Nodal stage of surgically resected non-small cell lung cancer and its effect on recurrence patterns and overall survival.
OBJECTIVE
Current National Comprehensive Cancer Network guidelines recommend postoperative radiation therapy (PORT) for patients with resected non-small cell lung cancer (NSCLC) with N2 involvement. We investigated the relationship between nodal stage and local-regional recurrence (LR), distant recurrence (DR) and overall survival (OS) for patients having an R0 resection.


METHODS
A multi-institutional database of consecutive patients undergoing R0 resection for stage I-IIIA NSCLC from 1995 to 2008 was used. Patients receiving any radiation therapy before relapse were excluded. A total of 1241, 202, and 125 patients were identified with N0, N1, and N2 involvement, respectively; 161 patients received chemotherapy. Cumulative incidence rates were calculated for LR and DR as first sites of failure, and Kaplan-Meier estimates were made for OS. Competing risk analysis and proportional hazards models were used to examine LR, DR, and OS. Independent variables included age, sex, surgical procedure, extent of lymph node sampling, histology, lymphatic or vascular invasion, tumor size, tumor grade, chemotherapy, nodal stage, and visceral pleural invasion.


RESULTS
The median follow-up time was 28.7 months. Patients with N1 or N2 nodal stage had rates of LR similar to those of patients with N0 disease, but were at significantly increased risk for both DR (N1, hazard ratio [HR] = 1.84, 95% confidence interval [CI]: 1.30-2.59; P=.001; N2, HR = 2.32, 95% CI: 1.55-3.48; P<.001) and death (N1, HR = 1.46, 95% CI: 1.18-1.81; P<.001; N2, HR = 2.33, 95% CI: 1.78-3.04; P<.001). LR was associated with squamous histology, visceral pleural involvement, tumor size, age, wedge resection, and segmentectomy. The most frequent site of LR was the mediastinum.


CONCLUSIONS
Our investigation demonstrated that nodal stage is directly associated with DR and OS but not with LR. Thus, even some patients with, N0-N1 disease are at relatively high risk of local recurrence. Prospective identification of risk factors for local recurrence may aid in selecting an appropriate population for further study of postoperative radiation therapy.
Department of Radiation Oncology, University of Massachusetts Medical Center, Worcester, Massachusetts. Electronic address: john.varlotto@umassmemorial.org.
John M
JM
Varlotto
Department of Healthcare Policy and Research, Virginia Commonwealth University, Richmond, Virginia.
Aaron N
AN
Yao
Division of Thoracic Surgery, Department of Surgery, Northwestern Memorial Hospital, Chicago, Illinois; Northwestern University School of Medicine, Chicago, Illinois.
Malcolm M
MM
DeCamp
Northwestern University School of Medicine, Chicago, Illinois.
Satvik
S
Ramakrishna
Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
Abe
A
Recht
Department of Radiation Oncology, Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
John
J
Flickinger
Northwestern University, Chicago, Illinois.
Adin
A
Andrei
Pennsylvania State University College of Medicine, Hershey, Pennsylvania; Heart and Vascular Institute, Pennsylvania State University-Hershey, Hershey, Pennsylvania.
Michael F
MF
Reed
Pennsylvania State University College of Medicine, Hershey, Pennsylvania; Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Pennsylvania State University-Hershey, Hershey, Pennsylvania.
Jennifer W
JW
Toth
Department of Radiation Oncology, University of Massachusetts Medical Center, Worcester, Massachusetts.
Thomas J
TJ
Fizgerald
Department of Radiation Oncology, Emory University, Atlanta, Georgia.
Kristin
K
Higgins
Department of Healthcare Policy and Research, Virginia Commonwealth University, Richmond, Virginia.
Xiao
X
Zheng
Department of Anesthesiology, Columbia University, New York, New York.
Julie
J
Shelkey
Department of Emergency Medicine, Baylor College of Medicine, Houston, Texas.
Laura N
LN
Medford-Davis
Pennsylvania State University-Hershey Cancer Institute, Hershey, Pennsylvania.
Chandra
C
Belani
Department of Radiation Oncology, Duke University Cancer Institute, Durham, North Carolina.
Christopher R
CR
Kelsey
D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000473:pathology* / Q000556:secondary / Q000601:surgery*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology* / Q000601:surgery*; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality; D012189:Retrospective Studies