Guidance for the assessment and management of prostate cancer treatment-induced bone loss. A consensus position statement from an expert group

Abstract

Context and objective: Incidence of prostate cancer (PC) is increasing, but androgen deprivation therapy (ADT) and other therapies are substantially improving survival. In this context, careful consideration of skeletal health is required to reduce the risk of treatment-related fragility fractures and their associated morbidity and mortality. This risk is currently not well-managed. ADT causes significant loss of bone mineral density (BMD). In the metastatic setting, systemic treatments (e.g. chemotherapy, abiraterone, enzalutamide) are used alongside ADT and may require concomitant glucocorticoids. Both ADT and glucocorticoids pose significant challenges to skeletal health in a population of patients already likely to have ongoing age-related bone loss and/or comorbid conditions. Current PC guidelines lack specific recommendations for optimising bone health. This guidance presents evidence for assessment and management of bone health in this population, with specific recommendations for clinical practitioners in day-to-day PC management.

Methods: Structured meetings of key opinion leaders were integrated with a systematic literature review. Input and endorsement was sought from patients, nursing representatives and specialist societies.

Summary of guidance: All men starting or continuing long-term ADT should receive lifestyle advice regarding bone health. Calcium/vitamin D supplementation should be offered if required. Fracture risk should be calculated (using the FRAX® tool), with BMD assessment included where feasible. BMD should always be assessed where fracture risk calculated using FRAX® alone is close to the intervention threshold. Intervention should be provided if indicated by local or national guidelines e.g. UK National Osteoporosis Guideline Group (NOGG) thresholds. Men requiring bone protection therapy should be further assessed (e.g. renal function), with referral to specialist centres if available and offered appropriate treatment to reduce fracture risk. Those near to, but below an intervention threshold, and patients going on to additional systemic therapies (particularly those requiring glucocorticoids), should have FRAX® (including BMD) repeated after 12-18 months.

Patient summary: Modern treatments for prostate cancer have led to significant improvements in survival and quality of life. However, some of these treatments may lead to weakening of patient's bones with risk of fracture and it is therefore important to monitor patients' bone health and provide bone protection where needed. This paper provides specific guidance to clinical teams, based on the most recent research evidence, to ensure optimal bone health in their patients.

Keywords: Fracture risk; Guidelines; Osteoporosis; Prostate cancer; Skeletal health.

Fig. 1

The UK FRAX® tool. Screenshot showing a FRAX®calculation of major fracture and hip fracture probability in a man aged 70 years with secondary osteoporosis (e.g. prostate cancer on ADT). Note that, because there is no BMD measurement included, the secondary osteoporosis factor has been checked as ‘Yes’ in recognition of the patient being on ADT. If a BMD measurement was included, the FRAX® risk calculation would take no account of whether the secondary osteoporosis box is checked or not as the BMD takes precedence.

Fig. 2

NOGG intervention thresholds. The thresholds depicted by the lines between the green and red areas above are the 10-year probabilities of a major osteoporotic fracture (left graph) or hip fracture (right graph) in women with a previous fracture. Applying the same criteria to men with PC, treatment should be strongly considered in those with fracture probabilities at or above the threshold. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 3

Algorithm for assessment of bone health in prostate cancer patients receiving ADT. Note regarding patients with mCRPC: Around 80% mCRPC patients develop bone metastases. In patients with bone metastases from CRPC at high risk for clinically significant SREs, ESMO guidelines recommend denosumab or zoledronate at doses higher than those required for protection against CTIBL alone. However, where mCRPC patients do not already receive bone protection for prevention of metastatic morbidity, in view of emerging data referred to in Section 3, it is strongly recommended that all such patients should be considered for bone protection to prevent osteoporotic fragility fractures.

Fig. 4

Guidance for clinicians. The following guidance is given for management of bone health in patients with prostate cancer starting ADT or for patients already receiving ADT who have not previously had a bone health assessment.