Background: In a meta-analysis of 9 phase III trials involving 8,820 pts with metastatic castration-resistant prostate cancer, overall survival progressively decreased from those with lymph node only disease to those with bone, lung, and liver metastases. Herein, we aimed to validate these results in a large real-world dataset based on pathologically confirmed site of metastasis.

Methods: PCa tissue specimens derived from the primary Pca (PPCa) and metastatic sites were molecularly profiled by Caris Life Sciences (Phoenix, AZ). Overall survival (OS) was assessed using insurance claims data, with OS calculated from date of initial tumor diagnosis to death or lost to follow-up using Kaplan Meier estimates and log-rank test. Molecular and immunologic differences by specific metastatic site are presented in a companion abstract. All the analyses were done using CODEai.

Results: 6,069 PCa specimens were included in the analysis [n= 3,411 prostate, n=1,634 non-visceral (bone and lymph node), n=1,029 visceral disease (lung, liver, peritoneum, brain, other.)]. PCa specimens (n=6,069) were stratified based on tumor biopsy site, including prostate (n= 3411), NV (bone and lymph node; n=1,631), and visceral (lung, liver, peritoneum, brain, other; n=1027) subgroups. The median OS from initial diagnosis was significantly longer for pts with PPCa compared to those with visceral metastatic PCa (median OS 70.2 vs 55.5 months; HR 1.42, 95% CI: 1.28-1.58, p,0.001) as well as nonvisceral PCa (median OS 70.2 vs 63.9 months; HR 1.15, 95% CI: 1.05 – 1.27, p=0.004). The comparison of median OS by site of metastatic disease compared to bone metastasis is presented in the Table.

Conclusions: We validate the results of prior studies in a real-world PCa population and show differential OS based on the site of metastases, with liver metastases associated with the shortest OS and lung metastases showing the longest OS. These data argue against combining liver and lung metastases into a single category of visceral metastases when visceral metastasis is used as stratification factor for randomized trials