Diagnostic Workup, Treatment Patterns, and Clinical Outcomes in Early-Stage IB–IIIA Non-Small-Cell Lung Cancer Patients in Denmark

SIMPLE SUMMARY: This real-world evidence study contributes important insights for clinicians to further optimize treatment options and improve clinical outcomes in patients with early-stage non-small-cell lung cancer (NSCLC), considering evolving clinical trials on new perioperative treatment modalities. This Danish register-based study followed 1341 stage IB-IIIA patients diagnosed with NSCLC in Aarhus University Hospital between 2010 and 2021. Half of all patients received surgery and 9% stereotactic body radiation therapy. EGFR testing was performed in 42% of patients, of whom 10% had an EGFR mutation. Filling an important evidence gap, this study reported a substantial increase in disease-free survival (DFS) from 2010 to 2020 and across different treatment modalities. Five-year DFS was 49%, 42%, and 22% for stage IB, II, and IIIA patients, respectively. Despite these improvements, disease relapse remained a challenge, with approximately 40% of stage IIIA having relapsed 3 years since diagnosis, highlighting the need for improved treatment strategies. ABSTRACT: Despite recent improvements in early-stage non-small-cell lung cancer (NSCLC), disease relapse remains challenging. Moreover, real-world evidence on long-term follow-up of disease-free survival (DFS) and recurrence patterns in a large, unselected cohort of early-stage NSCLC patients is lacking. This cohort study aimed to assess clinical characteristics, diagnostic workup, treatment, survival, and risk of disease relapse among early-stage NSCLC patients. Adult patients with stage IB, II, or IIIA NSCLC diagnosed and/or treated at Aarhus University Hospital in Denmark from January 2010 to December 2020 were included and followed-up until May 2021. Comprehensive clinical data were collected from electronic medical records of eligible patients and linked to Danish register data. The study population comprised 1341 early-stage NSCLC patients: 22%, 40%, and 38% were diagnosed with stage IB, II, and IIIA disease, respectively. In total, 42% of patients were tested for epidermal growth factor receptor (EGFR), of whom 10% were EGFR-mutation-positive (EGFRm(+)). Half of all patients received surgery, and nine percent of patients received stereotactic body radiation therapy (SBRT). Disease-free survival 5 years post-diagnosis was 49%, 42%, and 22% for stage IB, II, and stage IIIA patients, respectively. DFS improved over time both for patients treated with surgery and SBRT. However, disease relapse remained a challenge, with approximately 40% of stage IIIA having relapsed 3 years post-diagnosis. This study contributes important knowledge that puts clinical trials on new perioperative treatment modalities for early-stage NSCLC patients into perspective. Our findings cover an essential evidence gap on real-world DFS and recurrence dynamics, confirming that despite an improvement in DFS over time and across different treatment modalities, disease relapse remains a monumental challenge. Therefore, better treatment strategies are needed.