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In Reply

Department of Medical Oncology, National Cancer Center, Singapore, Singapore

We thank Drs Ryu and Lee for their insightful comments on our recent article.¹ We agree that comorbidity would be expected to be associated with survival and smoking status. This would be of particular relevance in the context of lung cancer as chronic smoking brings with it concomitant hazards such as cardiovascular disease and chronic obstructive pulmonary disease. Cigarette smoking has been shown to be an important risk factor for all cause, coronary heart disease, stroke, and cancer mortality.² However, in our study, the presence of comorbidities was not significantly different between never-smokers and smokers and was not significantly associated with survival on univariate and multivariate analysis. There are several reasons that may account for our findings. Firstly, there is an inherent limitation in a retrospective study with regards to the assessment of comorbidities. The limitation results from nonuniform determination of the conditions as the information is gathered and recorded differently by various doctors. Furthermore, severity of comorbidities is not routinely recorded and severity of the conditions is more likely to impact on survival outcome than just the mere presence. This information bias would affect the validity of our study.³ However, as self-reported and case records information on comorbidities has been shown to be reliable,⁴ it may be possible to overcome this limitation if a protocol for data collection has been predetermined and used for every patient.

The second reason relates to the definition of comorbidities in our study. Comorbidity was defined as the presence of any one or more of the following conditions: diabetes mellitus, ischemic heart disease, hypertension, asthma, chronic obstructive lung disease, and pulmonary tuberculosis. It is important to remember that such comorbidities are not entirely attributable to smoking, namely diabetes mellitus, hypertension, or asthma. Even ishemic heart disease can result from nontobacco related causes, such as diabetes mellitus or hypercholesterolemia. Another point to note is the increasingly prominent role that other environmental factors may play in contributing to comorbidities, in particular dietary habits and physical activities.⁵ This may explain the nonsignificant difference in comorbidities between the smokers and never-smokers and the lack of impact of comorbidities on survival outcome in this analysis. Finally, we have to bear in mind that the management of comorbidities have evolved through the years and have not remained static. The improved management of these conditions could well have negated their impact on survival outcome in these patients. Hence, what holds true in studies of yesteryear may have changed due to these reasons.

However, we fully agree that careful evaluation and assessment of the type of comorbidity and the severity of the comorbidity is essential in any studies assessing prognosis. This can be done in a retrospective study if the assessment can be predefined in a simple protocol and consistently used by all clinicians. However, in order to provide more conclusive answers with regards to the effect of comorbidities on survival of lung cancer patients, large prospective studies will be needed.

Authors' Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. Toh CK, Gao F, Lim WT, et al: Never-smokers with lung cancer: Epidemiologic evidence of a distinct disease entity. J Clin Oncol 24:2245-2251, 2006[Abstract/Free Full Text]

2. Kuller LH, Ockene JK, Meilahn E, et al: Cigarette smoking and mortality: MRFIT research group. Prev Med 20:638-654, 1991[CrossRef][Medline]

3. Grimes DA, Schulz KF: Bias and causal associations in observational research. Lancet 359:248-252, 2002[CrossRef][Medline]

4. Madans J, Reuben C, Rothwell S, et al: Differences in morbidity measures and risk factor identification using multiple data sources: The case of stroke. J Epidemiol Biostat 4:37-43, 1999[Medline]

5. Arnett D, McGovern P, Jacobs D, et al: Fifteen-year trends in cardiovascular risk factors (1980-1982 through 1995-1997): The Minnesota Heart Survey. Am J Epidem 156:929-935, 2002[Abstract/Free Full Text]

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