Since risk factors for recurrence in early-stage EGFR-positive NSCLC remains undefined, researchers conducted a study to determine clinicopathologic characteristics and recurrence patterns of resected early-stage EGFR-positive) NSCLC, using wildtype EGFR as a comparator cohort, and to identify features linked with recurrence.

In a recent publication in JAMA Network Open, researchers conducted a cohort study included patients treated for NSCLC at the National Cancer Centre Singapore between January 1, 2010, and June 30, 2018. The study was created to ascertain risk factors for recurrence in early-stage, EGFR–positive NSCLC and obtain information about adjuvant treatment decisions. The researchers examined 723 patients, 389 with EGFR–positive NSCLC and 334 with wildtype EGFR. They indicated that an estimated 50% of patients were women, and the median age was 64 years (range, 22-88 years). Patients had stage IA (41.4%), stage IB (21.4%), stage II (19.5%), and stage IIIA (17.3%) NSCLC.

All patients in the study underwent surgery. For adjuvant therapy, 6.9% of patients received radiation, and 22.7% received platinum doublet chemotherapy. There were no significant differences between the EGFR–positive and wildtype groups regarding adjuvant radiotherapy or chemotherapy. In the EGFR–positive group, 4.6% of patients received neoadjuvant EGFR tyrosine kinase inhibitors (TKIs), and 2.8% received adjuvant EGFR TKIs.

The median follow-up and the median time to recurrence was 46 months and 16 months, respectively. There was no significant difference between EGFR-positive and wildtype patients in 2-year disease-free survival (DFS) (70.2% and 67.6%, respectively [P = .70]) or 5-year DFS (50.3% and 50.0%, respectively [P = .70]). In addition, sites of disease recurrence were comparable between the groups. However, EGFR-positive patients did have better overall survival than wildtype patients at both 2 years (95.5% and 88.0%, respectively [P = .004)]) and 5 years (77.7% and 66.6%, respectively [P = .004]). In the EGFR-positive group, the 2–year DFS rate was 81.0% for patients with stage IA disease, 78.4% for stage IB, 57.1% for stage II, and 46.6% for stage IIIA. The 5-year DFS rate for EGFR–positive patients with stage IB-IIIA disease was 37.2%.

In the EGFR wildtype group, higher disease stage, lymphovascular invasion, and adjuvant radiation were associated with recurrence in multivariate analyses. In EGFR–positive patients, higher disease stage, nonacinar and nonlepidic adenocarcinoma subtype, sublobar resection, positive resection margins, and lymphovascular invasion were all associated with recurrence in multivariate analyses.

The authors concluded that findings of this cohort study agree with previous research findings that recurrence rates in early-stage EGFR–positive NSCLC, including stage IA, are high, yet a significant number of patients remain disease-free at 5 years without osimertinib.

The authors also indicated that prospective studies are required to confirm their risk estimation model incorporating both clinical and molecular features, with the goal of identifying patients who will benefit from adjuvant osimertinib and distinguish them from those who are cured without adjuvant treatment. Also, identifying individualized risk features can assist in tailored surveillance and adjuvant treatment strategies for early-stage EGFR-positive NSCLC.

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