Commentary (Jatoi/Loprinzi): Obesity and Cancer: The Risks, Science, and Potential Management Strategies

Dr. McTiernan provides a comprehensive, thoughtful overview of several studies that have focused on obesity and cancer. She discusses the preponderance of data that have shown both a direct relationship between obesity and the development of cancer as well as a direct relationship between obesity and cancer recurrence. Although both relationships are clinically relevant, the latter is particularly important to cancer health-care providers. Today, more than ever before, cancer patients are diagnosed early and treated effectively, thereby yielding a sizable cohort of cancer survivors and potential cancer survivors.[1] Understanding the relationship between obesity or overweight status and cancer recurrence is now more timely than it has ever been. Weight Loss/Control Advice in Cancer: Current Limitations
What advice on weight loss or weight control should we be providing to cancer survivors or cancer patients who have completed potentially curative therapy? This question is difficult to answer because of the limited data, and Dr. McTiernan acknowledges this difficulty. What we do know is that many published studies suggest that obesity is directly associated with a poor prognosis in cancer patients. But what we also know that no clinical trials have demonstrated is that weight loss improves prognosis in potential cancer survivors. To our knowledge, no such large-scale clinical trials have been undertaken. Based on little more than assumption, we continue to counsel cancer patients who have received potentially curative therapy to adopt and maintain a low body weight. Dr. McTiernan herself appears to acknowledge the limitations of this approach, commenting on how "strategies for weight control may be helpful for some cancer patients and survivors." We agree that counseling overweight cancer survivors to adopt a lower body weight is acceptable, if for no other reason than to attempt to limit the morbidity associated with other obesity-related diseases. We also believe, however, that it is important to acknowledge to cancer patients that there is a dearth of supportive clinical trial data, and that as a result, we cannot answer the question posed above with absolute certainty. Moreover, it is prudent to recognize that some studies have in fact questioned whether a low body weight does indeed truly enhance health. Does Low Body Weight Enhance Health?
With regard to this last point, two lines of investigation merit mention. First, Dr. McTiernan alludes to two studies in renal cell cancer patients. Both conclude that the relationship between obesity and cancer prognosis is the exact opposite of what we might have expected: Increased body mass index was, in fact, associated with better survival. Kamat and others provided data from a 400-patient cohort with renal cell carcinoma after nephrectomy.[2] These investigators found that an increased body mass index was associated with improvement in overall and cancer-free survival- results that are at odds with the assumption that being overweight detracts from survival. In a similar study, Schips and others assessed 693 patients with this same malignancy.[3] Focusing on this cohort postoperatively, they observed in a univariate analysis that patients with a body mass index greater than 25 had a more favorable overall and cancer-free survival. Although a multivariate analysis that included tumor grade, disease stage, patient gender, and age did not yield this same prognostic effect based on body mass index, these data nonetheless remain highly provocative. At the very least, they, in conjunction with the data from Kamat, challenge the assumption that a high body mass index is associated with a poor outcome in renal cell cancer. They also raise the possibility that in the future, when counseling potential cancer survivors, information on tumor type and other cancerrelated issues might need to be considered when attempting to impart sound advice to patients. Second, recent data from the National Health and Nutrition Examination Survey (NHANES) are intriguing.[ 4] NHANES data are derived from general populations, not specifically cancer patients or cancer survivors. Reporting on a cohort of over 30,000 individuals from 1971 to 1994, Flegal and others found that a low body mass index of less than 18.5 was associated with a higher risk of death, even among nonsmokers. These data challenge the tenet that being thin is always a good thing. What body mass index should we advise patients to strive for? The data from Flegal and others remind us that this question has not been completely answered for a general population and that among cancer survivors, we have only begun to look for answers. Future Directions
So, what advice on weight loss or weight control should we be providing to cancer survivors or cancer patients who have recently completed potentially curative therapy? The above data suggest that such advice may need to be qualified according to information such as type of cancer, and may also need to adhere to clinically validated definitions of optimal weight after curative cancer therapy. Whether interventions to decrease caloric intake or to encourage exercise truly enhance disease-free and overall survival in all potential cancer survivors remains to be determined. As greater success in cancer detection and therapy gives rise to a mounting population of survivors and potential survivors, Dr. McTiernan's article provides a timely starting point from which to pursue further clinical investigation on the prognostic effect of weight loss and weight maintenance within these cohorts.

Disclosures:

The authors have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

References:

1. Brenner H: Long-term survival rates of cancer patients achieved by the end of the 20th century: A period analysis. Lancet 360:1131- 1135, 2002.
2. Kamat AM, Shock RP, Naya Y, et al: Prognostic value of body mass index in patients undergoing nephrectomy for localized renal tumors. Urology 63:46-50, 2004.
3. Schips L, Lipsky K, Zigeuner R, et al: Does overweight impact on prognosis of patients with renal cell carcinoma? A single center experience of 683 patients. J Surg Oncol 88:57-62, 2004.
4. Flegal KM, Graubard BI, Williamson DF, et al: Excess deaths associated with underweight, overweight, and obesity. JAMA 293:1861-1867, 2005.