Reining in the Excessive Use of Medical Tests: What Are the Next Steps?

Women who receive treatment for metastatic breast cancer (MBC) typically are monitored at regular intervals to evaluate the effectiveness and toxicities associated with therapy. Disease monitoring tools may include combinations of radiographic imaging; symptom assessment; physical examination; performance status; routine laboratory evaluations; and in some cases, serum tumor markers (STMs) such as CEA, CA15-3, and CA27.29. The results of these evaluations typically are integrated to help with making decisions about continuing or changing therapies. Unfortunately, the optimal frequency and tools for monitoringMBC are not well defined, and significant concern exists that some tools may be overused. This relates in particular to the use of STM assessments in patients with breast cancer. Despite its availability for more than two decades and provision of prognostic information, no evidence indicates that STM monitoring changes the course of disease. Since 1999, ASCO has recommended explicitly against STM use for surveillance after treatment of early-stage breast cancer, yet 42% of Medicare-age breast cancer survivors undergo STM assessment an average of almost three times a year, which results in 29% higher medical costs with no known impact on survival. Similarly, ASCO has recommended against the routine use of STMs in MBC in the absence of other measurable disease since 1996, with all subsequent updates confirming this initial guideline. STM assessments are adjunctive measures that can be used in conjunction with diagnostic imaging, history, and physical examination during the course of disease monitoring but which are only used as independent measures of treatment failure in the absence of otherwise measurable disease. At this time, no data indicate that STM assessment in women with MBC has clinical utility, improves health outcomes, or is costeffective. Furthermore, one recent study revealed that STM assessments have little impact on clinical decisions, with only 2% of patients changing therapy after imaging studies are performed in response to rising STMs. In the article that accompanies this editorial, Accordino et al report the results of a population-based analysis of patterns and predictors of frequent use of disease monitoring tests in 2,460 elderly Medicare patients with de novo MBC diagnosed between 2002 and 2011. The authors defined extreme-use as more than 12 STM assessments and/or more than four radiographic imaging studies obtained within a 12-month period, thus identifying providers who ordered STM assessments more frequently than once a month and/or scans more frequently than once every 3 months. More than 37% of providers were extreme users, with 9% extreme users of STMs and 32.8% extreme users of radiographic imaging studies. Costs of care per year after diagnosis were 59.2% higher in extreme users than the rest of the study population. In addition, extreme users were more likely than the rest of the study population to use hospital-based health care services near the end of life and to enroll in hospice closer to the time of death, a marker of suboptimal care in the ASCO Quality Oncology Practice Initiative (QOPI). Of note, overall survival did not differ between extreme users and the rest of the study population (hazard ratio, 0.93; 95% CI, 0.86 to 1.02). The bottom line: Patients with MBC who are cared for by these providers had no change in survival at 59% higher cost and with worse end-of-life care. Given the unsustainable rising costs for cancer care and that in many cases, MBC is a chronic disease that requires serial therapies and monitoring over a span of several years, the ability to determine the optimal tools and schedule disease assessments is crucial in terms of improving both patient outcomes and costeffectiveness. The ultimate aim of monitoring during treatment of MBC is to determine whether the continuation of a particular therapy or a change to another therapy is beneficial to an individual patient. Unfortunately, no current data indicate that a change in therapy on the basis of a particular test at a particular time enhances outcomes in womenwithMBC. In the absence of such data, the standards for monitoring disease and changing therapy have evolved from a combination of extrapolation of schedules and tools applied in clinical trials to assess efficacy of new therapeutics and clinical experience. No clinical trials or treatment guidelines call for monthly STM assessments or radiographic imaging more frequently that approximately four times a year, and few if any clinical trials use STM assessments. Although it is tempting to try to identify progressive disease and institute new therapy as soon as possible, data do not indicate that early intervention improves outcomes. This assertion is supported by the results of the Southwest Oncology Group S0500 study, which assessed the use of increased circulating tumor cells, a known biomarker of poor prognosis, to guide therapy. In this trial, patients with persistently increased circulating tumor cells soon after the initiation of new therapies who were switched to early alternate therapies did not fare better than those whose