Greater Margins Advised for Some Patients With DCIS

Melvin J. Silverstein, MD, FACS

Melvin J. Silverstein, MD, FACS

Over the past few decades, the optimal margin width for minimizing recurrence after breast-conserving surgery (BCS; lumpectomy) has been a topic of much debate.

To provide some clarity to practitioners, the Society of Surgical Oncology and the American Society for Radiation Oncology recently released a consensus guideline on margins in BCS for invasive breast cancer (Table 1). Their definition of a clear margin is no ink on tumor, and the guidelines are meant for patients with invasive breast cancer who receive postexcisional radiation therapy.

These guidelines, however, do not address patients with noninvasive disease (ductal carcinoma in situ [DCIS]). At the 31st Annual MBCC, Melvin J. Silverstein, MD, FACS, a breast cancer expert and surgeon at Hoag Memorial Hospital Presbyterian in Newport Beach, California, discussed his research on optimal margin width in lumpectomy for patients with DCIS.

Silverstein, who is also a professor at the Keck School of Medicine of the University of Southern California, said that wider margins are important for patients with DCIS who are treated with excision alone; however, he stressed that margins alone are not the answer for determining optimal patient treatment.

A controversial meta-analysis published in theJournal of the National Cancer Institutein 2012 suggested that wide margins (≥10 mm) are optimal for lowering the risk of ipsilateral recurrence for all cases of DCIS treated with lumpectomy, regardless of radiotherapy use.¹

Table 1. Summary of SSO/ASTRO Consensus Guideline on Margins for Breast-Conserving Surgery With WBRT for Invasive Cancer

Category

Recommendation

Positive Margins

At least a two-fold increase in the risk of IBTR is associated with a positive margin (ink on invasive tumor or DCIS). A radiation boost, sytemic therapy, or favorable biology do not offset this risk.

Negative Margins

The risk of IBTR is minimized by negative margins, defined as no ink on the tumor; however, this risk is not significantly decreased with wider margins. Obtaining negative margin widths wider than no ink on tumor as standard practice is not indicated.

Systemic Therapy

Systemic therapy decreases IBTR rates. In the infrequent cases when adjuvant systemic therapy is not used, the data do not support the need for margins wider than no ink on tumor.

Systemic Therapy

Systemic therapy decreases IBTR rates. In the infrequent cases when adjuvant systemic therapy is not used, the data do not support the need for margins wider than no ink on tumor.

Biologic Subtypes

The data do not support the use of margins wider than no ink based solely on biologic subtype, such as triple-negative breast cancer.

Radiation Therapy Delivery

Margin width should not impact the selection of WBRT delivery technique, fractionation, and boost dose.

Invasive Lobular Carcinoma and LCIS

For patients with invasive lobular carcinoma, negative margins wider than no ink are not indicated. The presence of classic LCIS at the margin is not an indication for re-excision. It remains unclear what the significance is of pleomorphic LCIS at the margin.

Young Age

Women ≤40 years old have an increased risk of IBTR following BCT and postmastectomy local relapse on the chest wall. Young age is also more commonly linked with adverse pathologic and biologic characteristics. The data do not suggest that the higher risk of IBTR in these patients can be offset by wider margins.

Extensive Intraductal Component

An extensive intraductal component identifies patients who may have a large residual DCIS burden following lumpectomy. With negative margins, the data do not show a link between an extensive intraductal component and a higher risk of IBTR.

The guideline is based on a meta-analysis of 33 studies conducted by a multidisciplinary consensus panel. The studies included 28,162 patients with early-stage invasive breast cancer (stages I and II), all of whom had received BCT and adjuvant WBRT.

ASTRO indicates American Society for Radiation Oncology; BCT, breast-conserving therapy; DCIS, ductal carcinoma in situ; IBTR, ipsilateral breast tumor recurrence; LCIS, lobular carcinoma in situ; SSO, Society of Surgical Oncology; WBRT, whole-breast radiation therapy.

Source: Moran MS, Schnitt SJ, Giuliano AE, et al. Society of Surgical Oncology—American Society for Radiation Oncology consensus guideline on margins for breast-conserving surgery with whole-breast irradiation in stages I and II invasive breast cancer [published online February 10, 2014]. J Clin Oncol. doi:10.1200/JCO.2013.53.3935.

The results of the meta-analysis have been disputed since publication, and have not been adopted as the standard surgical approach in DCIS. One major critique was that the cases of margins ≥10 mm came from more recent studies than those with narrower excisions. Thus, the development of better diagnostic and treatment techniques, not margin width, might explain the better prognoses.

While Silverstein would agree that margins ≥10 mm should not be standard for all patients, he advocates for wider margins in patients with DCIS treated with surgery alone. “For patients with DCIS treated with excision alone (no radiation therapy), wider margins correlate with less residual disease and a lower local recurrence rate,” Silverstein said in an interview.

This principle is founded in his personal research. In 1999, Silverstein and colleagues published a paper in The New England Journal of Medicine that examined the impact of margin width on local control of DCIS.²The research included 469 DCIS specimens from women who received BCS with and without radiation.

