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

Table 1.

Non-metastatic hormone-sensitive prostate cancer

Question	Statement	Level of consensus
		Agree (%)	Disagree (%)	Uncertain (%)
1. Among patients receiving ADT, which are those at risk of fracture?⁹^,¹⁶	1.1 Adjuvant hormone therapy alone implies sufficient fracture risk to warrant antifracture therapy as primary or secondary prevention, independently of the presence of other fracture risk factors.	79.4	11.1	9.5
	1.2 All patients receiving short-term ADT (3-6 months) should be treated with antifracture prevention therapy.	48	37	15
	1.3 All patients receiving long-term ADT (>6 months) should be treated with antifracture prevention therapy.	88	2	10
2. When should antiresorptive therapy be started in patients with PCa starting hormone therapy?¹⁷	2.1 BTAs should be considered immediately from the start of hormonal therapy itself.	80	8.3	11.7
3. In males affected by PCa on ADT, which are the drugs to be used for the reduction of the risk of fracture?¹⁸^,¹⁹	3.1 In patients with PCa on ADT for the prevention of risk of fracture denosumab 60 mg every 6 months is advisable. In case of prescriptive ineligibility to therapy with denosumab and/or lack of reimbursement, the choice of another BTA (alendronate 70 mg weekly, risedronate 35 mg weekly or zoledronic acid 4 mg every 6 months) might be a choice.	93.7	0	6.3
4. Are vitamin D and calcium supplementations alone sufficient to maintain bone health or prevent fragility fractures in patients with PCa starting hormone therapy?²⁰	4.1 Vitamin D and calcium supplementation alone are not sufficient to maintain bone health and to prevent fragility fractures.²⁰	76.7	5	18.3
	4.2 Before starting and during any hormonal therapy, the levels of vitamin D (≥30 ng/ml) should be evaluated and normalized, regardless of the bone-modifying agent.	91.7	1.6	6.7
	4.3 The administration of calcium and daily dose of vitamin D 1500-2000 IU, to reach and maintain the value of 30 ng/ml (75 nmol/l), during antiresorptive therapy is mandatory.	93.3	0	6.7
5. Is intermittent ADT useful for maintaining bone health?²¹	5.1 The use of intermittent ADT does not yield a reduction in bone events (osteoporosis or fracture) and use of BTAs should be considered even in patients receiving intermittent ADT.	85.7	8	6.3
6. How to diagnose and monitor the bone health in nmHSPC during and after ADT?²²	6.1 To monitor bone health during ADT, the following assessments should be carried out at baseline and every 12-18 months thereafter: Vitamin D, serum calcium and PTH.	81.7	5	13.3
	6.2 To monitor bone health during ADT, the following assessments might be carried out, if possible, at baseline and every 18 months thereafter: DEXA scan (for BMD) and, if available, vertebral morphometry.	95.2	0	4.8
	6.3 To monitor bone health during ADT, the following assessments might be carried out, if possible, at baseline and every 18 months thereafter: DEXA scan with TBS.	92.1	1.6	6.3
	6.4 To monitor bone health during ADT, the following assessments should be carried out at baseline and every 12-18 months thereafter: Bone turnover markers, height, weight and BMI and body composition (by DEXA, bioelectrical impedance or plicometry) besides body mass index.	76.7	3.3	20
	6.5 Given the high prevalence of risk factors for fractures independent of hormone therapy and the high prevalence of vertebral fractures already present at the time of cancer diagnosis, all subjects with PCa should be investigated for the presence of fragility fractures by traditional radiography at baseline.	60	15	25
	6.6 Patients with nmHSPC receiving ADT may benefit from a supervised physical activity program in terms of bone health regardless of whether they are receiving antiresorptive therapy or not.	98.3	0	1.7
7. In nmHSPC patients treated with antiresorptive drugs (BPs and denosumab) for bone health, is an oral cavity assessment recommended before starting therapy, to reduce the risk of subsequent MRONJ?²³	7.1 Before starting treatment with BPs or denosumab, 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.	85	8.3	6.7
8. How to manage any dental procedures that may be necessary during antiresorptive treatments for bone health in nmHSPC?	8.1 In patients on treatment with BPs, their long half-life leads to an inhibition effect on osteoclastic function of unpredictable duration over time, even after a single administration. A temporary suspension of BPs (at least 7 days before and at least 6-8 weeks after the surgical procedure) could reduce their anti-angiogenic effect on the soft tissues, in order to therefore favor the vascularization of the healing tissues. The resumption of pharmacological therapy will be possible 6-8 weeks after the dental surgical procedure, once the post-surgical oral site has healed.	83.3	5	11.7
