Active Monitoring With or Without Endocrine Therapy for Low-Risk Ductal Carcinoma In Situ The COMET Randomized Clinical Trial

The comet trail is a prospective randomised noninferiority trail conducted across 83 sites between June 2017 and January 2023 (1). The aim of the trial was to identify patients with DCIS with a low-risk of progression to invasive malignancy, who could avoid surgery; addressing concerns about overdiagnosis and treatment.

Women aged 40 years or more with newly diagnosed low risk DCIS were enrolled and randomised 1:1 to receive either guidance – concordant care (GCC, n=498) Including surgery with or without radiation therapy, or active monitoring (AM, n=497). Low risk DCIS was defined as hormone receptor positive, grade 1 (26.3%) or grade 2 (73.7%), HER2-receptor negative ductal carcinoma in situ (DCIS). The active monitoring arm consisted of physical examination and imaging every 6 months. The study population was composed largely of postmenopausal women, with only 24% of participants younger than 55 years and only 34% without comorbidities.

In the intention-to-treat analysis, the 2-year cumulative rate of ipsilateral invasive mammary carcinoma (IMC) was 5.9% in the GCC group versus 4.2% in the AM group (difference 1.7%; upper limit of the 95% CI, 0.95%), demonstrating noninferiority of active monitoring. 

However, it is important to note that adherence to treatment varied between the two groups; in the GCC arm only 56% underwent surgery at 24 months (44% electing to decline surgery), while in the AM arm, only 86% had initiated the active monitoring protocol at 6 months (11% had crossed over to surgery). Patients had the option to take endocrine therapy, taken up by 65.5% of patients in the GCC group and 71.3% in the AM group. 

Therefore, in the subset who actually had surgery, the 2-year rate of invasive cancer rose to 8.7% (95% CI, 5.06%-12.21%). In the active monitoring group (the 86% that had initiated active monitoring at 6 months) the 2-year rate of invasive cancer was 3.1% (95% CI, 2.31%-6.0%). 

Among the 46 ipsilateral invasive cancers diagnosed, approximately 80% were T1 tumors in both groups, with no significant differences in tumor characteristics. At a median follow up of 37 months, six patients had died, with no deaths attributed to breast cancer.

The authors concluded that the results support the short-term safety of active monitoring in a low-risk DCIS cohort. However, there are notable limitations such as substantial crossover rate, very short follow-up and ascertainment bias for IMC in the GCC group – not all invasive events in the AM arm have been realized. This makes interpretation difficult, and thus the initial results of this trial must be interpreted carefully, considering what we know about the natural history of DCIS treated surgically (2).

Integrating these initial findings into everyday practice:

• The incidence of undersampled invasive cancer present in patients with low-risk DCIS at surgical excision is not negligible.
• Longer follow-up is required before active monitoring can be adopted as a standard management strategy as other studies with long term follow-up highlight an increased risk of invasive cancer development (4-6%) without surgery.
• Shared decision making should incorporate all patient preferences, noting that concern about recurrence is typically the most important factor in treatment selection.

References

1. Hwang ES, Hyslop T, Lynch T, et al. Active Monitoring With or Without Endocrine Therapy for Low-Risk Ductal Carcinoma In Situ: The COMET Randomized Clinical Trial. JAMA. 2025;333(11):972–980. doi:10.1001/jama.2024.26698
2. Morrow M, Barrio AV. Is It Time to Abandon Surgery for Low-Risk DCIS? JAMA. 2025;333(11):946–947. doi:10.1001/jama.2024.26723

Summary written by: 

Varun Patnam, Breast Fellow, Manchester University NHS Foundation Trust

Rajiv Dave, Consultant oncoplastic breast and Endocrine Surgeon, Manchester University NHS Foundation Trust, and Honorary Senior Lecturer, University of Manchester