The Comparison of Clinical Utility between Pan-Cancer Panel and Prostate Cancer-Specific Panel for Metastatic Castration Resistant Prostate Cancer

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: Among 486 studied patients with mCRPC, 250 patients underwent genomic profiling with a PCa-specific panel of 50 genes and 236 patients with a pan-cancer panel of 672 genes. Proportion test was used to compare the diagnostic efficiencies of pathogenic variants and clinical actionable variants (CAVs) between two groups. Findings: In PCa-specific panel group, AR was the most frequently altered gene, followed by CDK12, TP53, NCOR2 and PTEN. In pan-cancer panel group, AR remained as the most frequently altered gene, followed by TP53, CDK12, ZFHX3 and FOXL2. The diagnostic efficiency of pathogenic variants was significantly higher in pan-cancer panel group than in PCa-specific panel group (89∙4% vs. 65∙2%, p <0∙0001). In PCa-specific panel group, 382 of 709 genomic variants were defined as pathogenic variants among which 234 were classified as CAVs. In pan-cancer panel group, 1281 of 3104 genomic variants were defined as pathogenic variants among which only 246 were classified as CAVs. The detection rate of CAVs between the two groups (55∙6% vs. 58∙1%, p=0∙65) was no difference. Interpretation: The pan-cancer panel had increased detection yield of pathogenic variants. However, the PCa-specific panel proved to be as powerful as the pan-cancer panel in the detection of CAVs for tailored treatments. The PCa-specific panel might be better in guiding clinical decision making in a cost-effectiveness and time-saving way. Funding: The Science and Technology Commission of Shanghai Municipality, Shanghai Municipal Health Bureau, Shanghai Municipal Education Commission, Shanghai Jiao Tong University, National Natural Science Foundation of China, Shanghai Jiao Tong University School of Medicine, Renji Hospital Shanghai Jiao Tong University School of Medicine. Declaration of Interest: None to declare. Ethical Approval: The study was approved by the Committee for Ethics of Renji Hospital (approval number: [2016]115K)