Spinal Metastases

Spinal metastases are tumour deposits in the vertebral column, with or without extension to the epidural space. They are the commonest site of bone metastasis, and cause mechanical pain, neurological deficit and instability, so treatment is planned around pain, stability, neurological risk and expected survival.

They occur in 30% to 70% of patients with metastatic cancer at autopsy, and about 10% to 20% become symptomatic. The commonest primaries are breast, lung and prostate, followed by renal, thyroid, myeloma and gastrointestinal cancers. About 70% are thoracic, 20% lumbar and 10% cervical, and multiple levels are involved in more than 50%.

Pathophysiology. Haematogenous spread through the vertebral venous plexus (Batson plexus) seeds the vertebral body, with extension to the pedicles, posterior elements and epidural space. Destruction produces lytic collapse, kyphosis and instability, and retropulsion of bone or soft tissue compresses the cord or cauda equina.

Prognosis. Median survival is 3 to 24 months, depending on the primary tumour, extent of systemic disease, neurological state and performance status. Preserved ambulation at treatment strongly predicts retained function.

• Local pain (biological) that is worse at night or lying flat, improves with steroids, and may have a band like distribution.
• Mechanical pain from instability, worse on movement, standing or sitting up, improved lying flat, with "movement related" severe pain.
• Radicular pain, limb weakness, sensory loss, sphincter dysfunction.
• Spinal deformity, tenderness over the spinous process, and signs of cord or cauda equina compression.

Red flags.

• New neurological deficit or sphincter dysfunction.
• Severe mechanical pain suggesting instability.

• MRI of the whole spine with gadolinium (for epidural extension, cord compression and multilevel disease).
• CT for bone detail, vertebral collapse and instability, and spinal stability scoring (location, pain type, bone lesion quality, alignment, vertebral body collapse and posterolateral involvement) to classify stable, potentially unstable and unstable lesions.
• Biopsy when the primary is unknown. Systemic staging with PET-CT or CT and bone scan, and myeloma screen.
• Assessment of epidural spinal cord compression using a grading scale (grade 0 to 3 based on cerebrospinal fluid effacement and cord deformation).

Differential diagnosis.

• Osteoporotic fracture, degenerative disease, discitis or epidural abscess
• Primary bone tumour, myeloma and lymphoma
• Haemangioma and Paget disease

Management is decided jointly by oncology, radiation oncology and spine surgery, using the oncologic, neurologic, mechanical and systemic (NOMS) assessment.

Pain and neurological protection.

• Opioid analgesia: morphine sulfate immediate release 5 mg orally every 4 hours (2.5 mg in older adults) with 5 to 10 mg as needed for breakthrough pain (about one sixth of the daily dose). Convert to modified release morphine every 12 hours at the same total daily dose once pain is stable.
• Opioid maximum: no fixed ceiling, titrate to effect and review the plan above 120 mg daily oral morphine equivalent.
• Opioid monitoring: pain score, sedation, respiratory rate, constipation, nausea, myoclonus.
• Opioid adjustment: start at 2.5 mg every 4 hours and use an alternative opioid when creatinine clearance is under 30 mL/min. Co-prescribe senna 7.5 to 15 mg orally at night. Reduce the new opioid dose by 25% to 50% on changing opioid because of incomplete cross-tolerance
• Neuropathic pain: gabapentin 300 mg orally at night on day 1, 300 mg twice daily on day 2 and 300 mg three times daily on day 3, then titrated every 3 to 7 days to 900 to 1800 mg daily in 3 divided doses.
• Gabapentin maximum 3600 mg daily.
• Gabapentin monitoring: sedation, dizziness, oedema, mood, falls, respiratory depression with opioids.
• Gabapentin adjustment: creatinine clearance 30 to 59 mL/min 400 to 1400 mg daily in 2 divided doses, 15 to 29 mL/min 200 to 700 mg once daily, under 15 mL/min 100 to 300 mg once daily. Taper over at least 1 week when stopping
• Corticosteroids for epidural compression with neurological signs: dexamethasone 16 mg IV or orally once at diagnosis, then 8 mg twice daily with gastric protection until radiotherapy or surgery is complete, then tapered over 2 to 3 weeks.
• Dexamethasone maximum 16 mg daily after the first dose.
• Dexamethasone monitoring: glucose four times daily in diabetes, blood pressure, mood and sleep, gastric symptoms, infection, proximal myopathy.
• Dexamethasone adjustment: add an oral proton pump inhibitor, use the lowest dose that preserves neurological function, withhold before tissue sampling when lymphoma is suspected, adjust insulin or oral hypoglycaemic doses
• Thromboprophylaxis: enoxaparin 40 mg subcutaneously once daily for thromboprophylaxis during active disease and for 4 weeks after surgery (therapeutic dosing of 1 mg/kg twice daily if thrombosis is established).
• Enoxaparin maximum 40 mg daily for prophylaxis.
• Enoxaparin monitoring: platelet count at baseline and every 2 to 4 weeks, creatinine, signs of bleeding, anti-Xa level in obesity or renal impairment.
• Enoxaparin adjustment: 20 mg daily when creatinine clearance is under 30 mL/min. Hold for platelets under 50 x 10^9/L or active bleeding. Time the dose at least 12 hours before and 4 hours after a neuraxial procedure
• Pain flare prophylaxis with radiotherapy: dexamethasone 8 mg orally on the day of radiotherapy and daily for 4 days afterwards to prevent pain flare after a single palliative fraction.
• Dexamethasone maximum 8 mg daily.
• Dexamethasone monitoring: glucose, mood and sleep, gastric symptoms.
• Dexamethasone adjustment: give gastric protection, adjust diabetes treatment, omit if the patient already takes a higher steroid dose

