Serum-based biomarkers and liver metastases in metastatic castration-resistant prostate cancer (mCRPC).

Abstract

372 Background: Metastatic castrate-resistant prostate cancer patients with liver metastases have a poor prognosis. No large studies to date have investigated the clinical and biochemical parameters associated with liver metastases in this population. Methods: Patient data was obtained from 1,281 men with mCRPC that were enrolled on to three phase III clinical trials for the treatment of their disease. This clinical trial data was obtained from Project Data Sphere (www.projectdatasphere.org), an initiative of the CEO Roundtable on Cancer's Life Sciences Consortium. Multiple logistic regression was performed on clinical and biochemical baseline variables to test their association with the presence of liver metastases on baseline CT/MRI imaging. Variables assessed included prior docetaxel exposure, ECOG performance status, albumin, alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST), hemoglobin, lactate dehydrogenase (LDH), prostate specific antigen (PSA), and total bilirubin. The investigation included lab variables when treated as both dichotomous (based on normal-abnormal ranges) and continuous. Results: Multiple variable analysis demonstrated that an abnormally elevated serum AST and/or LDH was associated with an increased likelihood of having documented radiographic liver metastases (p < 0.0001). The predicted probability of having liver metastases for an abnormally elevated AST or LDH was 13.90% (95% CI 9.12 – 20.59) and 16.80% (95% CI 13.19 – 21.16), respectively. Patients with both an elevated AST and LDH had a 31.31% (95% CI 24.0 – 39.73) probability of having liver metastases as compared to only 6.67% (95% CI 5.17 – 8.57) for those with normal values. The ROC curve for the final model (AST + LDH) containing dichotomous predictors was 0.6683 (p < 0.0001), which was not significantly different when treating the predictors as continuous (p = 0.4858). Conclusions: Our analysis demonstrated a significant association between the presence of liver metastases and elevated serum levels of AST and LDH. More research is needed to validate these biomarkers and determine their application in the clinical setting.