Radium-223 Treatment of Patients with Metastatic Castration Resistant Prostate Cancer: Biomarkers for Stratification and Response Evaluation

SIMPLE SUMMARY: Radium-223 dichloride ([(223)Ra]RaCl(2); Ra-223) is an alpha-emitting radiopharmaceutical treatment for patients with metastatic castration resistant prostate cancer (mCRPC) with predominantly bone metastases. While responses to chemotherapeutic and antihormonal mCRPC treatments can be assessed by serum PSA levels, a decrease of serum PSA levels is not expected during Ra-223 therapy. Moreover, radiographic evaluation of bone metastases response is challenging. Therefore, novel biomarkers to select patients for Ra-223 treatment and monitoring response are urgently needed. In this review, we discuss the currently used and exploratory biomarkers for this purpose, including soluble and cellular factors detected in the peripheral blood, genetic defects and radiographic assessments. We conclude that some biomarkers, including metabolic products of collagen degradation and novel PET scan techniques, might hold promise as predictors of response to Ra-223 treatment. However, these biomarkers have not been extensively studied. Consequently, currently, no biomarker has established a place in patient stratification and response evaluation. ABSTRACT: Radium-223 dichloride ([(223)Ra]RaCl(2); Ra-223) is a targeted alpha-emitting radiopharmaceutical which results in an overall survival and health related quality of life (HRQoL) benefit in symptomatic patients with metastatic castration resistant prostate cancer (mCRPC) and predominantly bone metastasis. Although effective, options to select patients who will derive treatment benefit and to monitor and predict treatment outcomes are limited. PSA response and radiographic evaluation are commonly used in mCRPC treatment assessment but are not informative in Ra-223 treated patients. Consequently, there is a clear need for predictive and prognostic tools. In this review, we discuss the physiology of bone metastases and the mechanism of action and efficacy of Ra-223 treatment, as well as offering an outline of current innovative prognostic and predictive biomarkers.