Updated evidence of primary tumor resection in stage IV breast cancer: a systematic review and meta-analysis

Abstract

Background: In stage IV breast cancer, surgical resection of the primary tumor was traditionally performed solely to palliate symptoms such as bleeding, infection, or pain. The ongoing discussion has shown that there are many research gaps in the current literature and differences in clinical practice. Thus, this systematic review and meta-analysis was designed to evaluate how primary tumor resection (PTR) affects the overall survival (OS) of patients with stage IV breast cancer. Method: A thorough literature search was completed using different databases (PubMed, Google Scholar, Scopus, ScienceDirect, and Cochrane Library) to find papers contrasting PTR with no PTR. The quality of research articles was evaluated using the Cochrane Risk of Bias 2.0 Tool and the Newcastle-Ottawa Scale (NOS). Review Manager 5.4 was used to determine how much demographic and clinical factors contribute to heterogeneity through subgroup and meta-regression analysis. Results: Data derived from 44 observational studies (OS) and four randomized controlled trials (RCTs) including 227,889 patients were analyzed. Of all cases, 150,239 patients were included in the non-PTR group, and 70,795 patients in the PTR group (37 observational studies and 4 randomized control trials). The pooled outcomes of four RCT studies (Hazard Ratio (HR) = 1.03, 95%CI: 0.67-1.58; I 2 = 88%; P < 0.0001; chi-square 24.57) favor non-PTR. While pooled outcomes of 43 observational studies showed PTR significantly improved OS (HR = 0.66, 95%CI: 0.61-0.71; I 2 = 87%; P < 0.00001; chi-square 359.12). Additionally, subgroup analysis that compared PTR with non-PTR in patients with stage IV breast cancer for progression free-survival (HR = 0.89, 95%CI: 0.62-1.28; P = 0.03; I 2 = 71%) and locoregional progression-free survival (LPFS) (HR = 0.33, 95%CI: 0.14-0.74; P = 0.0004; I 2 = 87%) was found to be significant favoring the PTR group. Distant progression-free survival (DPFS) had a non-significant relationship (HR = 0.42, 95%CI: 0.29-0.60; P = 0.12; I 2 = 53%), while overall, there was a significant relationship (HR = 0.49, 95%CI: 0.32-0.75; P < 0.00001; I 2 = 90%). Subgroup analysis revealed that PTR is beneficial in patients with bone metastasis (HR = 0.83, 95%CI: 0.68-1.01; P = 0.01; I 2 = 56%), with one metastatic site (HR = 0.75, 95%CI: 0.63-0.59; P = 0.006; I 2 = 62%), but not in patients with positive margins (HR = 0.84, 95%CI: 0.67-1.06; P = 0.07; I 2 = 61%), negative margins (HR = 0.61, 95%CI: 0.59-0.63, P = 1.00; I 2 = 0%). Most of the patients in PTR and non-PTR groups belonged to white compared to other ethnic groups. Overall, observational studies were of high quality, while RCTs were of low quality. Conclusion: The current research suggests that PTR may be discussed as a possible option.