Abstract LB-C07: Predictive biomarkers for detection and therapeutic response in genitourinary cancers using enumeration of circulating tumor cells
Authors: Amato Robert J. , Brobey Reynolds , Murphy Kent , Smith Jeff , Patnaik Meeta 
Published: May 2016

Introduction: Genitourinary (GU) cancers are common tumor types that have multiple therapeutic options, but the cure rate is low, and adaptation or acquired resistance to treatment are common. Biomarkers are lacking in these cancer types; thus, it is essential to develop a reliable, reproducible biomarker of detection, treatment guidance, and prognosis, such as enumeration of circulating tumor cells (CTCs). The challenge of CTCs has been the ability to capture mixed cell populations. We describe the results of a concept study using the Axon nCYTE DxTM System to enumerate EpCAM-positive and –negative CTCs from patients with prostate, bladder, and renal cell cancer at various stages of disease.

Methods: One-time clinical blood samples (10 mL) were obtained from 50 patients with GU cancers; 6 mL (3 mL/slide) were used to enumerate CTCs (4 mL were stored for future study). Nucleated cells were fixed, permeabilized, and pelleted. Cell pellets were then rinsed and incubated in a proprietary cancer detection cocktail and run through the Axon nCYTE DxTM detection/enumeration instrument to detect and count CTCs (nucleus+/cytokeratin; non-specific binding-). All data was analyzed in a blinded manner.

Results: The Axon nCYTE DxTM System was able to isolate CTCs from all patient samples analyzed to date. CTC (&gt;4 μm) purity after the first enrichment step was in 100% (median, 2.1/mL; mean, 2.2/mL) of prostate samples, 100% (median, 2.1/mL; mean 2.1/mL) of bladder samples, and 100% (median, 1.6/mL; mean, 9.1/mL) of renal cell samples. We present data on the first 10 patient samples (table 1); another 18 are being analyzed and 22 being accrued.

Conclusions: The Axon nCYTE Dx™ System consistently detected CTCs among various subsets of patients with GU cancers. We are in the process of completing accrual and analysis of remaining patient samples. A complete data set will be presented at the meeting. Our initial proof of principle will be prospectively validated longitudinally as a complement to our clinical research program in GU cancers to establish CTCs as a biomarker of detection, treatment response, and prognosis.

Pt., cancer typeTreatmentPSA, ng/dLNo. CTCs/ml1, mRCCMTA1.32, mPCADT/chemo1.03.83, mPCADT/chemo28.62.74, CRPCSurveil0.52.65, mRCCMTA24.16, UT TCCChemo2.17, mRCCMTA1.68, mRCCMTA1.69, mCRPCABI4.2110, mCRPCABI8.21.6ABI, androgen biosynthesis inhibitor; ADT, androgen deprivation therapy; CRPC, castration-resistant prostate cancer; m, metastatic; MTA, molecular targeted agent; RCC, renal cell carcinoma; UT TCC, upper-tract urothelial cell carcinoma

ABI, androgen biosynthesis inhibitor; ADT, androgen deprivation therapy; CRPC, castration-resistant prostate cancer; m, metastatic; MTA, molecular targeted agent; RCC, renal cell carcinoma; UT TCC, upper-tract urothelial cell carcinoma

Citation Format: Robert J. Amato, Reynolds Brobey, Kent Murphy, Jeff Smith, Meeta Patnaik. Predictive biomarkers for detection and therapeutic response in genitourinary cancers using enumeration of circulating tumor cells. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr LB-C07.