Practice-based evidence of the beneficial impact of positron emission tomography in clinical oncology.

This issue of the Journal of Clinical Oncology contains a landmark article by Hillner et al that reports the results of a Center for Medicaid & Medicare Services (CMS)-sponsored trial of the National Oncology PET Registry (NOPR) study in patients with a variety of tumors. I have used the term “landmark” because it is the first time that CMS has used the mechanism of coverage with evidence development (CED) for the study of a diagnostic imaging methodology as a step toward a national coverage decision (NCD). Medicare has an obligation to provide its beneficiaries with technology advances that may result in improved health care, using the standard of “reasonable and necessary.” At present, the combination of positron emission tomography (PET) and the radiotracer [18F]fluorodeoxyglucose (FDG) is recognized to meet this standard; resulting in reimbursement by Medicare for nine oncology tumor types: non– small-cell lung cancer (NSCLC); breast, head and neck (including thyroid), colorectal, cervical, and esophageal cancers; melanoma and lymphoma (Hodgkin’s disease and non-Hodgkin’s lymphoma), for diagnosis, staging tumor extent and restaging recurrent tumor. Because the insurance industry as a whole follows the lead of the federal government in reimbursement decisions, PET is widely used in clinical oncology for the tumor types on the “approved” Medicare list. The decision to reimburse is referred to as an NCD, and CMS is responsible for this process. In making the positive PET reimbursement decision for these nine tumor types, CMS used the standard “that all evidence currently available must be adequate to conclude that the item or service is reasonable and necessary.” Of course, clinical oncology deals with many more than nine tumor types, and some major human diseases, such as pancreatic, ovarian, and prostatic cancers were not included; patients with these tumors and a variety of others were potentially being denied the benefits of PET imaging. For this reason a group of professional organizations concerned with imaging in oncology petitioned CMS for a broader NCD to include additional tumor types for PET reimbursement. These organizations argued that sufficient evidence would be unlikely to be developed for additional tumor types, because there was little support for this type of clinical trial with a substantial number of patients. Also, for a number of the tumor types that are uncommon or rare, it would be impossible to provide sufficient evidence from the literature related to patient outcomes. CMS agreed to work with these groups using a highly innovative mechanism, CED, to develop sufficient data so that a meaningful NCD could be made. Essentially, CMS and the investigators agreed on the study population, methods, and key study end points, and CMS agreed to provide covered services for PET scans performed as part of this clinical trial. The investigators agreed to establish the registry (NOPR) and oversee data collection and reporting. The study that was ultimately developed met the CMS criteria for such a trial, namely that there was no evidence that the procedure would cause harm, and there was a potential for patient benefit. In keeping with CMS policy, a particular emphasis was placed on evaluating evidence of an influence on clinical practice as a way to help Medicare beneficiaries and providers make appropriate diagnostic and therapeutic decisions. (CMS has spent a great deal of effort to make the entire process participatory and transparent; interested reader is referred to Federal Register, Vol 68, No 187, Friday Sept 26, 2003, 55,634, as well as several guidance documents on NCD available through the CMS website, https://www.cms.hhs.gov.) The goal of the study by Hillner et al was to assess the impact of PET on patient management in a group of tumors that are not generally reimbursed by Medicare. A total of 22,975 PET cases from 1,178 PET centers, or nearly 80% of the PET centers in the United States, were collected and entered into the NOPR registry in 1 year. Questionnaires were used to compare pre-PET management plans with postPET management plans. The main finding was that PET was associated with a 36.5% change in decisions to treat or not treat. In addition, there was a significant reduction in the use of additional types of diagnostic images and in biopsy application with the use of PET. The investigators concluded that, in more than one third of older patients undergoing PET for one of the cancer types covered under this CED policy, there was a major change in the intended management including type of treatment. This study has major strengths, particularly in its scale, with more than 22,000 cases collected during the course of 1 year. This is no small feat, and reflects the power of Medicare data when used for this type of focused clinical trial. The rapidity of data collection is an important positive feature because of changes that rapidly occur in diagnostic imaging technologies over time. Generating such large numbers in such a short time helps assure the relevance of the information. It is important to note that, during this interval, more than 400,000 PET scans were performed on Medicare beneficiaries for the nine approved tumor indications. Thus, although PET scans in the unapproved indications were performed with a frequency less than 10% of the total Medicare patients studied with PET, the sample size of the unapproved PET scans was more than adequate to cover the management question posed. Also, more than 80% of all PET centers in the United JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 26 NUMBER 13 MAY 1 2008