Neuropathy Associated with Prostate Cancer

To the Editor:

Peripheral neuropathies can occur in conjunction with malignancies from both metastatic and nonmetastatic processes. Peripheral neuropathy most commonly occurs in association with carcinoma of the lung, but it may also occur with primary tumors of the stomach, colon, and breast [1]. Less frequently, neuropathy has been reported to occur secondary to carcinoma of the rectum, pancreas, uterus, cervix, kidney, thyroid, prostate, and testis [1].

Before making the diagnosis of carcinomatous peripheral neuropathy, one must exclude other causes of peripheral neuropathy, such as diabetes mellitus, nutritional deficiencies, neurosyphilis, toxic conditions, alcoholism, collagen vascular disease, and plasma cell dyscrasias. In addition, one must be aware that a patient can present with neuropathy caused by a malignancy that has not yet been diagnosed. Identifying a malignancy depends both on obtaining a thorough history and performing a good physical examination and on diagnostic studies including magnetic resonance imaging, computed tomography, laboratory testing, and electrodiagnostic studies. Only once the physician has a complete medical understanding of the patient can a diagnosis of carcinomatous neuropathy be entertained.

Carcinomatous neuropathy can take the form of either sensory or mixed sensory and motor neuropathy, with the latter being more common. The predominant symptoms of sensory neuropathy are numbness, dysesthesia, and paresthesia of the extremities that spread proximally. In a study by Pettigrew et al [2], all patients with metastatic disease had pain that was described as a continuous “stabbing” or “burning” sensation. The symptoms of carcinomatous neuropathy can precede those of the tumor by as much as 3.5 years; however, the temporal relationship of the neuropathy to the carcinoma is inconsistent. Neuropathic signs can occur simultaneously with the signs of cancer or begin in the later stages of the illness. The onset is most commonly subacute, with progression occurring over several months. In rarer cases, there may be an acute onset over a period of several hours.

On physical examination, there is a sensory loss in the extremities, with only occasional involvement of the trunk and face. Position and vibratory sensation are usually severely impaired. The deep tendon reflexes may also be diminished. Owing to sensory ataxia, unsteadiness of gait may be present. The neuropathy can be either symmetrical or asymmetrical with some degree of muscle weakness and wasting.

In patients with a sensorimotor neuropathy secondary to prostate cancer, electromyogram studies show denervation with spontaneous fibrillation, reduction in the number of motor units, and an increased number of polyphasic units in the distal muscles.

Case Report

A 73-year-old man presented with a chief complaint of burning and tingling on the plantar aspects of both feet of 1 year’s duration. The patient stated that the burning was always present. At the time of presentation, the patient also complained of low back pain, which he attributed to monthly leuprolide acetate injections given in the lower back as a treatment for prostate cancer. The patient’s medical history was positive for metastatic prostate cancer and hypertension. The cancer was diagnosed approximately 6 months before the onset of neuropathy. Current medications included nifedipine taken orally and leuprolide acetate administered intramuscularly. The patient also received radiation therapy for several months after the diagnosis of prostate cancer.

Physical examination revealed dry and scaling skin on the dorsal and plantar aspects of both feet. The neurologic examination showed a moderate decrease in vibratory sensation bilaterally. Although the patellar reflex was normal, the Achilles deep tendon reflex showed hypotonicity. Sharp/dull sensation and position sense were both mildly decreased in the distribution of the medial and lateral plantar nerves. The patient walked with a cane owing to instability during the stance phase of gait. The patient was suspected to have neuropathy secondary to metastatic prostate cancer.

Laboratory tests revealed the following abnormal results: red blood cell count 2.7 × 10¹²/L (normal range, 5 to 6 × 10¹²/L), hemoglobin 9.2 g/dL (normal range, 14 to 18 g/dL), hematocrit 26.3% (normal range, 42% to 52%), and potassium 5.4 mEq/L (normal range, 4 to 5 mEq/L). Follow-up laboratory studies showed that the patient’s potassium levels had normalized. Although the laboratory results are consistent with possible anemia, which can also be a cause of neuropathy, subsequent magnetic resonance imaging (MRI) confirmed the diagnosis of neuropathy secondary to metastatic prostate cancer. The MRI scan showed a cord lesion that was causing compression at the sensory level between S1 and S5.

The patient was treated with capsaicin cream and amitriptyline, 50 mg at bedtime. After 1 week of treatment, the patient noticed improvement in the burning sensation and demonstrated improvement in balance when walking. Approximately 3 months after beginning amitriptyline therapy, cord decompression surgery was performed. The decompression did not relieve the symptoms of neuropathy, and the patient was continued on amitriptyline therapy.

Discussion

Neuropathy associated with carcinoma has most commonly been found with cancer of the lung; very rarely has it been found with prostate cancer. In this case, it was not determined whether the neuropathy was due to a lesion causing compressing of the spinal cord or whether there was a lesion that had infiltrated into the nerve proper, causing damage.

Amitriptyline, a tricyclic antidepressant, has been used alone or with other drugs for the treatment of pain encountered with diabetic neuropathy [3,4]. The mechanism of this analgesia is not known, although several have been proposed, including modulation of alpha-receptor activity, increased cortical inhibition of sensory input, and an increase in the activity of the reticular system of the brain stem [3,4,5]. Amitriptyline was given to this patient because of the reported benefit of the drug in cases of diabetic neuropathy.

The podiatric physician should be aware of carcinoma when attempting to identify the cause of peripheral neuropathy. A detailed history and physical examination with appropriate diagnostic testing will allow the physician to entertain various possibilities, including the presence of cancer.