Monitoring of Circulating Tumor Cells in Patients With High-Risk Nonmetastatic Prostate Cancer Treated With Radiation Therapy and Hormones: Preliminary Data of an Observational Prospective Phase 2 Study

Abstract

Circulating tumor cells (CTCs) are a cellular source repeatedly obtainable by blood sampling that could serve as a surrogate marker for treatment efficacy. The presence of CTCs is an established marker for prognosis in men with castration-resistant prostate cancer. In contrast, the value of CTCs detection in men with localized high-risk prostate cancer is unknown. The purpose of this study is to evaluate the proportion of patients with high-risk prostate cancer (HRPCa) that presents CTCs in peripheral blood (PB) before and after androgen deprivation therapy (ADT) and radiation therapy (RT) in order to establish its prognostic value. We present preliminary data of CTCs monitoring detection. Hypothesis: The detection of CTCs is a potential surrogate marker for treatment efficacy in HRPCa. Prospective analysis of biological material obtained from PB samples in 65 patients with HRPCa treatment naïve between 2014 and 2016. Blood samples were analyzed to detect CTCs using an immunomagnetic method based on the CellSearch system in 4 periods of time: 1) Before starting any treatment; 2) following neoadjuvant ADT and prior to RT; 3) at the end of RT; 4) 6-12 months following the end of RT in those patients with 0 CTCs in the first determination and positive CTCs in the following determinations. A cut off of 0 vs ≥ 1CTCs/7.5ml blood was defined as a threshold for negative versus positive CTCs status. We also analyzed whether CTCs presence was associated with clinic-pathological features using the chi-square or Fisher exact test. The median age was 71 years and median PSA was 12.6 ng/ml. Twenty-eight patients had Gleason score ≥ 8 and 48 patients had clinical stage T3. CTCs were detected in 5/66 patients (7.5%) at diagnosis (baseline), in 8/62 (12.9%) following neoadjuvant ADT and in 11/59 (18.6%) at the end of RT with a median CTC count/7.5ml of 1 (range:1-136). Only 1 patient presented positive CTCs detection 6-13 months after RT. Positive CTCs status (at any period) did not correlate with patient age, pre-treatment PSA, T stage, N stage or Gleason score. The preliminary data obtained from this observational feasibility study showed an infrequent detection of CTCs in patients with HRPCa with no correlation to known clinical prognostic factors. The positive cases for CTCs after ADT and RT (mostly with very low levels and not maintained over time) are probably due to a passive mechanism associated with the destruction of the tumor. A more acute assessment method to detect CTCs together with larger cohorts with extended follow-up are needed to validate this finding.