PCa18: Using bone-protective agents in advanced disease

15 September 2018

The issue of skeletal-related events (SREs) and the timing and use of bone-protective agents were among the topics discussed in the second-day plenary session at the 2nd EAU Update on Prostate Cancer (PCa18) which is on its second and last day in Milan.

Vijay Ramani (GB) lectured on the topic “When and How to Use Bone-Protective Agents,” addressing one of the challenging issues in providing optimal therapy to patients with systemic disease.

“Loss of bone mineral density (BMD) is inevitable in patients on androgen deprivation therapy (ADT),” said Ramani as he gave a comprehensive overview on the challenges and pitfalls in managing PCa patients with co-morbidities such as bone disease.

Ramani underscored the usefulness of bisphosphonates. “All bisphosphonates, such as alendronate zoledronic acid, etc.. increase BMD and avoid cancer tumour-induced bone loss (CTIBL),” he explained. “There is, however, no data on fracture risk in non-metastatic cases, and zoledronic acid is strongest and advised by ESMO, but dosing is still unclear.”

Regarding the use of low-dose denosumab, Ramani noted that it increases BMD and avoid CTIBL while reducing vertebral fracture risk.

He also pointed out that zoledronic acid does not reduce SREs when the drug is started prior to castration resistance.

With regards cases of metastatic castration-resistant prostate cancer (mCRPC), zoledronic acid is the only bisphosphonate that reduces SREs. He, however, added that zoledronic acid and denosumab have toxicities, particularly when used for extended periods.

Regarding the combination of Radium 223 with zoledronic acid, the combination significantly increases the time to first symptomatic skeletal event (SSE). He, however, cautioned against the combined use of Radium 223 plus abiraterone/prednisone, which is also restricted by EMA.

“There is a higher risk of early death and of fractures with this drug combination,” Ramani said.

On the entry of novel compounds such as abiraterone/enzalutamide, these show good quality reductions in SREs, but the added value of bisphosphonates or denosumab are unclear.

In the same session, J. Van Moorselaar discussed several updates on trials results in mHSPC, while P. Cornford examined drug developments and sequencing in mCRPC. The session was followed by breakout case discussion sessions that would look closely into treatment of oligometastatic disease, and treatment issues in mHSPC and CRPC.