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

Andra Kuske,Pierre Tennstedt,Athina Markou,Sabine Riethdorf,Tobias M Gorges,Thorsten Schlomm,Evi Lianidou,Klaus Pantel,Catherine Alix-Panabières,Martine Mazel,Anne-Kathrin Tiebel,Felix Preißer,Sven Peine,Burkhard Beyer,Raisa Pompe,Sandra Prues

doi:10.1038/srep39736

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.

Highlights

The aim of this study was to increase the sensitivity of CTC detection in patients with high-risk Prostate cancer (PCa) through the combination of three complementary assays: (i) the epithelial cell adhesion molecule (EpCAM)-dependent CellSearch technology, which received FDA-approval for metastatic prostate cancer, (ii) the GILUPI CellCollector (CellCollector) that captures EpCAM-positive CTCs in vivo by an antibody-coated needle introduced in the arm vein[17,18,19], and (iii) the EpCAM-independent EPISPOT assay that enriches CTCs by negative depletion of leukocytes and detects viable prostate cancer cells based on their active secretion of PSA20
Peripheral blood was analyzed directly before and 3 months after radical prostatectomy (RP) to assess early dynamic changes in CTC counts, and the results were correlated to established risk factors
Eighty six and 52 patients were recruited for the first visit before RP and for the second visit 3 month after surgery, respectively

Summary

Introduction

The aim of this study was to increase the sensitivity of CTC detection in patients with high-risk PCa through the combination of three complementary assays: (i) the epithelial cell adhesion molecule (EpCAM)-dependent CellSearch technology, which received FDA-approval for metastatic prostate cancer, (ii) the GILUPI CellCollector (CellCollector) that captures EpCAM-positive CTCs in vivo by an antibody-coated needle introduced in the arm vein[17,18,19], and (iii) the EpCAM-independent EPISPOT assay that enriches CTCs by negative depletion of leukocytes and detects viable prostate cancer cells based on their active secretion of PSA20. Peripheral blood was analyzed directly before and 3 months after radical prostatectomy (RP) to assess early dynamic changes in CTC counts, and the results were correlated to established risk factors

Objectives

Methods

Results

Conclusion