Abstract
Simple SummaryRadium-223 dichloride ([223Ra]RaCl2; 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.Radium-223 dichloride ([223Ra]RaCl2; 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.
Highlights
Prostate cancer (PCa) is the second most common cancer in men, accounting for 13.5% of all cancer diagnoses in males worldwide [1]
The differentiation of monocytes into osteoclasts is driven by macrophage colony stimulating factor (M-CSF), receptor activator of nuclear factor kappa-β ligand (RANKL), interleukin-6 (IL-6) and interleukin-8 (IL-8), which are secreted by osteoblasts into the bone micro-environment [28]
Ra-223 treatment is a valuable addition to the life-prolonging treatment options for patients with metastatic castration-resistant prostate cancer (mCRPC)
Summary
Prostate cancer (PCa) is the second most common cancer in men, accounting for 13.5% of all cancer diagnoses in males worldwide [1]. ADT is administered through suppression of testicular testosterone synthesis by chronic administration of analogues or agonists of gonadotropin-releasing hormone (GnRH) or by bilateral orchiectomy [5,6,7,8] These interventions result in very low levels of circulating testosterone, to which virtually all patients respond. Patients develop progression of the disease after a median of 2–3 years after treatment initiation [7,9,10,11] This stage of the disease is referred to as metastatic castration-resistant prostate cancer (mCRPC) and represents end-stage disease with significant morbidity and mortality. Significant decreases of serum levels of the biomarker prostate specific antigen (PSA) are rarely established This is in contrast to patients treated with ARTA or chemotherapy, where PSA is commonly used as a surrogate marker of efficacy. We discuss various aspects of bone metastatic mCRPC and treatment with Ra-223, with a focus on biomarkers for patient stratification and response evaluation
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