Journal of Thoracic Oncology:
Survival Prognostication in Non-small Cell Lung Cancer
Zell, Jason A. DO, MPH*; Ignatius Ou, Sai-Hong MD, PhD*
*Chao Family Comprehensive Cancer Center and Division of Hematology/Oncology, Department of Medicine and Genetic Epidemiology Research Institute and Department of Epidemiology, School of Medicine, University of California Irvine, Irvine, California.
Disclosure: The authors declare no conflict of interest.
Address for correspondence: Jason A. Zell, DO, MPH, Department of Epidemiology, School of Medicine, University of California, Irvine, 224 Irvine Hall, Irvine, CA 92697. E-mail: email@example.com
Clinical oncology is poised to benefit from continued advances in pharmacogenetics, molecular diagnostics, and targeted therapeutics. The importance of personalized medicine in oncology is reflected in the theme of the 2009 American Society of Clinical Oncology annual meeting: “Personalizing Cancer Care.” In concert with this era of discovery, important advances in non-small cell lung cancer (NSCLC) research have emerged. Molecular signatures of NSCLC have been used to prognosticate survival,1,2 and rational approaches to targeted therapy have been integrated with chemotherapy in clinical trials with successful outcomes.3,4 So, it may seem surprising that, despite technological advances in the field, identifying readily available prognostic factors for survival after NSCLC diagnosis continues to hold value. Clinicopathologic factors such as age at diagnosis, gender, stage at presentation, histologic cell type, degree of tumor differentiation, performance status, and smoking status may be technologically mundane, but they continue to have robust prognostic implications for survival after NSCLC diagnosis. Importantly, these factors are easily accessible from the medical record to the busy medical oncologist in clinical practice. Numerous studies have reported on the importance of readily available prognostic factors for survival in NSCLC, sometimes with conflicting results. This places the focus of interpreting prognostic NSCLC studies on data quality. In this issue of the Journal of Thoracic Oncology, Chansky et al. on behalf of the International Association for the Study of Lung Cancer (IASLC) International Staging Committee (ISC) and Participating Institutions performed a retrospective analysis of 9137 surgically managed stage I-III NSCLC cases from the original IASLC database.5
As first published in the JTO in 2007, the IASLC database represents a landmark achievement in establishing accurate reassessments of tumor, node, metastasis (TNM) descriptors and stage groupings for NSCLC and small cell lung cancer.6–11 The purpose of these studies was to inform the recently released 2009 revisions to the Union Internationale Contre le Cancer -7 staging system for lung cancer, which were clearly in need of revision (as best demonstrated by results of the IASLC ISC analyses). This project was the largest of its kind to date, involving analysis of 67,725 NSCLC cases collected worldwide during 1990–2000, along with an external validation study using data from the United States Surveillance, Epidemiology, and End Results SEER database. The original findings and recommendations from the IASLC ISC have refined the new Union Internationale Contre le Cancer staging system to more accurately define risk groups by stage. In doing so, results from the IASLC ISC will now inform therapeutic management decisions with practice-changing consequences. Findings from the IASLC database have been validated by IASLC as noted, externally validated by our group,12–14 and additional studies will likely emerge to test the relevance of these TNM descriptors and stage groupings in various NSCLC tumor databases. Already, IASLC has embarked on an ongoing project to create a prospectively derived NSCLC database that will provide future refinements to the lung cancer staging system and validations of many more clinical, laboratory, and molecular prognostic markers.
Previously, the Prognostic Factors Subcommittee of the ISC has reported on the relevant prognostic factors for survival among 12,428 NSCLC cases.15 The accompanying article by Chansky et al.5 reveals a detailed analysis of a less heterogenous group of NSCLC cases: stage I–III cases that received surgical resection. In this article, the authors demonstrate that the previously identified clinicopathologic characteristics: age >70 years, male gender, and advanced stage at presentation were associated with poor survival among resected NSCLC cases. Interestingly, histology (other than bronchioloalveolar carcinoma, BAC) was less important in their analysis. Squamous cell carcinoma histology was found to be an independent favorable prognostic factor for survival compared with adenocarcinoma, and a statistically significant interaction was observed between histology and gender on survival of NSCLC cases. Thus, the survival differences between squamous cell carcinoma and adenocarcinoma were observed only among males, and there was no difference by histologic subtype among females. With a new histology-based treatment paradigm emerging in NSCLC,16 such information may be useful for treatment, but also prognosis, and as potential stratification factors for clinical trial development. Using recursive partitioning and amalgamation analysis, the authors demonstrate that pathologic TNM stage is the most important prognostic factor for overall survival in NSCLC, and that female gender was a favorable prognostic factor for those less than 70 years of age. Subset analyses were performed where limited data were available for performance status and smoking status, which generally concur with previously reported findings.
