Event-Free Survival After Stereotactic Body Radiation Therapy for Oligoprogressive Metastatic Breast Cancer

Oligoprogressive advanced breast cancer (aBC) is becoming an increasingly frequent scenario in which prognosis can be meaningfully improved through targeted local interventions. However, evidence is still lacking. In this study, we aimed to evaluate the role of progression-directed radiation therapy (PDRT) in the management of oligoprogressive aBC.

We performed a single-institution retrospective analysis of consecutive patients with oligoprogressive aBC who underwent progression-directed radiation therapy (PDRT) between January 2018 and December 2024. Oligoprogression was defined as emergence of up to 5 progressing lesions across a maximum of 3 distinct organs, after at least 1 line of systemic therapy. The primary endpoint was the event-free survival (EFS), defined as interval from the completion of PDRT to one of the following: change of systemic therapy [which is also called time to next treatment (TNT)], progression < 6 months, or ≥ 3 new or progressing lesions, death, or last follow-up. Secondary endpoints included progression-free survival (PFS), and overall survival (OS).

We analyzed 56 patients, with 17 months [interquartile range (IQR): 8-27] of median follow-up. Median age at PDRT was 58 years (IQR: 49-68). Prior to PDRT, 28 patients (50%) had received only 1 line of treatment, 12 (21.4%) had received 2 lines, and 16 (28.6%) had undergone 3 or more lines. Before the onset of oligoprogression, in response to systemic therapy, 31 patients (55.4%) had achieved stable disease, 9 patients (16.0%) a partial response, and 16 patients (28.6%) a complete response at all disease sites. In 39 patients (69.6%) an event occurred after PDRT, with a median event free survival (EFS) of 7 months (IQR: 3-15). The 1-year and 2-year actuarial EFS rates were 39% (95% CI, 33.1%-45.9%) and 24% (95% CI, 17.2%-30.8%), respectively. Among these 39 patients, thirty-three (84.6%) initiated a new line of systemic therapy after PDRT, with a median TNT of 8 months (IQR 4-17), with a 1-year actuarial rate of 46.6%. At the multivariate analysis, HER2 positive and Luminal A subtypes were confirmed as significant predictive factors for increased EFS (adjusted HR = 0.31, P = .01; aHR = 0.27, P = .01, respectively). Furthermore, lymph nodal PDRT appeared to be associated with a protective effect in the univariate analysis (P = .04); however, this association was not retained in the multivariate analysis. Median PFS was 7 months (IQR: 3-12), with 41 patients (73.2%) experiencing disease progression, while the median OS was 17 months (IQR: 8-27). Multivariate analysis confirmed lobular histology as an independent adverse prognostic factor (HR = 9.05, P = .006).

Our findings suggest that PDRT may delay the occurrence of events and the need to change systemic therapy in selected patients. This benefit appears more prominent in cases of HER2 positive or luminal aBC and in cases of nodal progression. Future research should focus on refining selection criteria to identify patients with higher benefit from PDRT.