Discussion section, continued.

In spite of the clear local control superiority of radiation even in low risk patients and even in the setting of endocrine therapy, the narrative surrounding PRIME II has pivoted to focus on the lack of survival benefit with radiation. Comparing survival was not the purpose of PRIME II. In fact, an EBCTCG meta-analysis from over a decade ago estimated a 1% or less absolute reduction in breast cancer mortality at 15 years in patients with low risk disease. Furthermore, PRIME II and similar trials were based on the assumptions that 1) 6 weeks of 90’s era radiation therapy was burdensome and 2) 5+ years of endocrine therapy was a walk in the park. Fast forward to 2023 and most PRIME II patients could receive 5 days of radiation with modest side effects. They also have to deal with years of adverse effects of endocrine therapy that lead a large proportion to discontinue treatment.  These arguments have already been laid out and are explored further by an accompanying editorial. So, the interpretation of PRIME II really comes down to a subjective assessment of whether or not the increase in local recurrence risk by omitting radiation is “acceptable.” Such an assessment should be individualized by every patient and their radiation oncologist. | Ho, N Engl J Med 2023 & Naoum, J Clin Oncol 2022