Along with performance status and smoking status, other readily available prognostic factors are important in NSCLC research. Degree of tumor differentiation, for example, has been consistently and strongly associated with overall survival in NSCLC.17 In a large population-based analysis of stage IA NSCLC cases that underwent lobectomy, degree of tumor differentiation was prognostic but not histology (with the exception of bronchioloalveolar carcinoma) after factoring in age and gender among other clinical factors.17 Thus, it is possible that the results by Chansky et al.5 regarding survival differences by histology (with the exception of bronchioloalveolar carcinoma) and gender could be confounded by tumor grade of differentiation. Another potentially important and readily available prognostic factor for NSCLC survival is the extent of surgical resection, which was not incorporated into the multivariate models of the present analysis. We have shown that the number of lymph nodes removed in stage IA patients who underwent lobectomy was an independent prognostic factor for survival in NSCLC.17
Because of the high quality of the data source, large sample size, and the robust statistical analytic approach, Chansky et al. have provided compelling evidence on the prognostic importance of age, gender, stage, cell type, and (to a lesser extent) performance status, and smoking status. Future meta-analyses of recently published and ongoing adjuvant NSCLC treatment trials will provide additional information on how modern adjuvant treatment affects the prognostic significance of these factors, since only 8.5% of the patients in the study by Chanksy et al. received subsequent chemotherapy. Future studies of prognostic markers in NSCLC should attempt to validate as many of the prognostic factors as possible including tumor characteristics, patient characteristics, laboratory parameters, and indicators of tumor biology, as noted previously by IASLC.15
1. Chen HY, Yu SL, Chen CH, et al. A five-gene signature and clinical outcome in non-small-cell lung cancer. N Engl J Med
2. NSCLC survival is the extent of surgicalLau SK, Boutros PC, Pintilie M, et al. Three-gene prognostic classifier for early-stage non small-cell lung cancer. J Clin Oncol
3. Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med
4. Pirker R, Pereira JR, Szczesna A, et al. Cetuximab plus chemotherapy in patients with advanced non-small-cell lung cancer (FLEX): an open-label randomised phase III trial. Lancet
2009; May 2;373(9674):1525–31.
5. Chansky K, Sculier JP, Crowley J, et al. The IASLC lung cancer staging project: prognostic factors and pathologic TNM stage in surgically managed non-small cell lung cancer. J Thorac Oncol
6. Goldstraw P, Crowley J, Chansky K, et al. The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol
7. Groome PA, Bolejack V, Crowley JJ, et al. The IASLC Lung Cancer Staging Project: validation of the proposals for revision of the T, N, and M descriptors and consequent stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumours. J Thorac Oncol
8. Postmus PE, Brambilla E, Chansky K, et al. The IASLC Lung Cancer Staging Project: proposals for revision of the M descriptors in the forthcoming (seventh) edition of the TNM classification of lung cancer. J Thorac Oncol
9. Rami-Porta R, Ball D, Crowley J, et al. The IASLC Lung Cancer Staging Project: proposals for the revision of the T descriptors in the forthcoming (seventh) edition of the TNM classification for lung cancer. J Thorac Oncol
10. Rusch VW, Crowley J, Giroux DJ, et al. The IASLC Lung Cancer Staging Project: proposals for the revision of the N descriptors in the forthcoming seventh edition of the TNM classification for lung cancer. J Thorac Oncol
11. Shepherd FA, Crowley J, Van Houtte P, et al. The International Association for the Study of Lung Cancer lung cancer staging project: proposals regarding the clinical staging of small cell lung cancer in the forthcoming (seventh) edition of the tumor, node, metastasis classification for lung cancer. J Thorac Oncol
12. Zell JA, Ignatius Ou SH, Ziogas A, et al. Validation of the proposed International Association for the Study of Lung Cancer non-small cell lung cancer staging system revisions for advanced bronchioloalveolar carcinoma using data from the California Cancer Registry. J Thorac Oncol
13. Ou SH, Zell JA. Validation study of the proposed IASLC staging revisions of the T4 and M non-small cell lung cancer descriptors using data from 23,583 patients in the California Cancer Registry. J Thorac Oncol
14. Ou SH, Zell JA. The applicability of the proposed IASLC staging revisions to small cell lung cancer (SCLC) with comparison to the current UICC 6th TNM Edition. J Thorac Oncol
15. Sculier JP, Chansky K, Crowley JJ, et al. The impact of additional prognostic factors on survival and their relationship with the anatomical extent of disease expressed by the 6th Edition of the TNM Classification of Malignant Tumors and the proposals for the 7th Edition. J Thorac Oncol
16. Scagliotti GV, Parikh P, von Pawel J, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol
17. Ou SH, Zell JA. Prognostic significance of the number of lymph nodes removed at lobectomy in stage IA non-small cell lung cancer. J Thorac Oncol
© 2009International Association for the Study of Lung Cancer