New Guide on DCIS Margins: Bigger Not Always Better

Nick Mulcahy

August 15, 2016

Three major cancer specialty organizations have issued a new joint guideline about a controversial topic — what constitutes a successful surgery for ductal carcinoma in situ (DCIS) in terms of having cancer-free margins on the removed tissue.

There has been a lack of consensus about what constitutes an optimal cancer-free or "negative" margin, and as result, about one in three DCIS surgeries are currently repeated, say the guideline authors, who are a panel of surgeons, radiation oncologists, and medical oncologists.

So the team completed a new meta-analysis of 20 studies with 7883 patients and, with that fresh evidence, published a new guideline today.

The new guidance is a combined effort of the Society of Surgical Oncology (SSO), the American Society for Radiation Oncology (ASTRO), and the American Society of Clinical Oncology. The groups each published the new guideline online in their respective journals: the Annals of Surgical Oncology, Practical Radiation Oncology, and the Journal of Clinical Oncology.

The authors concluded that 2 mm should be the standard for an "adequate" margin because it is associated with a reduced risk for ipsilateral breast tumor recurrence (IBTR) compared with narrower cancer-free margins.

 
Margins larger than 2 millimeters did not convey any added benefit. Dr Monica Morrow
 

But the meta-analysis also yielded another "very important finding," said lead author Monica Morrow, MD, from the Memorial Sloan Kettering Cancer Center in New York City.

"Margins larger than 2 millimeters did not convey any added benefit," she said, referring to IBTR risk.

"There has been this prevailing idea that a bigger margin is a better margin," Dr Marrow told Medscape Medical News.

"That's important because to get these big margins, lots of women were undergoing re-excision," she continued.

Some experts have called the number of breast cancer resurgeries, including those for DCIS, an "epidemic" in the United States.

Dr Morrow encouraged critics to sympathize with the challenge of removing DCIS.

"When we excise DCIS, we are taking out something you can neither see nor feel in the operating room. We are relying on what it looks like on an x-ray to take it out," she said.

"You would expect that there are more re-excisions in DCIS than there are in invasive cancer, which is a lump you can feel," she added.

Nevertheless, the guideline authors hope that the new guidance can reduce the proportion of DCIS re-dos.

"Re-excision is traumatic to patients, reduces the cosmetic outcome and costs the healthcare system money," summarized Dr Morrow.

Notably, the new guidelines only address the management of DCIS with surgery and whole-breast irradiation — not with partial-breast irradiation or for invasive disease.

This reflects how DCIS cases are typically managed in the United States, said Dr Morrow.

Nationally, most DCIS (69%) is treated with lumpectomy, and nearly three quarters of that group will have the surgery combined with radiotherapy, she said, citing Surveillance, Epidemiology, and End Results data from 2007 to 2011.

The guidance recommends that DCIS be treated with both surgery and radiation. "Treatment with excision alone, regardless of margin width, is associated with substantially higher rates of IBTR than treatment with excision and WBRT, even in predefined low-risk patients," reads the document.

The guide also dictates that, in patients with negative margins of less than the new standard of 2 mm, performing a resurgery is not automatic. "Clinical judgment should be used in determining the need for further surgery," write the authors.

While 2 mm appears to be the optimal negative margin, the differences in outcomes (ie, IBTR) between smaller, narrower negative margins are "relatively small."

Furthermore, Dr Marrow emphasized that "a negative margin of less 2 millimeters is not a reason to do a mastectomy."

 
A negative margin of less 2 millimeters is not a reason to do a mastectomy. Dr Monica Morrow
 

"Very good outcomes have still been achieved with 'no ink on tumor' in DCIS," explained Dr Morrow, adding that all of the National Surgical Adjuvant Breast and Bowel Project clinical trials in DCIS have used that measure, which encompasses the smallest of cancer-free margins.

Clinicians should consider several factors when thinking about re-excision or not with the smaller (<2 mm) negative margins, according to the guidelines.

These include the amount of DCIS close to the margin, which margin is close (eg, the margin in the back is limited by the end of the breast and the pectoral muscle and therefore a smaller margin is less significant at that location), patient life expectancy, mammography review to ensure all calcium deposits have been removed, and the cosmetic effect of re-excision.

"We hope that adoption of this guideline will reduce the number of women undergoing re-excisions that are not a benefit to them," said Dr Morrow.

An invasive breast cancer margins guideline, which was issued by the SSO and ASTRO online in 2014 and in print in 2015 and was reported by Medscape Medical News, has resulted in "changes in practice," she said.

Several single-institution series have since shown reduced rates of follow-up surgeries for invasive disease. "We are also looking at some national data that suggests that national rates have gone down since that guideline [for invasive disease] was issued," said Dr Morrow.

What the Meta-Analyses Show

In the new meta-analysis that is reported in the guideline document, among the 7883 patients with DCIS and known margin status, 865 had IBTRs. The median proportion of patients receiving WBRT was 100%, and the median proportion receiving endocrine therapy was 20.8%.

The median follow-up was 78.3 months, with a median incidence of IBTR of 8.3%.

The authors performed two different types of meta-analyses on the data: a frequentist analysis and a Bayesian network analysis.

In the frequentist meta-analysis, comparison of specific margin width thresholds (2 mm, 3 or 5 mm, and 10 mm) relative to negative margins defined as greater than 0 mm (no ink on tumor) or 1 mm included 7883 patients with a median follow-up of 6.5 years.

The odd ratios (ORs) for 2 mm (0.51; P =.01), 3 or 5 mm (0.42; P =.04), and 10 mm (0.60; P = .09) showed similar reductions in the odds of IBTR compared with greater than 0 mm or 1 mm, and pairwise comparisons found no significant differences in the odds of IBTR between the 2-mm, 3- or 5-mm, and 10-mm margin thresholds (all P = .40).

In this model, the predicted 10-year IBTR probability was 10.1% for 2-mm negative margins (95% confidence interval [CI], 6.3% - 16.0%) compared with 8.5% for 3- or 5-mm margins (95% CI, 3.6% - 18.9%) and 11.7% for 10-mm margins (95% CI, 6.7% - 19.4%). In other words, to repeat Dr Morrow's statement, bigger was not necessarily better.

In the Bayesian network meta-analysis, the ORs of incrementally wider negative margins relative to the positive-margin category were 0.45 (95% credible interval [CrI], 0.32 - 0.61) for greater than 0 or 1 mm, 0.32 (95% CrI, 0.21 - 0.48) for 2 mm, 0.30 (95% CrI, 0.12 - 0.76) for 3 mm, and 0.32 (95% CrI, 0.19 - 0.49) for 10 mm.

Again, bigger margins were not better.

The study was supported by a grant from Susan G. Komen. The guidelines authors have disclosed no relevant financial relationships.

J Clin Oncol. Published online August 15, 2016. Abstract

Follow Medscape senior journalist Nick Mulcahy on Twitter: @MulcahyNick.

Follow Medscape Oncology on Twitter: @MedscapeOnc

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