• The most common presenting symptom, occurring in approximately 80–95% of patients. Unexplained back pain in cancer patients warrants immediate evaluation.

• Typically precedes neurological deficits.

• Local pain is thought to be due to periosteal stretching from tumor growth and/or local inflammatory process. It often responds to steroids.

• Radicular pain indicates neuroforaminal pathology due to nerve root compression or irritation and tends to be constant with dermatomal distribution of the involved nerve root.

• Mechanical pain is movement-related pain. It is indicative of bone etiology often caused by vertebral body collapse or compression as a result of instability. It is often worse with movement and is often refractory to steroids or narcotics.

• The presence of neurological impairment is indicative of high-grade ESCC.

• Motor weakness is the most common neurological symptom (indicative of impaired corticospinal tracks) [7–9].

• Approximately 60–85% present with motor weakness at the time of diagnosis [3].

• Sensory impairment (paresthesias, loss of sensation) often accompanies motor impairment (pinprick evaluates spinothalamic tracks; proprioception evaluates posterior columns).

• Sphincter control/continence and autonomic impairment such as urinary retention and hesitancy are often a late finding. Urinary retention is the most common and often correlates with the degree of motor deficit [10].

• Functional assessment can be objectively graded using Frankel classification [11].

• The cause of neurological impairment is thought to be commonly due to edema caused by increased vascular permeability when the epidural venous plexus is compressed by an epidural metastasis.

• Direct compression of the spinal cord by an expanding epidural mass can also lead to spinal cord ischemia and subsequent neurological injury.

• Bone fragments due to posterior displacement of fractured bone metastasis may also result in direct compression on the spinal cord [7].

• A comprehensive history should include characteristics of pain, presence, extent and duration of neurological symptoms, performance status, extent/status of extraspinal metastatic cancer, and GI/GU functions (including urinary retention and continence).

• Neurological symptoms:

 Include any motor, sensory, or autonomic (bladder/bowel) dysfunction.

 Details of onset (acute vs gradual), time since onset, severity, and extent of the neurological symptoms.

• Detailed history of the pain characteristics may elicit whether pain is due to local/axial, radiculopathic, or mechanical causes.

• Comprehensive examination to include: Inspection of spine alignment, palpation of focal tenderness/mass.

• Thorough neurologic examination including motor function, gait, sensation (pinprick, proprioception), reflexes (deep tendon reflex, abdominal, Babinski, Hoffman), clonus.

• Range of motion.

• MRI of the spine with and without gadolinium is the gold standard imaging modality for evaluation and should be performed immediately when metastatic spinal cord compression is suspected.

• MRI determines the location, extent of compression, single versus multiple lesions, and other epidural/cord compression sites. It also differentiates between metastasis and spondylodiscitis [19].

• The entire spine should be imaged because epidural compression may occur at multiple levels.

• To visualize the site of epidural compression:

 Sagittal T1-weighted images with and without contrast and T2-weighted images.

• To confirm the degree of compression:

 Axial T1-weighted images with and without contrast and T2-weighted images at the regions of interest based on sagittal imaging finding.

• Compression of the thecal sac and structures within the dura including the spinal cord and cauda equina by an extradural mass is diagnostic.

 Direct tumor extension from bone metastasis into the epidural space is the most common.

 Bone fragment due to vertebral metastasis into the spinal column is another cause.

• Spinal CT defines bony anatomy and the extent of bone involvement and is especially useful for evaluation of compression fracture, mechanical instability, and posterior bone fragment protrusion.

• Occasionally, biopsy or surgical decompression is considered when pathological diagnosis is needed in patients without known history of cancer diagnosis or if there is no evidence of other metastasis.

• All patients with suspected MESCC should receive prompt administration of dexamethasone when MESCC is suspected.

• A randomized trial by Sorensen et al. investigated patients treated with radiotherapy alone for spinal cord compression who were randomized to high-dose dexamethasone 96 mg/day vs. none; 81% of the patients who received dexamethasone were ambulatory, compared to 63% in the control arm, demonstrating the benefit of high-dose steroids [20].

• No consensus data on optimal dosing schedules of dexamethasone.

