Abstract
Introduction: Bone metastases are the most frequent site of secondary localization of prostate cancer (PCa) and are present in about 90% of cases of advanced disease. Consequently, an adequate management of bone involvement is of pivotal importance in the therapeutic approach and skeletal-related events (SREs) need to be closely monitored and promptly assessed and treated. Bone targeting agents (BTAs), consisting in bisphosphonates and denosumab, are an essential part of the treatment of metastatic prostate cancer that accompanies systemic treatments throughout the most part of the history of the disease. Activity and safety of bone targeting agents: These treatments are correlated to better outcomes in terms of reduction of SREs and, in metastatic castration resistant setting, of increased overall survival (OS), but several important adverse events have to be managed and prevented. Of these, osteonecrosis of the jaw (ONJ) is extremely invalidating and should be managed with a special attention. Discussion: The role of BTAs in prostate cancer is pivotal throughout many stages of the disease, but several toxicities should be quickly recognized and treated. We aim at recollecting evidence on clinical benefit of BTAs, common and specific toxicities, and explore the pathophysiology and clinical aspects of osteonecrosis of the jaw. We present a review of the literature to report the role of the different types of bone targeting agents in the management of prostate cancer with bone metastases with a particular focus on common toxicities and ONJ to recollect current evidences on the activity of these compounds and the correct management of their adverse events.
Highlights
Bone metastases are the most frequent site of secondary localization of prostate cancer (PCa) and are present in about 90% of cases of advanced disease
We present a review of the literature to report the role of the different types of bone targeting agents in the management of prostate cancer with bone metastases with a particular focus on common toxicities and ONJ to recollect current evidences on the activity of these compounds and the correct management of their adverse events
The need to properly address the bone health issue in PCa patients is due to the extremely high bone fragility correlated to several aspects: the pre-existing bone damage induced by ageing and comorbidities, the side effects of androgen deprivation therapy (ADT)–current standard of care in the management of both hormone-sensitive (HSPC) and castration resistant prostate cancer (CRPC)–and the high PCa bone tropism, intrinsic characteristic of this disease [2]
Summary
When compared to ZA, denosumab resulted to be better in terms of prevention of time to first SRE [12] Both ZA and denosumab have been approved in castration-resistant PCa with skeletal involvement; patients with metastatic hormone-sensitive disease do not benefit from the addition of BTAs to standard of care active treatment [13]. Due to their potent inhibition of bone resorption, bisphosphonates and denosumab share an important adverse event: ONJ. The need to properly address bone health preservation in the treatment approach to PCa is underlined by the inclusion of specific bone-related efficacy endpoints in clinical trials of novel androgen receptor-targeted agents (ARTA) (i.e., metastasis-free survival, time to first skeletal-related event) [23–25].
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