Efficacy and cosmetic outcomes of radiotherapy modalities in early-stage breast cancer: a systematic review and network meta-analysis.

UNLABELLED: Breast cancer (BC) is a common malignancy with increasing annual incidence. Radiotherapy shows favorable clinical efficacy in BC management, but limited randomized controlled trial data is a major limitation. Therefore, further validation of the optimal radiotherapeutic strategy for early-stage BC is required. This network meta-analysis evaluated radiotherapy regimens' effects on efficacy and cosmetic outcomes in early-stage BC, guiding clinical practice. A comprehensive literature search was conducted in PubMed, Cochrane Library, Embase, and Web of Science databases to identify randomized controlled trials and cohort studies investigating radiotherapy approaches for early-stage BC. Data screening and extraction were independently performed using a standardized protocol. Study quality was assessed using the Cochrane Risk of Bias tool and Newcastle-Ottawa Scale. The primary endpoint was ipsilateral breast recurrence (IBR), and secondary endpoints included locoregional recurrence, overall survival, disease-free survival, and cosmetic outcomes. Statistical analyses were performed using R 4.4.1 and STATA 18.0. A total of 36 studies involving 32,655 patients and 9 interventions were included. The lowest IBR rate was observed in patients treated with hypofractionated whole-breast irradiation (HF-WBI) (surface under the cumulative ranking curve [SUCRA], 10.54%), followed by conventional fractionated whole-breast irradiation (CF-WBI) (SUCRA, 35.70%). Compared with CF-WBI, intraoperative electron radiotherapy (IOeRT) (odds ratio [OR], 4.19; 95% credible interval [CrI], 1.83-10.26), intraoperative radiotherapy (IORT) (OR, 1.75; 95% CrI, 1.06-2.87), and HF-WBI (OR, 0.78; 95% CrI, 0.56-0.99) demonstrated statistically significant differences. The best cosmetic outcomes were achieved with three-dimensional conformal radiotherapy (3D-CRT) (SUCRA, 14.43%), followed by intensity-modulated radiotherapy (IMRT) (SUCRA, 16.04%). Compared with CF-WBI, 3D-CRT (OR, 0.11; 95% CrI, 0.01-0.85), IMRT (OR, 0.13; 95% CrI, 0.01-0.72), and IOeRT (OR, 0.25; 95% CrI, 0.04-0.78) showed statistically significant improvements. Since evidence supporting cosmetic outcomes is limited, findings should be interpreted with caution. Among patients with early-stage BC, HF-WBI was associated with the lowest rate of postoperative ipsilateral recurrence, whereas CF-WBI was associated with the second-lowest rate. In terms of cosmetic outcomes, 3D-CRT and IMRT demonstrated favorable clinical efficacy. Additional randomized controlled trials are necessary to clarify the comparative advantages and limitations of CF-WBI, HF-WBI, 3D-CRT, and IMRT, thereby strengthening the evidence base for early-stage BC radiotherapy strategies. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251173161.