There were 133 patients in the study with margins ≥10 mm, including 93 who received surgery alone and 40 who also received radiation.

In these patients, Silverstein said that local recurrence rates were “very low” (about 2%-3% at 10 years) for patients receiving excision alone with clear margins ≥10 mm. He updated these data at MBCC, reporting that at an average follow-up of 11.2 years, the local recurrence rate was now 8.6%.

The initial study data also showed no benefit with postoperative radiation therapy in patients with margins ≥10 mm. However, Silverstein reported that this has changed with longer follow-up. “What’s happened over time is that the curves have widened, with the patients who received radiation therapy doing better than the patients who did not get radiation therapy in terms of local recurrence. Survival, however, was the same.”

As a whole, Silverstein interprets the data to mean that a wider margin is critical when determining the appropriate DCIS patients for treatment with excision alone; however, it should not be the sole determinant. “Margins are important for DCIS when you’re not irrad-iating the patient, but they’re not the whole answer. You cannot choose patients for excision alone with just margin status.”

“There are about 66,000 new cases of DCIS each year in the United States, and about one-third of them are treated with excision alone. So the issue is, how do you pick the one-third who can be treated with excision alone?” said Silverstein.

In addition to wide margins, Silverstein said, “The ideal patient for excision alone is older, has a low-grade tumor, and has a tumor that is relatively small in size. If you have all of those factors, the addition of radiation therapy doesn’t add much for DCIS.” He added that the NCCN Clinical Practice Guidelines in Breast Cancer support these criteria.³“The NCCN Guidelines cite all of those factors and say that selected favorable patients with DCIS can be treated with excision alone.”

These prognostic factors, as well as comedonecrosis, form the basis for the University of Southern California/ Van Nuys Prognostic Index (USC/VNPI), which Silverstein uses to help with treatment decisions for patients with pure DCIS. USC/VNPI scores indicate whether patients’ recurrence risk would be lowest with excision alone, excision plus radiation, or mastectomy. Scores range from 4 to 12, with a lower score indicating a better prognosis.

Table 2. University of Southern California/Van Nuys Prognostic Index (USC/VNPI) Treatment Recommendations for Patients With DCIS⁵

USC/VNPI Score, Margin Width

Patients (N = 1673)

Treatment Needed

12-Year Recurrence

All 4, 5, or 6

420

Excision alone

≤7%

7, margins ≥3 mm

196

Excision alone

16%

7, margins <3 mm

117

Excision plus radiation

14%

8, margins &ge;3 mm

128

Excision plus radiation

14%

8, margins <3 mm

183

Mastectomy

0%

9, margins &ge;5 mm

43

Excision plus radiation

17%

9, margins < 5 mm

197

Mastectomy

0%

All 10, 11, 12

389

Mastectomy

7%

The USC/VNPI algorithm assigns DCIS patients scores (4-12) based on a series of prognostic factors, including tumor size, margin width, grade, age, and comedonecrosis.

The above table includes data for 1673 patients with DCIS with 86 months of follow-up. The recommendations are based on USC/VNPI score stratified by margin width and indicate the treatment needed to achieve a <20% probability of local recurrence at 12 years.

The original USC/VNPI, published in 1996, was based on 333 patients.⁴At the MBCC, Silverstein presented the latest data on the USC/VNPI, which include 5 times as many patients, with 86 months of follow-up.5 While the initial treatment recommendations were based on USC/ VNPI score alone, the additional patients and longer follow-up have allowed for more refined recommendations based on USC/VNPI score stratified by margin width (Table 2).

Silverstein described two groups of patients with DCIS for whom the USC/VNPI predicts a probability of recurrence of <20% at 12 years with excision alone. The first group included all patients with USC/VNPI scores of 4, 5, or 6, regardless of margin width. The other group comprised patients with a score of 7 who have margin widths &ge;3 mm.

All other DCIS subgroups on the USC/VNPI spectrum require treatment beyond excision, regardless of margin width, Silverstein said.

References

1. Wang SY, Chu H, Shamliyan T, et al. Network meta-analysis of margin threshold for women with ductal carcinoma in situ.J Natl Cancer Inst.2012;104(7):507-516.
2. Silverstein MJ, Lagios MD, Groshen S, et al. The influence of margin width on local control of ductal carcinoma in situ of the breast.N Engl J Med. 1999;340(19):1455-1461.
3. NCCN Clinical Practice Guidelines in Oncology: Breast Cancer: Version I.2014. www.nccn.org. Accessed February 22, 2014.
4. Silverstein MJ, Lagios MD, Craig PH, et al. A prognostic index for ductal carcinoma in situ of the breast.Cancer.1996;77(11):2267-2274.
5. Silverstein MJ, Lagios MD. Choosing treatment forpatients with ductal carcinoma in situ: fine tuning the University of Southern California/Van Nuys Prognostic Index.J Natl Cancer Inst Monogr. 2010;41:193-196.