Predictive Versus Prognostic Value of Lung Adenocarcinoma Classification
Authors: Ming-Sound Tsao, Frances A. Shepherd, Elizabeth Brambilla, Jean-Charles Soria
Journal: Journal of Clinical Oncology (2014)

TO THE EDITOR: Hung et al recently investigated the pattern of recurrence and the predictive value of the new International Association for the Study of Lung Cancer/American Thoracic Society/ European Respiratory Society histologic classification for lung adenocarcinoma in 573 patients who had been treated primarily by surgical resection. In this classification, nonmucinous invasive adenocarcinoma was classified into five categories on the basis of the presence of predominant histological patterns. The authors reported that among all 573 patients, those with micropapillary/solid predominant pattern adenocarcinoma had higher extrathoracic versus intrathoracic recurrence than patients with lepidic/acinar/papillary predominant pattern tumors. Micropapillary/solid predominant pattern had poorer overall survival (OS), freedom from recurrence, and disease-specific survival compared with lepidic/acinar/papillary predominant patients. Importantly, they reported that among 215 of 573 patients who received adjuvant chemotherapy, solid-predominant adenocarcinoma was also a significant predictive factor for OS (P .04) and tended to be significant for freedom from recurrence (P .08). The authors concluded that in lungadenocarcinoma,theInternationalAssociationfortheStudyofLung Cancer/American Thoracic Society/European Respiratory Society classification system has significant prognostic and predictive value regarding death and recurrence. Solid-predominant adenocarcinoma was also a significant predictor in patients undergoing adjuvant chemotherapy. It is generally accepted that prognostic markers are patient/tumor factors that affect patient outcome (usually survival) independently of treatment administered, whereas predictive markers are factors that predict response of the tumor to the treatment, either in terms of tumor shrinkage or survival benefit from the treatment. In patients with early-stage resectable non–small-cell lung cancer, the term “predictive” should be reserved for survival benefit from adjuvant chemotherapy. In the absence of a randomized trial with a notreatment control arm, a differential survival benefit from therapy cannot be determined, as the prognostic role of the marker may exert similar effects in both the treated and nontreated arms. This is the case in this report by Hung et al as shown clearly in Figures 1G to I, where OS and disease-specific survival were poorer for patients with solidpredominant compared with nonsolid histology, regardless of whether they received or did not receive adjuvant chemotherapy. In fact, nowhere in the manuscript or in the Data Supplement was significant interaction between chemotherapy and histologic subtype reported by comparing the hazard ratios for survival benefit in treated and nontreated patients in the two histologic groups, and by applying an interaction P value. Therefore, we believe the use of term “predictive” was inappropriate and misleading, and that this retrospective study was neither designed nor powered to be able to demonstrate significant treatment by histology interaction. Note: A reply to this Correspondence was not provided.