‘Less is more’ approach is changing cancer treatment for some patients

It’s a worry almost all of Dr. Ursina Teitelbaum’s colorectal cancer patients have: How severe are the side effects of radiation therapy? The treatment, though effective at fighting cancer, could cause diarrhea and fatigue in the short term, as well as fertility problems in the long term.

But more than anything, people want to survive cancer, and emerging research suggests that reducing the intensity of such treatments may not affect patients’ chances of survival.

With that clearer data, more oncologists appear to be scaling back the use of aggressive or uncomfortable therapies in consideration of their patients’ quality of life, a move described as de-escalation.

For instance, for rectal cancer, chemotherapy, radiation therapy and surgery are usually the three main components of treatment plans – unless the person qualifies for a de-escalation approach, in which one or more of those therapies might be safely omitted.

“I tell patients, ‘I want you to live longer, but I also want you to live better,’ ” said Teitelbaum, a medical oncologist at Penn Medicine who specializes in pancreatic and colorectal cancer.

“Sometimes, we can give a two- or three-month chemo holiday. Patients love a chemo holiday, and then we can re-intensify again and not compromise the patient’s outcome at all. Basically, this can spare side effects,” she said. “So what can we de-escalate in the concentration of your therapy so that you not only live longer but you feel better? That is the goal.”

She added that her patients are often “very eager” for a de-escalation approach.

‘Less is more sometimes’

When Alex Wood was diagnosed with cancer about three years ago, his immediate thought was to do anything and everything he could to treat it.

“You don’t think as much about the quality of life piece,” said Wood, who lives in Pennsylvania.

He had what he describes as a “normal” treatment plan for colorectal cancer: He underwent about eight rounds of chemotherapy and then surgery to remove the tumor. That was in June 2020. But about six months later, additional traces of cancer were detected in Wood’s liver and lungs.

“So I’ve had, since that, six surgeries basically to remove those nodules. And I’ve had I think 50 rounds of chemo, something in that ballpark, as well as radiation,” Wood said.

During all those bouts of chemotherapy IV infusions and radiation, the 46-year-old rock climbing enthusiast experienced extreme nausea and fatigue.

To ease those side effects, Teitelbaum, who was treating him at Penn Medicine, proposed a de-escalation approach that would eliminate two drugs from his three-drug regimen. Wood agreed, and he is now doing well and back to regularly climbing at the gym.

“Over about a probably four- to five-month period, we were able to gradually back off on the medications so that now I’m just on one, and it has greatly reduced the side effects to the point that I’m able to exercise the day after I get the infusion now,” Wood said. “From what I understand, 20 years ago, people really were not able to live their lives while they were undergoing treatment.”

Teitelbaum is just one of many oncologists practicing a balancing act: de-escalating the intensity of cancer therapies while ensuring that patients still are receiving optimal treatment.

“We’re fine-tuning things. We’re learning when we can give less,” she said. “Less is more sometimes, because there’s a lot of toxicities with all of these treatments.”

Doing more harm than good?

De-escalation describes when optimal care could be achieved with less treatment rather than more. A growing body of research – including several studies presented in June at the annual meeting of the American Society of Clinical Oncology – suggests that the approach could have benefits for people with certain cancers.

One late-stage trial of women with cervical cancer showed that they had a low risk of cancer progressing after a simple hysterectomy, in which only their uterus and cervix were surgically removed. The results were similar to those after a more aggressive radical hysterectomy, in which surrounding parts of the cervix, part of the vagina and some tissues and ligaments around the area are removed, as well as the uterus.

A separate study on the treatment of rectal cancers found that among more than 1,000 patients, those who received chemotherapy alone before surgery had similar outcomes of survival and recurrence as those who had chemotherapy plus radiation.

The findings suggest that, in some cases, rectal cancer patients may be able to skip radiation, which can have side effects in the area being treated, such as fertility problems after radiation therapy to the pelvis.

“We’ve used chemoradiation since 1990 because it’s been remarkably effective at reducing the rate of local recurrences in the pelvis,” gastrointestinal oncologist Dr. Deb Schrag, chair of the Department of Medicine at Memorial Sloan Kettering Cancer Center and first author of that study, said in a news release in June.

“My colleagues and I began seeing more young women with rectal cancer who were devastated – not just because they had cancer but because the standard treatment we had to offer them would mean that they would not be able to carry a pregnancy to term,” Schrag said. “That was one of the big reasons we looked for a way to help patients and to see if we could achieve favorable outcomes without the uniform application of radiation.”