Radiotherapy. Conventional radiotherapy (8 Gy in 1 fraction, 20 Gy in 5, or 30 Gy in 10) for painful lesions. Stereotactic body radiotherapy (24 Gy in 2 fractions, or 18 to 24 Gy in 1 fraction) offers higher local control and durable pain relief, particularly in radioresistant tumours, oligometastatic disease or recurrence after prior radiotherapy.

Surgery. Decompression and stabilisation (separation surgery followed by stereotactic radiotherapy) for high grade epidural compression, instability, retropulsed bone, or deterioration during radiotherapy. Percutaneous cement augmentation (vertebroplasty, kyphoplasty) for painful stable pathological compression fractures without epidural disease.

Bone targeted drugs.

• Bisphosphonate: zoledronic acid 4 mg IV over at least 15 minutes every 4 weeks for the first 3 to 6 months and then every 12 weeks for up to 2 years (longer when benefit continues). Give calcium 500 mg and vitamin D 400 to 800 units orally daily.
• Zoledronic acid maximum 4 mg in one dose.
• Zoledronic acid monitoring: creatinine before each dose, calcium, phosphate, dental review before starting, jaw and thigh pain, acute phase reaction.
• Zoledronic acid adjustment: reduce the dose to about 3.0 to 3.5 mg when creatinine clearance is 30 to 60 mL/min. Avoid when creatinine clearance is under 30 mL/min. Withhold for osteonecrosis of the jaw or pending dental surgery
• Denosumab (alternative): denosumab 120 mg subcutaneously every 4 weeks (every 12 weeks may be used after 1 year in selected patients). Give calcium 500 mg and vitamin D 400 to 800 units orally daily.
• Denosumab maximum 120 mg in one dose.
• Denosumab monitoring: calcium before each dose (severe hypocalcaemia is a risk, especially with renal impairment), dental review before starting, jaw and thigh pain, rebound vertebral fractures if stopped.
• Denosumab adjustment: no renal dose adjustment but monitor calcium closely when creatinine clearance is under 30 mL/min. Correct low vitamin D before starting. Do not stop abruptly (give a bisphosphonate after the last dose)

Systemic therapy. Directed at the primary tumour (hormonal, chemotherapy, targeted or immunotherapy).

Rehabilitation and bracing. Physiotherapy, spinal bracing for symptomatic thoracolumbar instability when surgery is not appropriate, and early mobilisation with supervision.

Monitoring. Pain and neurological examination at each visit, MRI at 3 months after stereotactic treatment and every 3 to 6 months afterwards, and monitoring for vertebral fracture after radiotherapy (up to 10% to 40% with stereotactic treatment).

Referral and escalation.

• Same day spinal team discussion for any neurological symptoms.
• Urgent assessment for severe mechanical pain.

Special groups.

• Myeloma and lymphoma: systemic therapy and radiotherapy with bracing.
• Prior radiotherapy: stereotactic techniques or surgery, with attention to cumulative cord dose.
• Pregnancy: MRI without gadolinium and individualised treatment.