What is the management of a spinal pathological fracture due to metastatic prostate cancer?

From the Guidelines

Management of a spinal pathological fracture due to metastatic prostate cancer requires a multidisciplinary approach involving oncology, spine surgery, radiation oncology, and pain management. Initial treatment focuses on pain control with analgesics including opioids (such as morphine 5-15mg every 4 hours as needed), NSAIDs (if not contraindicated), and adjuvant medications like gabapentin (300mg three times daily, titrated as needed) 1. Spinal stability must be assessed immediately, with unstable fractures requiring surgical intervention such as vertebroplasty, kyphoplasty, or spinal fusion with instrumentation to prevent neurological compromise, and for patients with pathologic fracture with neurologic effects, surgical consultation and radiation oncology consultation are usually appropriate 1. Radiation therapy (typically 30Gy in 10 fractions or 20Gy in 5 fractions) is often administered to reduce tumor burden, alleviate pain, and prevent further bone destruction. Systemic therapy for the underlying prostate cancer includes androgen deprivation therapy (such as leuprolide 7.5mg monthly or goserelin 3.6mg monthly), possibly combined with anti-androgens like enzalutamide (160mg daily) or abiraterone (1000mg daily with prednisone 5mg twice daily). Bone-modifying agents such as zoledronic acid (4mg IV every 3-4 weeks) or denosumab (120mg subcutaneously every 4 weeks) are essential to reduce skeletal-related events and strengthen bone, with zoledronic acid every 3-4 weeks recommended to prevent disease-related skeletal complications, including pathologic fractures, spinal cord compression, and the need for surgery or radiation therapy to bone 1. Some key points to consider in the management include:

• The use of bisphosphonates like zoledronic acid must be balanced with the risk of toxicity, including renal damage and jaw necrosis 1.
• MRI of the spine should be considered to detect subclinical cord compression in men with castration-refractory prostate cancer with vertebral metastases and back pain 1.
• External beam radiotherapy should be offered for patients with painful bone metastases from castration-refractory disease, with a single fraction of 8 Gy having equal pain-reducing efficacy to multifraction schedules 1. This comprehensive approach addresses both the structural compromise of the spine and the underlying malignancy, aiming to preserve neurological function, provide pain relief, and improve quality of life while treating the cancer that caused the pathological fracture.

From the FDA Drug Label

The design of these clinical trials does not permit assessment of whether more than one-year administration of zoledronic acid injection is beneficial Each study evaluated skeletal-related events (SREs), defined as any of the following: pathologic fracture, radiation therapy to bone, surgery to bone, or spinal cord compression. Results for the two zoledronic acid injection placebo-controlled studies are given in Table 13 Table 13: Zoledronic Acid Injection Compared to Placebo in Patients with Bone Metastases from Prostate Cancer or Other Solid Tumors Prostate CancerZoledronic acid injection 4 mg(n=214)Placebo(n=208) 33% 44% -11%(-20%, -1%) 0.02 Not Reached 321 0.67(0.49,0.91) 0. 011

The management of a spinal pathological fracture due to metastatic prostate cancer may include zoledronic acid injection to reduce the risk of skeletal-related events (SREs), which include pathologic fractures.

• The use of zoledronic acid injection 4 mg has been shown to decrease the proportion of patients with a SRE by 11% compared to placebo in patients with metastatic prostate cancer.
• The median time to the first SRE was not reached in the zoledronic acid injection group, compared to 321 days in the placebo group.
• However, the optimal duration of zoledronic acid injection administration is not known, and the design of the clinical trials does not permit assessment of whether more than one-year administration is beneficial 2.

From the Research

Management of Spinal Pathological Fracture

The management of spinal pathological fracture due to metastatic prostate cancer involves a multidisciplinary approach.

• The use of osteoclast-targeted agents such as zoledronic acid and denosumab has been shown to decrease the incidence of skeletal-related events in patients with metastatic castration-resistant prostate cancer (mCRPC) and bone metastases 3.
• Disease-modifying agents, including androgen-pathway inhibitors like abiraterone and enzalutamide, have also been shown to reduce the incidence of skeletal-related events 3.
• Radium-223, a bone-seeking alpha emitter, has been demonstrated to significantly improve median overall survival in prostate cancer patients with bone metastases compared to placebo 4.

Diagnosis and Prevention

• Early diagnosis of spinal cord compression is crucial, and magnetic resonance imaging (MRI) can be used to detect asymptomatic radiological spinal cord compression (rSCC) in patients with metastatic prostate cancer 5.
• Serial screening MRI spine is required to maintain a low incidence of clinical spinal cord compression, with the optimum frequency depending on the subset of patients studied 5.
• Patients with hormone-resistant prostate cancer who develop persistent back pain should undergo imaging studies and prophylactic local radiotherapy to the spine if bony metastases are identified 6.

Treatment

• Corticosteroid therapy should begin immediately in patients with spinal cord compression, followed by hormonal therapy in those who have not previously undergone hormonal manipulation 7.
• Radiation therapy is the standard approach to definitive therapy, while surgical decompression plays a role in patients with severe myelopathy, spinal instability, or those whose neurologic status deteriorates during or after radiation therapy 7.
• Laminectomy and radiotherapy can improve ambulation in patients with spinal cord compression, with 8 out of 9 patients treated with this combination being ambulant after treatment 6.