Major Trial: A Win-Win in Treating Good-risk DCIS

Nick Mulcahy

January 30, 2015

UPDATED Februay 2, 2015 // Two-group randomized controlled trials often have a winner and a loser. But sometimes the results are "win–win."

This appears to be the case with the first-ever randomized trial that compares adjuvant radiotherapy (RT) with observation in women with "good-risk" ductal carcinoma in situ (DCIS).

The investigators, led by Beryl McCormick, MD, from the Memorial Sloan Kettering Cancer Center in New York City, expect that their data will be used to endorse both treatment choices in the setting of good (or low-risk) DCIS.

They say the trial results both "support" the decision to omit RT and "confirm" that RT offers "significant benefit in further reducing in-breast recurrence."

The study was published online January 20 in the Journal of Clinical Oncology.

The primary end point of the study was ipsilateral local failure after lumpectomy for DCIS. Of the 585 women, 287 women were treated with RT and 298 were followed with observation. Median follow-up was 7 years, and average age of the participants was 58 years.

There were fewer local failures in the RT group than in the observation group (2 vs 19).

At 7 years, the local failure rate was 0.9% in the RT group (95% confidence interval [CI], 0.0% - 2.2%) and 6.7% in the observation group (95% CI, 3.2% - 9.6%; hazard ratio, 0.11; P < .001).

The failure rate was "low with observation but was decreased significantly with the addition of RT," conclude Dr McCormick and colleagues.

All patients in the trial, known as the Radiation Therapy Oncology Group (RTOG) 9804, had low-risk disease, defined as mammographically detected low- or intermediate-grade DCIS less than 2.5 cm in diameter with margins 3 mm or greater.

These inclusion criteria for RTOG 9804 "now serve as the gold standard for defining low-risk DCIS," writes radiation oncologist Benjamin Smith, MD, from the University of Texas M.D. Anderson Cancer Center in Houston, in accompanying editorial.

Of the two local failures in the RT group, one was invasive and one noninvasive. Of the 19 in the observation group, eight were invasive and 11 were noninvasive.

The number of women who underwent mastectomy was low in both the RT and observation groups (4 vs 8).

RT was more toxic than observation, but the difference was almost completely related to less serious adverse events. There were more grade 1/2 acute toxicities in the RT than in the observation group (76% vs 30%), but grade 3/4 toxicities were similar in the two groups (4.0% vs 4.2%).

Late RT toxicity was grade 1 in 30.0% of treated patients, grade 2 in 4.6%, and grade 3 in 0.7%.

So, how do clinicians and low-risk DCIS patients make a decision about RT? Dr. Smith suggests a four-step approach.

First, estimate long-term survival, because younger, healthier patients are more likely to benefit from the adjuvant treatment.

Second, evaluate anticipated risks related to RT. Patients who have cardiac disease or other risk factors might want to forgo the treatment. Those with collagen vascular disease and obese patients might also want to forgo the treatment because of the risk for skin and soft tissue complications.

Third, listen for patient preferences.

Fourth, discuss salvage surgery in the event of a same-breast recurrence. Some breasts are better suited to a second lumpectomy, whereas others will require a mastectomy, Dr. Smith explains. The difference could influence initial treatment decisions, he asserts.

Time Will Tell

The importance of RTOG 9804 is best understood in the context of four other large prospective randomized trials that compared adjuvant RT with observation after surgery. All four demonstrated that the addition of RT resulted in a reduction in the risk for local failure, the researchers report.

But there is a problem: none of the trials was conceived to address the low-risk subset.

The RTOG 9804 results are most important because they "imply that clinical pathologic criteria can be used to define a cohort of patients who can expect a low rate of in-breast recurrence," write Dr. Smith and colleagues.

But will the low rate last over time?

Only time will tell, Dr. McCormick told Medscape Medical News.

"The next steps for us, with this study population, will be to update results at 10 years to assess whether this 'good risk' DCIS continues to recur over time, especially in the surgery-only group," she explained.

There is a hint in the current data that recurrence rates will grow in both groups. Local failure rates were lower with RT than with observation at 5 years (0.4% vs 0.9%) and at 7 years (3.5% vs 6.7%).

In short, the rate more or less doubled in just 2 years.

Another trial provides lessons in the setting of low-risk DCIS. Although important, it is less authoritative because it is a single-group study.

The Eastern Cooperative Oncology Group (ECOG) 5194 trial reported a 7-year local failure rate of 10.5% with observation only in women with low-risk DCIS after lumpectomy (J Clin Oncol. 2009;27:5319-5324).

The difference in local failure rates between these two trials might be explained by the fact that more women in RTOG 9804 than in ECOG 5194 were taking tamoxifen (62% vs 33%).

Dr. McCormick has disclosed no relevant financial relationships. A number of her coauthors report financial ties with industry. Dr. Smith reports ties with Varian Medical Systems.

J Clin Oncol. Published online January 20, 2015. Abstract

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