Surveillance Instead of Surgery for Low-Risk DCIS?

SAN ANTONIO — A large trial has begun to make the case for active surveillance as an alternative to immediate surgery for low-risk ductal carcinoma in situ (DCIS).

At 2 years, investigators on the COMET trial found no clinically meaningful difference in the rates of ipsilateral invasive breast cancer among women randomized to active surveillance vs standard upfront surgery with or without radiation.

The 2-year findings suggest that surveillance is safe in the short term.

“While these results are provocative, I don't think they're quite practice-changing yet,” said lead investigator Shelley Hwang, MD, a surgical breast oncologist at Duke University in Durham, North Carolina, who presented the findings at the San Antonio Breast Cancer Symposium (SABCS) 2024.

For one thing, it generally takes longer than 2 years for DCIS to convert to invasive cancer, so it will be important to wait for the planned analyses at 5, 7, and 10 years to make sure there isn’t an excess number of invasive breast cancers in the surveillance arm, Hwang said.

If the results prove durable, however, the findings will likely be "practice-changing" for women who were at least 40 years old and had grade 1 or 2 hormone receptor–positive DCIS at low risk for conversion, Hwang said.

The goal of active surveillance is to prevent unnecessary treatment. During surveillance, lesions are monitored for changes that indicate conversion to more advanced disease, at which point guideline-concordant care begins.

Although DCIS can convert to invasive breast cancer, this doesn’t always happen. As a result, upfront surgery and radiation aren’t necessary for some women.

The COMET trial aimed to determine the short-term safety of an active monitoring approach compared with guideline-concordant care in patients with low-risk DCIS.

The prospective, randomized noninferiority trial included women aged 40 years or older with a new diagnosis of HR–positive grade 1 or grade 2 DCIS without invasive cancer from 100 US Alliance Cancer Cooperative Group clinical trial sites.

In the trial, 484 women with DCIS were randomized to active surveillance — breast mammography and physical exam every 6 months — and 473 were randomized to standard upfront surgery with or without radiation. Overall, 15.7% of participants were Black and 75.0% were White.

Patients in either group could elect to have endocrine therapy, typically over a 5-year period (71% of women in the active monitoring group and 65.5% in the surgery group opted for endocrine therapy).

At 2 years, the cumulative rate of ipsilateral invasive breast cancer was 4.2% in the surveillance group vs 5.9% in the upfront surgery arm.

The study also included a planned per-protocol analysis among 673 patients who strictly followed the study protocol — 246 in the guideline-concordant care group who had received surgery by 6 months and 427 in the surveillance group who initiated the active monitoring protocol at 6 months.

With almost half of patients randomized to surgery declined to have it, which indicates that patients are interested in active monitoring, Hwang said.

At 2 years, the cumulative rate of invasive breast cancer was 3.1% in the active surveillance group vs 8.7% in the upfront surgery arm.

Among patients receiving endocrine therapy, the rate of invasive cancer was 7.15% in the surgery group and 3.21% in the surveillance arm.

Endocrine therapy "may have resulted in a reduced rate of invasive cancer in the active monitoring group," the study authors noted.

These findings bring up the question of whether endocrine therapy might be just as good as surgery for low-risk DCIS, Hwang added. Given that one third of women undergo mastectomy for DCIS, "I think it’s not an inconsequential question,” Hwang said.

The findings, however, also suggest that surveillance sometimes leaves invasive cancer behind, Hwang explained. Nearly all invasive cancers in the surgery group were found during the initial operation , which may explain the slightly higher rates of invasive cancers in this group. Had the active monitoring group undergone surgery as well, the incidence of invasive cancer may have been the same in both arms, Hwang said.

However, when invasive cancers were removed, there were no significant differences in tumor size, node status, or tumor grade between the two groups, suggesting that there might not be a clinical penalty for delayed intervention with active monitoring, Hwang said.

With more than 10% of patients in the surgery group opting for mastectomy, compared with 1.8% in the active monitoring group, the active monitoring approach may not increase the likelihood of an eventual need for more extensive surgery, the COMET authors explained.

What Strategy Do Patients Prefer?

A companion analysis of patient-reported outcomes in COMET found no meaningful differences in quality of life, symptoms, or anxiety among patients who opted for surveillance over surgery. Results from questionnaires on quality of life, anxiety, depression, and breast cancer concerns were comparable between the two groups, with no evidence of a substantial impact of one approach over the other at 2 years.

"The results of this secondary analysis suggest that the lived experiences of individuals with low-risk DCIS are similar during early follow-up regardless of treatment allocation," the COMET investigators concluded.

Overall, the findings from COMET provide reassuring short-term data, said Neil Iyengar, MD, a medical breast oncologist at Memorial Sloan Kettering Cancer Center in New York City.

DCIS is not an aggressive cancer, and it’s not going to invade any time soon, so patients have time to consider their options, Iyengar told Medscape Medical News.

The 2-year findings from COMET also help inform patient discussions. “I can tell patients if they decide not to have surgery what the likelihood is that they are going to convert into invasive cancer” after 2 years, he said.

COMET was published in JAMA, and the PRO analysis was published in JAMA Oncology to coincide with the study presentations.

COMET is funded by the Patient-Centered Outcomes Research Institute and others. Hwang is a consultant for Merck and on the advisory board of Clinetic, Exai Bio, and Havah Therapeutics. Iyengar is an advisor and/or researcher for AstraZeneca, Novartis, Pfizer, and other companies.

M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape Medical News. Alex is also an MIT Knight Science Journalism fellow. Email: aotto@mdedge.com