Are the Randomized Trials of Radiation Therapy for Ductal Carcinoma in Situ Still Relevant?
Authors: Abram Recht
Journal: Journal of Clinical Oncology (2014)

The article by Warnberg et al that accompanies this editorial completes a recent series of updates of four randomized trials begun between 1985 and 1990 comparing outcome with or without radiation therapy (RT) after breast-conserving surgery for patients with ductal carcinoma in situ (DCIS; Table 1). Rates of local failure (sometimes referred to as ipsilateral breast events [IBE]) at median follow-up intervals of approximately 13 to 17 years were 25% to 35% in the unirradiated arms compared with 10% to 20% in the irradiated arms. But are these findings still relevant today? So many aspects of patient evaluation and selection for breast-conserving therapy were different then than they are now. There was much less use of magnification mammography resulting in underestimation of lesion extent. Pathologic evaluation was not standardized, and only limited sampling was performed even with large specimens. For example, in the National Surgical Adjuvant Breast and Bowel B-17 trial, a median of nine slides were sent for central pathology review with a range of one to 70 slides. Interestingly, that review also reclassified 18% of patients as having involved or inevaluable margins. The trials had broad selection criteria with regard to patient age at diagnosis, the means of presentation (mammographically detected or symptomatic), lesion size, and histologic features. Finally, they required only negative resection margins, which was defined as the absence of tumor at the inked specimen edges. The Swedish trial also accepted patients with positive or unknown margins, who constituted approximately 20% of the study population. Clues appeared in the late 1980s, and after that, the minimum tumor-free margin width was a critical variable for the risk of IBE for unirradiated patients. Other studies found that larger size and the presence of high nuclear grade and comedo-type necrosis increased local recurrence rates. An influential study assigned points for histology, tumor size, and margin width and combined them into a single number, which predicted the risk of relapse after lumpectomy with or without RT. This index was later revised to include patient age. With a median follow-up of 75 months, unirradiated patients with a University of Southern California-Van Nuys Prognostic Index score of 4 to 6 had a 10-year IBE rate of 6%—only slightly higher than those who were irradiated. A study from the S. Orsola Malpighi Hospital in Bologna, Italy, found a 10-year disease-free survival rate of 5% among 144 such low-score patients with mean follow-up of 130 months. Other groups have also proposed prognostic indices, although these have not always been reliable. The first prospective trial in the United States testing whether a group could be chosen that would do well with excision alone was conducted from 1995 to 2002 in Boston. Patients were eligible if they had DCIS of predominant nuclear grade 1 or 2 that was 25 mm or smaller, a minimum tumor-free margin width of 10 mm or no tumor on reexcision, and no calcifications on postoperative mammography.