Incidence of second primary cancers in lung cancer survivors by oncological treatment: a nationwide prospective cohort study in Spain.

Abstract

Among patients with lung cancer, treatment with novel oncological agents may influence the risk of developing Second Primary Cancers (SPCs). We aimed to evaluate the incidence of SPCs in patients with lung cancer according to the type of oncological treatment received. We conducted an observational, prospective, nationwide study based on the Spanish Thoracic Tumour Registry (TTR), between August 2016 and March 2023. Eligible patients aged over 18 years, diagnosed with lung cancer, and who achieved tumour remission were included. A total of 20,574 patients were included. After a median follow-up of 41.2 months (95% CI 40.2-42.2), 480 patients developed a SPC (2.3%). The overall incidence was higher among those treated with chemotherapy (2.9%) compared with those receiving immunotherapy (2.1%) or targeted therapy (1.5%) (p < 0.001). The cumulative incidence of SPCs at 12 months for patients that received chemotherapy was 1.22% (95% CI 0.99-1.45), 0.85% (95% CI 0.62-1.08) for immunotherapy and 0.67% (95% CI 0.34-0.99) for targeted therapy (p < 0.001). In the adjusted multivariate model, both immunotherapy and targeted therapy were associated with a reduced risk of SPCs: HR = 0.470 (95% CI 0.338-0.654) and HR = 0.701 (95% CI 0.574-0.855), respectively. Additional associated factors with SPCs included metastatic disease, HR = 0.456 (95% CI 0.377-0.552); history of tobacco use, HR = 1.599 (95% CI 1.127-2.269); and current smoking, HR = 1.319 (95% CI 0.923-1.884) p < 0.001. Patients treated with immunotherapy and targeted therapy exhibited a significantly lower incidence of SPCs. Tobacco use was a key associated factor. Strengthening oncological follow-up and promoting interventions to address modifiable risk factors are essential for optimising long-term outcomes in lung cancer survivors. This study was supported by the Spanish Lung Cancer Group (Fundación GECP).