Synchronous Primary Stage I Non-Small Cell Lung Cancer: Trends in Management and Survival

W. Stina. Brandt¹, D. B.. Eaton², T. Thomas³, M. Schoen⁴, P. Samson⁵, M. Patel⁶, Y. Yan⁷, S. Chang⁸, N. E. Rosetti⁹, S. Tohmasi⁷, G. Patterson¹⁰, D. Kreisel¹¹, B. Kozower¹¹, R. Nava⁷, B. Meyers¹¹, V. Puri^7
1Washington University St Louis, St. Louis, Missouri ²John Cochran Veterans Hospital, St. Louis, MO, St. Louis, Missouri ³Washington University St. Louis School of Medicine, Webster Groves, Missouri ⁴Washington University in St. Louis, St. Louis, Missouri ⁵Washington University St. Louis, Webster Groves, Missouri ⁶Veterans Hospital Administration, Saint Louis, Missouri ⁷Washington University in St. Louis School of Medicine, Saint Louis, Missouri ⁸Washington University St. Louis School of Medicine, Saint Louis, Missouri ⁹Washington University St. Louis, St Louis, Missouri ¹⁰Washington University St. Louis, Saint Louis, Missouri ¹¹Washington University in St. Louis School of Medicine, St. Louis, Missouri

Purpose: Synchronous primary stage I non-small cell lung cancers (NSCLC) are seen in ~2% of patients diagnosed with lung cancer every year.1 Though previous studies have analyzed outcomes for surgical resection in this population2-4, the outcomes after multi-modality definitive-intent therapies [(resection or stereotactic-body radiotherapy (SBRT)] are inadequately understood.

Methods: Using a highly collated cohort of Veterans assembled using extensive database abstraction, chart review, and natural language processing, we performed a retrospective study (2006-2024) to evaluate patients diagnosed with two synchronous primary clinical stage I NSCLC within 6 weeks of each other and treated via stereotactic body radiation therapy (SBRT) and/or surgery within 1 year of diagnosis. We excluded patients who had no tissue diagnosis, >2 tumors, and those with two tumors with identical histologic subtypes in the same lobe. We evaluated patient clinicopathologic details including: age, sex, comorbidity index, tumor size, tumor stage, treatment modalities , interval between treatments, comorbidities, and histology. Our primary endpoint was overall Survival (OS), calculated from the time of treatment of the second tumor. We secondarily evaluated the trend in use of SBRT and/or surgery over time. Cox Proportional hazard modeling and Kaplan Meier analysis were used to evaluate OS.

Results: In total, 807 patients met inclusion criteria. The cohort had a Median age of 70 years and was predominantly male (N=776, 96.5%) and white (N=650, 80.6%). Two-hundred and seven (26%) patients had two adenocarcinomas, 121 (15%) had two squamous cell carcinomas, and 260 (32.2%) had mixed histology. The larger tumor was treated first in 527 (65%) patients. Overall, 294 (36.4%) received SBRT for both lesions, 143 (17.7%) had surgery and SBRT, and 370 (45.8%) had surgery for both lesions. Patients in the SBRT-SBRT group had higher comorbidity index than surgical groups (p < 0.00001). Utilization of SBRT increased over time,: in 2008 SBRT was utilized for both cancers in < 20% of cases versus 50% of cases of in 2017. Five-year OS for the entire cohort was 45.5%. Adjusted 5-year OS was 40.9 % (95% CI 24.9-67.2) for those who had SBRT-SBRT versus 73.1% (95% CI 57.9-92.3) for those who had surgery-SBRT and 66.2% (95% CI 53.7-81.5) for those who underwent surgery for both lesions (Figure 1). Multivariable analysis for OS demonstrated that patients treated with SBRT-SBRT, who were older or had increased comorbidity had worse OS, and treatment in more recent year protective (Table 1).

Conclusion: Among Veterans with synchronous stage I NSCLC, adjusted 5yr-OS is 45.5%. Improved OS is associated with two adenocarcinoma primaries and those who undergo resection over SBRT therapies. Overall, survival for this population is improving over time, which is likely associated with improved patient selection and increased utilization of SBRT for suboptimal surgical candidates.

Identify the source of the funding for this research project: VA Merit Award (Varun Puri)