Experimental, minimally invasive “liquid biopsy” blood tests might soon help to personalize prostate cancer treatment by predicting androgen resistance and survival benefits from particular treatments, researchers announced at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 3–7 in Chicago.
Liquid biopsies detect circulating tumor cells (CTCs) or bits of tumor DNA (ctDNA). Not all tumors shed cells or DNA into a patient’s bloodstreams, but most do. And when they do, they can reveal a lot about themselves—including molecular signatures that can be targeted with specific treatments.
Recent years have seen an explosion of candidate biomarkers for prostate cancer and other malignancies, including both liquid biopsies and tumor-sample gene panels. Most candidate biomarkers have been prognostic gene-mutation signatures that can estimate patient survival regardless of what treatment strategies are attempted. These prognostic tests can be useful for risk-stratifying patients who are participating in clinical studies, or in communicating prognosis to a patient and his loved ones.
But other proposed biomarkers are predictive: their results correlate with a given patient population’s outcomes following treatment with a particular treatment strategy. Of particular interest among prostate cancer experts at this year’s ASCO meeting was the development of biomarkers that predict tumor androgen-receptor (AR) resistance.
One suspected factor in AR resistance is nuclear androgen-receptor splice variant 7 (AR-V7), which lacks a normal AR ligand-binding domain. Detecting AR-V7 protein in prostate CTCs can predict the failure of abiraterone and enzalutamide (two AR signaling inhibitors), according to a cross-sectional cohort study reported at the ASCO meeting (abstract 5013). The study was also published online in JAMA Oncology.
Among patients whose CTCs harbor AR-V7, taxane-based chemotherapy regimens are associated with significantly longer progression-free and overall survival (OS) as well (OS: 8.9 vs 4.6 months; multivariate hazard ratio for risk of death on taxane vs abiraterone or enzalutamide therapy, 0.24 [95% CI, 0.10–0.57]; P = .035).
A total of 161 evaluable men diagnosed with metastatic castration-resistant prostate cancer (mCRPC) were included in the study; pretreatment blood samples were taken and tested using immunofluorescence to identify nucleated cells with the AR-V7 protein. Response to AR therapy was defined as a decline in patients’ PSA levels of greater than 50%.
None of the patients with AR-V7–positive CTCs responded to AR therapy.
The findings imply that AR-V7 testing can help ensure that patients receive appropriate treatment earlier in disease progression, when therapy might be more effective.
“We found that a novel liquid biopsy for AR-V7 was able to identify, with specificity, patients who will not benefit from these therapies and should instead start chemotherapy independent of the line of therapy being administered,” said lead study author Howard I. Scher, MD, chief of genitourinary oncology services at Memorial Sloan Kettering Cancer Center in New York.
1. Scher HI, Lu D, Schreiber NA, et al. Association of AR-V7 on circulating tumor cells as a treatment-specific biomarker with outcomes and survival in castration-resistant prostate cancer. JAMA Oncology. Published online June 4, 2016.
2. Antonarakis ES, Lu C, Luber B, et al. Androgen receptor splice variant 7 and efficacy of taxane chemotherapy in patients with metastatic castration-resistant prostate cancer. JAMA Oncology. 2015;1(5):582-591.
3. Montgomery RB, Plymate SR. AR-V7 protein in circulating tumor cells—the decider for therapy? JAMA Oncology. Published online June 4, 2016.