It has been extensively documented in the literature that obesity has a positive relationship with the incidence of numerous cancers and negatively impacts survival among cancer patients (4
). However, details regarding individual sites of cancers and their relation to mortality are less available. Associations of obesity with an increased risk of mortality have been noted for various cancers including endometrial, kidney, gallbladder, esophageal, and post-menopausal breast cancer (4
). However, the data are scant and inconsistent regarding obesity and the risk of mortality among lung cancer patients. Our study shows the beneficial role obesity or the absence of weight loss at presentation has on lung cancer survival, which has been previously suggested in the literature (4
In our cohort, approximately 15% and 5% of patients presented with weight loss and obesity, respectively at time of diagnosis. In the evaluation of co-morbid conditions, weight losing patients displayed a higher propensity (odds ratio > 1) for almost every co-morbid condition as compared to non-weight losing patients, suggesting that weight loss might be a marker of /contributor towards general overall lower health. Obese patients, however, also showed increased rates and propensities (odd ratios > 1) of nearly all co-morbidities analyzed, indicating that obese patients also suffered reduced overall health relative to non-obese patients.
Interestingly, despite their overall increased morbidity, patients who were reportedly obese had a 4.4 month overall survival advantage over patients who were not obese (14 vs. 8.6 months respectively). This inverse relationship between obesity and lung cancer survival has been previously documented in the literature (5
). In a prospective study of close to 900,000 U.S. Adults, Calle et al. demonstrated a significant inverse relationship between obesity and lung cancer mortality. This inverse relationship was present when analyzing data for both smokers and non-smokers. But, interestingly, when excluding smokers from the analysis, the apparent inverse relationship between BMI and lung cancer mortality was not present. This later data was not statistically significant but there appeared to be a trend of decreasing relative risk of mortality with increasing BMI in lung cancer patients (4
). Also, in Great Britain’s prospective Million Women Study with 45,037 incident cancers and17,203 cancer deaths, they showed an inverse association between increasing BMI and cancer mortality in premenopausal breast, squamous cell carcinoma of the esophagus and lung cancer (16
). Also, Leung et al. performed a prospective cohort analysis in China (2000–2003) following 60,000 patients for 3 years ultimately showing that obesity was associated with lower lung cancer mortality (6
). Parr et al. studied the relationship between BMI and cancer mortality in a large (424,519) Asia-Pacific (Asia, Australia, New Zeland) cohort and showed increased mortality along all types of cancers except for lung and upper aerodigestive tract cancers, with both displaying an inverse relationship (8
This inverse association supports the phenomenon of paradoxically improved survival with obesity in the face of a chronic condition, as seen in congestive heart failure with preserved systolic function (17
). This population appears to display an “obesity paradox”, where being overweight increases one’s likelihood of suffering from congestive heart failure, but being obese with heart failure decreases their mortality (17
). Therefore, it appears an “obesity paradox” may also be present in lung cancer since multiple studies, as well as ours have shown an increased risk of lung cancer with increasing BMI as well as waist circumference (5
) and a decreasing mortality when overweight (6
Weight loss among cancer patients has been reported in up to 50% of all cancer patients (23
) and lung cancer is one of the more prevalent cancers where weight loss has been observed (24
). Among patients with small cell cancer, weight loss has been noted in nearly 57% of patients; similarly patients with non-small cell cancer have had reported weight loss rates of approximately 54% (25
). The observed rate of weight loss among our cohort was 15.4%; however, this rate was static, observed at time of diagnosis, and could not be measured as a function of disease progression. Despite the static nature of this variable, weight loss noted at diagnosis remained an independent negative predictor of overall outcomes with shorter MST in patients with weight loss (6.4 months) versus those without weight loss (9.2 months). Our observations support current literature demonstrating that weight loss is a poor prognostic factor in cancer survival (26
MST was also clearly related to stage of disease, as advanced disease demonstrated shorter MST which is consistent with reports documenting weight loss and cachexia with increased lung cancer staging (28
). In our study a greater percentage of patients reported to have weight loss had regional and distant disease. Similarly, patients with advanced disease were less likely to be obese.
