Low-risk Breast Ductal Carcinoma In Situ (DCIS): Results From the Radiation Therapy Oncology Group 9804 Phase 3 Trial

Reporter: Gita Suneja, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: October 29, 2012

Presenter: Beryl McCormick
Affiliation: Memorial Sloan Kettering Cancer Center, New York


  • Several randomized clinical trials have demonstrated the benefit of adjuvant radiation therapy on local control for women with ductal carcinoma in situ (DCIS) of the breast following lumpectomy with breast conversation therapy. The reduction in local failure is approximately 50-60%.
  • Nonetheless, there may be a subset of women with favorable DCIS who do not benefit from adjuvant radiation following wide local excision with negative margins.
  • RTOG 9804 sought to identify a cohort of women with favorable risk DCIS in whom radiation therapy could be omitted.
  • "Good-risk" was identified based on the best available pathologic knowledge of the time of study design, and included method of detection, size, margin status, and nuclear grade.


  • The study aimed to enroll 1,790 patients with good-risk DCIS defined as detected by mammogram, size < 2.5 cm, resection margins > 3 mm, and low to intermediate nuclear grade.
  • Women were randomized to RT or observation following lumpectomy.
  • Radiation dose was 50 Gy in 25-28 fractions or 42 Gy in 16 fractions to the whole breast, with no boost allowed.
  • Tamoxifen for 5 years was optional in both arms.
  • The primary endpoint of this study was ipsilateral local failure. Secondary endpoints were contralateral failure, overall survival, and disease-free survival.


  • The study opened in 1999, but did not meet the target for accrual and was closed early in 2006 with 636 patients. 585 patients were included in this analysis.
  • Median follow-up was 7.2 years.
  • Mean age of the sample was 59 years. Tamoxifen was used in treatment of 69% of women. Patient characteristics were well balanced between the two arms. In both arms, the majority of patients had small tumors with negative margins of resection.
  • Central pathology review was not conducted, however 10% of cases were sampled and reviewed.
  • Local failure in the radiation arm was 0.9% vs. 6.4% in the observation arm, p=0.0005.
  • 19 women failed in the ipsilateral breast in the observation arm; of these, 8 were invasive recurrences.
  • 2 women failed in the ipsilateral breast in the radiation arm, both were invasive.
  • Age, grade, margin status, and size did not correlate with local failures.
  • Rates of contralateral breast events were similar between the two arms.
  • Toxicities were greater in the radiation arm but were not severe, with 35% grade 1 and 40% grade 2 skin toxicity.
  • Overall survival and disease-free survival were very high in both arms, and did not differ between the two arms.

Author's conclusions

  • Using standard pathologic assessment and imaging characteristics to define a cohort of good-risk DCIS, the study demonstrated that local failure rate was decreased significantly with the addition of adjuvant radiation.
  • The authors plan to continue long-term follow-up, which may provide additional information as failures continue to occur.


  • DCIS is a prevalent disease and detection of lesions has increased since the advent of mammographic screening.
  • While typically described as pre-invasive disease, DCIS has a high chance of progressing to invasive disease if left untreated. Appropriate treatments include mastectomy and breast conservation therapy, involving surgical resection (lumpectomy) followed by whole breast radiation therapy.
  • Three large randomized trials (NSABP B-17, EORTC 10853, and UKCCCR) demonstrated a benefit to adjuvant radiation following breast conservation therapy for all subgroups of patients with DCIS.
  • However, some groups (Van Nuys et al) have attempted to retrospectively define subgroups of women for whom adjuvant radiation therapy does not offer substantial benefit over breast conservation surgery alone.
  • In an effort to minimize over-treatment, the quest for a low-risk subpopulation has continued, however much debate exists about which features may portend a better or worse prognosis.
  • This area has continued to be a research focus and merit considerable resources, given the potential to de-escalate treatment in a large number of women who currently receive adjuvant radiation therapy to the whole breast.
  • In this large, randomized study, the authors demonstrated that adjuvant radiation could not be omitted even in a favorable or good-risk population. With extended follow-up, they will likely continue to see local failures occur, which will provide further evidence that radiation therapy should not be omitted, even in this favorable subset.
  • The study did not meet its target accrual. With the study size originally intended (1,790 patients), the authors would have had 80% power to detect a reduction in 5-year local failure from 6.0% to 3.5%. Given the much smaller sample size that was actually enrolled, the study may not have been adequately powered to detect a difference between the two arms. Still, the increased local failure rate in the non-radiation group was highly statistically significant. This was true despite a smaller sample size than had been initially planned.
  • It is also important to note that while this study used the best available techniques of the time to categorize women as good-risk, newer methods of categorizing patient risk have been developed and validated in the interim. One possible explanation for these results is that molecular markers or genetic signatures, which were not used at the time of this study, may be critical in identifying a low-risk population with DCIS for which adjuvant radiation therapy may be omitted.
  • Other large randomized studies such as ECOG E-5194 did succeed in identifying a subset of low risk DCIS patients that did not appear to benefit from adjuvant radiation. That study used rigorous pathologic processing which may not be feasible and realistic for other centers.
  • At present, the standard of care in the United States remains adjuvant radiation therapy for all patients with DCIS who elect to have breast conservation surgery.