The value of PET/CT with FES or FDG tracers in metastatic breast cancer: a computer simulation study in ER-positive patients.

BACKGROUND: The aim of this study was to evaluate the effect on the number of performed biopsies and costs associated with implementing positron emission tomography (PET) and computed tomography (PET/CT) with 16α-[(18)F]fluoro-17ß-oestradiol (FES) or 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG) as an upfront imaging test for diagnosing metastatic breast cancer (MBC) in comparison with the standard work-up in oestrogen receptor-positive women with symptoms. METHODS: A published computer simulation model was adapted and validated. Three follow-up strategies were evaluated in a simulated cohort of women with primary breast cancer over a 5-year-time horizon: (1) the standard work-up, (2) upfront FES-PET/CT and (3) upfront FDG-PET/CT. The main outcome was the number of avoided biopsies to assess MBC. The costs for all three strategies were calculated based on the number of imaging tests and biopsies. The incremental cost-effectiveness ratio (ICER) to avoid a biopsy was calculated only based on the costs of initial imaging and staging tests. RESULTS: The FES-PET/CT strategy decreased the number of biopsies by 39 ± 9%, while upfront FDG-PET/CT increased the number of biopsies by 38 ± 15% when compared with the standard work-up. Both PET/CT strategies reduced the number of imaging tests and false positives when compared with the standard work-up. The number of false negatives decreased only in the FES-PET/CT strategy. The ICER in the FES-PET/CT strategy per avoided biopsy was 12.1 ± 3.4 thousand Euro. In the FDG-PET/CT strategy, the costs were higher and there were no avoided biopsies as compared with the standard work-up, hence this was an inferior strategy in terms of cost effectiveness. CONCLUSIONS: The number of performed biopsies was lower in the FES-PET/CT strategy at an ICER of 12.1 ± 3.4 thousand Euro per biopsy avoided, whereas the application of the FDG-PET/CT did not reduce the number of biopsies and was more expensive. Whether the FES-PET/CT strategy has additional benefits for patients in terms of therapy management has to be evaluated in clinical studies.

To screen or not to screen for breast cancer? How do modelling studies answer the question?

Breast cancer screening is a topic of hot debate, and currently no general consensus has been reached on starting and ending ages and screening intervals, in part because of a lack of precise estimations of the benefit-harm ratio. Simulation models are often applied to account for the expected benefits and harms of regular screening; however, the degree to which the model outcomes are reliable is not clear. In a recent systematic review, we therefore aimed to assess the quality of published simulation models for breast cancer screening of the general population. The models were scored according to a framework for qualitative assessment. We distinguished seven original models that utilized a common model type, modelling approach, and input parameters. The models predicted the benefit of regular screening in terms of mortality reduction; and overall, their estimates compared well to estimates of mortality reduction from randomized controlled trials. However, the models did not report on the expected harms associated with regular screening. We found that current simulation models for population breast cancer screening are prone to many pitfalls; their outcomes bear a high overall risk of bias, mainly because of a lack of systematic evaluation of evidence to calibrate the input parameters and a lack of external validation. Our recommendations concerning future modelling are therefore to use systematically evaluated data for the calibration of input parameters, to perform external validation of model outcomes, and to account for both the expected benefits and the expected harms so as to provide a clear balance and cost-effectiveness estimation and to adequately inform decision-makers.