A Lost Opportunity: Underutilization of Systemic Therapy in T3N0M0 Non-Small Cell Lung Cancer

Treatment guidelines for non-small cell lung cancer (NSCLC) include systemic therapy for tumors >5 cm, even in the absence of metastatic/nodal disease. This study sought to evaluate the utilization rate of systemic therapy and any association with survival in this unique population with large tumors but no evidence of nodal spread.

Patients with resected NSCLC tumors >5 and ≤7 cm diagnosed between 2010 and 2019 were retrospectively selected from the National Cancer Database. Exclusion factors were metastatic disease, nodal involvement, and ≥R1 resection. Survival was compared between patients who received systemic therapy (chemotherapy, immunotherapy, or targeted therapy) and those treated with surgery alone.

Of 8274 identified patients, 3787 (45.8%) received systemic therapy. Recipients tended to be younger (64.6 versus 69.5; P < 0.001), female (45.1% versus 42.1%; P = 0.01), privately insured (37.4% versus 24.4%; P < 0.001), treated at an academic center (39.2% versus 35.7%; P < 0.001), have a Charlson Comorbidity Index of 0 (54.0% versus 50.5%; P < 0.001), and have adenocarcinoma (47.5% versus 40.7%; P < 0.001). Five-year survival was 69.5% with systemic therapy compared to 54.0% with surgery only. Using a multivariable Cox regression, systemic therapy remained associated with a decreased mortality risk (hazard ratio: 0.78, 95% confidence interval: 0.72-0.85; P < 0.001). The primary reason for lack of systemic therapy for 3368 (75.1%) patients was "not planned as part of treatment", followed by "recommended but refused" by patients/caregivers for 742 patients (16.5%).

Although systemic therapy for locally advanced NSCLC (T3N0M0) is associated with survival, it remains underutilized. Surgeons should be aware of this phenomenon and advocate accordingly.