Risk Factors Associated with a Second Primary Lung Cancer in Patients with an Initial Primary Lung Cancer

Abstract

Background: Increased patient survivorship following initial primary lung cancer (IPLC) diagnosis and treatment has uncovered new clinical challenges as individuals post-IPLC are at growing subsequent risk of developing second primary lung cancer (SPLC). Proper SPLC surveillance guidelines aimed at monitoring IPLC survivors are crucial to enhancing health outcomes. This study aims to categorize risk factors associated with SPLC emergence in IPLC survivors for clinical use following IPLC treatment.

Materials and methods: Using the Karmanos Cancer Institute Tumor Registry, patients diagnosed with IPLC from 2000 to 2017 were identified. Patients diagnosed with SPLC were matched to individuals who did not develop SPLC. Logistic and Cox regression analyses were performed to identify risk factors for SPLC emergence and overall survival (OS).

Results: One hundred twenty-one patients diagnosed with IPLC who later developed SPLC were identified and compared with 120 patients with IPLC who did not develop SPLC. Several factors such as stage at first diagnosis, histology, age, and smoking history were not associated with SPLC risk. The median time to SPLC was 1.79 years. Patients who were treated with surgical resection had a significantly higher probability of developing SPLC. After correcting for potential immortal time bias, the median OS was 3.63 years (95% confidence interval [CI], 3.05-5.00) and 7.31 years (95% CI, 4.62-10.90) for SPLC and no SPLC groups, respectively.

Conclusion: This study uncovered notable associations and lack thereof between several competing SPLC risk factors, as well as mortality. Further characterization of SPLC risk factors is essential for enhancing surveillance recommendations.

Keywords: Mortality; Surgical resection; Surveillance; Survival; Targeted monitoring.

Figure 1

Kaplan-Meier curve of time to second primary lung cancer (SPLC) among patients who had second diagnosis. Abbreviations: CI = confidence interval.

Figure 2

Kaplan-Meier curve of overall survival by the status of second primary lung cancer (SPLC) (A) before and (B) after correcting potential immortal time bias using time-varying covariate. (A) The median overall survival is 6.96 years (95% CI, 5.17–8.32) and 3.09 years (95% CI, 2.11–4.49) for group 1 (SPLC) and group 2 (no SPLC), respectively. The median follow-up time of overall survival is 13.20 years (95% CI, 11.18–16.00) and 10.30 years (95% CI, 7.84–13.30) for groups 1 and 2, respectively. (B) The median overall survival is 3.63 years (95% CI, 3.05–5.00) and 7.31 years (95% CI, 4.62–10.90) for group 1 (SPLC) and group 2 (no SPLC), respectively. The median follow-up time of overall survival is 10.41 years (95% CI, 8.81–14.41) and 4.86 years (95% CI, 4.09–6.11) for groups 1 and 2, respectively. The follow-up time was calculated using the reverse Kaplan-Meier estimate. Abbreviations: CI = confidence interval; HR = hazards ratio.