Adjuvant radiation therapy (RT) for good-risk ductal carcinoma in situ (DCIS) reduced long-term ipsilateral breast recurrence (IBR) by more than 50% compared with observation, results of a large intergroup study showed.

RT, following surgery with or without tamoxifen, decreased 15-year IBR from 15.1% with observation to 7.1%. RT also reduced the odds of invasive local recurrence by more than 50%. A multivariable analysis showed that receipt of RT had the greatest impact on IBR, exceeding the risk-reducing effect of tamoxifen, reported Beryl McCormick, MD, of Memorial Sloan Kettering Cancer in New York City, and co-authors.

“Radiation is the most effective approach for reducing IBR following lumpectomy in this population,” the authors concluded in their study online in the Journal of Clinical Oncology. “In discussing radiation after BCS [breast-conserving surgery] with these patients, factors such as age, life expectancy, and willingness (if estrogen receptor-positive) to take antiestrogen therapy should be taken into consideration in this patient-doctor shared decision.

“Since IBR risk continues to increase through at least 15 years, the data presented support the decision to treat patients who wish to minimize their IBR and particularly the invasive cancer risk in the long term,” the researchers wrote.

Multiple randomized trials and a meta-analysis showed that adjuvant radiation for DCIS reduced the risk of IBR by about 50%. With increased uptake of screening mammography, smaller and lower-grade DCIS was diagnosed with increasing frequency. Whether the benefits of adjuvant RT applied to such good-risk lesions remained unclear, McCormick and co-authors noted.

RTOG 9804 (and subsequently NRG/RTOG 9804) evaluated the impact of post-lumpectomy RT in women with good-risk DCIS. The study included 636 patients enrolled from 1999 to 2006, randomized to lumpectomy followed by whole-breast irradiation or observation. Adjuvant tamoxifen was optional.

The study population had a median age of 58 and mean pathologic DCIS size of 0.60 cm. By intention-to-treat analysis, 69% of patients received tamoxifen, but actual receipt of the hormonal therapy differed between the groups (58% for RT vs 66%, P=0.05). The primary endpoint was IBR.

The primary analysis after a median follow-up of 7 years showed a significant reduction in IBR in favor of adjuvant RT. The cumulative incidence of IBR in the observation arm was similar to a priori predicted values, but IBR in the RT group was substantially lower than hypothesized or seen in prior trials, McCormick and co-authors noted.

Long-term follow-up reporting was not planned, but given the lower-than-expected hazard ratios associated with RT, the investigators decided to evaluate the long-term durability of the primary results.

A subsequent report after a median follow-up of 12 years continued to favor adjuvant RT, which resulted in an IBR rate of 2.6% versus 11.4% with observation. Rates of invasive recurrence were 1.5% with RT and 5.8% with observation.

The investigators reported the estimated cumulative 15-year IBR and invasive recurrence rates after a median follow-up of 13.9 years. The analysis showed that RT reduced the hazard for IBR by 64% (95% CI 0.20-0.66) and the hazard for invasive local recurrence by 56% (95% CI 0.21-0.91).

Multivariable analysis showed that RT had an independent association with reduced IBR (HR 0.34, 95% CI 0.19-0.64, P=0.0007), as did tamoxifen use (HR 0.45, 95% CI 0.25-0.78, P=0.0047).

“The fear of recurrence, as well as the actual diagnosis of IBR, can be a stressful situation for patients with breast cancer,” the team wrote. “It is important to clearly communicate the estimated IBR rates for patients who have good-risk DCIS, with a goal of reaching a shared decision regarding the use of RT or not.

“This trial demonstrates that clinical pathologic criteria reliably identify good-risk DCIS resulting in reduced incidence of IBR events after lumpectomy,” the researchers concluded. “Practitioners can now use commercially available multigene expression assays to assist adjuvant radiation decision-making for DCIS by providing individualized risk prognostication for IBR after lumpectomy alone at 10 years, and benefit from radiation.”

The findings remain relevant to current clinical practice for managing DCIS, according to Bruce G. Haffty, MD, of Rutgers Cancer Institute of New Jersey in New Brunswick.

“The importance of this study is that it documents the benefits of radiation therapy with long-term follow-up in these favorable DCIS cases,” Haffty, a clinical/scientific expert for the American Society for Radiation Oncology, told MedPage Today via email. “It is important to note that the average age of patients in this study is 58 years, typical for the average age of women diagnosed with any DCIS. Since these women have a long life expectancy, it is important when weighing the risks and benefits of undergoing radiation that long-term data is available to aid patients in their decision-making.

“While there is no evidence of an impact on overall survival, and women diagnosed by screening mammography with favorable DCIS will do extremely well with radiation or observation, with or without hormonal therapy, it is important for women faced with the diagnosis of favorable DCIS that clinicians share these long-term results, so they can make an informed decision about the long-term risks and benefits of undergoing radiation therapy,” Haffty said.