Intraoperative radiation therapy and brachytherapy in early-stage breast cancer: a narrative review of their role in the era of modern hypofractionated whole-breast irradiation

Background and Objective: Accelerated partial breast irradiation (APBI), including intraoperative radiation therapy (IORT), interstitial and balloon-based brachytherapy, and external beam techniques, was developed to reduce the duration of radiation following breast-conserving surgery. The landscape has shifted dramatically over the past decade with the maturation of moderate hypofractionated whole-breast irradiation (HF-WBI) and the establishment of 5-fraction ultrahypofractionated whole-breast irradiation (UHF-WBI) as a standard option. An October 2025 National Broadcasting Company (NBC) News story argued that the limited adoption of IORT in the United States (U.S.) is principally a financially motivated decision. The objective of this narrative review is twofold: (I) to compare the oncologic and toxicity outcomes of IORT and brachytherapy with those of modern HF-WBI, UHF-WBI, and external beam APBI; and (II) to engage with the published health-economic literature on IORT.

Methods: PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched across time for phase III randomized trials, long-term follow-up reports, large prospective cohorts, systematic reviews, and health-economic analyses comparing IORT, brachytherapy-based APBI, external beam APBI, conventional whole-breast irradiation (WBI), and HF-WBI. Reference lists of included reviews and society guidelines were hand-searched. Only English-language publications were included.

Key Content and Findings: TARGIT-A and ELIOT, the only phase III randomized trials of IORT vs. WBI, demonstrated higher ipsilateral breast tumor recurrence (IBTR) with IORT; in TARGIT-A (pre-pathology stratum), 5-year IBTR was 2.11% with risk-adapted IORT vs. 0.95% with WBI, and in ELIOT, 15-year IBTR was 12.6% with IORT vs. 2.4% with WBI. Multicatheter brachytherapy [European Group of Curietherapy-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO)] and intensity-modulated radiation therapy (IMRT)-based APBI (Florence) achieved IBTR rates within an acceptable range of WBI at 10 years, with favorable late toxicity and cosmesis. NSABP B-39/RTOG 0413, which enrolled a broader population including women with 1–3 positive nodes, did not meet equivalence at 10 years. FAST-Forward, MC1635, and the Canadian/START trials have established 5- and 15-fraction WBI as standards of care.

Conclusions: Modern HF-WBI provides excellent oncologic control over 1–3 weeks and remains the most broadly applicable adjuvant strategy after breast-conserving surgery. Multicatheter brachytherapy and external beam APBI in appropriately selected patients are reasonable alternatives consistent with the 2023 American Society for Radiation Oncology (ASTRO) and 2025 American Society of Breast Surgeons (ASBrS) guidelines.