The comparison of clinical utility between pan-cancer panel and PCa-specific panel for mCRPC.

47 Background: To compare the diagnostic efficiency of pathogenic variants and the value for clinical decision making between a pan-cancer panel and a prostate cancer (PCa)-specific panel among patients with metastatic castration-resistant PCa (mCRPC). Methods: 637 mCRPC patients underwent panel-based targeted gene sequencing (Cohort A), among which, 327 patients underwent genomic profiling with a PCa-specific panel of 50 genes and 310 patients with a pan-cancer panel of 672 genes. Furthermore, 56 patients in Cohort A received both panel-based targeted gene sequencing approaches at the same time (Cohort B). The comparisons of the diagnostic efficiencies of pathogenic variants and clinical actionable variants (CAVs) were analyzed by proportion test. Results: The diagnostic efficiency of pathogenic variants was significantly higher in pan-cancer panel group than in PCa-specific panel group either in cohort A or cohort B (p<0.0001). In cohort A, 504 of 970 genomic variants were defined as pathogenic variants among which 304 were classified as CAVs in PCa-specific panel group. In pan-cancer panel group, 1457 of 4205 genomic variants were defined as pathogenic variants among which only 304 were classified as CAVs. In cohort B, 96 of 182 genomic variants were defined as pathogenic variants among which 56 were classified as CAVs in PCa-specific panel group. In pan-cancer panel group, 260 of 788 genomic variants were defined as pathogenic variants among which only 59 were classified as CAVs. The detection rate of CAVs between the two groups was no difference either in cohort A or cohort B (p>0.05). Conclusions: The pan-cancer panel had increased detection yield of pathogenic variants and provided a rich source of data, which was helpful for genetic researches. However, the PCa-specific panel proved to be as powerful as the pan-cancer panel in the detection of CAVs for tailored treatments, which might be better in guiding clinical decision making in a cost-effectiveness and time-saving way. Thus, the NGS panels available in different sizes might be chosen depending on basic research or clinical objectives.