DURHAM, NC — Nearly a decade ago, the U.S. Food and Drug Administration approved the first liquid biopsy assay to monitor patients with prostate, breast, and colon cancer by measuring circulating tumor cells (CTC) in patients’ blood.
In the intervening nine years, liquid biopsies have come to play an ever-greater role in the diagnosis of multiple types of cancer, survival prognosis, and assessment of response to therapy.
Their status as a preferred method of detecting and monitoring cancer seems assured, given the high-quality data provided. Further, their non-invasive nature makes liquid biopsies ideal for serial assessments, difficult-to-access tumors, and other challenging situations. As liquid biopsy tests have become increasingly more sophisticated, the information they can reveal has grown, with recent research demonstrating their utility in genomic, transcriptomic, and epigenomic tumor profiling, all of which can inform the selection of the cancer therapy most likely to work for the given patient while also minimizing the risk of serious adverse events.
Liquid biopsies that measure circulating tumor DNA (ctDNA) in plasma, in particular, have emerged as an alternative to genomic profiling using tumor tissue obtained by biopsy. Their performance, however, depends on the “total amount and proportion of ctDNA in the total circulating DNA pool,” observed a team that included researchers from the VAMCs in Los Angeles and Durham, NC, in a study presented at the American Society of Clinical Oncologists annual meeting in June.
Understanding that restriction, the researchers, led by Aixia Guo, MD, of the Durham VAMC, sought to define the factors that predict successful genomic profiling using liquid biopsy in veterans with prostate cancer. Their study included 764 veterans with prostate cancer who received liquid biopsy testing between February 2019 and February 2021 with results reported in the VA National Precision Oncology Program (NPOP) database.
To identify the key factors in successful genomic profiling, the researchers extracted information on patient age at specimen collection date, race, prostate-specific antigen (PSA) level, PSA doubling time (PSADT), sites of metastases, number of metastatic sites, Gleason score, and Gleason grade group from the VA Corporate Data.
The team used two approaches to define a successful liquid biopsy. In Approach 1, the liquid biopsies detected an alteration in one or more prostate cancer-related genes such as AR, CDK12, SPOP, MED12, CCND1, BRAF, AKT1, or TMPRSS2. In Approach 2, the liquid biopsies detected alterations in any gene also detected by the Foundation One Liquid CDx assay.
Among the 337 biopsies that detected an alteration in Approach 1, those in the fourth PSA quantile had an odds ratio (OR) nearly five times that of those in the first PSA quantile (P < 0.001; 95% CI [3.09, 7.47]). The OR was nearly four times greater for PSADT less than three months vs. PSADT more than 60 months (P < 0.001; 95% CI [2.0, 6.5]). Brain metastases demonstrated the highest OR value of all metastatic sites at 2.47 (P = 0.008; 95% CI [1.27. 4.8]). Notably, PSA, PSADT, and metastasis sites differed markedly between groups in which genomic profiling using the liquid biopsy was successful and those in which it failed.
“In Approach 2, no statistically significant associations were observed between the studied variables and any outcome,” a finding the researchers attributed to the “likelihood that a significant number of non-prostate cancer mutations are likely due to clonal hematopoiesis.”
The researchers concluded that the association between PSA, PSADT, and metastatic site and successful genomic profiling to identify prostate cancer-related mutations “may facilitate clinical decisions around genomic profiling by liquid biopsies in the absence of tumor tissue, thereby increasing the success rate of sequencing efforts for treatment selection.”
- Gua A, Ahmed S, Rowe K, Pritchard CC, Montgomery RB, Kelley MJ, Rettig M. Clinical markers of successful liquid biopsy-based genomic profiling in veterans with prostate cancer. J Clin Oncol. 2022;40(suppl 16; abstr e17031).