Dr Barata on Considerations for Molecular Testing in mCRPC

“We need to improve efforts and optimize care team structures to effectively provide sequencing testing for patients with metastatic solid tumors.”

Pedro Barata, MD, associate professor of medicine, Case Western Reserve University School of Medicine, medical oncologist, director, Clinical Genitourinary Medical Oncology Research Program, University Hospitals Seidman Cancer Center, Miggo Family Chair in Cancer Research, University Hospitals, discusses considerations for selecting appropriate molecular testing methods in patients with metastatic castration-resistant prostate cancer (mCRPC).

Genomic testing has become an essential component of care for metastatic prostate cancer by helping identify actionable alteration and molecular markers that may inform treatment decisions, Barata notes. However, selecting the optimal testing method is complex and requires consideration of multiple factors, including the timing of tissue collection, sample quality, and the specific assay being used.

Tissue from a primary tumor may not accurately represent the biology of progressing disease, especially after multiple lines of therapy, Barata continues. Liquid biopsy techniques used for circulating tumor DNA (ctDNA) analysis offer a noninvasive approach to capture real-time tumor dynamics, although the interpretation of low variant allele frequencies or subclonal mutations can be challenging, Barata explains.

The choice of assay—such as next-generation sequencing (NGS) of DNA or RNA, smaller gene panels, or immunohistochemistry (IHC)—should align with clinical objectives, Barata continues. For some patients, focused panels targeting key mutations, such as BRCA1/2 or ATM, may be sufficient, whereas others may benefit from comprehensive genomic profiling. These decisions must balance depth of information with clinical utility and turnaround time, he says.

Operational challenges in genomic testing are also significant, Barata notes. Care teams must coordinate pre-test genetic counseling, timely test execution, and the interpretation of results. Access to genetic counseling services, whether in-house or remote, is critical, particularly for germline testing and the discussion of familial cancer risks, he explains Structuring workflows to accommodate these steps while ensuring efficient patient visits is a growing area of focus for oncology practices, Barata says.

Barata emphasizes that testing strategies must be adaptable to the specific needs of individual care teams. What works well for one institution may not be feasible for another due to differences in resources, expertise, and infrastructure. Developing flexible approaches that can be tailored to local contexts is essential for optimizing the use of genomic testing in metastatic prostate cancer, he concludes.