	8.2 In patients on treatment with denosumab, the urgency of the surgical procedure must first be assessed. In the presence of urgent invasive dental procedures, it is advisable to carry out the dental surgical maneuvers 3 weeks after the last administration of denosumab 60 mg and to apply ad hoc medical–surgical protocol. In the presence of invasive dental procedures that can be postponed, it is advisable to carry out the surgical maneuvers starting from the end of the fifth month after the last administration of denosumab. The resumption of pharmacological therapy will be possible 6-8 weeks after the dental surgical procedure, once the post-surgical oral site has healed.	91.7	0	8.3
9. Patients on adjuvant ADT: how long should be treated with BTAs for the prevention of the risk of fractures?	9.1 For patients on adjuvant ADT, therapy with antiresorptive drugs should be continued at least for the entire duration of the adjuvant hormone therapy itself. After the end of adjuvant ADT, the risk fracture of the patient should be reassessed to evaluate the possible continuation of antiresorptive therapy.	93.3	0	6.7
10. How to continue denosumab or BPs beyond the duration of adjuvant ADT? Is there maximum treatment duration and what to do after discontinuation?	10.1 In PCa patients on treatment with BPs or denosumab for CTIBL, after discontinuation of ADT, the fracture risk should be reassessed (using a validated algorithm for fracture risk, such as DeFRA, FRAX). If the patient experienced no fracture during treatment and has no other risk factors (BMD T-score > −2.5, obesity, age, sarcopenia, previous osteoporotic fractures, parent fractured hip, current smoking or alcohol, glucocorticoids, rheumatoid arthritis, secondary osteoporosis), BTAs can be discontinued, and bone health can continue to be monitored. If the patient presents any additional risk factor, monitoring and antiresorptive therapy with BPs or denosumab should be carried on.	85	1.7	13.3
	10.2 For patients who experienced fragility fracture or a decline in BMD during BPs, treatment could be switched to denosumab 60 mg 6 months.	75	0	25
	10.3 A decision to discontinue denosumab could be made after discontinuation of ADT, but bone turnover rebound and rapid bone loss must be monitored. Bisphosphonate (mainly zoledronic acid) therapy should be considered, especially in high-risk patients, according to prescriptive rules.	87.3	4.8	7.9
	10.4 Patients considered at high fracture risk could either continue denosumab therapy or be switched to BPs, in the absence of contraindications.	83.3	3.3	13.3
	10.5 For patients who discontinue denosumab and experience rapid bone loss or new fracture despite bisphosphonate administration, retreatment with denosumab is likely to stop fracture risk and restore BMD by reducing bone turnover.	61.7	0	38.3
	10.6 In patients who are not candidates for bisphosphonate therapy or who remain at high risk of fracture despite denosumab treatment, denosumab should be continued.	75	0	25
11. How to improve bone health in nmHSPC patients?²⁴^,²⁵	11.1 All patients with nmHSPC should undergo a total body composition by DEXA, in addition to weight detection and BMI, for lean body mass and fat mass assessment at baseline and during androgen deprivation treatment to reduce cardiovascular risk and sarcopenic obesity risk and improve bone health.	81.7	3.3	15
	11.2 All patients with nmHSPC should undergo a nutritional assessment at baseline and during androgen deprivation treatment in order to reduce cardiovascular risk and sarcopenia risk and improve bone health.	85	8.3	6.7
	11.3 Supervised clinical exercise programs should be included in clinical care programs for nmHSPC.	93.3	0	6.7

ADT, androgen deprivation therapy; BMD, bone mineral density; BMI, body mass index; BPs, bisphosphonates; BTAs, bone-targeting agents; CTIBL, cancer treatment-induced bone loss; DEXA, dual-energy X-ray absorptiometry; MRONJ, medication-related osteonecrosis of the jaw; nmHSPC, non-metastatic hormone-sensitive prostate cancer; PCa, prostate cancer; PTH, parathyroid hormone; TBS, trabecular bone score.