Abstract
BACKGROUND: The role of various serum tumor markers (TMs) has been reported in non-small cell lung cancer (NSCLC). However, the prognosis of patients with multiple TM-negative NSCLC remain unclear. AIMS: This study aimed to describe the characteristics and outcomes of patients with NSCLC undergoing surgery and to investigate their prognostic association with preoperative serum TM-negative cases. METHODS AND RESULTS: We retrospectively evaluated 442 patients who underwent complete resection of stage I NSCLC between January 2004 and December 2019. These 442 patients were classified into a group whose preoperative serum levels of carcinoembryonic antigen (CEA), cytokeratin-19 fragment (CYFRA21-1), carbohydrate antigen 19-9 (CA19-9), and squamous cell carcinoma antigen (SCC Ag) were all negative (TM-negative group; n = 249, 56%) and a group with at least one positive marker (TM-positive group; n = 193, 44%). Among all patients, the TM-negative group showed higher 5-year recurrence-free survival (RFS) (92.6% vs. 79.1%; p < .01), and overall survival (OS) rates (86.3% vs. 68.6%; p < .01). After propensity score matching, patients in the TM-negative group still exhibited good 5-year RFS (92.1% vs. 81.4%; p = .01) and OS rates (87.6% vs. 72.6%; p < .01). CONCLUSION: Our study suggests that NSCLC patients who are preoperatively negative for all serum TMs, such as CEA, CYFRA21-1, CA19-9, and SCC Ag, represent a subgroup with a particularly good prognosis.