Active Monitoring May Be Safe Vs Surgery in Certain Low-Risk DCIS Populations

To conclude his presentation, Alastair M. Thompson, FRCSEd, FACS, noted that active monitoring is “not for everyone,” but the “right size for some.”

Active monitoring rather than surgery may show short-term safety among patients with low-risk ductal carcinoma in situ (DCIS) and yield acceptable outcomes among those in a clinical trial setting, according to a presentation from Alastair M. Thompson, FRCSEd, FACS, at the 2025 Miami Breast Cancer Conference.1

Thompson, Olga Keith Weiss Chair of Surgery at Baylor College of Medicine in Houston, Texas, began his presentation by discussing the factors that may influence whether certain patients are suitable candidates to receive active monitoring instead of undergoing surgery. According to Thompson, it may be appropriate to consider actively monitoring the following populations:

• Patients younger than 40 years who do not want surgery;
• Those with high-grade DCIS;
• Patients with a palpable mass prior to a biopsy of DCIS;
• Those with estrogen receptor (ER)–negative, HER2-positive DCIS
• Select patients 40 years or older with low-risk DCIS;
• Those with ES oncotype low or a PreludeDx DCISionRT score of less than 3;
• And all patients with histologically confirmed DCIS.

As part of determining the patients who are most suitable to receive active monitoring over surgery, Thompson outlined prior work assessing these modalities across different fields.

The History of Active Monitoring Vs Surgery

Previous trials that have assessed the utility of active monitoring in low-risk cancers include the ProtecT trial (NCT02044172), in which investigators compared monitoring, radical prostatectomy, and external-beam radiotherapy (EBRT) for patients with clinically localized prostate cancer.2 In this randomized clinical trial including 1643 patients, after a median follow-up of 10 years, investigators reported 17 deaths; 8 in the monitoring group, 5 in the surgery group, and 4 in the radiotherapy group had died.

In another randomized clinical trial including 1433 patients with prostate cancer, investigators determined that active surveillance may represent a strategy to mitigate overtreatment in young patients with low-risk disease in the early term.3 According to Thompson, similar findings have been reported in populations with cervical neoplasia, thyroid cancer, and small renal cancers. The efficacy of active monitoring for these low-risk cancers indicated the possibility that it may work for DCIS as well.

Regarding the treatment of patients with DCIS, Thompson characterized it as a heterogenous disease that should be managed like an invasive cancer. Treatment options include lumpectomy with or without radiotherapy or mastectomy with or without endocrine therapy.

Thompson then posed the question of whether all patients with DCIS needed surgery. Previous trials included a population-based cohort study of 57,222 patients with DCIS, in which investigators assessed the survival benefit of breast surgery for low-grade DCIS.4 Overall, multivariate analysis showed no significant difference in breast cancer-specific survival between the surgery and non-surgery groups for low-grade DCIS. Investigators concluded that there was a smaller survival benefit with surgery for low-grade DCIS vs intermediate- or high-grade DCIS.

When reviewing the literature, Thompson stated “yes,” patients with high-grade DCIS likely need surgery. The answer was “maybe not,” however, for those with low-grade DCIS.

Deciding the factors that constituted “low-risk” disease was another question altogether. Thompson listed the following as factors that may influence the development of low-risk disease:

• Disease grade;
• No comedo necrosis;
• Age and menopausal status;
• Exact Sciences Oncotype;
• PreludeDx DCISionRT score of less than 3;
• Other signatures such as RNA sequencing and microenvironment.

In a previous multicenter study, DCIS grade appeared to only confer a moderate association with prognostic value when using whole slide images scored by 9 breast pathologists.5 In another observational study, investigators found a highly variable threshold for comedo necrosis as a marker of increased risk in patients with DCIS.6 With these findings in mind, Thompson highlighted that not all cases of DCIS are the same, as pathologists cannot agree on comedo necrosis or grade as a risk factor in this population.

As part of elucidating the potential benefit of active monitoring vs surgery in certain DCIS populations, Thompson highlighted an ongoing international collaboration of active surveillance trials.7 These phase 3 trials include LORIS (ISRCTN27544579) in the UK, LORD (NCT02492607) in Europe, COMET (NCT02926911) in the US, and LORETTA in Japan (UMIN000028298). According to Thompson, this collaboration may allow for meta-analyses of the utility of active monitoring vs surgery while including assessments of patient-reported outcomes (PROs) and quality of life (QOL).

Thompson offered a brief overview of how these trials differed in factors such as trial design, patient accrual, and standards of care. Additionally, he specifically focused on the methodology and current findings from the US-based COMET trial.

