SUBMIT: Systemic therapy with or without up front surgery of the primary tumor in breast cancer patients with distant metastases at initial presentation

Abstract

BackgroundFive percent of all patients with breast cancer have distant metastatic disease at initial presentation. Because metastatic breast cancer is considered to be an incurable disease, it is generally treated with a palliative intent. Recent non-randomized studies have demonstrated that (complete) resection of the primary tumor is associated with a significant improvement of the survival of patients with primary metastatic breast cancer. However, other studies have suggested that the claimed survival benefit by surgery may be caused by selection bias. Therefore, a randomized controlled trial will be performed to assess whether breast surgery in patients with primary distant metastatic breast cancer will improve the prognosis.DesignRandomization will take place after the diagnosis of primary distant metastatic breast cancer. Patients will either be randomized to up front surgery of the breast tumor followed by systemic therapy or to systemic therapy, followed by delayed local treatment of the breast tumor if clinically indicated.Patients with primary distant metastatic breast cancer, with no prior treatment of the breast cancer, who are 18 years or older and fit enough to undergo surgery and systemic therapy are eligible. Important exclusion criteria are: prior invasive breast cancer, surgical treatment or radiotherapy of this breast tumor before randomization, irresectable T4 tumor and synchronous bilateral breast cancer. The primary endpoint is 2-year survival. Quality of life and local tumor control are among the secondary endpoints.Based on the results of prior research it was calculated that 258 patients are needed in each treatment arm, assuming a power of 80%. Total accrual time is expected to take 60 months. An interim analysis will be performed to assess any clinically significant safety concerns and to determine whether there is evidence that up front surgery is clinically or statistically inferior to systemic therapy with respect to the primary endpoint.DiscussionThe SUBMIT study is a randomized controlled trial that will provide evidence on whether or not surgery of the primary tumor in breast cancer patients with metastatic disease at initial presentation results in an improved survival.Trial registrationNCT01392586.

Surgery of the primary tumor in de novo metastatic breast cancer: To do or not to do?

“…33 However, as all the included studies were retrospective, and based on this, one cannot conclude that surgical removal of the primary breast tumor improves overall survival. Therefore, several randomized controlled trials were designed to determine if local therapy would improve survival in a randomized fashion in patients with de novo metastatic breast cancer (Table 2) 34,35 In the last couple of years, presented but unpublished results from two of these randomized controlled trials did not confirm the favorable role of primary surgery for all the patients with de novo metastatic breast cancer that was previously suggested by most retrospective studies. In the study from the Turkish Federation of Societies for Breast Diseases Soran et al, suggested that patients with isolated bone metastases may benefit from surgery, whereas such an approach was even detrimental in patients with visceral involvement.…”

ESO-ESMO 2nd international consensus guidelines for advanced breast cancer (ABC2)

“…Since 2011 several randomized trials have started accrual comparing loco-regional treatment of primary vs. no treatment in stage IV patients at presentation [124,125].…”

Surgical treatment of the primary tumour improves the overall survival in patients with metastatic breast cancer: A systematic review and meta-analysis

“…One ongoing trial may answer some of these questions. It is randomised cohort trial comparing immediate resection of the primary tumour, followed by systemic therapy and systemic therapy, followed by delayed surgical resection (24). It is prudent to revise this meta-analysis when the results of this and other similar trials become available.…”