, who is now cancer free.
“You are not just doing this for yourself,” she said. “You are helping the best scientists and researchers. You take a risk but you are contributing something.”