Evaluating the cost-effectiveness of genetic testing in high-risk families with confirmed germline cancer mutations.

Abstract

e23164 Background: First-degree relatives (FDRs) of cancer patients with hereditary mutations may benefit from germline genetic testing, enabling early interventions such as enhanced screening and treatment of limited stage cancers. This study evaluates the cost-effectiveness of germline testing, enhanced screening efforts, and potential cost savings associated with identifying high-risk FDRs. Methods: Costs were modeled for enhanced screening and localized disease treatment in tested FDRs identified as mutation carriers versus standard screening and metastatic disease treatment in untested FDRs carrying mutations. Screenings and therapies followed US Preventive Services Task Force and American Cancer Society guidelines. Costs were averaged across five cancer types: breast, prostate, lung, colon, and pancreatic. A decision tree model assessed costs over 20 years. Using progression-free and overall survival data, we assumed 5 years of screening with definitive treatment for tested FDRs versus 10 years of screening with metastatic disease and death within 2.7 years for untested FDRs. Simulated data included 10,000 reference patients (RP) with cancer and known germline mutations, with 1 to 6 first-degree relatives per RP. Probabilities reflected autosomal dominant inheritance (50% risk) and variable penetrance (0-100%). Testing uptake by FDRs was set to 50%. Cost differences were evaluated using permutation tests and bootstrap resampling (p < 0.05). Results: Genetic testing of an FDR was estimated at $448, with a minimal annual cost increase of $22 compared to standard screening ($837/year vs $815/year). Costs for genetic testing and enhanced screening of identified mutation carriers were $1,135 higher than standard screening ($1,950/year vs $815/year). Estimated per-FDR total cost is summarized below in thousands of US dollars ($1,000s), broken down by germline testing decision. Dollar values describe total care costs including germline testing, screening, and treatment regimens. Germline testing of FDRs led to significantly lower long-term costs, achieving an overall per-FDR cost reduction of $56,972 (95% CI: $40,972–$71,615; p < 0.0001) compared to untested FDRs. Conclusions: Our model supports the cost-effectiveness of germline genetic testing for FDRs of cancer patients with known mutations, demonstrating substantial healthcare cost reductions through early detection and prevention of advanced disease. These findings advocate for broader implementation of genetic testing in high-risk families, highlighting potential to improve outcomes and decrease healthcare costs. Overall – Total Cost per FDR ($1,000s USD) Tested – Total Cost per FDR ($1,000s USD) Untested – Total Cost per FDR ($1,000s USD) Mean ± SD 108.22 ± 63.18 80.55 ± 57.31 137.52 ± 55.66 Median [IQR] 133.64 [16.30, 166.42] 122.06 [16.30, 133.64] 166.42 [122.06, 166.42]