Even under multivariate analysis, when accounting for possible confounding variables (demographics, SES, smoking status, tumor characteristics, and treatment strategies), we were able to show that the absence of obesity was an independent negative predictor of survival (HR: 1.12, P<0.0001)) and the absence of weight loss was an independent positive predictor of improved overall survival (HR:0.792, P<0.0001).
When evaluating lung cancer survival one must take into account smoking status because it may be a confounding variable. It is well known that smoking is a major cause of lung cancer and lung cancer patients that are current smokers present with lower BMI’s as compared to former and never smokers(20
). Therefore, heavy smokers will be more likely to be in the lower BMI categories and at greater risk of lung cancer. However, the relationship of obesity and lung cancer mortality when taking into account smoking status has not been well documented. Some studies have displayed an inverse relationship between obesity and lung cancer mortality when not restricting for smoking status. But, when restricting the analysis to never smokers the inverse relationship between obesity and lung cancer mortality disappears (4
). The Cancer Prevention Study II demonstrated through complex statistical control models, the inverse relationship between obesity and lung cancer mortality disappeared entirely when restricted to never smokers (20
). They suggested the inverse relationship between lower BMI and increased lung cancer mortality could be explained by possible pre-clinical disease upon disease presentation. On the other hand Leung et al. found an inverse relationship between BMI and lung cancer mortality in both smokers and non-smokers (6
). Therefore, it remains to be clarified whether in fact smoking status is a confounding variable in the overall survival of obese lung cancer patients.
Our dataset was limited to self reported current smoking status which by and of itself is a statistic notoriously under representing the actual prevalence of the condition (30
). However, weight losing patients reported smoking slightly more often than non-weight losing patients (OR:1.17), while obese patients reported smoking slightly less often than non-obese patients (OR:0.84) (). Also, when limiting survival analysis to non smokers we found obesity and the absence of weight loss to significantly improve survival (). Under multivariate analysis smoking was found to be an independent negative predictor of survival (HR:1.073, P<0.0001) ().
The power of our study is improved by the linkage of the FCDS to the AHCA database giving us access to a very large cohort which represents approximately 6% of the total United States population. This provides us with additional data modifiers including co-morbid conditions, improved follow-up, socioeconomic details, and improved treatment information. Data from such a large population-based cancer registry provides insight into tumor behavior and it allows examination of outcomes based on current treatment strategies (31
). A database of this size, however, is not without its limitations. When examining obesity and weight loss, it would be ideal to quantify obesity in terms of BMI. Without access to BMI we were unable to discern whether the degree of obesity influenced mortality. We can simply state that among our cohort a diagnosis of obesity at presentation was associated with improved overall outcomes even when accounting for demographics, co-morbidities, tumor characteristics, and treatment variables. Also, both obesity and weight loss in this dataset are provided as a categorical variable as opposed to a continuous variable. Thus, we cannot abstract either co-morbid condition as a response to disease progression, nor can we examine the degree of weight loss or obesity in each patient. Moreover, we cannot discern whether obesity is a risk factor for developing lung cancer, but this has already been well established in the literature (11
). Therefore, with a decreased mortality associated with obesity, it is imperative in future studies to delineate whether the improved mortality is a result of a positive prognostic factor and whether or how obesity affects disease progression in the course of lung cancer.
Our observations support the literature documenting weight loss and cachexia being poor prognostic factors in lung cancer survival. Currently, data in the literature are inconsistent regarding the prognostic strength of obesity in outcomes for lung cancer. However, our observations reinforce the idea that patients diagnosed with obesity appear to have a survival advantage over those patients who are not obese. This is similar to the improved survival of obese patients in diseases displaying high catabolic states, including CHF, chronic kidney disease, chronic heart failure, chronic obstructive lung disease, AIDS, rheumatoid arthritis, and the elderly. These data may reflect an overall protective effect of greater physiological reserve in the form of excess fat and muscle, both of which are lost in the final phases of lung cancer. The knowledge of this protective effect could ultimately play a significant role in prolonging the lives of lung cancer patients. Therefore, more studies are needed to evaluate the mechanisms explaining the inverse association between obesity and lung cancer mortality.