Improved detection of circulating tumor cells in non-metastatic high-risk prostate cancer patients

Abstract

The relevance of blood-based assays to monitor minimal residual disease (MRD) in non-metastatic prostate cancer (PCa) remains unclear. Proving that clinically relevant circulating tumor cells (CTCs) can be detected with available technologies could address this. This study aimed to improve CTC detection in non-metastatic PCa patients by combining three independent CTC assays: the CellSearch system, an in vivo CellCollector and the EPISPOT. Peripheral blood samples from high-risk PCa patients were screened for CTCs before and three months after radical prostatectomy (RP). Combining the results of both time points, CTCs were detected in 37%, 54.9% and 58.7% of patients using CellSearch, CellCollector and EPISPOT, respectively. The cumulative positivity rate of the three CTC assays was 81.3% (87/107) with 21.5% (23/107) of patients harboring ≥5 CTCs/7.5 ml blood. Matched pair analysis of 30 blood samples taken before and after surgery indicated a significant decrease in CTCs captured by the CellCollector from 66% before RP to 34% after therapy (p = 0.031). CTC detection by EPISPOT before RP significantly correlated with PSA serum values (p < 0.0001) and clinical tumor stage (p = 0.04), while the other assays showed no significant correlations. In conclusion, CTC-based liquid biopsies have the potential to monitor MRD in patients with non-metastatic prostate cancer.

How localized is pathologically localized prostate cancer? The use of secondary circulating prostate cells as a marker of minimal residual disease and their association with patient outcome

“…the CellSearch ® system, which uses a cutoff of 5 cells/sample in metastatic disease, 1-5 cells/sample for nonmetastatic disease a cutoff of between 1-5 cells/sample has been suggested. [20] The EpiSPOT ® is an EpCAM independent assay that enriches CTCs by negative depletion of leukocytes and detects viable cells based on their active secretion of PSA [20] , with this assay 40% of T1c cancers were positive for CTCs. [20] The clinical utility of secondary CPC based early detection of recurrence could be associated with the success of postoperative radiotherapy.…”

“…[20] The EpiSPOT ® is an EpCAM independent assay that enriches CTCs by negative depletion of leukocytes and detects viable cells based on their active secretion of PSA [20] , with this assay 40% of T1c cancers were positive for CTCs. [20] The clinical utility of secondary CPC based early detection of recurrence could be associated with the success of postoperative radiotherapy. Radiotherapy has the potential to eliminate microscopic residual disease and cure local recurrence.…”

Liquid biopsies

“…A novel technology enables the in vivo isolation of CTCs through the insertion of a nanodetector, (GILUPI CellCollector) into the patient's arm vein via a standard 20‐gauge needle. Circulating EpCAM‐positive tumor cells bind in vivo to anti‐EpCAM antibodies that are covalently attached to the CellCollector, while the functionalized surface prevents the nonspecific binding of other blood constituents . This technology was first used in patients with metastatic prostate cancer (PCa), in which tumor‐associated transcripts of EGFR and PSMA were detected in 42.8% and 14.3% of the analyzed samples, respectively .…”

Materials and microfluidics: enabling the efficient isolation and analysis of circulating tumour cells

“…Applications of CTC analyses including enumeration, 258 genomic mutation screening (FISH, 34 Sanger sequencing, 41 aCGH, 218 and NGS), 97 RNA expression profiling (RNA-ISH, 28 qRT-PCR, 259 expression microarrays, 231 and single cell RNA-seq), 260 protein analysis (EPISPOT), 261 and ex vivo culturing (CTC expansion, xenograft models, and drug susceptibility). 111 Adapted from Pantel and Speicher.…”