Cascade genetic testing (CGT) female first-degree relatives (FDR) of men with germline BRCA2 mutations (gBRCA2mut) and prostate cancer (PCa): A cost-effectiveness analysis.

Abstract

110 Background: g BRCA2mut are associated with increased risk of PCa, breast cancer (BC), and ovarian cancer (OC). ~5% of men with metastatic PCa have g BRCA2mut. CGT is recommended for their relatives as there are implications for cancer prevention and early detection strategies. Little is known about CGT initiated by men with PCa. Here we evaluate the cost-effectiveness of CGT in FDR of men with PCa and g BRCA2mut. Methods: A decision-analytic model was created with TreeAge software to compare BC and OC outcomes for female FDRs who underwent CGT for g BRCA2mut versus no CGT. Our theoretical cohort contained 100,000 females, a conservative estimate of patients who could benefit from CGT. We used literature derived estimates to determine the percentage of patients that would pursue risk-reducing mastectomy, risk-reducing salpingo-oophorectomy, both surgeries, or surveillance after CGT. Outcomes included BC or OC diagnoses, survivorship, and cancer death. We derived all probabilities, costs, utilities, and life expectancies from the literature and discounted quality adjusted life years (QALYs) at a rate of 3%. Incremental cost-effectiveness (ICER) was calculated to determine the cost per QALY gained and set the willingness-to-pay threshold at $100,000/QALY. We assessed the robustness of the model with sensitivity analyses. Results: In our theoretical cohort, CGT of female FDRs resulted in 12,910 less BC diagnoses and 6,360 less BC deaths. CGT was associated with lower BC death rates (26.1%) compared to no CGT (35.8%). CGT was not associated with reduction in OC diagnoses or deaths. Our model resulted in lower costs and higher QALYs (a dominant strategy) among the CGT cohort with an ICER of -$4,190.10 per QALY, saving an estimated $595 million. We found that CGT in females was the dominant strategy in 100% of the samples, once uncertainty was incorporated into our model inputs via Monte Carlo simulation. The cost-effectiveness of CGT for male FDRs will be presented at the meeting. Conclusions: In this study, CGT of female FDRs of men with PCa and g BRCA2mut was the dominant strategy to improve BC outcomes, including increased survivorship and reduced BC development. Despite a lack of demonstrated benefit for OC, CGT was associated with reduced costs and increased QALYs. CGT for female FDRs of patients with PCa and g BRCA2mut may be a cost-effective approach for identifying and informing individuals with potentially harmful mutations. [Table: see text]