Chest
Volume 122, Issue 3, September 2002, Pages 1037-1057
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Reviews
Prognostic Factors in Non-small Cell Lung Cancer: A Decade of Progress

https://doi.org/10.1378/chest.122.3.1037Get rights and content

Study objectives

To provide a systematic overview of the literature investigating patient and tumor factors that are predictive of survival for patients with non-small cell lung cancer (NSCLC), and to analyze patterns in the design of these studies in order to highlight problematic aspects of their design and to advocate for appropriate directions of future studies.

Design

A systematic search of the MEDLINE database and a synthesis of the identified literature.

Measurements and results

The database search (January 1990 to July 2001) was carried out combining the MeSH terms prognosis and carcinoma, nonsmall cell lung. Eight hundred eighty-seven articles met the search criteria. These studies identified 169 prognostic factors relating either to the tumor or the host. One hundred seventy-six studies reported multivariate analyses. Concerning 153 studies reporting a multivariate analysis of prognostic factors in patients with early-stage NSCLC, the median number of patients enrolled per study was 120 (range, 31 to 1,281 patients). The median number of factors reported to be significant in univariate analyses was 4 (range, 2 to 14 factors). The median number of factors reported to be significant in multivariate analyses per study was 2 (range, 0 to 6 factors). The median number of studies examining each prognostic factor was 1 (range, 1 to 105 studies). Only 6% of studies addressed clinical outcomes other than patient survival.

Conclusions

While the breadth of prognostic factors studied in the literature is extensive, the scope of factors evaluated in individual studies is inappropriately narrow. Individual studies are typically statistically underpowered and are remarkably heterogeneous with regard to their conclusions. Larger studies with clinically relevant modeling are required to address the usefulness of newly available prognostic factors in defining the management of patients with NSCLC.

Section snippets

Materials and Methods

We performed a systematic overview of the last decade of literature investigating patient and tumor factors that were predictive of patient survival rates for patients with NSCLC. A MEDLINE database search (January 1990 to December 1999) was carried out combining the MeSH terms prognosis and carcinoma, nonsmall cell lung. At the request of an external reviewer, the eligibility period was extended to June 2001. Indexed articles were reviewed and sorted by the targeted patient cohort (ie,

Results

Overall, 887 articles met the search criteria. These studies identified 169 prognostic factors relating either to the tumor or the host. Figure 1shows the pattern of this indexed research and illustrates that the literature regarding prognostic issues in NSCLC seems to have grown almost exponentially.

The recognized heterogeneity among lung cancer patients has led to the definition of major clinical subgroups that are seen as being clinically dissimilar from one another, and these groups are

Advanced Disease

Tumor, host, and environment factors pertaining to the prognosis of patients with advanced NSCLC are listed in Table 2. As shown in the table, factors essential to decision making are the extent of disease, weight loss, and performance status, as these are the most predictive indicators of median patient survival time after undergoing systemic chemotherapy. For patients without substantial systemic manifestations of illness, chemotherapy is known to improve median survival time when compared to

Integration and Clinical Application of Prognostic Factors

In the context of a very large amount of literature reporting putative prognostic factors in lung cancer patients, many authors have highlighted methodological issues in the interpretation and integration of existing studies.69 In this section, we address the integration and clinical application of research knowledge pertaining to prognostic factors by discussing seven main observations and their implications.

First, existing reports of prognostic factors comprise a body of literature that is

Acknowledgment

The authors gratefully acknowledge the helpful comments of the three anonymous reviewers, and the excellent research assistance of Ms. Leanne Findlay in updating and collating the database and tables.

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    Supported in part by a grant from the National Cancer Institute of Canada.

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