Abstract PS1-42: Locoregional treatment in de novo metastatic breast cancer: An overview of the current evidence
Authors: Chongxi Ren 
Published: February 2021

Abstract
Background: Patients presenting with de novo metastatic breast cancer (dnMBC) is considered incurable but treatable. Despite the advances in systemic therapies, the role of locoregional treatment (LRT, primary tumor surgery and/or radiotherapy) for dnMBC remains controversial.
Aim: To review and discuss the present evidence of surgery- and radiation-based treatment strategies for dnMBC.
Settings and design: A systematic review and meta-analysis of the literature were carried out.
Methods: We did a systematic review and meta-analysis of observational studies and randomised controlled trials (RCTs) published from database inception to Feb 28, 2020, which reported on survival outcomes of LRT in patients with dnMBC. Studies were identified by searches in PubMed, MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and by hand searching of previous publications. The review and meta-analysis were conducted to assess the effect of LRT on overall survival (OS). Robustness of pooled estimates from random-effects models was considered with sensitivity analyses, meta-regression, and subgroup analyses. All statistical analyses were performed with Stata 16.0.
Findings: Data on 714 patients in 3 RCTs and 173476 patients in 39 observational studies were included. In total 174190 patients, 76711 patients (44.04 %) underwent LRT ± systemic therapy, and 97479 patients (55.96 %) received systemic therapy alone (STA). Observational data showed LRT significantly improved overall survival (HR=0.63; 95%CI, 0.57 to 0.69, P&lt;0.001, I2=96.3%). The subgroup analysis found a favorable impact on survival in both patients undergoing surgery plus radiotherapy and surgery. However, the pooled outcomes of prospective trials suggested a 19.0% reduction in mortality which was not statistically significant (HR=0.81; 95% CI, 0.57 to 1.14, P=0.06, I2=64.4%).
Interpretation: Due to the paucity of RCTs exploring LRT in patients with dnMBC, this was a meta-analysis which included retrospective and prospective data; both sets provide a complete picture of the effect. However, withstanding for retrospective bias, separate analyses was conducted to specifically examine the prospective trials. Findings from observational studies and RCTs associated with LRT and OS in these patients were inconsistent. Given the retrospective nature of observational studies, its results cannot be used as level I evidence to support LRT in patients with dnMBC. As level I evidence, prospective data suggest that the relationship between the LRT and survival benefit in these patients could not be causal. Although these trials have been criticized due to systemic therapy protocols which differ from standard modern treatments, they continue to provide important data. Ongoing well-designed prospective studies, including ECOG 2108 trial, are awaiting mature data.
Conclusions: Based on the results of current level I evidence, LRT should not be part of routine clinical practice in patients with dnMBC but might be performed in specific patients.
Key words: Locoregional treatment; De novo metastatic breast cancer; Systematic review; Meta-analysis
Citation Format: Ren Chongxi. Locoregional treatment in de novo metastatic breast cancer: An overview of the current evidence [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-42.