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

<bold>Importance: </bold>Active monitoring for low-risk ductal carcinoma in situ (DCIS) of the breast has been proposed as an alternative to guideline-concordant care, but the safety of this approach is unknown. <bold>Objective: </bold>To compare rates of invasive cancer in patients with low-risk DCIS receiving active monitoring vs guideline-concordant care. <bold>Design, setting, and participants: </bold>Prospective, randomized noninferiority trial enrolling 995 women aged 40 years or older with a new diagnosis of hormone receptor-positive grade 1 or grade 2 DCIS without invasive cancer at 100 US Alliance Cancer Cooperative Group clinical trial sites from 2017 to 2023. <bold>Interventions: </bold>Participants were randomized to receive active monitoring (follow-up every 6 months with breast imaging and physical examination; n = 484) or guideline-concordant care (surgery with or without radiation therapy; n = 473). <bold>Main outcomes and measures: </bold>The primary outcome was 2-year cumulative risk of ipsilateral invasive cancer diagnosis, according to planned intention-to-treat and per-protocol analyses, with a noninferiority bound of 0.05%. <bold>Results: </bold>The median age of the 957 participants analyzed was 63.6 (95% CI, 55.5-70.5) years in the guideline-concordant care group and 63.7 (95% CI, 60.0-71.6) years in the active monitoring group. Overall, 15.7% of participants were Black and 75.0% were White. In this prespecified primary analysis, median follow-up was 36.9 months; 346 patients had surgery for DCIS, 264 in the guideline-concordant care group and 82 in the active monitoring group. Forty-six women were diagnosed with invasive cancer, 19 in the active monitoring group and 27 in the guideline-concordant care group. The 2-year Kaplan-Meier cumulative rate of ipsilateral invasive cancer was 4.2% in the active monitoring group vs 5.9% in the guideline-concordant care group, a difference of -1.7% (upper limit of the 95% CI, 0.95%), indicating that active monitoring is not inferior to guideline-concordant care. Invasive tumor characteristics did not differ significantly between groups. <bold>Conclusions and relevance: </bold>Women with low-risk DCIS randomized to active monitoring did not have a higher rate of invasive cancer in the same breast at 2 years compared with those randomized to guideline-concordant care.