Markers may predict failure of metastatic prostate cancer treatment

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 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, Ph.D., of Palacký University and University Hospital Olomouc said: "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, researchers collected plasma samples 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.

They used digital PCR to assess androgen receptor (AR) gene amplification, and they measured the expression levels of microRNA (miR)-375 wby quantitative PCR. They evaluated 16 other clinical markers, 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, Ph.D., of Palacký University and University Hospital Olomouc explained: "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 support the survival and growth of established metastatic tumors by suppressing the immune response.

Bouchal concluded: "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."

About The Journal of Molecular Diagnostics

The Journal of Molecular Diagnostics, the official publication of the Association for Molecular Pathology, co-owned by the American Society for Investigative Pathology, and published by Elsevier, seeks to publish high-quality original papers on scientific advances in the translation and validation of molecular discoveries in medicine into the clinical diagnostic setting, and the description and application of technological advances in the field of molecular diagnostic medicine.

The editors welcome review articles that contain: novel discoveries or clinicopathologic correlations, including studies in oncology, infectious diseases, inherited diseases, predisposition to disease, or the description of polymorphisms linked to disease states or normal variations; the application of diagnostic methodologies in clinical trials; or the development of new or improved molecular methods for diagnosis or monitoring of disease or disease predisposition.