Date Published: December 26, 2018
Author(s): Diomidis Kozyrakis, Dionyssios Paridis, Stefanos Perikleous, Konstantinos Malizos, Anastasios Zarkadas, Antonios Tsagkalis.
Prostate cancer (PCa) is one of the most frequently diagnosed malignancies worldwide. Hormonal deprivation therapy is a well-established treatment for locally advanced or metastatic diseases but exposes patients to the risk of osteoporosis and fragility fractures. Furthermore, the tropism of the PCa cells to osseous metastases increases the incidence of skeletal-related events (SREs).
A nonsystematic review of the international literature was performed in respect to the use of osteoclast inhibitors zoledronic acid (ZA) and denosumab (DEN) in PCa patients.
DEN and ZA have proved their efficacy in preventing osteoporosis and bone mass loss in patients treated with hormonal therapy with no proven superiority of one agent over the other. However, the effectiveness in reducing fragility fractures has been proved only for DEN so far. In metastatic-free castrate-sensitive high-risk PCa patients, ZA has not shown any efficacy in preventing osseous metastasis, and evidence is lacking in favor or against the use of DEN. The use of osteoclasts inhibitors had no evident positive effect in overall and disease-specific survival in this group of patients. In advanced castrate-refractory malignancy, DEN has shown clinical superiority over ZA in preventing new SRE but not in overall survival.
Superiority of DEN over ZA has been proved only in advanced castrate refractory disease in terms of preventing new SRE. In the rest of the cases, the selection of either agent should be based on the clinical condition of each patient and the cost of the treatment.
Prostate cancer (PCa) is the second most prevalent malignancy worldwide [1, 2]. According to the US Cancer Statistics, during the year 2014, 172,258 new cases were diagnosed and 28,343 deaths were attributed to the disease in this country . Despite the efforts for cancer control, about 6% patients will eventually develop skeletal metastasis during follow-up. This rate climbs up to 80%, should a poorly differentiated PCA is left untreated [3–7].
A search in Medline/PubMed and Scopus databases from 1980 till now was performed using the following key words: prostate cancer, bone metastasis, zoledronic acid, denosumab, and bisphosphonates. Additional articles were identified by using the “similar articles” search tool of the Medline electronic platform, as well as by reviewing the list of references of related articles. A list of 2133 titles of articles and 24 additional records were initially evaluated by 2 authors DK and DP for relevance, and 102 abstracts of all types of articles (reviews, randomized controlled trials, and case series) were further examined. Full texts were retrieved by 57/102 articles and, after having the consensus of all the co-authors, 31 of them were included in the study (Figure 1). The clinical effects of osteoclast inhibitors were examined in various prostate cancer subpopulations (for example, castration-sensitive, castration refractory, and with or without skeletal metastasis), and the relevant results are presented herein.
Both main antiresorptive agents have proven their safety and effectiveness in preventing bone mass loss and osteoporosis in patients treated with hormonal therapy. In this population, a face to face comparison of DEN with ZA did not reveal superiority of any regimen over the other. However, effectiveness in reducing fragility fracture risks has been proven only for DEN. In castration-sensitive high risk for metastases PCa patients, ZA has not shown any efficacy in preventing osseous metastasis but DEN has not been extensively evaluated in these patients. Regarding cases with advanced disease in castration-resistant malignancy, DEN has shown clinical superiority over ZA in preventing new skeletal events and complications, but not in overall survival. One study indicates that clodronate may prolong survival in metastatic PCa, but before any generalization, the results should be replicated by others in comparative studies.