Genomic Testing in mCRPC
An expert emphasizes that genomic profiling—including both germline and somatic testing—is now essential in metastatic prostate cancer management because it identifies key mutations such as homologous recombination repair (HRR) gene alterations that guide targeted therapies such as PARP inhibitors, informs the use of immune checkpoint inhibitors in select cases, and helps predict disease aggressiveness to tailor monitoring and treatment strategies.
Genomic profiling has become an essential component in the management of metastatic prostate cancer, especially in the castration-resistant stage. Current guidelines recommend performing both germline and somatic tumor testing at the time when metastatic disease is first identified. This dual testing approach helps identify specific genetic alterations that can influence treatment decisions, guide monitoring strategies, and provide valuable information for family members who may also be at risk.
One of the most important findings from genomic profiling is the presence of homologous recombination repair (HRR) HRR gene mutations. Patients with these mutations tend to have a more aggressive disease course and respond for a shorter duration to androgen receptor pathway inhibitors (ARPIs). Because of this, treatment with PARP inhibitors has shown a benefit for this subgroup. Additionally, a small percentage of patients may harbor mutations such as high microsatellite instability (MSI-high)or high tumor mutational burden (TMB-high), who which can respond well to immune checkpoint inhibitors. Recognizing these mutations allows for personalized therapies that can significantly impact patient outcomes.
Besides actionable mutations, profiling also identifies tumor suppressor gene losses, such as p53, PTEN, or RB1. When two 2 or more of these alterations are present, patients typically exhibit very aggressive disease, which may progress rapidly. This knowledge prompts more frequent monitoring, including imaging and laboratory tests, to catch progression early and adjust treatment promptly. Overall, genomic testing informs not only treatment choice but also surveillance and family risk assessment, making it a cornerstone in modern prostate cancer care.
