Background of Urgent Problem

Prostate cancer is one of the most common cancers among men. Metastatic castration-resistant prostate cancer (mCRPC) is an advanced form of prostate cancer characterized by resistance to castration therapy. Radium-223 is an α-emitting radiopharmaceutical that has been shown to improve overall survival (OS) and reduce skeletal events in mCRPC patients. However, in current clinical practice, there is a lack of available biomarkers to predict which patients are likely to respond to Radium-223 treatment, timely monitor the effect of the treatment, and assess patient prognosis. Therefore, the development of relevant circulating and imaging biomarkers is of great significance.

Source of the Paper

The paper was authored by Philip J. Saylor and other researchers from Harvard Medical School, Brigham and Women’s Hospital, and Massachusetts General Hospital. The research results were published in the journal “JCO Precision Oncology,” with DOI information: https://doi.org/10.1200/po.23.00230, and were published on February 14, 2024.

Research Methods and Workflow

This prospective single-arm study included 22 mCRPC patients who received standard Radium-223 treatment. 99mTc-MDP bone scan images collected at baseline, 2 months, and 6 months were quantified using the automated bone scan index (aBSI). Additionally, circulating tumor cells (CTCs) were assessed using microfluidic enrichment and droplet digital polymerase chain reaction (ddPCR) at baseline, 1 month, and 2 months, and RNA expression of prostate cancer-specific genes was analyzed.

Research Findings

The research results indicate that lower baseline aBSI and smaller changes in aBSI within 2 months (<10.7) were associated with better OS (p-values .00341 and .0139, respectively). Baseline CTC counts ≥5 CTC/7.5 ml were associated with poorer OS (10.1 months vs. 32.9 months, p = .00568). CTC count decreased in 4 out of 15 patients with baseline detectable CTCs at 2 months. Baseline expression of the AR-V7 splice variant in CTCs was significantly associated with poor prognosis (hazard ratio of 5.20 [95% CI, 1.657 to 16.31]; p = .00195). Even after controlling for prostate-specific antigen or alkaline phosphatase, detectable baseline AR-V7, higher aBSI, and CTC counts ≥5 CTC/7.5 ml still had independent negative impacts on OS.

Conclusion and Significance

aBSI and CTC analysis serve as prognostic markers for patients undergoing Radium-223 treatment. Notably, AR-V7 expression in CTCs is a particularly promising prognostic biomarker, worthy of validation in larger cohorts.

Research Highlights

The highlights of this study include the development and evaluation of circulating and imaging biomarkers related to the response of castration-resistant prostate cancer patients to Radium-223. The use of these biomarkers could improve therapeutic decision-making, predicting, and monitoring patient responses and prognoses.

Scientific Value and Application of the Research

This study provides significant insights into the use of biomarkers in the treatment of mCRPC with Radium-223. It not only offers valuable tools for patient management in clinical practice but also opens new avenues for more personalized treatment of prostate cancer in the future. The research results may have important implications for improving the effectiveness of patient screening and monitoring in Radium-223 treatment.

Additional Information

Microfluidic enrichment and ddPCR for CTCs represent a prospective technological approach, highlighting the advancement of this study in developing new and advanced diagnostic and therapeutic monitoring methods. Furthermore, this study successfully integrated various assessment types into a unified cohort within a stringent scientific framework, providing a robust model for the application of CTC technology in prostate cancer.