Circulating tumor cells and survival in abiraterone- and enzalutamide-treated patients with castration-resistant prostate cancer

Background: The outcome to treatment administered to patients with metastatic castration-resistant prostate cancer (mCRPC) greatly differs between individuals, underlining the need for biomarkers guiding treatment decision making. Objective: To investigate the prognostic value of circulating tumor cell (CTC) enumeration and dynamics, in the context of second-line endocrine therapies (ie, abiraterone acetate or enzalutamide), irrespective of prior systemic therapies. Design, Settings, and Participants: In a prospective, multicentre study blood samples for CTC enumeration were collected from patients with mCRPC at baseline (n=174). In patients who responded for minimally 10-12 weeks a follow-up sample was collected. Outcome Measurements and Statistical Analysis: For baseline analysis, patients were stratified in <5 or ≥5 CTCs/7.5mL, whereas for the analysis of CTC dynamics at 10-12 weeks, in patients with stable, increasing or decreasing CTC counts. Progression-free survival (PFS), overall survival (OS), and PSA changes at 10-12 weeks were compared between groups. Results: Patients demonstrating increasing CTCs on therapy had a shorter median PFS (4.03 vs 12.98 vs 13.67 months, HR 3.6, 95%CI 1.9-6.8; P<0.0001) and OS (11.2 months vs not reached, HR 9.5, 95%CI 3.7-24; P<0.0001), compared to patients with decreasing or stable CTCs. Multivariable Cox regression showed that prior chemotherapy (HR 4.1, 95%CI 1.9-8.9; P=0.0003), a high baseline CTC count (HR 1.5, 95%CI 1.2-1.9; P=0.002) and increasing CTCs at follow-up (HR 3.3, 95%CI 1.4-7.6; P=0.005) were independent predictors of worse PFS. Previous chemotherapy (HR 7, 95%CI 1.9-25; P=0.003), high baseline CTC counts (HR 2.2, 95%CI 1.4-3.7; P=0.002) and increasing CTCs during therapy (HR 4.6, 95%CI 1.4-15; P=0.01) were independently associated with shorter OS. ≥30% and ≥50% PSA responses less frequently occurred in patients with CTC inclines at 10-12 weeks on therapy (χ2 test: P<0.01). Conclusions: CTC dynamics during therapy are associated with PSA response and provide independent clinical prognostication over PSA declines. Hence the study demonstrates the pharmacodynamic properties of CTCs.

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