October 27, 2009 — Women with low- to intermediate-grade ductal carcinoma in situ (DCIS) with margins 3 mm or wider had an "acceptably low rate" of ipsilateral breast events 5 years after excision without irradiation, according to the results of a new study published online October 13 in the Journal of Clinical Oncology.
It is the first multi-institutional prospective study to examine foregoing radiation therapy (RT) in DCIS patients.
However, because longer-term follow-up is needed, the results do not mean that radiation should be skipped; therefore, the results are not practice-changing, says an editorial that accompanies the study.
[DCIS] has almost no risk of mortality.
The editorialists, Jay R. Harris, MD, from the Dana-Farber Cancer Institute in Boston, Massachusetts, and Monica Morrow, MD, from Memorial Sloan–Kettering Cancer Center in New York City, also believe that the results might not be generalizable to the majority of women with DCIS because of the select nature of the patients involved.
Furthermore, given that fact that patients with DCIS are increasingly choosing bilateral mastectomy as their treatment, the "major clinical dilemma in DCIS today" is probably not choosing between local excision with or without radiation, suggest the editorialists. Instead, the bigger challenge might be trying to improve patients' understanding of the risks and benefits of therapies for "a disease that has almost no risk of mortality," they write.
In the new study, the 5-year rate of ipsilateral breast events in 565 patients with low- or intermediate-grade DCIS was 6.1% (95% confidence interval [CI], 4.1% to 8.2%). This prospectively determined local failure rate is in keeping with the 5% to 10% rates found in retrospective studies of similar patients treated with local excision alone, note the study authors, led by Lorie L. Hughes, MD, from Emory University in Atlanta, Georgia.
However, for patients in the study with high-grade lesions, excision alone is probably an "inadequate treatment," write Dr. Hughes and her colleagues from 8 other institutions involved in the study.
The 5-year rate of ipsilateral breast events for 105 patients with high-grade DCIS was "much higher" (15.3%; 95% CI, 8.2% to 22.5%).
The study authors also note that the overall survival was "excellent" for all of the participants in the study, and that none of the small number of deaths was related to breast cancer.
Take a Good Look at the Patients
In their editorial, Drs. Harris and Morrow question the generalizability of the results, saying that the "entered patients were generally older than the usual median age of diagnosis of DCIS, had lesions smaller than 1 cm, had margins greater than 5 mm."
Dr. Hughes and her colleagues also called attention to their patients' characteristics, noting that "patients entered in this trial had a more favorable median lesion size and width of margins than the entry criteria required."
These favorable characteristics were further delineated by the editorialists, who note that "median lesion size for this group was only 6 mm (rather than the 25 mm allowed by the protocol), and only approximately a quarter of entered patients had lesions 10 mm or larger."
About margins, the editorialists note that "approximately two thirds of patients had margins greater than 5 mm, and approximately half of patients had margins greater than 10 mm (rather than the 3 mm allowed by the protocol)."
Finally, only 9% were younger than 45 years, the editorialists highlight.
Dr. Hughes and colleagues seemed to have anticipated criticisms about their patients' characteristics. In the paper's conclusions and in its discussion section, they specify that the results in low- or intermediate-risk DCIS applied to "rigorously evaluated and selected patients."
Despite suggesting that the participating patients are not typical and emphasizing the relatively wide median margin width and relatively small median lesion size, the editorialists go on to say that excision and lesion size are not of ultimate importance in DCIS outcomes.
For the low- to intermediate-grade group, there was no significant difference in the 5-year rate of local recurrence based on margins greater or less than 10 mm (6.7% and 5.6%, respectively), and lesion size was also not a predictor of local recurrence, they write.
The long-cherished concept that widely excised, small, low-grade DCIS lesions are least likely to recur is an overly simplistic notion.
"Taken together, these observations indicate that the long-cherished concept that widely excised, small, low-grade DCIS lesions are least likely to recur is an overly simplistic notion," they continue.
The editorialists note that the "underlying biology of the disease, rather than the mechanics of the excision, will be the primary determinant of outcome."
"The challenge for the future is to identify markers that reliably predict behavior," they write.
What About Other Trials That Showed That RT Helped?
In their editorial, Drs. Harris and Morrow point out that the study is not a randomized controlled trial and wonder if local excision plus RT might have been better than excision alone.
"Because the study is not a randomized clinical trial, what it cannot tell us is what the reduction in the incidence of local recurrence in this highly favorable group of patients would be with the addition of RT," they write.
They note that 4 randomized trials have shown a reduction of approximately 50% in local recurrence when RT is added to excision.
"So why is the use of RT in DCIS controversial?" ask the editorialists.
The answer is found, foremost, in the lack of survival benefit. "None of the individual trials of breast-conserving surgery with and without RT showed a survival benefit for breast irradiation," they note.
However, they also note that invasive breast cancer offers a "cautionary tale" in this regard. It took 15 years of follow-up in multiple randomized clinical trials to show that local recurrence affected overall survival, observe the editorialists.
The authors and editorialists have disclosed no relevant financial relationships.
Medscape Medical News © 2009
Cite this: For DCIS, Outcomes With Excision Alone Acceptable at 5 Years - Medscape - Oct 27, 2009.