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


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.


CONCLUSIONS
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.
Hideki Ujiie, Kyuichi Kadota, Daniel Buitrago, Camelia S. Sima, Ming-Ching Lee, James Huang, William D. Travis, Nabil P. Rizk, David R. Jones, and Prasad S. Adusumilli, Memorial Sloan Kettering Cancer Center; Jamie E. Chaft and Charles M. Rudin, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY; and Hideki Ujiie, Chiba University, Chiba, Japan.
Hideki
H
Ujiie
Hideki Ujiie, Kyuichi Kadota, Daniel Buitrago, Camelia S. Sima, Ming-Ching Lee, James Huang, William D. Travis, Nabil P. Rizk, David R. Jones, and Prasad S. Adusumilli, Memorial Sloan Kettering Cancer Center; Jamie E. Chaft and Charles M. Rudin, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY; and Hideki Ujiie, Chiba University, Chiba, Japan.
Kyuichi
K
Kadota
Hideki Ujiie, Kyuichi Kadota, Daniel Buitrago, Camelia S. Sima, Ming-Ching Lee, James Huang, William D. Travis, Nabil P. Rizk, David R. Jones, and Prasad S. Adusumilli, Memorial Sloan Kettering Cancer Center; Jamie E. Chaft and Charles M. Rudin, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY; and Hideki Ujiie, Chiba University, Chiba, Japan.
Jamie E
JE
Chaft
Hideki Ujiie, Kyuichi Kadota, Daniel Buitrago, Camelia S. Sima, Ming-Ching Lee, James Huang, William D. Travis, Nabil P. Rizk, David R. Jones, and Prasad S. Adusumilli, Memorial Sloan Kettering Cancer Center; Jamie E. Chaft and Charles M. Rudin, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY; and Hideki Ujiie, Chiba University, Chiba, Japan.
Daniel
D
Buitrago
Hideki Ujiie, Kyuichi Kadota, Daniel Buitrago, Camelia S. Sima, Ming-Ching Lee, James Huang, William D. Travis, Nabil P. Rizk, David R. Jones, and Prasad S. Adusumilli, Memorial Sloan Kettering Cancer Center; Jamie E. Chaft and Charles M. Rudin, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY; and Hideki Ujiie, Chiba University, Chiba, Japan.
Camelia S
CS
Sima
Hideki Ujiie, Kyuichi Kadota, Daniel Buitrago, Camelia S. Sima, Ming-Ching Lee, James Huang, William D. Travis, Nabil P. Rizk, David R. Jones, and Prasad S. Adusumilli, Memorial Sloan Kettering Cancer Center; Jamie E. Chaft and Charles M. Rudin, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY; and Hideki Ujiie, Chiba University, Chiba, Japan.
Ming-Ching
MC
Lee
Hideki Ujiie, Kyuichi Kadota, Daniel Buitrago, Camelia S. Sima, Ming-Ching Lee, James Huang, William D. Travis, Nabil P. Rizk, David R. Jones, and Prasad S. Adusumilli, Memorial Sloan Kettering Cancer Center; Jamie E. Chaft and Charles M. Rudin, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY; and Hideki Ujiie, Chiba University, Chiba, Japan.
James
J
Huang
Hideki Ujiie, Kyuichi Kadota, Daniel Buitrago, Camelia S. Sima, Ming-Ching Lee, James Huang, William D. Travis, Nabil P. Rizk, David R. Jones, and Prasad S. Adusumilli, Memorial Sloan Kettering Cancer Center; Jamie E. Chaft and Charles M. Rudin, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY; and Hideki Ujiie, Chiba University, Chiba, Japan.
William D
WD
Travis
Hideki Ujiie, Kyuichi Kadota, Daniel Buitrago, Camelia S. Sima, Ming-Ching Lee, James Huang, William D. Travis, Nabil P. Rizk, David R. Jones, and Prasad S. Adusumilli, Memorial Sloan Kettering Cancer Center; Jamie E. Chaft and Charles M. Rudin, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY; and Hideki Ujiie, Chiba University, Chiba, Japan.
Nabil P
NP
Rizk
Hideki Ujiie, Kyuichi Kadota, Daniel Buitrago, Camelia S. Sima, Ming-Ching Lee, James Huang, William D. Travis, Nabil P. Rizk, David R. Jones, and Prasad S. Adusumilli, Memorial Sloan Kettering Cancer Center; Jamie E. Chaft and Charles M. Rudin, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY; and Hideki Ujiie, Chiba University, Chiba, Japan.
Charles M
CM
Rudin
Hideki Ujiie, Kyuichi Kadota, Daniel Buitrago, Camelia S. Sima, Ming-Ching Lee, James Huang, William D. Travis, Nabil P. Rizk, David R. Jones, and Prasad S. Adusumilli, Memorial Sloan Kettering Cancer Center; Jamie E. Chaft and Charles M. Rudin, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY; and Hideki Ujiie, Chiba University, Chiba, Japan.
David R
DR
Jones
Hideki Ujiie, Kyuichi Kadota, Daniel Buitrago, Camelia S. Sima, Ming-Ching Lee, James Huang, William D. Travis, Nabil P. Rizk, David R. Jones, and Prasad S. Adusumilli, Memorial Sloan Kettering Cancer Center; Jamie E. Chaft and Charles M. Rudin, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY; and Hideki Ujiie, Chiba University, Chiba, Japan. adusumip@mskcc.org.
Prasad S
PS
Adusumilli
D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging