When Hope Hinders Science and Patient-Centered Care
Authors: Jennifer L. Malin
Journal: Journal of Clinical Oncology (2012)

The last four decades have witnessed remarkable advances in the treatment of cancer and significant improvements in outcomes. Survival rates for childhood cancer now approach 80%. Chronic myelogenous leukemia has become a chronic disease. Cervical cancer can be prevented with a vaccine. Eighty percent of women with breast cancer receive breast-conserving therapy. Encouraged by these advances, and in a manner largely intrinsic to the culture of oncology, we approach each new treatment or technology with tremendous optimism that it will result in improved outcomes. In the article that accompanies this editorial, Presley et al report the results of a comparative effectiveness research (CER) study of brachytherapy compared with whole-breast irradiation (WBI). Among women in the Medicare program who had breastconserving surgery followed by radiation during 2008 and 2009, 16% received brachytherapy, with regional variation of 0% to 71% (Lafayette, IN), suggesting that factors other than the clinical characteristics may have contributed to its use. This should give us pause, given that another recent study reported that 66% of women who received brachytherapy would be classified as cautionary or unsuitable according to the American Society for Radiation Oncology consensus guidelines criteria. Presley et al found that women who were treated with brachytherapy had higher rates of wound and skin complications—approximately 17 additional complications per 100 women treated— compared with WBI, but no difference in deep tissue or bone complications. This study extends the work of Smith et al, who found that, in addition to increased complications, brachytherapy was associated with a two-fold increase in subsequent mastectomies, which indicated that disease control was worse compared with WBI, although the absolute increase was only 2%. Part of a growing body of CER in radiation therapy, these studies highlight the important role CER can have in providing data on therapies for which outcomes from randomized clinical trials are lacking. Nevertheless, several limitations must be kept in mind when interpreting the results. As with any observational study, the results are susceptible to selection bias. However, if, as in the case of brachytherapy, the criteria for patient selection include less advanced disease, the effect of this bias would be to favor the newer technology. Additionally, studies that use claims data to identify complications only capture toxicity that prompts a medical intervention or a physician report of an International Classification of Diseases diagnosis code, and these may not be directly related to the treatment itself. In fact, a number of the diagnosis codes in the categories of outcomes that did not differ between brachytherapy and WBI in the study by Presley et al were likely not related to radiation therapy and thus may not be relevant to their comparative effectiveness (eg, 785.59, “Other shock without mention of trauma” [International Classification of Diseases, 9th revision, clinical modification, code 785.59]). Routine collection of patient-reported toxicity data in all patients receiving treatment would augment these data and provide much needed outcomes data to evaluate the effectiveness of new radiation technologies in real time as they are incorporated into clinical practice. Although the results of these recent studies are disappointing and raise more questions than they answer, they should not come as a complete surprise. Fewer than one third of phase III clinical trials of new systemic treatments for cancer succeed. Similarly, more than half of the innovations in radiation therapy that were evaluated by the Radiation Therapy Oncology Group (RTOG) have not demonstrated improved outcomes when compared with standard of care. However, unlike devices, new therapeutics are subject to prospective trials before US Food and Drug Administration approval for initial marketing, and reimbursement for off-label indications requires inclusion in an approved compendium. Although the compendia vary significantly in their methodology and completeness, they help to ensure that a less effective or more toxic therapy will not be widely adopted. In contrast, US Food and Drug Administration criteria for approval to market a new device, including catheters and machines that are used to deliver radiation therapy, are limited to demonstrating that the device is safe and effective, but in this case effectiveness refers to the device reliably performing the function it is intended to do, not demonstrating improvement in patient outcomes. After a capital investment has been made to acquire the device, as the recent studies by Presley et al and others have shown, uptake of the new technology occurs even in the absence of evidence of improved or even comparable outcomes. Once adopted, it becomes much harder to change practice when definitive studies demonstrate that it is inferior to the status quo. This phenomenon of medical reversal has other negative consequences. In addition to potentially harming patients who undergo the discredited therapy during the years it is in favor, it creates a JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 30 NUMBER 35 DECEMBER 1