Background: mCRPC patients with liver metastases have a poor prognosis and often progress rapidly on a variety of treatments. Previously, preliminary ctDNA analyses of mCRPC patients with liver metastases showed a range of commonly altered genes in patients with liver metastases (Ranasinghe et al; 2019). In this follow-up, we evaluated ctDNA alterations in an expanded cohort of mCRPC patients with liver metastases. Methods: From Tulane Cancer Center, retrospective review of mCRPC patients was used to identify patients with confirmed liver metastasis. All liver metastases were confirmed based on imaging data. All patients included had ctDNA evaluated with a multi-gene cancer panel via Guardant 360 assay (Guardant Health, Inc). Additional clinical annotation including family history, germline testing, staging, imaging, and laboratory values. Statistical analyses were performed with Fisher’s Exact and Wilcoxon Rank Sum tests. Results: 158 mCRPC patients with appropriate diagnostic imaging as well as ctDNA testing. From this group, 8% (n= 12) had confirmed liver metastases. Among the patients with liver metastasis, the most common alterations detected were in AR (50%; 6/12) and PIK3CA (25%; 3/12). Patients with liver metastasis were more likely to have amplifications in FGFR1 detected in their ctDNA (OR= 14.40; 95% C.I. (1.83, 113.22); p= 0.03). In addition to ctDNA, germline data was assessed, and it was found that patients with liver metastasis were more likely to have a pathogenic germline mutation (OR= 7.61; 95% C.I. (2.85, 20.31); p<.0001). The most common germline mutations detected in patients with liver metastasis were in BRCA2 (n= 3) and TP53 (n= 2). Conclusions: Though liver metastasis are less common in prostate cancer, it often occurs following extensive treatment and results in a poor prognosis for patients. In patients with liver metastasis, FGFR1 amplification was more often detected in ctDNA. Importantly, patients with liver metastasis were significantly more likely to have a pathogenic germline alteration.