In their article, Xiao and Lichtman do an excellent job of assembling the available evidence on treating colon cancer in the elderly. It is clear from their review that healthy elderly patients should be offered a wide range of therapeutic options, if not all standard treatments currently available for colon cancer. At the same time, their report illustrates the limitations of how we obtain data on the treatment of older colon cancer patients, and more broadly, of older cancer patients in general.
The authors' review can be summarized as follows:
(1) Most of the data presented come from retrospective subgroup analyses of large trials in which elderly patients are underrepresented.
(2) These data mostly pertain to the young and "fit" elderly. For example, in the Sargent et al meta-analysis, only 23 of 3,351 patients, or 0.7%, were over 80 years of age. Yet this age group represents one-fourth of colon cancer patients in the population.
(3) These datasets rarely provide any information on comorbidity. This has two consequences. First, these datasets ignore potential confounding factors that can have effects as great as the treatment itself. Consider, for example, Figure 1. The impact of diabetes on disease-free survival is comparable to the impact of adjuvant fluorouracil(Drug information on fluorouracil) (5-FU)/levamisole on disease-free survival in stage III colon cancer.[2,3] Therefore an uncontrolled imbalance in diabetic patients could significantly flaw the results of an adjuvant trial. Similarly, an imbalance in inflammatory diseases could skew findings on the use of nonsteroidal anti-inflammatory drugs (NSAIDs).
The second consequence of the lack of comorbidity data is that we are deprived of extremely helpful information when it comes to translating results to the everyday patient. For example, as highlighted by Xiao and Lichtman, patients with major cardiovascular conditions were excluded from the bevacizumab(Drug information on bevacizumab) (Avastin) trials. But how many patients had stable coronary artery disease? Or well compensated congestive heart failure? Or vascular renal disease? Or a history of peptic ulcer? Or a diabetic microangiopathy? What was the outcome in these subgroups?
Cooperative Group Studies