Importance
A blood test to determine whether to treat patients with metastatic castration-resistant prostate cancer (mCRPC) with an androgen receptor signaling (ARS) inhibitor or taxane is an unmet medical need.
Objective
To determine whether a validated assay for androgen receptor splice variant 7 (AR-V7) protein in circulating tumor cells (CTCs) that is localized to the nucleus can predict differential overall survival (OS) in mCRPC patients treated with taxanes vs. ARS inhibitors.
Design
Blinded correlative study. Patients were followed up to 4.3 years.
Setting
Multi-institution outpatient clinics at Memorial Sloan Kettering Cancer Center (USA), Institute for Cancer Research (UK) and London Health Sciences Centre (Canada).
Participants
A cross-sectional cohort of 248 patients with mCRPC drawn prior to 286 drug exposures were considered. The analysis subset included 142 patients drawn prior to administration of ARS inhibitors or taxanes at the second or greater line of systemic therapy for progressing mCRPC.
Main Outcome(s) and Measure(s)
OS following an ARS inhibitor or taxane in relation to pretherapy AR-V7 status.
Results
For mCRPC patients designated as high-risk by conventional prognostic factors, AR-V7-positive patients treated with taxanes have superior OS relative to those treated with ARS inhibitors, and AR-V7-negative patients treated with ARS inhibitors have superior OS relative to taxane-treated patients.
Conclusion and Relevance
Nuclear-localized AR-V7 protein in CTCs can identify patients who may live longer on taxane chemotherapy than on ARS inhibitors (abiraterone, enzalutamide, apalutamide).
The analysis of circulating tumor cells (CTCs) is an important capability that may lead to new approaches for cancer management. CTC capture devices developed to date isolate a bulk population of CTCs and do not differentiate subpopulations that may have varying phenotypes with different levels of clinical relevance. Here, we present a new device for CTC spatial sorting and profiling that sequesters blood-borne tumor cells with different phenotypes into discrete spatial bins. Validation data are presented showing that cancer cell lines with varying surface expression generate different binning profiles within the device. Working with patient blood samples, we obtain profiles that elucidate the heterogeneity of CTC populations present in cancer patients and also report on the status of CTCs within the epithelial-to-mesenchymal transition (EMT).
CTCs can be successfully isolated in patients with advanced-stage HNSCC using the CellSearch system. CTC detection may be important for prognosis, evaluating treatment outcome, and for determining efficacy of adjuvant treatments.
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