Title: Circulating Tumor Cells as Biomarker for Minimal Residual Disease in Prostate Cancer

Project Coordinator:
Klaus PANTEL (Germany) University Medical Center Hamburg-Eppendorf, Department of Tumor Biology, Hamburg

Project Partners:
Catherine ALIX-PANABIÈRES (France) University Medical Centre of Montpellier, Saint-Eloi Hospital – IRB, Laboratory of Rare Human Circulating Cells, Montpellier
Evi LIANIDOU (Greece) University of Athens, Department of Analytical Chemistry, Athens
Peter SEDLMAYR (Austria) Medical University of Graz, Institute for Cell Biology, Histology and Embryology, Center of Molecular Medicine, Graz
Maciej ZABEL (Poland) Poznan University of Medical Sciences, Department of Histology and Embryology, Poznan

Project Abstract:
Circulating tumour cells (CTCs) have been verified as prognostic markers for disease progression in various cancer types. This project is aimed to validate the number of CTCs isolated from patient’s blood as a prognostic marker for relapse in high-risk prostate cancer (PCA) patients treated with primary radical prostatectomy or radiotherapy. CTC isolation and enumeration will be realized by three different assay formats in comparison. (i) Isolation of CTCs from blood samples using CellSearch® as the current “gold standard” for CTC detection, (ii) EPISPOT assay that detects viable CTCs and (iii) GILUPI nanodetector that captures CTCs in vivo. The isolated CTCs will be further characterized by molecular techniques. The numbers of CTCs detected by each assay will be compared to PSA serum levels as the gold standard biomarker in PCA and to clinical outcome to identify the CTC detection assay(s) with the best prognostic value. The systematic approach chosen in this project will validate CTC detection as a novel biomarker for predicting clinical outcome in PCA patients. A validated procedure for CTC detection and characterization will improve risk assessment and contribute to a better stratification of PCA patients to future adjuvant therapies adjusted to the individual risk of each cancer patient.

Publishable Summary:
Circulating tumor cells (CTCs) are promising biomarkers that predict progression in patients with advanced cancers. Furthermore, CTC counts are superior to PSA serum measurements in predicting outcome in metastatic prostate cancer (PCa). In contrast, the clinical relevance of CTCs in earlier PCa stages without metastases is unclear. It was therefore unclear if the technologies applied so far were not sensitive enough or if patients with non-metastatic PCa have very low amounts of CTCs and are therefore not suitable for CTC-based liquid biopsies. This is an important question for the biomarker field with implications for future studies trying to detect therapeutic targets or identify resistance mechanisms in earlier PCA stages to block progression to incurable metastatic disease. Here we combined three complementary CTC assays and revealed, for the first time, an unexpectedly high incidence of CTCs in non-metastatic high-risk PCa patients. Furthermore, we could establish reliable protocols for further molecular characterization of CTCs that allow us to identify therapeutic target molecules and resistance mechanisms. Moreover, the analysis of CTCs will provide unique information on the biology of minimal residual disease in PCa patients. CTCs could also represent research tools to personalize treatment by serving as a so-called “liquid biopsy” of an individual's disease. Our findings should help to improve risk assessment and contribute to a better stratification of PCa patients to future additional (adjuvant or salvage) therapies. Although follow-up analysis is still ongoing, the correlation to established risk factors, as demonstrated in this study, suggests a potential clinical relevance of CTCs in non-metastatic PCa. In future clinical trials, more aggressive adjuvant treatment strategies could lead to an improved outcome for CTC positive, high-risk PCa patients.

(Project funded under JTC 2011)