Blood-based biomarkers predict therapy failure in prostate cancer patients

New research has identified specific blood-based biomarkers that can predict the failure of prostate cancer treatment in both hormone-sensitive and castration-resistant patients. The study in The Journal of Molecular Diagnostics, published by Elsevier, identifies platelets, C-reactive protein, and chromogranin A as important indicators in hormone-sensitive prostate cancer patients for the combined androgen deprivation and androgen receptor pathway inhibitors therapy failure to guide alternate treatment.

One of the most prevalent cancers, prostate cancer is characterized by its significant heterogeneity, metastatic tendencies, and treatment resistance. The disease typically evolves in a hormonal-dependent manner, initially categorized as hormone-sensitive prostate cancer, with treatment strategies focused on reducing androgen levels, the primary drivers of prostate cancer growth. This strategy exhibits limited efficacy over time and sooner or later fails. Following progression to castration-resistant prostate cancer, androgen receptor pathway inhibitors are commonly used. Despite its usage, the precise mechanisms underlying androgen receptor pathway inhibitors therapy failure and the progression of prostate cancer remain unclear.

Lead investigator Jan Bouchal, PhD, Department of Clinical and Molecular Pathology, Institute of Molecular and Translational Medicine, Palacký University and University Hospital Olomouc, Olomouc, Czechia, says, "Androgen deprivation therapy has long been the first-line treatment for hormone-sensitive prostate cancer. Recently, combined therapy with androgen deprivation therapy and androgen receptor pathway inhibitors has been recommended for metastatic hormone-sensitive prostate cancer patients. To monitor the disease and optimize outcomes for these patients, oncologists need new or re-established markers."

In this study plasma samples were collected from 140 patients with either metastatic hormone-sensitive (N=72) or castration-resistant (N=68) prostate cancer before the start of androgen receptor pathway inhibitors therapy. Digital PCR was used to assess androgen receptor (AR) gene amplification, while the expression levels of microRNA (miR)-375 were measured by quantitative PCR. Sixteen other clinical markers were also evaluated, including prostate specific antigen (PSA), chromogranin A (CGA), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), C-reactive protein (CRP), lymphocyte-to-monocyte ratio (LMR), and platelets.

Co-lead investigator Hana Študentová, PhD, Department of Oncology, Palacký University and University Hospital Olomouc, Olomouc, Czechia, explains, "A multivariate analysis, adjusted for age and metastatic dissemination, identified miR-375 expression and LMR to be the only independent negative predictors for androgen receptor pathway inhibitors therapy failure in castration-resistant prostate cancer patients. Regarding the hormone-sensitive prostate cancer patients, we report the priority finding on the independent negative predictive value of platelets, CRP, and CGA for the therapy failure of the combined androgen deprivation therapy and androgen receptor pathway inhibitors. Monitoring these biomarkers can provide crucial insights into disease progression and potential therapy failure, enabling more timely and personalized therapeutic interventions."

The discovery of platelet counts as an independent negative predictive factor for hormone-sensitive prostate cancer treated with the combined androgen deprivation therapy and androgen receptor pathway inhibitors is especially important in light of recent research that emphasizes the vital role of platelets in promoting the growth of existing metastases. This research demonstrates that platelets play a dual role in metastasis progression. They aid in the initial stages of metastasis by binding to tumor cells, and they also support the survival and growth of established metastatic tumors by suppressing the immune response.

Dr. Bouchal concludes, "Evaluation of platelets, CRP, and CGA is established in many laboratories and can easily be exploited for the care of patients with metastatic hormone-sensitive prostate cancer. Our study validates the utility of blood-based biomarkers in predicting therapy outcomes for patients with both types of prostate cancer. Following further validation on larger cohorts, the markers identified in our analysis may be beneficial for making therapeutic decisions in patients with aggressive variants of metastatic prostate cancer."