Genomic Testing in Patients with Metastatic Castration-resistant Prostate Cancer: A Pragmatic Guide for Clinicians

Area of Science:

• Oncology
• Genetics
• Molecular Biology

Background:

• Advanced prostate cancer (PC) management is increasingly influenced by genomic insights.
• Genomic alterations in tumors drive cancer progression and represent therapeutic targets.

Purpose of the Study:

• To review the current understanding of genomic alterations in metastatic castration-resistant prostate cancer (mCRPC).
• To assess the status of genomic testing in mCRPC and its clinical utility.
• To explore the potential of genomic tests in guiding treatment decisions.

Main Methods:

• Systematic review of publications from PubMed, scientific conferences, and guidelines over the past 15 years.
• Selection of reports focusing on genomic alteration identification, molecular characterization, and targeted therapy trials in mCRPC.

Main Results:

• mCRPC tumors exhibit targetable molecular alterations, with therapies like PARP inhibitors and PD-1 inhibitors under development.
• Next-generation sequencing (NGS) of tumor DNA identifies somatic alterations; cell-free DNA (cfDNA) testing is under evaluation.
• International guidelines recommend germline/somatic testing for advanced/high-risk PC to identify eligibility for PARP inhibitors or pembrolizumab.

Conclusions:

• Genomic testing in mCRPC provides prognostic, predictive, and resistance biomarker information.
• Despite challenges in clinical integration, routine genomic testing is recommended for advanced PC to guide management.
• Genomic testing aids in selecting targeted therapies for patients with specific genetic defects.