Association of Survival With Adjuvant Chemotherapy Among Patients With Early-Stage Non–Small Cell Lung Cancer With vs Without High-Risk Clinicopathologic Features | Lung Cancer | JAMA Oncology | JAMA Network
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    Original Investigation
    September 17, 2020

    Association of Survival With Adjuvant Chemotherapy Among Patients With Early-Stage Non–Small Cell Lung Cancer With vs Without High-Risk Clinicopathologic Features

    Author Affiliations
    • 1Department of Medicine (Medical Oncology), Yale School of Medicine, New Haven, Connecticut
    • 2Cancer Outcomes, Public Policy and Effectiveness Research Center, Yale School of Medicine, New Haven, Connecticut
    • 3Array Biostatistics, Wilmington, North Carolina
    • 4Section of Thoracic Surgery, Department of Surgery, Yale School of Medicine, New Haven, Connecticut
    JAMA Oncol. 2020;6(11):1741-1750. doi:10.1001/jamaoncol.2020.4232
    Key Points

    Question  Is adjuvant chemotherapy associated with survival in patients with node-negative, early-stage non–small cell lung cancer (NSCLC) with vs without high-risk clinicopathologic features?

    Findings  In this cohort study of 50 814 patients with NSCLC, adjuvant chemotherapy use was associated with a survival benefit if the tumor was larger than 3 to 4 cm and sublobar resection was performed, the tumor was larger than 4 to 5 cm and at least 1 high-risk pathologic feature was present, or the tumor was larger than 5 cm irrespective of high-risk pathologic features.

    Meaning  The findings suggest that high-risk pathologic features, extent of resection, and tumor size should be simultaneously considered when evaluating patients with early-stage NSCLC for adjuvant chemotherapy.


    Importance  Tumor size larger than 4 cm is accepted as an indication for adjuvant chemotherapy in patients with node-negative non–small cell lung cancer (NSCLC). Treatment guidelines suggest that high-risk features are also associated with the efficacy of adjuvant chemotherapy among patients with early-stage NSCLC, yet this association is understudied.

    Objective  To assess the association between adjuvant chemotherapy and survival in the presence and absence of high-risk pathologic features in patients with node-negative early-stage NSCLC.

    Design, Setting, and Participants  This retrospective cohort study using data from the National Cancer Database included 50 814 treatment-naive patients with a completely resected node-negative NSCLC diagnosed between January 1, 2010, and December 31, 2015. The study was limited to patients who survived at least 6 weeks after surgery (ie, estimated median time to initiate adjuvant chemotherapy after surgery) to mitigate immortal time bias. Statistical analysis was performed from December 1, 2018, to February 29, 2020.

    Exposures  Adjuvant chemotherapy use vs observation, stratified according to the presence or absence of high-risk pathologic features (visceral pleural invasion, lymphovascular invasion, and high-grade histologic findings), sublobar surgery, and tumor size.

    Main Outcomes and Measures  The association of high-risk pathologic features with survival after adjuvant chemotherapy vs observation was evaluated using Cox proportional hazards regression models.

    Results  Overall, 50 814 eligible patients with NSCLC (27 365 women [53.9%]; mean [SD] age, 67.4 [9.5] years]) were identified, including 4220 (8.3%) who received adjuvant chemotherapy and 46 594 (91.7%) who did not receive adjuvant chemotherapy. Among patients with tumors 3 cm or smaller, chemotherapy was not associated with improved survival (hazard ratio [HR], 1.10; 95% CI, 0.96-1.26; P = .17). For patients with tumors larger than 3 cm to 4 cm, adjuvant chemotherapy was associated with a survival benefit among patients who underwent sublobar surgery (HR, 0.72; 95% CI, 0.56-0.93; P = .004). For tumors larger than 4 cm to 5 cm, a survival benefit was associated with adjuvant chemotherapy only in patients with at least 1 high-risk pathologic feature (HR, 0.67; 95% CI, 0.56-0.80; P = .02). For tumors larger than 5 cm, adjuvant chemotherapy was associated with a survival benefit irrespective of the presence of high-risk pathologic features (HR, 0.75; 95% CI, 0.61-0.91; P = .004).

    Conclusions and Relevance  In this cohort study, tumor size alone was not associated with improved efficacy of adjuvant chemotherapy in patients with early-stage (node-negative) NSCLC. High-risk clinicopathologic features and tumor size should be considered simultaneously when evaluating patients with early-stage NSCLC for adjuvant chemotherapy.