The COMET Trial

Investigators of the prospective, pragmatic noninferiority COMET trial randomly assigned patients with newly diagnosed DCIS 1:1 to receive guideline-concordant care (GCC) or active monitoring. GCC consisted of surgery at diagnosis with breast-conserving surgery or mastectomy with adjuvant radiotherapy per radiation oncologist recommendation; adjuvant endocrine therapy was permitted in this arm. Patients in the active monitoring arm received an ipsilateral mammogram once every 6 months, biopsy for imaging changes, and GCC upon detection of ipsilateral breast cancer with the option of adjuvant endocrine therapy.

The trial’s primary end point is the 2-year cumulative rate of invasive breast cancer following randomization. The trial also includes an analysis of PROs and QOL outcomes such as anxiety, depression, and specific symptoms associated with active monitoring vs surgery. Female patients 40 years and older with grade 1 or 2 hormone receptor–positive DCIS and 2 biopsies if the extent of disease exceeded 4 cm were eligible for inclusion.

Across the intent-to-treat (ITT) population, the 2-year cumulative rate of invasive cancer was 5.9% (95% CI, 3.71%-8.04%) with GCC vs 4.2% (95% CI, 2.31%-6.00%) with active monitoring.8 In the per-protocol analysis, the 2-year rates were 8.7% (95% CI, 5.06%-12.21%) vs 3.1% (95% CI, 2.31%-6.00%), respectively.

Thompson also highlighted QOL findings from the COMET trial.9 Based on average SF-36 General Health T-scores in each treatment arm over time, general health was relatively stable and did not significantly differ between groups (P = .757).

With these findings, Thompson stated that active monitoring was both safe at 2 years and acceptable to patients in terms of QOL among those with DCIS. However, he noted some caveats to these results. First, he highlighted that 70% of patients received endocrine therapy in the active monitoring arm. Additionally, these 2-year findings indicated that active surveillance was safe “so far,” and that the mean follow-up was 37 months. He posed the question of whether a mammography should be given every year or at every 6 months given that other trials around the world use annual tests.

Overall, Thompson stated that active monitoring was safe, in the short term, for patients with low-risk DCIS based on data from the COMET trial. Investigators are currently awaiting longer-term follow-up from this study as well as results from other active monitoring trials in the previously described international collaboration. These trials will likely include a meta-analysis of the effects and PROs associated with active monitoring.

To conclude his presentation, Thompson noted that active monitoring is “not for everyone,” but the “right size for some.”

References

1. Thompson AM. Active monitoring or surgery for DCIS? Presented at the 42nd Annual Miami Breast Cancer Conference; March 6-9, 2025; Miami, FL.
2. Hamdy FC, Donovan JL, Lane JA, et al. 10-year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer. N Engl J Med. 2016;375(15):1415-1424. doi:10.1056/NEJMoa1606220
3. Leapman MS, Cowan JE, Nguyen HG, et al. Active surveillance in younger men with prostate cancer. J Clin Oncol. 2017;35(17):1898-1904. doi:10.1200/JCO.2016.68.0058
4. Sagara Y, Mallory MA, Wong S, et al. Survival benefit of breast surgery for low-grade ductal carcinoma in situ: a population-based cohort study. JAMA Surg. 2015;150(8):739-745. doi:10.1001/jamasurg.2015.0876
5. van Seijen M, Jóźwiak K, Pinder SE, et al. Variability in grading of ductal carcinoma in situ among an international group of pathologists. J Pathol Clin Res. 2021;7(3):233-242. doi:10.1002/cjp2.201
6. Harrison BT, Hwang ES, Partridge AH, Thompson AM, Schnitt SJ. Variability in diagnostic threshold for comedo necrosis among breast pathologists: implications for patient eligibility for active surveillance trials of ductal carcinoma in situ. Mod Pathol. 2019;32(9):1257-1262. doi:10.1038/s41379-019-0262-4
7. Kanbayashi C, Thompson AM, Hwang ES, et al. The international collaboration of active surveillance trials for low-risk DCIS (LORIS, LORD, COMET, LORETTA). J Clin Oncol. 2019;37(suppl 15):TPS603. doi:10.1200/JCO.2019.37.15_suppl.TPS603
8. 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. Published online December 12, 2024. doi:10.1001/jama.2024.26698
9. Partridge AH, Hyslop T, Rosenberg SM, et al. Patient-reported outcomes for low-risk ductal carcinoma in situ: a secondary analysis of the COMET randomized clinical trial. JAMA Oncol. Published online December 12, 2024. doi:10.1001/jamaoncol.2024.6556