Skeletal-Related Events in Metastatic Prostate Cancer and the Number Needed to Treat: A Critical Consideration

Abstract

Purpose: With stage migration induced by early diagnosis of prostate-specific antigen, the course of disease for prostate cancer (PCa) patients has changed. Increasingly, patients undergo long-term androgen ablation with consecutive risks including osteoporosis and pathologic fractures. A recent randomized trial found that the RANK ligand inhibitor denosumab was more effective preventing skeletal-related events in patients with metastatic PCa as compared to treatment with the bisphosphonate zoledronic acid. This improved efficacy was linked to an increase of side effects. Methods: The present analysis compares results reported for both substances using a number needed to treat analysis approach. Based upon these findings, risk-benefit calculations were performed. Results: The results demonstrate that for patients with bone metastatic castration-resistant PCa, decision for or against treatment with either denosumab or zoledronic acid must not only consider efficacy but needs to balance the desired effects versus potential side effects. This is of specific relevance since life expectancy is limited in this patient cohort with end-stage disease. Conclusions: Further scientific efforts are necessary to identify optimal dosing and application intervals for denosumab and zoledronic acid as well as to answer the question of optimal duration of treatment. These findings will directly impact the risk versus benefit relations for both therapeutic options.

XPO1/CRM1-Selective Inhibitors of Nuclear Export (SINE) reduce tumor spreading and improve overall survival in preclinical models of prostate cancer (PCa)

“…In addition, androgen deprivation resistant PCa bone metastases are usually resistant to standard therapies including radiation and chemotherapy. The major characteristic of PCa cancer bone metastases is that they typically produce osteoblastic or mixed osteoblastic/osteolytic bone lesions that are not as efficiently treated with the osteoclast inhibitors [ 3 – 6 ]. Treatments that target the bone microenvironment such as bisphosphonates including zolendronic acid [ 4 ] and the RANKL inhibitor, denosumab [ 5 ], which inhibits osteoclasts and associated osteolysis, have been effective in delaying the onset of skeletal related events (SREs) in some cancers, but mixed results in PCa.…”

Oncologic Response and Hospitalization Rate of Patients Receiving Cabazitaxel in the Fourth-Line and Beyond in Castration-Resistant Prostate Cancer: Analysis of a Retrospective Cohort and a Structured Literature Review

“…In this cohort, the hospitalization rate was high. It is difficult to keep the CAB-related and the advanced disease-related symptoms apart, which might also be influenced by the management of bone metastases [26]. Hospitalization rate might be affected by the German health care system, with less treatment applied in the ambulatory sector than in other countries.…”

Treatment of Bone Metastases in Urologic Malignancies

“…Particularly in patients with renal insufficiency, a critical consideration of alternatives and prophylaxis of hypercalcemia is required [21]. Generally, the expected benefit of treatment with denosumab or zoledronic acid has to be weighed against the risk of side effects [9,22]. Current guidelines recommend prophylactic measures such as calcium and vitamin D supplementation for the prevention of hypocalcemia [8,9] as well as pretreatment dental evaluation with the elimination of dental risks and consulting on oral hygiene [9] in order to prevent osteonecrosis of the jaw.…”