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

AI Article Synopsis

  • The study focuses on the treatment outcomes for patients with metastatic castration-resistant prostate cancer (mCRPC), emphasizing the variability in response and the importance of biomarkers for treatment decisions.
  • Researchers assessed the prognostic value of circulating tumor cell (CTC) counts and their changes over time in patients receiving second-line endocrine therapies such as abiraterone or enzalutamide.
  • Results indicated that patients with increasing CTC counts during treatment had significantly shorter progression-free survival (PFS) and overall survival (OS) compared to those with decreasing or stable CTC counts, highlighting the potential of CTCs as predictive indicators for therapy response.

Article Abstract

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/7.5 mL, 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 (χ 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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Source
http://dx.doi.org/10.1002/pros.23488DOI Listing

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