Histologic Subtype Classification of Lung Adenocarcinoma Predicts Disease-Free but Not Overall Survival Benefit From Adjuvant Chemotherapy
In an analysis reported in the Journal of Clinical Oncology, Tsao et al found that classification by histologic subtype for invasive lung adenocarcinoma was not predictive of overall survival benefit of adjuvant therapy in patients undergoing complete resection but did appear to predict benefit of adjuvant therapy in disease-free survival and specific disease-free survival.
Study Details
The study assessed outcomes in 575 patients from four clinical trials of adjuvant chemotherapy according to histologic subtype classifications of lepidic, papillary, acinar, micropapillary, or solid proposed by the International Association for the Study of Lung Cancer, American Thoracic Society, European Respiratory Society, and World Health Organization. Tumor histologies were reclassified according to this classification scheme and then combined into three groups, consisting of lepidic, acinar/papillary, and micropapillary/solid histologies. The primary endpoint was overall survival; secondary endpoints were disease-free survival and specific disease-free survival (time from randomization to cancer-related event, with noncancer deaths being censored at the date of death).
Association With Outcomes
On multivariate analysis, there were no significant associations of subtype with overall survival (P = .22 for global test). Marginally significant associations were observed for disease-free survival (P = .05) and specific disease-free survival (P = .04), with poorer outcomes for micropapillary/solid vs lepidic (reference group) for disease-free survival (hazard ratio [HR] = 1.32, 95% confidence interval [CI] = 0.56–3.13) and specific disease-free survival (HR = 1.29, 95% CI = 0.55–3.07). Hazard ratios were < 1 for acinar/papillary vs lepidic, and the overall significant difference primarily reflected poorer outcome for micropapillary/solid vs acinar/papillary for disease-free survival and specific disease-free survival (HR = 1.52, 95% CI = 1.09–2.11, and HR = 1.58, 95% CI = 1.12–2.24).
Association With Effect of Adjuvant Therapy
Due to small numbers, the lepidic subgroup was omitted from the analysis of effect of adjuvant therapy. In multivariate analysis, adjuvant chemotherapy benefit was marginally significant for overall survival for micropapillary/solid (HR = 0.71, P = .04) and not for acinar/papillary (HR = 1.00, P = .99), but the treatment by histology interaction was not significant (P = .18 for interaction). There were significant benefits from chemotherapy for disease-free survival for micropapillary/solid (HR = 0.60, P < .001) but not for acinar/papillary (HR = 1.11, P =.57; P = .009 for interaction) and for specific disease-free survival for micropapillary/solid (HR = 0.59, P < .001) but not for acinar/papillary (HR = 1.12, P = .56; P =.01 for interaction).
The investigators concluded: “The new lung adenocarcinoma classification based on predominant histologic pattern was not predictive for [adjuvant chemotherapy] benefit for [overall survival], but it seems predictive for disease-specific outcomes.”
Ming-Sound Tsao, MD, of the University of Toronto, is the corresponding author of the Journal of Clinical Oncology article.
The study was supported by grants from Ligue Nationale Contre le Cancer and le Programme National d’Excellence Specialisé Cancer du Poumon de l’Institut National du Cancer, National Cancer Institute, and Canadian Cancer Society and by a grant from Sanofi-Aventis, personal funding from the investigators, Gustave Roussy Foundation, the Princess Margaret Cancer Foundation, and a European CURELUNG contract.
For full disclosures of the study authors, visit jco.ascopubs.org.
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