Neurological Complications of Advanced Prostate Cancer

[Dilantin] if radiotherapy is anticipated, because of the risk of Stevens-Johnson syndrome with concomitant treatment)Oncology referral
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*—The rarer neurologic complications include paraneoplastic syndromes such as peroneal neuropathy (peroneal nerve palsy related to local metastasis), cerebellar ataxia, limbic encephalitis and brain-stem encephalitis.

Prostate cancer has been shown to metastasize by following the venous drainage system through the lower paravertebral plexus, or Batson’s plexus.1,4 Although hematogenous spread of other malignancies is most commonly to the lungs and liver, 90 percent of prostatic metastases involve the spine, with the lumbar spine affected three times more often than the cervical spine. Prostate cancer also spreads to the lungs in about 50 percent of patients with metastatic disease, and to the liver in about 25 percent of those with metastases.1

SYMPTOMS
The symptoms of spinal cord compression include progressive pain that is aggravated by movement. This pain can be confused with the pain caused by an osteodegenerative process of the spine. However, reclining does not alleviate back pain in men with spinal cord compression resulting from metastatic prostate cancer. Back pain is present in nearly all men with prostate cancer that has metastasized to the spine. Percussion over the involved vertebral body may evoke tenderness.

Muscle weakness often evolves over a few days to weeks after feeling the initial pain. Weakness usually affects the proximal muscles of the lower extremities and may or may not involve sensory loss. Autonomic dysfunction can cause urinary retention or, less frequently, bladder or bowel incontinence.

DIAGNOSIS
In 85 to 90 percent of patients with epidural cord compression, plain-film radiographs (x-rays) of the spine detect abnormalities such as collapse or erosion of the vertebral body or pedicle, but these findings are not specific.5 If spinal cord compression is suspected, magnetic resonance imaging (MRI) should be performed on an emergency basis. If MRI is not available, computed tomographic (CT) myelography can be used. Neuroimaging of the entire spine is necessary because epidural tumors may develop at different levels of the spine.6

A spinal tap to evaluate the cerebrospinal fluid (CSF) is not very helpful and is rarely required for the diagnosis of spinal cord compression, especially if an MRI is available.

The serum prostate-specific antigen (PSA) level is highly predictive of bone metastasis. If the serum PSA level is above 100 ng per mL, the positive predictive value is 74 percent. If the serum PSA level is less than 10 ng per mL, the negative predictive value is 98 percent.7 The CSF PSA level may prove useful for identifying intradural metastasis of prostate cancer in patients with an as yet unestablished primary tumor or with multiple malignancies. The medical literature contains a report of a 79-year-old man with lumbosacral pain who repeatedly had normal serum PSA levels and neuroimaging studies, but a CSF PSA level that was elevated to 29 ng per mL; MRI studies ultimately detected spinal metastasis from prostate cancer.

TREATMENT
Treatment should be initiated as soon as spinal cord compression is diagnosed to try and preserve ambulation. When prompt treatment is given there is an 89 to 100 percent likelihood of preserved ambulation in men who present without walking difficulties. The likelihood of subsequent ambulatory function drops to 39 to 83 percent in men who present with impaired ambulation, and to 10 to 20 percent in those who present with paralysis (9,10)

Best treatment involves reducing or alleviating pain as well as maintaining overall neurologic function. By using a combination of pharmaceutical and nonpharmaceutical modalities, physicians can achieve pain control in 85 to 95 percent of patients.11 Opioid medication is the mainstay of therapy for patients with severe, debilitating pain. Regimens using morphine, hydromorphone (Dilaudid), fentanyl (Duragesic), and oxycodone (Roxicodone) should follow the analgesic “ladder” developed by the World Health Organization, with rescue doses of an opioid available to manage breakthrough pain. (11,12)

Intravenously administered corticosteroids help to decrease cord swelling and pain, retain motor function, and improve outcome after treatment. In one placebo-controlled study,13 corticosteroids improved ambulatory function from 63 percent to 81 percent in patients with high-grade radiologic lesions. After six months, 59 percent of the steroid-treated patients still ambulated, compared with 33 percent of placebo-treated patients; however, median survival remained equal. Nonetheless, dexamethasone sodium phosphate (Decadron) is the treatment of choice in patients with spinal cord compression caused by metastatic prostate cancer.

In men with only one spinal lesion surgical decompression can be considered, however it is rare that there is just one lesion. In hormone-naïve patients, corticosteroids and androgen ablation therapy are given priority, followed by radiotherapy in patients who become refractory to corticosteroids and hormone-deprivation therapy.

The treatment of spinal cord compression generally improves motor strength and function in men with metastatic prostate cancer. However, there is a 45 percent risk of another episode of compression at the same site or a new site within two years. (6)

Brain Metastasis usually occur only in late stage disease brain metastasis are rare in prostate cancer.

Data collected before the importance of PSA values was recognized indicate that the average time from the diagnosis of prostate cancer to the occurrence of metastasis is 19 months for bone metastasis, 35 months for lung metastasis, and 60 months for brain metastasis. (22,23) The long time between diagnosis and brain involvement strongly favors the cascade theory of tumor spread. (16)

The most common intracranial sites of prostate cancer metastasis are the leptomeninges (67 percent), cerebrum (25 percent), and cerebellum (8 percent). (14)

SYMPTOMS
Patients rarely present with neurologic symptoms as the first manifestation of prostate cancer. Presentation with a solitary brain metastasis as the only site of prostate cancer spread is even more rare. (17)

DIAGNOSIS

No test other than gadolinium-enhanced MRI is required to exclude or confirm the presence of brain metastases. Compared with CT scanning, MRI is more sensitive in detecting multiple metastases, especially at the gray-white junction. (18)

TREATMENT
Unless seizures occur, the use of prophylactic anticonvulsants, particularly phenytoin (Dilantin), is not encouraged.19,20 In combination with radiotherapy, phenytoin may cause Stevens-Johnson syndrome (erythema multiforme major). (20) Dexamethasone therapy should be started early.

A two-week course of radiotherapy is the most common treatment for men with multiple brain metastases or leptomeningeal involvement. Surgical removal of a solitary lesion usually extends survival. (21)

Various stereotactic radiosurgical techniques, including the proton beam, gamma knife, linear accelerator (LINAC) X-knife and multileaf collimators with intensity modulators, can be used. Because these modalities provide a precise beam of radiation, damage to surrounding normal tissue is limited. (22)

Brain metastasis is associated with a poor prognosis. Once prostate cancer has spread to the brain, the one-year survival rate is 18 percent, with an average survival of 7.6 months. (6,29)
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REFERENCES
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Am Fam Physician. 2002 May 1;65(9):1834-1841. RAMSIS BENJAMIN, M.D., M.P.H., Keck School of Medicine of the University of Southern California, Los Angeles, California

Joel Nowak, M.A., M.S.W.