A cost-effectiveness analysis of an integrated clinical-radiogenomic screening program for the identification of BRCA 1/2 carriers (e-PROBE study

Current approach to identify BRCA 1/2 carriers in the general population is ineffective as most of the carriers remain undiagnosed. Radiomics is an emerging tool for large scale quantitative analysis of features from standard diagnostic imaging and has been applied also to identify gene mutational status. The objective of this study was to evaluate the clinical and economic impact of integrating a radiogenomics model with clinical and family history data in identifying BRCA mutation carriers in the general population. This cost‑effective analysis compares three different approaches to women selection for BRCA testing: established clinical criteria/family history (model 1); established clinical criteria/family history and the currently available radiogenomic model (49% sensitivity and 87% specificity) based on ultrasound images (model 2); same approach used in model 2 but simulating an improvement of the performances of the radiogenomic model (80% sensitivity and 95% specificity) (model 3). All models were trained with literature data. Direct costs were calculated according to the rates currently used in Italy. The analysis was performed simulating different scenarios on the generation of 18‑year‑old girls in Italy (274,000 people). The main outcome was to identify the most effective model comparing the number of years of BRCA‑cancer healthy life expectancy (HLYs). An incremental cost‑effectiveness ratio (ICER) was also derived to determine the cost in order to increase BRCA carriers‑healthy life span by 1 year. Compared to model 1, model 2 increases the detection rate of BRCA carriers by 41.8%, reduces the rate of BRCA‑related cancers by 23.7%, generating over a 62‑year observation period a cost increase by 2.51 €/Year/Person. Moreover, model 3 further increases BRCA carriers detection (+ 68.3%) and decrease in BRCA‑related cancers (− 38.4%) is observed compared to model 1. Model 3 increases costs by 0.7 €/Year/Person. After one generation, the estimated ICER in the general population amounts to about 3800€ and 653€ in model 2 and model 3 respectively. Model 2 has a massive effect after only one generation in detecting carriers in the general population with only a small cost increment. The clinical impact is limited mainly due to the current low acceptance rate of risk‑reducing surgeries. Further multicentric studies are required before implementing the integrated clinical‑radiogenomic model in clinical practice.