The Cost-Effectiveness of Germline BRCA Testing in Prostate Cancer Followed by Cascade Testing of First-Degree Relatives of Mutation Carriers

OBJECTIVES: Prostate cancer (PCa) patients with gene mutations can benefit from targeted treatments. Furthermore, relatives of affected patients who test positive may benefit from early prevention. International guidelines recommend genetic testing, however, the most cost-effective approach for PCa testing is unclear. The aim of this study was to identify and assess the value for money of potential genetic testing strategies.

METHODS: We systematically reviewed international guidelines for prostate cancer genetic testing and summarized key strategies. A modified Delphi technique using two rounds of surveys was administered to build consensus on potential genetic testing strategies for implementation in Australia. Cost-utility analyses from the Australian health system perspective of targeted germline BRCA testing with and without cascade testing (i.e., testing family) was conducted to evaluate the strategies that reached consensus. A semi-Markov multi-health-state transition model was constructed using a lifetime time horizon, populated using relative evidence from the literature and expert opinion. Decision uncertainty was characterized using probabilistic analyses.

RESULTS: Four genetic testing strategies reached consensus: 1) metastatic prostate cancer (mPCa); 2) high/very high-risk localised PCa; 3) localised PCa patients with family history; 4) localised PCa patients with Ashkenazi-Jewish ancestry. The incremental cost-effectiveness ratio (ICER) of BRCA testing compared to no testing was not cost effective in mPCa (AU$265,942/quality-adjusted life year (QALY)), in high/very high-risk PCa (AU$591,408/QALY), localised PCa patients with family history (AU$3.9 million/QALY), or in Ashkenazi-Jews (AU$650,098/QALY). Extending testing to family members resulted in favourable ICERs of AU$16,392/QALY in mPCa, AU$18,872/QALY in high-risk PCa, AU$47,294/QALY in patients with family history, and AU$14,637/QALY in Ashkenazi-Jews. Probability of cost-effectiveness at a willingness-to-pay of AU$75,000/QALY was 0% testing patients only and 100% with cascade testing of family members.

CONCLUSIONS: Germline BRCA testing may not be cost-effective in patients with PCa but demonstrates significant value for money when extended to blood related family members.