Circulating Tumor Cells Are Detectable and Independent of PSA and PSMA-PET Metrics in Localized High-Risk and Biochemically Recurrent Prostate Cancer

PurposeThis study evaluated the feasibility of detecting circulating tumor cells (CTCs) in localized high risk (HR) and biochemically recurrent (BCR) prostate cancer (PCa) patients and examined the correlation between CTCs, serum prostate specific antigen (PSA) levels, 18F-DCFPyL PET parameters and clinical progression. MethodsBaseline samples were collected from 105 PCa patients enrolled in clinical trial NCT03181867 before 18F-DCFPyL PET/CT imaging. Patients were divided into two cohorts-localized HR and BCR. CTCs were enriched using magnetic EpCAM-PE beads and enumerated by flow cytometry (n=82) or by CD45 depletion followed by EpCAM/PSMA expression analysis by ddPCR (n=23). CTC value of [≥]3 CTCs/10 mL blood was established as abnormal using 10 healthy female controls. Correlations were assessed between CTCs, PSA, PET parameters and clinical progression. ResultsIn the flow group, >3 EpCAM CTCs/10 mL were found in 14% (n=2/14) of HR and 24% (n=16/68) of BCR patients. In the ddPCR group, 53% (n=9/17) of HR and 17% (n=1/6) of BCR patients had greater than normal EPCAM expression, whereas higher than normal PSMA expression was observed in 29% (N=5/17) of HR and 17% (N=1/6) of BCR patients. Furthermore, in the combined cohorts within the ddPCR group, six patients had only EPCAM expression, two had only PSMA and four had both. No significant correlation was found between CTCs and serum PSA or 18F-DCFPyL PET parameters or clinical progression in either group. ConclusionCTCs were detectable in both HR and BCR patients using flow cytometry and ddPCR based methods even in localized disease, suggesting that CTCs can be used as a liquid biopsy that may reflect underlying disease activity. These findings support the potential role of CTCs as a minimally invasive biomarker independent of serum PSA levels and 18F-DCFPyL PET parameters.