The study is just one example of de-escalation and how in some cases “less is more,” said Dr. Paul Oberstein, a medical oncologist at NYU Langone Perlmutter Cancer Center, who was not involved in that research.

“This is a perfect example of less is more. One group got two things – surgery and chemo – and the other group got three – surgery, chemo and radiation – and you’re able to avoid the potential complications of the radiation because you just left it out. So we think that’s a really favorable trend,” Oberstein said.

“The good news is that there’s no increased risk of death, which is obviously the major endpoint, or with a local recurrence of the cancer coming back in that area in the rectum. But we don’t know for sure in 10 years from now or 20 years from now whether we’re going to see a signal,” he said. “We need to keep following this.”

Another study suggests that, for certain people with early breast cancer, a simpler treatment of targeted drug therapies was associated with improved survival and was comparable to when the treatment is given with chemotherapy.

And earlier this year, results from a long-running study in the United Kingdom showed that men who partnered with their doctors to keep a close eye on their low- to intermediate-risk prostate tumors – a strategy called surveillance or active monitoring – avoided the life-altering complications such as incontinence and erectile dysfunction, but were no more likely to die of their cancers than men who had surgery to remove their prostate or who were treated with hormone blockers and radiation.

“The trouble in cancer care is, the medicine can definitely give people side effects,” damaging healthy cells or organs, said Dr. Tatjana Kolevska, medical director for the Kaiser Permanente National Cancer Excellence Program.

“In cancer, the fear and anxiety are huge, so it’s very frequent that we may use more, which could make people very sick,” she said. “We want to try everything to treat a patient, but in some cases, too much of an aggressive treatment could do more harm than good.”

‘Not all patients want exactly the same thing’

For years, scientists have called for more research into the risks and benefits of de-escalation. In 2014, a paper published in the Cochrane Database of Systematic Reviews analyzed data on de-escalation protocols for the treatment of mouth and throat cancers associated with human papillomavirus (HPV) infections. The data showed that there was “insufficient high-quality evidence for, or against, de-escalation of treatment” for these cancers.

But it remains well-known that HPV-related head and neck cancers are much more curable than the head and neck cancers that are not associated with the virus, said Dr. Lori Wirth, medical director of the Center for Head and Neck Cancers at Mass General Cancer Center in Boston, who was not involved in the Cochrane review.

“So the patients who have HPV-related disease would have a somewhat different approach compared to those patients who have HPV-negative disease,” Wirth said, referring to a personalized approach to de-escalation.

“One of the things that we’re doing now is trying to get smarter to identify who those patients are who can be de-escalated and they’ll still be fine,” she said. “Not all patients want exactly the same thing, and I think our job as clinicians is to really make sure that when there isn’t just one cookie-cutter approach, when there are options, that we’ve really helped the patient explore what those options are and made sure that we’re heading down a path that makes the most sense for that one particular patient.”

Younger cancer patients have shown particular interest in de-escalation approaches to treatment. And studies touting the benefits of a de-escalation approach are emerging alongside a rise in younger people diagnosed with certain cancer types, such as colorectal cancer.

The share of colorectal cancer diagnoses among adults younger than 55 in the United States has been rising since the 1990s. A report released in March by the American Cancer Society shows that the proportion of colorectal cancer cases among adults in that age group increased from 11% in 1995 to 20% in 2019.

Colorectal cancer is “alarmingly rising in younger patients,” and many of them are requesting de-escalated approaches to their care, said Dr. Aparna Parikh, a gastrointestinal oncologist at Mass General Cancer Center.

“You would think more people would say, ‘I don’t want to cut any corners at all, just give me everything,’ ” she said. “But people are wanting this approach, and we’re counseling them on the pros and cons more than anything. So it is something we use and we have careful conversations on.”

Some of the surgeries that treat colorectal cancer can leave the person with a bag or pouch, called an ostomy bag, surgically attached to the abdomen to collect waste passing through the intestines.

“That’s quite life-altering, to have a permanent ostomy,” Parikh said.

But for some people, “just with a couple of doses of immunotherapy, people’s tumors went away completely, and they didn’t need radiation. They didn’t need surgery. You have to continue to watch people carefully if you’re going to proceed with either no surgery or no radiation, but I think it’s exciting to be able to really pick now which patients may or may not benefit from each of these options,” she said. “But at the same token, understand that there are nuances to each tumor in each patient.”