SIDEBAR: Nonrandomized Analysis Viewed with Skepticism

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Lori J. Pierce, MDThe findings from Grumley et al contradict the results from randomized trials of lumpectomy vs lumpectomy and radiotherapy for ductal carcinoma in situ (DCIS) and highlight the potential pitfalls of retrospective analyses. The meta-analysis of the DCIS trials revealed a significant 54% reduction in ipsilateral breast events with the addition of radiotherapy,1 and unlike the Grumley USC analysis, an equal proportion of these ipsilateral events were invasive in both the radiotherapy and nonradiotherapy arms. As a result, breast cancer–specific and overall survivals were identical with or without radiotherapy.

Furthermore, in a recent analysis by the National Surgical Adjuvant Breast and Bowel Project (NSABP), which considered the long-term outcomes of women enrolled in the B‑17 and B-24 trials who specifically experienced an invasive ipsilateral recurrence, again no significant differences were observed in breast cancer mortality and overall mortality with or without radiotherapy.2 Clearly, the NSABP investigators found no deleterious effect of radiotherapy, as suggested in the USC analysis.

Differences in nonrandomized comparisons for factors such as tumor size, nuclear grade, margin width, patient age, and year of treatment clearly affect reported outcomes. Moreover, treatment algorithms such as (modifications of) the Van Nuys Prognostic Index, by design, select patients with higher tumor burden to receive radiotherapy.  So it is not surprising that the results from the nonrandomized analysis from USC differ from those reported in the randomized trials. It is only through studies that are without selection bias that the long-term benefits of radiotherapy can be fully appreciated. ■

Financial Disclosure: Dr. Pierce reported no potential conflicts of interest.


1. Early Breast Cancer Trialists’ Collaborative Group: Overview of the randomized trials of radiotherapy in ductal carcinoma in situ of the breast. J Natl Cancer Inst Monogr 41:162-177, 2010.

2. Wapnir IL, Dignam JJ, Fisher B, et al: Long-term outcomes of invasive ipsilateral breast tumor recurrences after lumpectomay in NSABP B-17 and B-24 randomized clinical trials for DCIS. J Natl Cancer Inst 103:478-488, 2011.

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