Real-world precision medicine data in metastatic prostate cancer — a retrospective cohort study

Background Prostate cancer (PC) is the most common cancer in men in the United States with a 5-year relative survival rate for people with distant metastases of 36%. We conducted a single institution, retrospective cohort study of patients with metastatic PC to investigate whether certain gene mutations can be used as predictive biomarkers. Methods 200 patients with metastatic hormone sensitive (mHSPC) and castration resistant (mCRPC) prostate cancer who had a FoundationOne report and were treated from June 2007 to October 2024 were included in the study. Disease progression was evaluated according to RECIST criteria, PCWG3 criteria, and PSA values. Assessed gene mutations included SPOP, p53, Rb, PTEN , and HRR genes. Overall survival (OS) and progression-free survival (PFS) were calculated for mHSPC and mCRPC. Results Among 200 patients, there were 182 patients with mHSPC and 174 patients with mCRPC. Average age at diagnosis of metastatic disease was 71.5, ECOG was 0.76, and median PSA was 75.6 ng/mL. 152 patients had high-volume disease. 102 patients passed away. Patients with a p53 mutation (n=99) had lower OS in mHSPC (50.7 months vs 86.2 months, p0.01). Patients with a PTEN mutation (n=50) had a lower OS in mHSPC (50.6 months vs 65.8 months, p=0.03) and mCRPC (29.5 months vs 46.0 months, p=0.04). Patients with HRR mutations (n=43) had lower OS in mHSPC (41.4 months vs 64.6 months, p0.01) and mCRPC (18.4 months vs 42.8 months, p=0.04). p53 and PTEN mutations were associated with shorter PFS in mCRPC (13.8 months vs 23.2 months, p=0.03; 12.2 months vs 22.6 months, p0.01, respectively). Mutations in SPOP (n=13 mHSPC, n=9 mCRPC) and RB1 (n=12 mHSPC, n=10 mCRPC) were not associated with statistically significant differences in OS and PFS. Conclusions PTEN , and HRR mutations were associated with shorter OS in both mHSPC and mCRPC. p53 mutations are associated with shorter OS only in mHSPC. p53 and PTEN mutations were associated with shorter PFS only in mCRPC.