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Updated: Feb 23, 2026
Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel
Published on: September 8, 2017
Prospective Evaluation of Neuromediator Dynamics in Castration-Resistant Prostate Cancer Patients During Docetaxel
Jost VON Hardenberg1, Maike Schwartz1, Thorsten Werner2
1Department of Urology, University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany.
Aim:
Aim of the study was to detect small cell/neuroendocrine (SCNC) transformation in metastatic castration-resistant prostate cancer (mCRPC) that is a challenging procedure. We investigated the role of neuromediator dynamics as potential evidence of SCNC in patients undergoing docetaxel therapy.
Patients And Methods:
A multi-institutional, prospective observational study was conducted. Patients undergoing docetaxel treatment were included. Chromogranin A (CGA), neuron-specific enolase (NSE), and pro-gastrin releasing peptide (Pro-GRP) were sequentially evaluated at predefined time points. Outcome measures were overall survival (OS), progression-free survival (PFS) and PSA nadir.
Results:
Fifty-two patients were included. A general rise in CGA levels was observed. Patients with a high CGA rise (100%ULN: CGA ≥98.1ng/ml) between the 1st and 3rd cycle trended towards a decreased OS (p=0.0649) and showed a decreased PFS (p=0.0369). In multivariate analysis, continuous CGA rise correlated with PFS (p=0.0553; HR 1.136), but was not an independent predictor of OS.
Conclusion:
Patients with an early high CGA rise may demonstrate a subgroup with poor outcome due to underlying SCNC transformation. Monitoring of CGA appears to be an option worth considering.
Insights
Detecting small cell/neuroendocrine cancer transformation in metastatic castration-resistant prostate cancer (mCRPC) is challenging. Rising Chromogranin A (CGA) levels during docetaxel therapy may indicate this transformation and predict poorer outcomes.
Area of Science:
- Oncology
- Prostate Cancer Research
- Biomarker Discovery
Background:
- Metastatic castration-resistant prostate cancer (mCRPC) can undergo small cell/neuroendocrine (SCNC) transformation, a challenging diagnostic and therapeutic issue.
- Neuromediator dynamics are explored as potential indicators of SCNC transformation in mCRPC.
Purpose of the Study:
- To investigate the role of neuromediator dynamics, specifically Chromogranin A (CGA), in detecting SCNC transformation in mCRPC patients undergoing docetaxel therapy.
- To assess the correlation between CGA levels and patient outcomes, including overall survival (OS) and progression-free survival (PFS).
Main Methods:
- A multi-institutional, prospective observational study included 52 patients undergoing docetaxel treatment.
- Sequential evaluation of Chromogranin A (CGA), neuron-specific enolase (NSE), and pro-gastrin releasing peptide (Pro-GRP) at predefined time points.
- Outcome measures included OS, PFS, and PSA nadir.
Main Results:
- A general rise in CGA levels was observed across patients.
- Patients with a high CGA rise (≥98.1 ng/ml) between the 1st and 3rd docetaxel cycles showed a trend towards decreased OS (p=0.0649) and significantly decreased PFS (p=0.0369).
- Continuous CGA rise correlated with PFS (p=0.0553) but was not an independent predictor of OS in multivariate analysis.
Conclusions:
- An early, significant rise in CGA may identify a subgroup of mCRPC patients with SCNC transformation and poor prognosis.
- Monitoring CGA levels during docetaxel therapy is a potential strategy to identify patients with underlying SCNC transformation and guide treatment decisions.
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