Should aggressive thoracic therapy be performed in patients with synchronous oligometastatic non-small cell lung cancer? A meta-analysis

Abstract

Background: We performed a meta-analysis to compare overall survival (OS) outcomes in patients with synchronous oligometastatic non-small cell lung cancer (NSCLC) who underwent aggressive thoracic therapy (ATT) with those who did not. Methods: A systematic review of controlled trials of ATT on survival in synchronous oligometastatic NSCLC was conducted. Hazard ratio (HR) for the main endpoint OS was pooled using a fixed-effects model. Subgroup analysis was performed in patients with single organ metastases, or with different numbers of brain metastases, or with different stages of thoracic disease. Pooled survival curves of OS were constructed. Results: Seven eligible retrospective observational cohort studies were identified including 668 synchronous oligometastatic NSCLC patients, of whom 227 (34.0%) received ATT. For patients with synchronous oligometastatic NSCLC, ATT was associated with a significant improvement of OS (HR, 0.48; 95% CI, 0.39-0.60; P<0.00001). In subgroup analysis, the association with OS was similar or even strengthened, with a HR of 0.42 (95% CI, 0.31-0.56) in single organ metastases group, 0.49 (95% CI, 0.31-0.75) in solitary brain metastasis group, and 0.38 (95% CI, 0.20-0.73) in thoracic stage I-II group, respectively. The pooled cumulative survival rates for patients received ATT were 74.9% at 1 year, 52.1% at 2 years, 23.0% at 3 years, and 12.6% at 4 years. The corresponding pooled survival for patients who did not receive ATT were 32.3%, 13.7%, 3.7%, and 2.0%, respectively. Conclusions: Survival benefit from ATT is common in synchronous oligometastatic patients. Selected patients with synchronous oligometastatic NSCLC could also achieve long-term survival with ATT. Targeted therapy have shown efficacy in the treatment of advanced NSCLC, however, most patients progress after a median survival of 12 months because of resistance (4-6).Hellman and Weichselbaum proposed the existence of a clinically recognisable state termed 'oligometastases', which is an intermediate state of metastases characterized by a limited number and site of metastatic tumors. In these selected patients, eradication of oligometastases could be curative (7,8). However, whether the aggressive thoracic therapy (ATT) could potentially improve overall survival (OS) in oligometastatic NSCLC remains unclear. Removal of the primary tumor was shown to improve OS in patients with metastatic renal cancer (9), by contrast, locoregional treatment of the primary tumor did not affect OS in patients with metastatic breast cancer (10). More and more studies reported favorable long-term survivals in oligometastatic NSCLC treated with aggressive local therapy (11-13). However, these studies are retrospective and the validity of the survival benefit are challenging due to patient selection.Recently, Ashworth et al. did a systematic review of literature considering NSCLC patients with 1-5 metastases treated with local therapy and found that definitive treatment of the primary tumor was a good prognostic factor for survival (14). Moreo...

Radiotherapy improves the survival of patients with stage IV NSCLC: A propensity score matched analysis of the SEER database

“…Theoretically, local control of the primary and metastatic tumor can reduce the intra‐thoracic disease burden and symptoms and might result in a better OS . This notion is supported by a study of extensive‐stage SCLC .…”

“…It has been shown that using RT to control primary and metastatic tumors can reduce intra‐thoracic disease burden, bronchial/vascular compression, and pulmonary symptoms . In addition, local control of primary and metastatic tumors might result in better OS . Recently, a phase III randomized controlled trial (RCT) showed that thoracic radiotherapy (TRT) also improved OS of patients with extensive‐stage small cell lung cancer (SCLC) who responded to chemotherapy .…”

Complete resection of the primary lesion improves survival of certain patients with stage IV non-small cell lung cancer

“…Some studies have analyzed oligometastatic disease (4,(6)(7)(8)(9)(10) and pleural dissemination in stage IV NSCLC (2,3). However, there are few reports that deal only with stage IV NSCLC.…”

“…For patients with NSCLC stage IV, if we select complete resection of the primary lesion as the initial treatment, an important consideration is whether local therapy, such as surgical resection or radiotherapy, is possible for the metastasis. These issues have been considered in both prospective and retrospective studies on oligometastasis (4,(6)(7)(8)(9).…”

“…Local therapies such as surgery or radiotherapy, given alone or combination with systemic therapy, may allow curative treatment of oligometastasis (4,7,8). In synchronous oligometastatic patients, local therapy may significantly prolong the overall survival time (4,(7)(8)(9)(10). It is therefore important to clarify the selection of appropriate candidates for radical local therapy.…”