Radium-223 decreases PD-L1 expression in bone metastases: A study with [ 89 Zr]Zr-atezolizumab PET and immunohistological correlation.

In 30 seconds

This prospective, multicenter clinical study examined immune changes during standard-of-care radium-223 treatment in 28 patients with metastatic castration-resistant prostate cancer and predominantly bone metastases. Serial ⁸⁹Zr-atezolizumab PET showed lower PD-L1 uptake in PSMA-positive bone lesions after three treatment cycles: median SUVmean was 2.5 (IQR 0.9–3.4) at baseline and 0.9 (IQR 0.5–2.5) afterward. Lymphocyte numbers in tumor tissue and blood also decreased. The findings suggest radium-223 alters the immune microenvironment, with possible implications for response to PD-(L)1 inhibitors.

Key findings

• Median ⁸⁹Zr-atezolizumab SUVmean in PSMA-positive bone lesions fell from 2.5 (IQR 0.9–3.4) at baseline to 0.9 (IQR 0.5–2.5) after three radium-223 cycles.
• PD-L1 uptake decreased in bone metastases independently of response on ⁶⁸Ga-PSMA PET.
• Lymphocyte numbers decreased concomitantly in tumor tissue and blood.

Why it matters

The study provides imaging and tissue-based evidence that radium-223 is associated with changes in the immune environment of bone metastases, rather than acting only on tumor lesions. Because PD-(L)1 inhibitors have limited benefit for most patients with mCRPC, these findings raise a relevant question about how radium-223 exposure may affect the immune context for checkpoint inhibition. The study does not establish clinical outcomes from combining or sequencing these treatments.

What to keep in mind

Paired PET analysis included nine patients, and sequential biopsy analysis included two, limiting the paired imaging and tissue evidence. The study reports immune markers, not outcomes of PD-(L)1 inhibitor treatment.