Abstract ES11-2: Local therapy of limited disease in ABC: what is the evidence?
Authors: Khan SA 
Published: February 2018

Abstract
Surgery and radiotherapy have been used as adjunctive treatments for women with Stage IV breast cancer and a low volume of disease, for many years. This encompasses patients with intact or recurrent disease at the primary site, as well as those with oligometastatic distant disease. The evidence to support local therapy (LT) approaches in this group of patients is largely retrospective, although randomized trials are ongoing. For patients with an intact primary tumor, over 20 retrospective analyses suggest that women undergoing primary site LT (PSLT) experience longer survival than those whose primary tumor receives no LT, with one meta-analysis of these data reporting a hazard ratio (HR) of 0.69 (95%CI 0.63, 0.77). However, a concern about selection bias as the explanation for this apparent benefit has led to several randomized trials. Two of these were reported recently, with mixed results. The design and the results of the two completed trials were different. In Mumbai, India (NCT00193778), initial therapy consisted of chemotherapy followed by randomization to PSLT or not; results showed no overall survival difference, but local control was improved in the PSLT arm. In Turkey, MF07-01 randomized Stage IV patients to PSLT or not, followed by usual systemic therapy; results suggest an improvement in overall survival at 5 years for women in the PSLT arm. Two other randomized trials are ongoing, both designed with initial systemic therapy. In the meantime, existing data do not clearly support the use of PSLT as a means of improved survival, but the local control advantage was clear in both trials, and therefore PSLT may be offered to women whose primary tumors do not respond well to systemic therapy.
For women with oligometastatic disease, the data supporting LT measures is again retrospective, and consists of small, highly selected series. However, interest in LT approaches spans back many decades, and studies suggest that various strategies of surgery, radiotherapy, and more recently stereotactic body radiotherapy (SBRT), are associated with prolonged survival. The distant sites that have been subjected to these approaches include isolated metastases in lung, liver, bone, and brain. For isolated lung lesions in particular, resection also allows a clear distinction between primary and metastatic disease, since a large fraction of solitary lung lesions may in fact be primary lung tumors. In the liver, small retrospective series of highly selected patients undergoing resection suggest that longer-than-expected median survival can be observed in patients with limited disease and a long disease-free interval. Minimally invasive ablation techniques are being used with similar intent. For osseous sites, retrospective analyses of high-dose radiotherapy with ablative intent reflect similar caveats and similar results to the data on lung and liver. An important ongoing trial (NCT02364557) is randomizing women with a controlled primary tumor site and ≤2 metastatic lesions that are amenable to treatment with SBRT or surgery, to usual care or usual care with the addition LT to distant sites that must be separated by a distance of &gt;5 cm. These ongoing studies will bring much-needed clarity to the role pf LT approaches to both the primary site and limited distant disease.
Citation Format: Khan SA. Local therapy of limited disease in ABC: what is the evidence? [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr ES11-2.