Histopathologic Response Criteria Predict Survival of Patients with Resected Lung Cancer After Neoadjuvant Chemotherapy

Introduction: We evaluated the ability of histopathologic response criteria to predict overall survival (OS) and disease-free survival (DFS) in patients with surgically resected non-small cell lung cancer (NSCLC) treated with or without neoadjuvant chemotherapy. Methods: Tissue specimens from 358 patients with NSCLC were evaluated by pathologists blinded to the patient treatment and outcome. The surgical specimens were reviewed for various histopathologic features in the tumor including percentage of residual viable tumor cells, necrosis, and fibrosis. The relationship between the histopathologic findings and OS was assessed. Results: The percentage of residual viable tumor cells and surgical pathologic stage were associated with OS and DFS in 192 patients with NSCLC receiving neoadjuvant chemotherapy in multivariate analysis (p = 0.005 and p = 0.01, respectively). There was no association of OS or DFS with percentage of viable tumor cells in 166 patients with NSCLC who did not receive neoadjuvant chemotherapy (p = 0.31 and p = 0.45, respectively). Long-term OS and DFS were significantly prolonged in patients who had ⩽10% viable tumor compared with patients with >10% viable tumor cells (5 years OS, 85% versus 40%, p < 0.0001 and 5 years DFS, 78% versus 35%, p < 0.001). Conclusion: The percentages of residual viable tumor cells predict OS and DFS in patients with resected NSCLC after neoadjuvant chemotherapy even when controlled for pathologic stage. Histopathologic assessment of resected specimens after neoadjuvant chemotherapy could potentially have a role in addition to pathologic stage in assessing prognosis, chemotherapy response, and the need for additional adjuvant therapies.

[1]  M. Alifano,et al.  Which patients should be operated on after induction chemotherapy for N2 non-small cell lung cancer? Analysis of a 7-year experience in 175 patients. , 2010, The Journal of thoracic and cardiovascular surgery.

[2]  T. Gauler,et al.  Correlation of PET/CT Findings and Histopathology after Neoadjuvant Therapy in Non-Small Cell Lung Cancer , 2008, Oncology.

[3]  A. Borczuk,et al.  Histologic Assessment of Non–Small Cell Lung Carcinoma after Neoadjuvant Therapy , 2003, Modern Pathology.

[4]  Roy S Herbst,et al.  Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 2. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[5]  G. Mason American and British thoracic surgery. , 1968, The Journal of thoracic and cardiovascular surgery.

[6]  M. Thomas,et al.  Grading of tumor regression in non-small cell lung cancer : morphology and prognosis. , 2001, Chest.

[7]  U. G. Dailey Cancer,Facts and Figures about. , 2022, Journal of the National Medical Association.

[8]  J. Roth,et al.  Long-term follow-up of patients enrolled in a randomized trial comparing perioperative chemotherapy and surgery with surgery alone in resectable stage IIIA non-small-cell lung cancer. , 1998, Lung cancer.

[9]  J. Padilla,et al.  Preresectional chemotherapy in stage IIIA non-small-cell lung cancer: a 7-year assessment of a randomized controlled trial. , 1999, Lung cancer.

[10]  J. Milanowski,et al.  Phase III study of erlotinib in combination with cisplatin and gemcitabine in advanced non-small-cell lung cancer: the Tarceva Lung Cancer Investigation Trial. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[11]  R. Stupp,et al.  Prognostic factors affecting long-term outcomes in patients with resected stage IIIA pN2 non-small-cell lung cancer: 5-year follow-up of a phase II study , 2006, British Journal of Cancer.

[12]  E. Lemarié,et al.  Preoperative chemotherapy followed by surgery compared with primary surgery in resectable stage I (except T1N0), II, and IIIa non-small-cell lung cancer. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[13]  L. Tanoue,et al.  The new lung cancer staging system. , 2009, Chest.

[14]  J. Crowley,et al.  Induction chemotherapy before surgery for early-stage lung cancer: A novel approach. Bimodality Lung Oncology Team. , 2000, The Journal of thoracic and cardiovascular surgery.

[15]  Chronic Disease Division Cancer facts and figures , 2010 .

[16]  K. Schulmann,et al.  Tumour regression in non-small-cell lung cancer following neoadjuvant therapy. Histological assessment , 2005, Journal of Cancer Research and Clinical Oncology.

[17]  M Volante,et al.  ERCC1 and RRM1 gene expressions but not EGFR are predictive of shorter survival in advanced non-small-cell lung cancer treated with cisplatin and gemcitabine. , 2006, Annals of oncology : official journal of the European Society for Medical Oncology.

[18]  Y. Ichinose,et al.  Copyright © 2012 BY THE INTERNATIONAL ASSOCIATION FOR THE STUDY OF LUNG CANCER , 2012 .

[19]  Yang Liu,et al.  Survival Benefit of Neoadjuvant Chemotherapy in Non-small Cell Lung Cancer: An Updated Meta-Analysis of 13 Randomized Control Trials , 2010, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[20]  R. Stupp,et al.  Mediastinal lymph node clearance after docetaxel-cisplatin neoadjuvant chemotherapy is prognostic of survival in patients with stage IIIA pN2 non-small-cell lung cancer: a multicenter phase II trial. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  G. Bepler,et al.  RRM1 modulated in vitro and in vivo efficacy of gemcitabine and platinum in non-small-cell lung cancer. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[22]  Y. Shimada,et al.  A Novel Histopathological Evaluation Method Predicting the Outcome of Non-small Cell Lung Cancer Treated by Neoadjuvant Therapy: The Prognostic Importance of the Area of Residual Tumor , 2010, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.