Abstract 2294: Plasma progastrin level as a predictive and prognostic biomarker in advanced prostate cancer

Abstract

Abstract Background and Aims: Progastrin is a tumor promoting peptide which is detectable in the blood of patients with different cancers. Progastrin gene is a direct target of the WNT/ß-catenin oncogenic pathway involved in tumorigenesis and possibly tumor progression/ treatment efficacy. Since WNT/ß-catenin oncogenic pathway is dysregulated in advanced prostate cancer we evaluated plasma progastrin in metastatic prostate cancer as a predictive and prognostic biomarker. Methods: Metastatic hormone sensitive prostate cancer (mHSPC) and metastatic castration resistant prostate cancer (mCRPC) states were enrolled in a cohort study of blood sample collection and follow-up for outcomes between 9/2009 and 11/2013. Patients were enrolled in mHSPC unique sub-cohorts before initiating androgen deprivation therapy (ADT); during ADT; at the time of failure of ADT and before starting chemotherapy. Plasma progastrin was measured using the ELISA cancerREAD®. Progastrin concentrations in the cancer patients (test set) was assessed against 213 samples from asymptomatic volunteers from the French blood establishment (control set) and prograstin levels were also compared for each of the above four mHSPC and mCRPC cohorts as well as for association with time to failure on AA for the mHSPC cohort and overall survival for both mHSPC and mCRPC subcohorts. We also determined progastrin levels in patients with two serial samples to evaluate if changes were predictive for overall survival. Results: Of the 523 mHSPC+mCRPC patients 96 were in mHSPC state enrolled before starting ADT; 101 mHSPC patients were enrolled while receiving ADT; 143 mHSPC patients were enrolled at the time of ADT failure and 143 were clinically progressive mCRPC. All cohorts were unique and 246/523 patients had two serial samples collected and analyzed across all subcohorts. The median time of follow up of the whole cohort was 8.34 years (IQR: 4.53-12.97) and 371/523 had died at the time of the analysis. Plasma progastrin levels was detected in 87.6% of all the patients (cut-off value 1 pM, range 0 to 311 pM, median value of 4.7 pM) compared to the control set (median value=0.61 pM; IQR 0.00-1.58). The Receiver Operating Characteristic analysis indicated an area under the curve of 0.84 (p<0.0001; 95% CI 0.81 to 0.87). Of these, 106 patients had a decrease and 140 patients an increase of progastrin levels. Patients with a serial increase of progastrin had a worst overall survival compare to the other group (p=0.019). Conclusion: Progastrin is a blood based biomarker elevated in advanced prostate cancer patients serial increases in progastrin levels during treatment are predictive of poor survival. Progastrin assay might be useful for monitoring therapeutic interventions like androgen deprivation therapy effects as well for advanced prostate cancer patients. Citation Format: Manish Kohli, Winston Tan, Lea Payen, Carole Langlois-Jacques, Pierre Liaud, Delphine Maucort-Boulch, Dominique Joubert, Alexandre Prieur. Plasma progastrin level as a predictive and prognostic biomarker in advanced prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2294.