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. 2015 Sep 10;33(26):2877-84.
doi: 10.1200/JCO.2015.60.9818. Epub 2015 Aug 10.

Solid Predominant Histologic Subtype in Resected Stage I Lung Adenocarcinoma Is an Independent Predictor of Early, Extrathoracic, Multisite Recurrence and of Poor Postrecurrence Survival

Hideki Ujiie  1 , Kyuichi Kadota  1 , Jamie E Chaft  1 , Daniel Buitrago  1 , Camelia S Sima  1 , Ming-Ching Lee  1 , James Huang  1 , William D Travis  1 , Nabil P Rizk  1 , Charles M Rudin  1 , David R Jones  1 , Prasad S Adusumilli  2
Affiliations

Solid Predominant Histologic Subtype in Resected Stage I Lung Adenocarcinoma Is an Independent Predictor of Early, Extrathoracic, Multisite Recurrence and of Poor Postrecurrence Survival

Hideki Ujiie et al. J Clin Oncol. .

Abstract

Purpose: To examine the significance of the proposed International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society (IASLC/ATS/ERS) histologic subtypes of lung adenocarcinoma for patterns of recurrence and, among patients who recur following resection of stage I lung adenocarcinoma, for postrecurrence survival (PRS).

Patients and methods: We reviewed patients with stage I lung adenocarcinoma who had undergone complete surgical resection from 1999 to 2009 (N = 1,120). Tumors were subtyped by using the IASLC/ATS/ERS classification. The effects of the dominant subtype on recurrence and, among patients who recurred, on PRS were investigated.

Results: Of 1,120 patients identified, 188 had recurrent disease, 103 of whom died as a result of lung cancer. Among patients who recurred, 2-year PRS was 45%, and median PRS was 26.1 months. Compared with patients with nonsolid tumors, patients with solid predominant tumors had earlier (P = .007), more extrathoracic (P < .001), and more multisite (P = .011) recurrences. Multivariable analysis of primary tumor factors revealed that, among patients who recurred, solid predominant histologic pattern in the primary tumor (hazard ratio [HR], 1.76; P = .016), age older than 65 years (HR, 1.63; P = .01), and sublobar resection (HR, 1.6; P = .01) were significantly associated with worse PRS. Presence of extrathoracic metastasis (HR, 1.76; P = .013) and age older than 65 years at the time of recurrence (HR, 1.7; P = .014) were also significantly associated with worse PRS.

Conclusion: In patients with stage I primary lung adenocarcinoma, solid predominant subtype is an independent predictor of early recurrence and, among those patients who recur, of worse PRS. Our findings provide a rationale for investigating adjuvant therapy and identify novel therapeutic targets for patients with solid predominant lung adenocarcinoma.

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Conflict of interest statement

Authors' disclosures of potential conflicts of interest are found in the article online at www.jco.org. Author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
(A) Cumulative incidence of recurrence (CIR) of patients with stage I lung adenocarcinoma. (B) CIR for patients with stage I lung adenocarcinoma for each architectural grade. (C) Hazard function of recurrence for architectural grade tumors. (D) Hazard function of recurrence for solid predominant tumors.
Fig 2.
Fig 2.
(A) Postrecurrence survival (PRS) curve for patients with stage I lung adenocarcinoma. (B) PRS curves for patients with high–architectural grade tumors versus patients with low– and intermediate–architectural grade tumors. (C) PRS curves for patients with solid predominant tumors versus patients with nonsolid predominant tumors.
Fig A1.
Fig A1.
Overall survival of patients with stage I lung adenocarcinoma for each architectural grade.
Fig A2.
Fig A2.
(A) Predominant morphology of primary site and metastatic site. (B) Morphology component of primary site and metastatic site. ACI, acinar predominant (invasive adenocarcinoma); COL, colloid predominant (invasive adenocarcinoma); LEP, lepidic predominant; MIP, micropapillary predominant (invasive adenocarcinoma); PAP, papillary predominant (invasive adenocarcinoma); SOL, solid predominant (invasive adenocarcinoma).
See this image and copyright information in PMC

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