Table 3. Comparison of gene testing strategies [9, 43].
Method of testing | Sample required | Advantages | Limitations |
---|---|---|---|
Germline Testing | Blood or saliva |
• Germline mutations detected reliably • Large panels of tests available which can detect germline mutations in mCRPC |
• Unable to detect somatic mutations relevant to treatment selection |
Somatic Testing | Tumor Tissue/metastatic tissue |
• Can detect germline and somatic mutations, which might be relevant for initiating targeted therapies • Provides information about translocations and amplifications • A multigene panel of tests available with testing for >300 genes possible |
• Tumor heterogeneity might result in missing late somatic mutations especially if testing is conducted on archival sample • Somatic testing is less sensitive, and thus robustly validated somatic testing is required |
Circulating Tumor DNA (ctDNA) | Plasma |
• Can identify germline and somatic mutations relevant for targeted therapies • Minimally invasive process for sample collection as the biomaterial required is blood • Provides insight into the subclonal population that may be more relevant to current disease state |
• Not enough evidence about shedding pattern of ctDNA in blood circulation in mCRPC • Availability of robustly validated HRR gene panel test • Panels may not have nonactionable genes still relevant for PCa • Chance of missing a germline variant if not sequencing the whole gene due to small size of ctDNA |
Abbreviations: mCRPC: metastatic castration-resistant prostate cancer; ctDNA: circulating tumor DNA; PCa: prostate cancer.