Circulating and Imaging Biomarkers of Radium-223 Response in Metastatic Castration-Resistant Prostate Cancer.

Area of Science:

• Oncology
• Medical Imaging
• Molecular Diagnostics

Background:

• Bone metastatic castration-resistant prostate cancer (CRPC) presents a significant clinical challenge.
• Radium-223 therapy offers improved survival and reduced skeletal events in CRPC patients.
• Effective prognostic biomarkers for radium-223 therapy are currently lacking.

Purpose of the Study:

• To evaluate the prognostic and activity-predicting capabilities of automated bone scan index (aBSI) and circulating tumor cell (CTC) analyses.
• To identify reliable biomarkers for patients with bone metastatic CRPC undergoing radium-223 treatment.

Main Methods:

• Prospective single-arm study involving 22 patients with bone metastatic CRPC receiving radium-223.
• Quantification of bone scan images using aBSI at baseline, 2 months, and 6 months.
• Enumeration and RNA expression analysis (including AR-V7) of CTCs at baseline, 1 month, and 2 months using microfluidic enrichment and droplet digital PCR.

Main Results:

• Lower baseline aBSI and minimal change in aBSI (<+0.7) from baseline to 2 months correlated with improved overall survival (OS).
• Higher baseline CTC counts (≥5 CTC/7.5 mL) were associated with worse OS (10.1 vs. 32.9 months).
• Baseline AR-V7 expression in CTCs was a significant independent predictor of worse OS (HR, 5.20; P = .00195), even after adjusting for PSA or alkaline phosphatase.

Conclusions:

• Quantitative aBSI and CTC analyses serve as valuable prognostic markers in radium-223 treated CRPC patients.
• AR-V7 gene expression in CTCs emerges as a highly promising prognostic biomarker.
• Further validation of AR-V7 in larger patient cohorts is warranted to confirm its clinical utility.