Early Cost-Effectiveness Analysis of Using Whole-Genome Sequencing for Patients With Castration-Resistant Prostate Cancer

• Published in: Value in health Vol. 28; no. 5; pp. 720 - 729
• Main Authors: Fu, Jinjing, Franzen, Nora, Aas, Eline, Koen van der Mijn, J.C., van Leeuwen, Pim J., Retel, Valesca P.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2025
• Subjects: biomarker-guided therapy; castrate-resistant prostate cancer; Cost-Benefit Analysis; cost-effectiveness; Cost-Effectiveness Analysis; Decision Support Techniques; Decision Trees; Humans; incremental cost-effectiveness ratio; Internal Medicine; Male; Netherlands; Phthalazines; Piperazines; Precision Medicine - economics; Prostatic Neoplasms, Castration-Resistant - drug therapy; Prostatic Neoplasms, Castration-Resistant - economics; Prostatic Neoplasms, Castration-Resistant - genetics; Public Health; Quality-Adjusted Life Years; Whole Genome Sequencing - economics; whole-genome sequencing; Netherlands; cost-effectiveness; incremental cost-effectiveness ratio; biomarker-guided therapy; whole-genome sequencing; castrate-resistant prostate cancer
• ISSN: 1098-3015; 1524-4733; 1524-4733
• DOI: 10.1016/j.jval.2025.02.004

This study aims to assess the potential cost-effectiveness of using whole-genome sequencing (WGS)-guided systemic therapy in metastatic castrate-resistant prostate cancer compared with the European Association of Urology guideline recommended diagnostics from a Dutch societal perspective. A decision analytic model combining a decision tree and partitioned survival models was developed to link diagnostic results with subsequent biomarker-guided treatments. Two diagnostic strategies, WGS and guideline-recommended practice—the genomic testing for breast cancer gene 1/2 (BRCA1/2) and deficient mismatch repair, were simulated to compare the health outcome and cost. Treatment effectiveness was estimated through survival analysis using published trial data. Sensitivity and scenario analyses were conducted to examine result robustness and to identify conditions under which WGS may be cost-effective. WGS identified an additional 21% of patients eligible for personalized therapy (PD-1/PDL-1 inhibitors and olaparib), resulting in an incremental increase in cost (€14 260) and quality-adjusted life years (QALY = 0.05). These results yielded an incremental cost-effectiveness ratio of €289 625 per QALY gained. WGS would become cost-effective if the cost of biomarker-guided therapies decreases by 62% and when identifying a proportion of 23% more patients with actional targets. Our findings suggest that future treatments with improved efficacy and reduced cost could potentially make the WGS strategy cost-effective. Its unaccounted potential value to identify prognostic biomarkers, diagnostic alternatives, and patient heterogeneity should be addressed in future research and considered for optimal implementation. New reimbursement options are needed considering the high prices of biomarker-guided therapies that drive the incremental cost-effectiveness ratio. •We explored the value of using whole-genome sequencing (WGS) in metastatic castration-resistant prostate cancer.•WGS identified 21% more patients eligible for personalized therapies compared with current European guideline-recommended diagnostics but incurred higher incremental costs, driven by expensive treatments.•With the exploration of tipping points, we found that WGS could become cost-effective with a significant reduction of novel treatment cost and treatment effect uncertainty. Our analysis will contribute to discussions on changing the framework for evaluating diagnostics.