Review of Palliative 223 Ra in Metastatic Castration-Resistant Prostate Cancer: Experience at West Virginia University Cancer Center.

The ALSYMPCA trial of the α-emitter 223 Ra in symptomatic bone-predominant metastatic castration-resistant prostate cancer (mCRPC) reported a median overall survival (OS) of 14.9 mo, versus 11.3 mo for placebo. However, subsequently reported real-world experience with 223 Ra in smaller mCRPC patient cohorts has appeared less successful. We performed a retrospective observational study to review our own 223 Ra experience at West Virginia University (WVU). Methods: Demographic, clinical, laboratory, and imaging data were reviewed in all bone-predominant mCRPC patients treated with 223 Ra at WVU from 2014 to 2019. The number of bone metastases per patient at the start of treatment with 223 Ra was quantified via nuclear bone scans (12 scans, 5 of which also included SPECT/CT), body CT scans (8 scans), and PET/CT scans (4 scans). Standard descriptive statistics were used to study institutional review board-exempted, deidentified patient data. Median survival in ALSYMPCA and WVU patients was compared using a 2-sided, 1-sample log-rank test based on the exponential distributions. The primary endpoint was patient OS after initiating 223 Ra. Results: Twenty-four patients received 98 infusions of 223 Ra; 83% of these patients were referred from outside WVU. Before the first infusion, all 24 had received androgen deprivation therapy. In total, 73 sequential combinations of androgen deprivation therapy were used, 68 of which (93%) preceded the first 223 Ra infusion. Also, before 223 Ra, 19 (79%) patients had received docetaxel and 19 (79%) had received 33 courses of radiation, 24 of which targeted nonprostatic sites. Eleven patients (46%) completed all 6 planned 223 Ra infusions; 13 (54%) stopped early because of clinical deterioration. As of August 2020, only 1 patient remained alive after completing 6 cycles of 223 Ra. Median OS from the first 223 Ra infusion to the last follow-up or death was 8.3 mo (range, 0-44 mo)-nearly 50% less than the ALSYMPCA median survival of 14.9 mo ( P = 0.01). Compared with ALSYMPCA, more WVU patients received bisphosphonates and docetaxel, more had an Eastern Cooperative Oncology Group performance status of at least 2, more used opiates for pain, more had a greater bone metastasis burden by imaging, and more had lower hemoglobin, albumin, alkaline phosphatase, and prostate-specific antigen levels. Conclusion: Although the science supporting the development and clinical use of 223 Ra is compelling, optimal clinical benefit will likely require earlier referral for 223 Ra, before patients have exhausted most conventional therapies. At WVU, we found that practically all our referred patients had androgen deprivation therapy, radiation, and cytotoxic therapy before starting 223 Ra. We continue to offer 223 Ra therapy to patients with symptomatic bone-predominant mCRPC but are encouraging earlier patient referral.
(© 2021 by the Society of Nuclear Medicine and Molecular Imaging.)