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. 2024 Jun 19;9(7):103484. doi: 10.1016/j.esmoop.2024.103484

Table 4.

Metastatic castration-resistant prostate cancer

Question Statement Level of consensus
Agree (%) Disagree (%) Uncertain (%)
  • 1.

    Among patients on treatment for mCRPC, who are those at risk of pathological and fragility fracture?28
  • 1.1

    All patients with mCRPC and bone metastases should be treated with bone-protecting agents with the aim of SRE reduction as well as to prevent CTIBL and, consequently, the risk of fragility fractures.

 93.6 1.6 4.8
  • 1.2

    All patients affected by mCRPC without bone metastases should be treated with bone-protecting agents with the aim to reduce CITBL and, consequently, the risk of fragility fractures.

 83.9 6.4 9.7
  • 1.3

    In patients with mCRPC without bone metastases, bone health should be treated, assessed and monitored as in nmCRPC patients.

 92 0 8
  • 2.

    In males affected by mCRPC, which drugs should be used for the reduction of the risk of SREs and for the prevention of CTIBL fragility fracture?29
  • 2.1

    Denosumab (120 mg every 4 weeks) should be used in patients with mCRPC as it may delay the onset of SREs.

 92 3.2 4.8
  • 2.2

    ZA is considered the BP of choice in patients with mCRPC as it may delay the onset of SREs. ZA at a dosage of 4 mg every 4 weeks is considered the standard, while higher doses are not recommended.

 91.9 3.2 4.8
  • 2.3

    Vitamin D and calcium supplementation is mandatory during treatment with BTAs. The administration of calcium and daily dose of vitamin D 1500-2000 IU after a load dose (5000 UI/day for 30 days), to reach and maintain the value between 30 ng and 50 ng/ml (75 nmol/l), during antiresorptive therapy is mandatory.

 95.2 1.6 3.2
  • 3.

    Who should be treated with denosumab and who should be treated with ZA?30
  • 3.1

    The physician’s choice between ZA and denosumab should consider comorbidities (i.e. renal impairment) and patient characteristics (i.e. easy vascular access, home therapy).

 100 0 0
  • 3.2

    Denosumab might be considered the preferred option in mCRPC patients with bone metastases according to the demonstration of reduction in SREs. However, the choice between denosumab and ZA could be based on many factors: direct costs (drug price for the health care system), indirect costs (commitment of health care structures), individual risk of side-effects (renal toxicity, ONJ, hypocalcemia) and preferences of the patient.

 84.1 6.4 9.5
  • 4.

    When should BTAs be started in patients with mCRPC?31
  • 4.1

    In mCRPC patients, bone-protecting agents should be started at the dose and schedule for SREs prevention at the time of the first metastasis diagnosis, even if already used to prevent CTIBL, in order to reduce incidence of SREs.

 88.7 4.8 6.4
  • 4.2

    Greater awareness of physicians about the importance of BTAs is needed to improve their use in patients with mCRPC and bone metastases.

 98.4 0 1.6
  • 5.

    How long should patients be treated with BTAs?32
  • 5.1

    In mCRPC after 12-15 months of treatment with ZA every 4 weeks, the shift to a 12-week schedule of ZA could be considered, after assessment of the risk-benefit ratio for the individual patient (e.g., burden of bone metastases, systemic disease control).

 80.6 0 19.4
  • 5.2

    Treatment with denosumab should be continued throughout the course of the disease because stopping it may expose to pathological and fragility fracture risk. After denosumab discontinuation, shift to ZA every 4 or every 12 weeks can be considered.

 77.8 9.5 12.7
  • 6.

    The switch from ZA to denosumab: when and how to do it?33
  • 6.1

    Switch from ZA to denosumab should be considered in patients who develop renal failure during ZA treatment or in patients who experience a new SRE during ZA.

 82.3 1.6 16.1
  • 6.2

    Switch from ZA to denosumab can be carried out after 4 weeks from the last ZA administration without adding adverse events, except for ONJ risk due to prolonged BTA exposure. For this reason, a close attention to oral cavity monitoring should be taken.

 92 3.2 4.8
  • 7.

    Should ZA or denosumab therapy be used to reduce bone pain?34
  • 7.1

    BPs and denosumab should be prescribed for the prevention of SREs, but an adequate treatment for pain should be added because the administration of BTAs did not demonstrate an analgesic effect compared to placebo.

 87.1 4.8 8.1
  • 8.

    Radiometabolic therapies in mCRPC patients: why and how to pay attention to bone health?35,36
  • 8.1

    Before, during and after treatment with radium-223, bone health should be monitored. Radium-223 may be interrupted or stopped if fragility fractures occur.

 82.3 3.2 14.5
  • 8.2

    Before starting and during treatment with radium-223, BTAs (denosumab 120 mg or ZA every 14 weeks) should be administered to protect bone from pathological and fragility fractures.

 87.1 0 12.9
  • 9.

    How to diagnose and monitor the bone health in mCRPC?
  • 9.1

    Monitor metastases by scintigraphy, NMR or any other evaluation at physician’s discretion and monitor bone health by assessing the fracture risk as in non-metastatic disease (monitor: vitamin D; serum calcium and PTH; DEXA scan with trabecular bone score, if available; if possible: bone turnover markers; height, weight, BMI and body composition. In case of back pain or height loss, carry out a spine radiography). Closer attention should be paid to vitamin D, serum calcium and PTH serum levels because of the higher risk of hypocalcemia during administration of ZA or denosumab at the dose for SRE prevention.

 96.8 1.6 1.6
  • 10.

    In mCRPC patients treated with antiresorptive drugs (BPs, denosumab) for SRE prevention, is an oral cavity assessment recommended before starting therapy, in order to reduce the risk of subsequent MRONJ?
  • 10.1

    Before starting treatment with BPs or denosumab with schedule for SRE prevention, adequately informed patients have to carry out a dental visit to evaluate their oral health, to set up an adequate prevention program and possibly treat local pathologies before starting BTA therapy.

 100 0 0
  • 11.

    How to manage any dental procedures that may be necessary during antiresorptive treatments for bone metastases in mCRPC?37
  • 11.1

    Plan an assessment by the prescriber (high risk versus low risk of SREs) and by the dentist (high risk versus low risk of post-extraction complications) to determine the need for a precautionary suspension of ZA or denosumab before and after the dental procedure.

 93.5 0 6.5
  • 11.2

    No definitive data have been published and, especially with ZA, there is no safe timing for invasive oral/dental procedures due to its mechanism of action. If procedure is urgent, a suspension frequently applied of ZA or denosumab consists of a period of 4 weeks, at least, from the last assumption before any elective invasive oral or dental procedures. BTA re-assumption should occur not before 6 weeks and only after a complete healing assessed by the dentist.

 87.3 3.2 9.5

BMI, body mass index; BPs, bisphosphonates; BTAs, bone-targeting agents; CTIBL, cancer treatment-induced bone loss; DEXA, dual-energy X-ray absorptiometry; mCRPC, metastatic castration-resistant prostate cancer; MRONJ, medication-related osteonecrosis of the jaw; NMR, nuclear magnetic resonance; ONJ, osteonecrosis of the jaw; PTH, parathyroid hormone; SREs, skeletal-related events; ZA, zoledronic acid.