Editing AUA: Advanced Prostate Cancer (2023) (section)

===== Bone health =====
* Risk factors for bone complications in patients with metastatic prostate cancer (3):
*# Age-related decreases in bone mineral density
*# ADT is associated with progressive loss of bone mineral density
*# Bones are the most common site of metastatic disease
* Risk of osteoporosis associated with ADT should be discussed
* '''<span style="color:#ff0000">Diagnosis and Evaluation</span>'''
** '''<span style="color:#ff0000">Assess the risk of fragility fracture in patients with advanced prostate cancer.</span>'''
*** The Fracture Risk Assessment Tool is a validated resource to help predict a patient’s 10-year probability of hip fracture and the 10-year probability of a major osteoporotic-related fracture (spine, forearm, hip or shoulder fracture). This tool can be used with or without measurement of bone mineral density.
** '''<span style="color:#ff0000">Baseline bone mineral density measurement with dual x-ray absorptiometry (DXA) may be considered in men receiving ADT and other systemic treatments for prostate cancer.</span>'''
*** '''The largest decrease in bone mineral density occurs within the first year of therapy'''
**** Reasonable to re-assess osteoporotic-related risk (FRAX® and DXA) 1-year after initiating systemic treatment, and at longer intervals thereafter.
* '''<span style="color:#ff0000">Management</span>'''
** '''<span style="color:#ff0000">Preventative treatment for fractures and skeletal-related events (3):</span>'''
**# '''<span style="color:#ff0000">Supplemental calcium and vitamin D</span>'''
**#* Estimated daily calcium requirement is 1,000-1,200 mg from food and supplements.
**#* Estimated daily vitamin D requirement is 1,000 IU from food, supplements, and sunlight.
**# '''<span style="color:#ff0000">Smoking cessation</span>'''
**# '''<span style="color:#ff0000">Weight-bearing exercise</span>'''
*** Insufficient evidence to inform the optimal strategies for the prevention of bone loss and frailty fractures.
** '''<span style="color:#ff0000">Pharmacologic strategies for osteoporosis prevention and treatment (2):</span>'''
**# '''<span style="color:#ff0000">Bisphosphonates</span>'''
**#* '''<span style="color:#ff0000">Oral bisphosphonates (e.g., alendronate, pamidronate)</span>'''
**#* '''<span style="color:#ff0000">Intravenous bisphosphonates (e.g., zoledronic acid)</span>'''
**#* Amongst bisphosphonates, the greatest reduction in fractures was observed for zoledronic acid
**# '''<span style="color:#ff0000">Subcutaneous RANK ligand inhibitors (e.g., denosumab).</span>'''
*** The recommended dose and treatment schedules for zoledronic acid and denosumab are different for the indications of osteoporotic fracture prevention and skeletal-related event prevention.
**** For example, zoledronic acid is usually administered yearly for osteoporosis-related fracture prevention compared to monthly or every three months for metastatic cancer skeletal-related event prevention. Similarly, denosumab has been administered as 60mg every 6 months for osteoporosis compared to 120mg monthly for skeletal-related event prevention.
*** '''<span style="color:#ff0000">Because men who need dental extractions while on zoledronic acid or denosumab are at higher risk for ONJ, clinicians should consider evaluation by a dentist prior to initiation.</span>'''
** '''<span style="color:#ff0000">In advanced prostate cancer patients at high fracture risk due to bone loss, preventative treatment with a bone-protective agent (denosumab or zoledronic acid) is recommended and referral to physicians who have familiarity with the management of osteoporosis when appropriate.</span>'''
** '''<span style="color:#ff0000">In mCRPC patients with bone metastases, a bone-protective agent (denosumab or zoledronic acid) is recommended</span>''' to prevent skeletal-related events.
*** In mCRPC, zoledronic acid has been shown to
***# Lower rates of skeletal-related events
***# Increase time to first skeletal-related event
***# Decrease rate of pathologic fracture
*** '''Denosumab vs. zoledronic acid'''
**** Non-inferiority trial of 1,904 men with mCRPC with bone metastases
**** Randomized to receive denosumab or zoledronic acid
**** Primary outcome: time to skeletal-related event.
**** Results:
***** Denosumab non-inferior to zoledronic acid for the primary endpoint of outcome of time to SRE
***** Denosumab was superior to zoledronic acid in improving time to first skeletal-related event in a secondary analysis (p = 0.008).
***** '''Rates of hypocalcemia were higher with denosumab than zolendronic acid; as such, clinicians should monitor calcium levels prior to infusions, and repletion of vitamin D prior to starting these agents, along with calcium and vitamin D maintenance.'''
**** Fizazi, Karim, et al."Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study." ''The Lancet'' 377.9768 (2011): 813-822.
*** CALGB 90202
**** Early treatment with zoledronic acid in men with mHSPC and bone metastases was not associated with lower risk for SREs or death.
*'''Follow-up'''
**In mCRPC patients without PSA progression or new symptoms, clinicians should perform imaging at least annually.
**'''<span style="color:#ff0000">In mCRPC patients with disease progression (PSA or radiographic progression or new disease-related symptoms) having previously received docetaxel and androgen pathway inhibitor, 177Lu-PSMA-617 should be offered</span>'''
***PSMA PET imaging should be offered in patients who are considering 177Lu-PSMA-617