The ipsilateral local failure rate in women with good-risk ductal carcinoma in situ was low with observation after breast-conserving surgery, but was significantly lower with the addition of radiotherapy, according to findings from a prospective, randomized, Radiation Therapy Oncology Group trial.
Failure occurred in 19 of 298 patients in the observation group, compared with 2 of 287 patients in the radiotherapy group; the cumulative rates of ipsilateral local failure at 7 years were 6.7% and 0.9% in the groups, respectively (hazard ratio, 0.11), Dr. Beryl McCormick of Memorial Sloan Kettering Cancer Center, New York, and her colleagues reported online Jan. 19 in the Journal of Clinical Oncology.
Local failures were invasive in 42% of cases in the observation arm and in one of the two patients in the radiotherapy arm. The 7-year cumulative mastectomy incidence was 2.8% in the observation arm and 1.5% in the radiotherapy arm. Survival was excellent and did not differ between the arms, the investigators said (J. Clin. Oncol. 2015 Jan. 19 [doi:10.1200/JCO.2014.57.9029]).
Study subjects were women with a mean age of 58 years and mammographically detected low- or intermediate-grade ductal carcinoma in situ (DCIS) that measured less than 2.5 cm with margins of at least 3 mm. Those assigned to the radiotherapy group underwent whole-breast radiotherapy at a dose of 50 Gy in 25 fractions, 50.4 Gy in 28 fractions, or 42.5 Gy in 16 fractions, and most received tamoxifen, which was required in both arms when the study opened before being made optional in 2001.
The women were followed for a median of 7.2 years.
Grade 1 and 2 toxicities occurred more often in the radiotherapy group (30% vs. 76%), but grade 3 and 4 toxicities occurred in 4% of women in both groups. Late toxicity in the radiotherapy patients was grade 1 in 30%, grade 2 in 4.6%, and grade 3 in 0.7% of subjects, the investigators said.
Breast-conserving surgery and radiation have been shown to produce results that are equivalent to mastectomy in patients with DCIS, and in four large prospective trials, radiation therapy reduced the risk of local failure by at least 50%. About half of the recurrences in those trials were DCIS and half were invasive breast cancer, but survival was excellent regardless of local treatment, the investigators explained.
“More recently, an understanding of DCIS as not just one disease but a group of related subtypes of cancers has emerged, with a spectrum of local failure risk. Is there a low-risk DCIS for which the benefit of radiotherapy would not be seen?” they wrote.
The current study was designed to address the question of radiotherapy benefit in a good-risk DCIS subset. Although it didn’t meet the targeted accrual of 1,790 patients and was thus closed early, the findings – along with those from an Eastern Cooperative Oncology Group trial, “imply that clinical pathologic criteria can be used to define a cohort of patients with DCIS who can be expected to have a much lower rate of in-breast recurrence without radiotherapy in the first 7 years after lumpectomy than previously reported in past randomized trials,” they said.
These data may support decisions to forego adjuvant radiotherapy after breast-conserving surgery, particularly given the low mastectomy rate, but they also confirm that radiotherapy provides significant benefit with respect to further reducing local failure risk, they added.
However, given historic patterns of increasing local failure rates over 10 to 15 years, longer follow-up of these patients is needed to fully realize the rates of local failure, they said.
This study was supported by grants from the National Institutes of Health. Dr. McCormick reported having no disclosures.