Best Marginal Threshold for Ductal Carcinoma in Situ Still Not Clear

A wide negative margin during breast-conserving surgery should be attempted for women with ductal carcinoma in situ (DCIS)-this is the conclusion from an analysis published last week in the Journal of the National Cancer Institute.[1] Shi-Yi Wang, MD, MS, the University of Minnesota School of Public Health in Minneapolis, Minnesota and colleagues analyzed the outcomes from 21 studies published over the past 40 years-a total of over 7,500 patients. The authors found that a negative margin of at least 10 mm during surgery was associated with a more reduced risk of same-breast tumor recurrence in both patients who had or did not have radiotherapy treatment compared with a 2 mm margin.

However, an accompanying editorial is skeptical of the recommendation, and suggests that the 10 mm margin may result in more mastectomies and reexcisions that do little to actually improve the health of women with DCIS.[2]

Negative margins are defined by a tissue excision where no cancer cells are detected on the outer edge of the excised tissue. Typically a clear or negative margin means that no follow-up surgery is necessary. While negative margins are incorporated into guidelines, the width of surgical margins in breast cancer is not well defined, with some hospitals defining a clear margin as anywhere from 1 mm to 2 mm. Only a small proportion of surgeons typically believe that a 10 mm negative margin is the minimum, according to previous surgeon surveys. Margin status is important for women with DCIS as this is one of the most important predictors of local recurrence, regardless of whether a patient also receives postsurgery radiotherapy.

The vast majority of patients with solid breast tumors have surgery to remove the tumor, and positive margins from surgery are associated with a higher risk of recurrence. Local cancer recurrence is associated with invasiveness, further underscoring the importance of removing all of the tumor cells.

Breast-conserving surgery is typically a balance of excision of the entire tumor (obtaining a clear or negative margin) and cosmetic outcomes. While a total mastectomy can eliminate DCIS, breast-conserving surgery with clear margins is the minimal standard of care.

The new meta-analysis from Dr. Wang and colleagues also leads the authors to suggest that radiotherapy cannot be relied upon to decrease the risk of recurrence if tumor removal results in positive margins. "We highlight that RT should complement (and not be supplanted by) the targeting of wider free margins to minimize [same breast tumor recurrence]," write the authors.

One of the issues with assessing the most optimal margin, according to the authors, is that it is unethical to execute a trial assigning women at random to different margin widths during surgery. According to the study authors, this is why all outcome assessments must rely on analysis of observational studies, not the optimal way to assess patient data.

The editorial, by Monica Morrow, MD, the department of surgery at the Memorial Sloan-Kettering Cancer Center in New York and Steven J. Katz, MD, MPH, the department of medicine and health management and policy at the University of Michigan, highlight the study’s limitation and biases.[2]

"It is important to consider the consequences of adopting new management or treatment recommendations on delivery and ultimately patient health," says Dr. Katz, who suggests that if the authors’ recommendation of a larger margin clearance was widely adopted, "the likely consequence would be surgeons reducing their decision threshold for contraindication to breast-conserving surgery [resulting in more initial mastectomies] and more reexcision post breast-conserving surgery as surgeons would strive to achieve the 10 mm or more clear margins which are rarely achieved currently."

Dr. Katz and Dr. Marrow also note that only 5 of the 21 studies included in the meta-analysis by Dr. Wang and colleagues reported margins of 10 mm or more, questioning the validity of the conclusion reached in the study. The editorial authors also question whether a randomized trial to test optimal margin widths would be worth the large cost, especially since previous studies have suggested that finely defined margins only have a negligible incremental cost benefit to the patient.

Instead, Dr. Katz and Dr. Marrow suggest that adopting a standard method of excised tissue processing and examination would result in better data and better results from observational studies.

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 Mar 22. [Epub ahead of print]

2. Morrow M, Katz SJ. Margins in Ductal Carcinoma In Situ: Is Bigger Really Better? J Natl Cancer Inst. 2012 Mar 22. [Epub ahead of print]