Abstract：
OBJECTIVE: Metastatic prostate cancer (mPCa) patients with BRCA mutations benefit from targeted treatments (e.g., olaparib). Additionally, family members of affected patients have increased risk of hereditary cancers and benefit from early detection and prevention. International guidelines recommend genetic testing in mPCa, however, the value for money of testing mPCa patients and cascade testing of blood-related family members has not been assessed. In this context we evaluated the cost-effectiveness of germline BRCA testing in mPCa patients followed by cascade testing of first-degree relatives (FDRs) of mutation carriers.
METHODS: We conducted a cost-utility analysis of germline BRCA testing using two scenarios: 1) testing mPCa patients only; 2) testing mPCa patients and first-degree relatives (FDRs) of those who test positive. A semi-Markov multi-health-state transition model was constructed using a lifetime time horizon. The analyses were performed from an Australian payer perspective. Decision uncertainty was characterized using probabilistic analyses.
RESULTS: Compared with no testing, BRCA testing in mPCa was associated with an incremental cost of AU$3,731 and a gain of 0.014 quality-adjusted life years (QALYs), resulting in an incremental cost-effectiveness ratio (ICER) of AU$265,942/QALY. Extending testing to FDRs of variant positive patients resulted in an ICER of AU$16,392/QALY. Probability of cost-effectiveness at a willingness-to-pay of AU$75,000/QALY was 0% in the standalone mPCa analysis and 100% in the cascade testing analysis.
CONCLUSIONS: BRCA testing when performed as a standalone strategy in patients with mPCa may not be cost-effective but demonstrates significant value for money after the inclusion of cascade testing of FDRs of mutation carriers.
METHODS: We conducted a cost-utility analysis of germline BRCA testing using two scenarios: 1) testing mPCa patients only; 2) testing mPCa patients and first-degree relatives (FDRs) of those who test positive. A semi-Markov multi-health-state transition model was constructed using a lifetime time horizon. The analyses were performed from an Australian payer perspective. Decision uncertainty was characterized using probabilistic analyses.
RESULTS: Compared with no testing, BRCA testing in mPCa was associated with an incremental cost of AU$3,731 and a gain of 0.014 quality-adjusted life years (QALYs), resulting in an incremental cost-effectiveness ratio (ICER) of AU$265,942/QALY. Extending testing to FDRs of variant positive patients resulted in an ICER of AU$16,392/QALY. Probability of cost-effectiveness at a willingness-to-pay of AU$75,000/QALY was 0% in the standalone mPCa analysis and 100% in the cascade testing analysis.
CONCLUSIONS: BRCA testing when performed as a standalone strategy in patients with mPCa may not be cost-effective but demonstrates significant value for money after the inclusion of cascade testing of FDRs of mutation carriers.
摘要：
目的：具有BRCA突变的转移性前列腺癌（mPCa）患者受益于靶向治疗（例如，奥拉帕利)。此外,受影响患者的家庭成员患遗传性癌症的风险增加，并从早期发现和预防中受益。国际指南建议在mPCa中进行基因检测，然而,mPCa患者检测和血液相关家庭成员级联检测的资金价值尚未评估.在这种情况下，我们评估了mPCa患者种系BRCA测试的成本效益，然后对突变携带者的一级亲属（FDR）进行级联测试。
方法：我们使用两种情况进行了种系BRCA测试的成本效用分析：1）仅测试mPCa患者；2）测试mPCa患者和测试阳性患者的一级亲属（FDRs）。使用生命周期时间范围构建了半马尔可夫多健康状态转移模型。这些分析是从澳大利亚付款人的角度进行的。使用概率分析来表征决策不确定性。
结果：与未测试相比，mPCa中的BRCA测试与3,731澳元的增量成本和0.014质量调整寿命年(QALYs)的收益相关，导致增量成本效益比（ICER）为265,942澳元/QALY。将测试扩展到变异阳性患者的FDR导致ICER为AU$16,392/QALY。在独立mPCa分析中，愿意支付$75,000/QALY的成本效益概率为0％，在级联测试分析中为100％。
结论：BRCA检测在mPCa患者中作为独立策略进行时可能不具成本效益，但在纳入突变携带者FDRs级联检测后显示出显著的资金价值。
方法：我们使用两种情况进行了种系BRCA测试的成本效用分析：1）仅测试mPCa患者；2）测试mPCa患者和测试阳性患者的一级亲属（FDRs）。使用生命周期时间范围构建了半马尔可夫多健康状态转移模型。这些分析是从澳大利亚付款人的角度进行的。使用概率分析来表征决策不确定性。
结果：与未测试相比，mPCa中的BRCA测试与3,731澳元的增量成本和0.014质量调整寿命年(QALYs)的收益相关，导致增量成本效益比（ICER）为265,942澳元/QALY。将测试扩展到变异阳性患者的FDR导致ICER为AU$16,392/QALY。在独立mPCa分析中，愿意支付$75,000/QALY的成本效益概率为0％，在级联测试分析中为100％。
结论：BRCA检测在mPCa患者中作为独立策略进行时可能不具成本效益，但在纳入突变携带者FDRs级联检测后显示出显著的资金价值。
