Circulomic variables predict pathologic staging preoperatively in treatment-naïve non-small cell lung cancer

Background: Therapeutic decisions in non-small cell lung cancer (NSCLC) are stage-dependent, and, consequently, changes in an individual’s stage carry potential for substantial alterations in management. Malignancy-related disturbances of the circulomic inflammatory environment may affect platelets quantitatively, ultimately leading to changes in tumor characteristics. Our objective was to identify circulomic characteristics associated with upstaging among chemotherapy-naïve patients with resected NSCLC and to assess the consequent impact on overall survival (OS). Methods: A retrospective review of a prospectively maintained thoracic surgery database was performed, identifying chemotherapy-naïve patients who underwent resection of clinical stage I–III NSCLC between 1998 and 2021. Clinicopathologic characteristics were gathered; circulomic variables comprised of platelet and lymphocyte count from the last blood draw prior to resection. Platelet-to-lymphocyte ratio (PLR) was calculated. A multivariate model evaluated variables that might affect upstaging. Kaplan-Meier analysis was performed to assess OS. Results: A total of 4,141 patients met inclusion criteria (median age: 67.0 years) among whom the sex distribution was fairly equal (2,189 female, 52.9%), and 1,016 (24.5%) individuals were upstaged. Patients with elevated PLR were found to have reduced risk of upstaging [odds ratio (OR): 0.757, 95% confidence interval (CI): 0.650–0.882]. Analyses revealed that median OS for patients who were upstaged was 80.0 months compared to 130.7 months among those who weren’t upstaged (P<0.0001). Conclusions: PLR appears to predict upstaging in treatment-naïve patients with resected NSCLC. In addition to clinicopathologic characteristics, circulomic variables may provide insight relating to pathologic staging prior to resection. These findings may guide patient counseling regarding survival probability, as well as referral patterns for adjuvant therapy.