CLINICAL AND LABORATORY CHARACTERISTICS THAT INFLUENCE PROGNOSIS OF MEN WITH METASTATIC CASTRATE RESISTANT PROSTATE CANCER TREATED WITH RADIUM-223

Abstract

Background: Radium-223 is an alpha-emitting radioactive calcium-mimetic nuclide preferentially distributed into high turnover bone affected by cancer cells after intravenous administration. It has been shown to reduce mortality in patients with boney metastases due to metastatic castration-resistant prostate cancer (mCRPC). However, which patients benefit most from radium-223 therapy remains an important unanswered question. Methods: Patients diagnosed with prostate adenocarcinoma and treated at least once with radium-223 in the province of Ontario between March 3, 2014 and March 31, 2023 were identified by the Institute for Clinical Evaluative Sciences (IC/ES) database. Physician billing codes were used to identify radium-223, chemotherapy, radiation therapy and surgical interventions. Drug identification numbers (DIN) were used to identify patients who had been exposed to androgen receptor axis-targeted agents (ARAT) and bone modifying agents (denosumab or zoledronate). Laboratory data was extracted from the Ontario Laboratories Information System (OLIS) and included blood prostate-specific antigen (PSA), albumin, alkaline phosphatase (ALP), hemoglobin levels; and blood leukocyte, lymphocyte and neutrophil counts. Results: A total of 1588 patients with prostate cancer received radium-223 treatment. Median age at treatment was 68 with approximately 20% (322) of patients diagnosed between 2002-2008, 50% (754) between 2009-2015 and 30% (512) between 2016-2022. Patients with metastatic disease at diagnosis comprised the majority of patients who received treatment (45.8% [728]), followed by 12.6% (200) with stage III and 23.8% (377) diagnosed at an early stage (I+II). Prior use of ARATs was seen in 27.6% (438) and 25.3% (401) of patients had prior use of a bone modifying agent. Median overall survival from diagnosis was 85.6 months while median overall survival from starting radium-223 was 12.3 months. In a multivariable model, higher pre-treatment hemoglobin (HR 0.82, 95% CI 0.78-0.85) and calcium (HR 0.21, 95% CI 0.14-0.32) levels were associated with longer survival and higher pre-treatment neutrophil count (HR 1.08, 95% CI 1.05-1.11), ALP (HR 1.08, 95% CI 1.06-1.11) and PSA levels (HR 1.02, 95% CI 1.01, 1.03) with shorter survival. Excluding laboratory values, older age (HR 1.02, 95% CI 1.02-1.03), prior use of ARATs (HR 1.24, 95% CI 1.06-1.45) and chemotherapy (HR 2.11, 95% CI 1.78, 2.51) were associated with worse survival while early stage at diagnosis (stage I [HR 0.41, 95% CI 0.23-0.74] and stage II [HR 0.73, 95%CI 0.61-0.88) were associated with longer survival. Analysis of demographic factors showed that rurality was associated with lower chance of receiving radium-223 but was not associated with worsening survival. Conclusion: Survival after radium-223 treatment in patients with mCRPC was influenced by disease biology, burden, and patient age. Patients residing in rural areas were less likely to receive radium-223 treatment suggesting barriers to access.