Tissue biopsy has been the gold standard for characterizing the biology of malignancies, and much of what we know about prostate cancer and its treatment has been informed by tissue biopsy–based characterization. For instance, efforts to understand the landscape of genomic alterations in prostate cancer have been enormously productive (eg, identifying DNA repair defects that are potentially amenable to PARP inhibition and microsatellite instability–high disease that may respond to immunotherapy). Still, tissue biopsies in advanced prostate cancer can present distinct challenges, such as obtaining viable tumor samples from bone, a key metastatic site. In addition, due to the heterogeneity of the malignancy, a biopsy of a single lesion may not provide an accurate representation of the biologic features of other disease sites.

With liquid biomarkers such as ctDNA, we have the potential for a minimally invasive test (ie, a simple blood draw) that may provide a sampling of DNA from lesions across multiple sites of disease involvement. Further, one can follow genomic changes over time and even retest with the relative ease of a simple blood draw. Analysis and enumeration of CTCs can be performed similarly, without a tissue biopsy, and such testing also represents an important reservoir of disease: the circulating component. Thus, these serum-based methods can assess tumor biology and tumor burden (ie, if quantitative), and are reproducible with the ease of a blood draw. At the very least, they offer a representation of the disease that is distinct from that of a tissue biopsy from a single site of disease. However, there is still work to be done to determine which testing platforms will become the validated standards. Dong et al recently reported disparities in the positive rates and enumerated CTC counts detected by 2 different platforms, and these types of issues are problematic from the perspective of clinical decision making. Ongoing research is underway to establish a standardized panel that is analytically and clinically validated and would address current reproducibility issues and eliminate discrepancies that occur with the different commercial assays. So, there is more work to be done, but this technique is quite promising.