Prognostic Factors Affecting Survival in Patients with Non-small Cell Lung Cancer Treated with Salvage Surgery After Drug Therapy: a Multi-institutional Retrospective Study

Background: The prevalence of salvage surgeries after drug therapy for non-small cell lung cancer (NSCLC) has risen, mainly due to recent progress in molecular-targeted drugs and immune checkpoint inhibitors for NSCLC. While the safety and effectiveness of salvage surgery after drug therapy for NSCLC have been studied, its indications remain unclear. We aimed to identify the prognostic factors affecting survival in patients with advanced-stage (stages III-IV) NSCLC treated with salvage surgery after drug therapy.

Methods: A retrospective investigation was conducted on patients who received salvage surgery after drug therapy at four hospitals between 2007 and 2020. Salvage surgery was defined as surgery after drug therapy for local progression, tumor conversion to resectable status, and discontinuation of prior drug therapy owing to serious complications.

Results: Thirty-two patients received cytotoxic agents alone (n = 12 [38%]), tyrosine kinase inhibitors (TKIs; n = 16 [50%]), or immune checkpoint inhibitors (n = 4 [13%]) as prior drug therapy. In 11 (34%) and 21 (66%) patients, the clinical stage before treatment was III or IV, respectively. The median initial and preoperative serum carcinoembryonic antigen (CEA) levels were 10.2 (range, 0.5-1024) ng/mL and 4.2 (range, 0.6-92.5) ng/mL, respectively. Among the patients, 28 (88%) underwent lobectomy, 2 (6%) underwent segmentectomy, and 2 (6%) underwent wedge resection. Complete resection of the primary lesion was accomplished in 28 (88%) patients. Postoperative complications were documented in six (19%) patients. Mortality rates were 0% at 30 days and 3% at 90 days post-operation. The 5-year overall survival rate stood at 66%, while the 5-year progression-free survival rate was 21%. Multivariate analyses showed that prior TKI therapy and preoperative serum CEA level < 5 ng/mL were prognostic factors influencing overall survival (hazard ratio [95% confidence interval]: 0.06 [0.006-0.68] and 0.03 [0.002-0.41], respectively). The 5-year overall survival in the 11 patients with both favorable prognosticators was 100%.

Conclusions: In this study, prior TKI therapy and preoperative serum CEA level < 5 ng/mL were favorable prognostic factors for overall survival in patients with NSCLC treated with salvage surgery. Patients with these prognostic factors are considered good candidates for salvage surgery after drug therapy.