Resection of the Primary Tumor and Survival in Patients with Single-Site Synchronous Oligometastatic Non-Small Cell Lung Cancer: Propensity-Matched Analysis of the National Cancer Database

Background: Local therapy for the primary tumor is postulated to remove resistant cancer cells as well as immunosuppressive cells from the tumor microenvironment, potentially improving response to systemic therapy. We sought to determine whether resection of the primary tumor was associated with overall survival in a multicentric cohort of patients with single-site synchronous oligometastatic NSCLC. Study Design: Using the National Cancer Database (2018-2020), we evaluated patients with clinical stage IVA disease who received systemic therapy and stratified the cohort based on receipt of surgery for the primary tumor (S). We used multivariable and propensity-score matched analysis to study factors associated with S (logistic regression) and overall survival (Cox regression and Kaplan-Meier), respectively. Results: Among 12,215 patients identified, 2.9% (N=349) underwent S and 97.1% (N=11,886) systemic therapy (chemotherapy/immunotherapy) without surgery (ST). Patients who underwent S were younger, more often white, had higher income levels, more likely to have private insurance, and were more often treated at an academic facility. Among those who received S, 22.9% (N=80) also underwent resection of the distant metastatic site. On multivariable analysis, metastasis to bone, N+ disease, and higher T-stages were independently associated with less S. On Cox-regression, S and resection of the metastatic site were associated with improved survival (HR 0.67, 95%CI 0.56-0.80 and HR 0.80, 95%CI 0.72-0.88, respectively). After propensity-matching, overall survival was improved in patients undergoing S (median 36.8 vs. 20.8 months, log-rank p<0.001). Conclusions: Advances in systemic therapy for NSCLC may change the paradigm of eligibility for surgery. This study demonstrates that surgical resection of the primary tumor is associated with improved overall survival in selected patients with single-site oligometastatic disease.