To the Editor Vaidya et al1 report 5-year outcomes in 1153 patients enrolled in the TARGIT-A trial of intraoperative radiotherapy (IORT) vs standard-of-care external beam radiotherapy (EBRT) for low-risk breast cancer in the postpathology setting. Their report provides a somewhat rare opportunity to revisit the debate in the literature at the time of the original publication of trial outcomes. The following points take stock of what we now know. First, not only is delayed second-procedure targeted IORT not noninferior to EBRT, but it is actually highly significantly inferior to EBRT with local recurrence rates at 5 years of 3.96% after IORT vs 1.05% after EBRT (2-tailed P = .002). Second, IORT may be “better than nothing,”2 but certainly not by much. The recurrence rate after IORT is 3.96% (95% CI, 2.7%-5.9%), very close to the 4.1% (95% CI, 2.4%-5.7%) local recurrence rate observed in those randomized to no radiotherapy in the PRIME trial3 after a median follow-up of 5 years. Interestingly, the rate after whole-breast radiotherapy in the control arm of PRIME was 1.3% (95% CI, 0.2%-2.3%), in very good agreement with the outcome in the EBRT arm of the TARGIT-A trial. Third, any—nonsignificant at the time—imbalances in noncancer-related mortality are long gone, and with it the suggestion that IORT should spare potentially fatal adverse effects of EBRT. To summarize, while hindsight is 20/20, the take-home message is that the warning flags were there4 already in the statistical analysis of the original publication from the TARGIT-A trial.5 Now we know.
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Bentzen SM, Haviland JS, Yarnold JR. Targeted Intraoperative Radiotherapy for Early Breast Cancer. JAMA Oncol. 2020;6(10):1636. doi:10.1001/jamaoncol.2020.2716
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