Cancer Survivorship Research and Guidelines: Maybe the Cart Should Be Beside the Horse

In its recent report, From Cancer Patient to Cancer Survivor: Lost in Transition, the Institute of Medicine had as its third recommendation that “Health care providers should use systematically developed evidence-based clinical practice guidelines, assessment tools, and screening instruments to help identify and manage late effects of cancer and its treatment. Existing guidelines should be refined and new evidence-based guidelines should be developed.” In this issue of the Journal of Clinical Oncology, Carver et al, writing for the ASCO Cancer Survivorship Expert Panel, present an evidence review of cardiac and pulmonary late effects. It did not start out as an evidence review, though. It was intended to be an evidence-based clinical practice guideline, the first of several for survivorship care. The panel chose two of the most common, well-known, and well-studied long-term and late effects for which survivors of cancer are at risk. Yet, after a rigorous evaluation of the evidence, it was concluded that it was not sufficient to support an evidence-based guideline. As a potential user of such a guideline, this is very disappointing. If there is insufficient evidence on which to base management of these relatively common problems, it is clear that the creation of comprehensive evidence-based guidelines for the care of adult cancer survivors is not currently feasible. Why is evidence about what to do for cancer survivors so hard to obtain? One reason is that cancer survivors are a very heterogeneous population. Their risk for recurrence or late effects usually depends on the specific site, stage, and histology of their disease, the treatments they received, when those treatments were delivered (since regimens and techniques change over time), the length of time that has elapsed since those exposures, and underlying risk factors independent of their cancer or its treatment. Moreover, cancer is largely a disease of the elderly, so determining late effects from unrelated comorbid conditions can be difficult. Consequently, creation of a truly homogeneous population often leaves an investigator with relatively few patients to study. Another reason research in survivorship is difficult is that many of the end points of interest occur infrequently. Although the cumulative burden of long-term and late effects of treatment is significant among cancer survivors, therapies are generally developed so that any particular severe late effect is a relatively uncommon occurrence. As a result, surveillance strategies or other interventions have to be applied to many patients over a long period of time in order to have the power to detect a difference in important outcomes among approaches. Furthermore, even if a homogeneous population of survivors with a relevant exposure can be identified in sufficient numbers, the interpretations of current privacy laws by some institutional review boards make it difficult to contact survivors outside of their usually infrequent clinic visits. Such restrictions make assembly of a representative population-based cohort very difficult, and importantly, deprive survivors of the opportunity to participate in cancer research. Lastly, the fact that there is currently little guidance available on how to care for survivors is itself a challenge to research. For example, we do not routinely screen asymptomatic people in the general population for subclinical cardiac dysfunction, so there is not a clear model for what oncologists should do with someone who has had significant anthracycline exposure and chest irradiation. In such situations, each physician uses his/her judgment to do what s/he thinks is best for his/her patients. This usually leads to large practice variation, however. High quality evidence is generally only obtained when the outcomes of uniform practices applied to a large number of subjects can be observed. In both observational studies and even prospectively designed trials, disparate interventions make data synthesis and metaanalysis difficult to perform and interpret. Consensus guidelines from a respected source can accelerate the evolution of knowledge by standardizing care. When practice is more uniform, it then becomes more feasible to study the effects of care, thereby gaining the evidence needed to alter the guidelines in an iterative way until sufficient data have accumulated with which to create evidence-based guidelines. If done thoughtfully and judiciously with attention to economic and manpower implications, a consensus recommendation can at least raise awareness of an issue among some providers, while at the same time may decrease overutilization of interventions by others. They are also much appreciated by practicing physicians eager to have clear standards within which to function. There are successful examples of consensus guidelines that are informed by evidence as opposed to being strictly evidence based. Such efforts incorporate literature review with the clinical experience of experts and multisite and multidisciplinary guideline review and revision. Since 1995, the National Comprehensive Cancer Network has developed more than 100 guidelines estimated to cover 95% of the clinical situations with which cancer patients present. This organization considered creating survivorship guidelines but decided that the scope would be too great and so instead incorporated limited recommendations for surveillance JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 25 NUMBER 25 SEPTEMBER 1 2007