Real world data of precision medicine in the management of metastatic prostate cancer: A retrospective cohort study.

e17037 Background: Prostate cancer (PC) is the most diagnosed 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 (pts) with metastatic PC to investigate whether certain gene mutations can be used as prognostic biomarkers. Methods: 147 pts with metastatic prostate cancer who were treated at Northwell Health Monter Cancer Center from January 2012 to November 2021 who had a FoundationOne report were included in the study. This study was approved by the Northwell Health Institutional Review Board. Pts who had cancer that was not prostatic adenocarcinoma, such as prostate neuroendocrine tumors, were also excluded. Pts with metastatic hormone sensitive prostate cancer (mHSPC) and metastatic castrate resistant prostate cancer(mCRPC) were included. Demographic data, Gleason score, locations of metastatic disease, and treatment data were recorded. RECIST criteria, PCWG3 criteria, and PSA values were used to evaluate disease progression. Data from FoundationOne genetic analysis were used to investigate whether genetic mutations involving SPOP, p53, Rb, PTEN, and HRR genes (BRCA1, BRCA2, ATM, ATR, BRIP1, BARD1, CDK12, CHEK1, CHEK2, FANCA, FANCL, MLH1, MRE11A, NBN, PALB2, RAD51B, RAD51C, RAD51D, and RAD54L) were associated with differences in OS and PFS (using the Kaplan-Meier method). Results: Among the 147 pts, there were 131 instances of mHSPC and 143 instances of mCRPC cancer. Average age of metastatic disease was 71, ECOG was 0.8, and median PSA was 98. 28 pts had low volume disease and 119 pts had high volume disease. All 23 HRR mutant pts had mHSPC and then developed mCRPC. In these pts, there was a significantly lower OS for pts with both mHSPC (49 months (m) vs 70 m; p=0.0097) and mCRPC cancer (41 m vs 70 m; p=0.015). There was also a shorter PFS in pts with mCRPC cancer (12 m vs 21 m; p=0.026). In pts who had a PTEN mutation (n=37), 33 had mHSPC while 37 had mCRPC. In these pts, there was a lower OS for both mHSPC (52 m vs 83 m; p=0.03) and mCRPC(52 m vs 72 m; p=0.014). There was also a shorter PFS in pts with mCRPC (12 m vs 23 m; p=0.00054). In both mHSPC and mCRPC, no significant differences in OS or PFS were noted for pts with SPOP (n=10 mHSPC, n=9 mCRPC), p53 (n=69 mHSPC, n=75 mCRPC), or Rb (n=10 mHSPC, n=9 mCRPC) mutations. 84 pts passed away. Conclusions: In our study, HRR and PTEN mutations were associated with shorter overall survival in both mHSPC and mCRPC, with shorter PFS only in mCRPC. The study was limited by small sample size, and future studies may evaluate whether treatments targeting these mutations are associated with an improvement in clinical outcomes.