• High-dose dexamethasone is associated with severe gastrointestinal toxicity including bowel perforation, ulcer, and bleeding.

 Sorensen et al. reported 11% of patients had serious GI side effects including perforation [20].

• A common inpatient regimen is immediate administration of dexamethasone 10 mg IV bolus followed by 4–8 mg q 6–8 hours, with taper completed in 2 weeks.

• An alternative is administration of a medium dose of dexamethasone (8 mg twice a day) from the day of MESCC diagnosis until the end of radiotherapy with taper completed in 2 weeks [21].

• Recommendation for outpatient regimen: initial dose of 4 mg q 6 hours of dexamethasone, with a taper started after surgery and/or radiotherapy. Taper usually consists of an empiric reduction in dose of 2–4 mg every 1–3 days as tolerated.

• Common side effects of dexamethasone include stomach irritation, insomnia, irritability, and fluid retention/lower extremity swelling. Prophylaxis against dexamethasone-induced ulceration with proton pump inhibitor or ranitidine 150 mg BID should be used.

• SRS/SBRT permits high dose conformal photon radiation therapy to deliver higher biologically ablative doses to improve local control while sparing spinal cord with a steep dose gradient, using a single-fraction or hypofractionated regimen.

• SRS/SBRT was initially investigated in vertebral metastases without epidural extension and has demonstrated excellent pain relief of approximately 90% and local control of 80% regardless of histology [31,32].

• However, SRS/SBRT has limited application in most patients with MESCC since many patients who present with MESCC have poor performance status, extensive disease, and/or poor prognosis.

• A recent prospective study from a single institution by Ryu et al. demonstrated radiosurgical decompression of epidural metastasis using a single fraction of 16 Gy is feasible.

 An overall 81% improvement in neurological function, with mean epidural tumor volume reduction of 65% at 2 months after radiosurgery [33].

 Dose constraint of the spinal cord is a major limitation: the portion of epidural mass directly compressing the spinal cord has to receive less therapeutic dose to protect the spinal cord.

• The ASTRO evidence-based guideline for palliative radiotherapy for bone metastases recommended SRS/SBRT be limited within a prospective trial [34].

 Only selected patients without high-grade epidural compression, with isolated bone metastasis confined to 1–2 vertebral bodies, with no neurological deficits, and good performance status may be considered for SRS/SBRT.

• Toxicities for SRS/SBRT are generally mild and include esophagitis, mucositis, dysphagia, diarrhea, radiculitis, paresthesia, and pain flare.

 Radiation-induced myelopathy is approximately 0.6% [35].

 Vertebral fracture has been reported as a delayed complication [36].

• Prompt neurosurgical evaluation is critical for patients with suspected spinal cord compression. Goals of surgery include circumferential decompression of the spinal cord to preserve neurological function and preservation or restoration of mechanical instability.

• Postoperative radiotherapy usually follows surgery.

• Patient selection is an important consideration; combined surgery and postop radiotherapy should be limited to surgical candidates with an expected survival of minimum of 3 months, good performance status (Karnofsky performance score (KPS) of ≥70), and with limited MESCC.

• Radiosensitive tumors, such as lymphoma, myeloma, and germ cell tumors, may be treated with radiotherapy without upfront surgical decompression.

• Mechanical instability includes fracture-dislocation, translational deformity, and significant collapse of vertebral body with associated mechanical pain.

• This can lead to mechanical injury to the spinal cord resulting in detrimental neurological function.

• The spinal instability neoplastic score (SINS) was developed by expert consensus from the Spine Oncology Study Group to evaluate mechanical stability [43,44].

 See Appendix E (Palliative Care Toolkit) for SINS classification.

 Factors that predict instability include >50% vertebral body collapse, bilateral facet destruction, pain associated with movement, progressive deformity, presence of subluxation, and location in the junctional segments of the spine.

• Surgical stabilization should be strongly considered in patients with mechanical instability (e.g., high SINS score).

• Percutaneous cement augmentation such as vertebroplasty and kyphoplasty is not indicated for patients with spinal cord compression.

 Although this approach may be effective in reducing pain due to compression fracture in cancer patients, patients with epidural metastasis were excluded in the CAFÉ study [45].