With the aging of the population and the widespread use of prostate specific antigen (PSA) as a screening test for prostate cancer, there has been an increasing awareness of the prevalence of this disease. Many cases are now diagnosed at an early stage and have an excellent long-term survival. However, prostate cancer varies widely in its presentation and growth rate. It may respond to treatment, even when widespread, and can be cured when it is localized. The following case makes many illustrative points.

Case Report

A 64-year-old African-American man presented to a community hospital emergency room with inability to walk of several hours' duration. He had previously gone to the hospital clinic, where he reported a two to three-month history of anorexia, a 30-pound weight loss, urinary frequency, nocturia and back pain. His initial evaluation in the clinic included detection of a mildly enlarged prostate gland on digital rectal exam and a markedly elevated PSA of 106 ng/ml (normal 0-4) suggesting possible prostate cancer. A total body bone scan showed multiple areas of increased activity throughout the ribs, skull, sternum, thoracic and lumbar spine, pelvis and right femur consistent with extensive bone metastases. A CT scan of the abdomen and pelvis confirmed the mildly enlarged prostate and a probable enlarged lymph node (2 cm) in the right side of the pelvis. Trans-rectal needle biopsy of the prostate was negative for malignancy. During the two weeks prior to his admission via the emergency room, he noticed progressive lower extremity weakness.

In the community hospital emergency room on the day of admission, he was found to have bilateral lower extremity weakness (2/5 motor strength) and urinary retention. He was treated with high-dose i.v. dexamethasone, an H₂-blocker (to protect the GI tract against the adverse effects of high dose dexamethasone) and a urinary catheter and transferred to the medical center.

Physical and Laboratory Findings

At the medical center, physical exam revealed a thin male with flaccid paraparesis, temporal muscle wasting, a firm prostate gland with a palpable nodule but no other pertinent findings. Initial laboratory findings were: Hct 25%, WBC 5.0 x 10⁹/L, with 66 segmented forms, 1 band, 25 lymphocytes, 6 monocytes, 1 metamyelocyte, 1 myelocyte and 7 nucleated red blood cells. Platelet count was normal at 184 x 10⁹/L. The reticulocyte count was 0.8%.

Chemistries included a serum creatinine of 0.8 mg/ml, LDH 1369 U/L (normal 110-225), GGT 86 U/L (Normal 1-45), alkaline phosphatase 1839 U/L (35-110), CPK 1437 U/L (24-195), albumin 4.3 g/dl (3.9-4.8) and a total bilirubin of 0.8 (0.2-1.3). Chest X-ray showed clear lung fields and sclerotic rib lesions. Lumbar x-rays revealed multiple metastases to lumbar vertebrae. An emergency MRI scan of the spine with gadolinium revealed diffuse osteoblastic metastases with extradural extension involving the cord at T6, T7, T8 and T12 without conus involvement. An extension at the L4 level reached the cauda equina on the left side.

Treatment

Since the entire clinical picture was most consistent with metastatic prostate cancer, he was started on hormonal therapy and radiation therapy to the involved spine on the day of transfer. The hormonal manipulation consisted of flutamide (Eulexin^®) 250 mg P.O. T.I.D. and ketoconazole 400 mg P.O. T.I.D.

During the first few weeks of radiation treatment, his neurologic condition improved slightly to 3/5 motor strength. He then underwent ultrasound-guided needle biopsy of right and left lobes of the prostate, revealing areas of poorly, moderate and well differentiated infiltrating adenocarcinoma. After discussions regarding treatment options, he decided on a bilateral orchiectomy that was performed nine days after admission. He received a total of 3500cGy of radiation to the spine.

His treatment was complicated by fever because of a urinary tract infection, anemia and neutropenia. The infection required antibiotic treatment. The anemia required transfusion and erythropoietin (Procrit^®). The neutropenia was treated with granulocyte colony stimulating factor (Neupogen^®). He was discharged to a nursing home, ambulating with a walker. The PSA decreased to 1.7 ng/ml from its peak level of 131. He no longer had pain and the hematocrit rose to 31.5% after three months. He later underwent a transurethral resection of the prostate for persistent urinary obstruction.

Discussion

Prostate cancer is predominantly seen in older men. The disease may be curable when it is localized but even widespread disease usually responds to treatment. PSA screening has led to the detection of many cases at an early stage where treatment can be curative but where it is uncertain that the disease would progress, even if untreated. However, because a high percentage of tumors identified by PSA screening alone has spread outside the prostate, PSA screening may not improve life expectancy. The appropriate use of screening is still controversial.(1),(2) A multicenter trial sponsored by the National Cancer Institute is underway to test the value of early detection on reducing mortality.(3)

This patient's course is typical of an individual who has had no screening and whose cancer is detected because of symptoms. Looking back on his course, it would have been wise to do an imaging study of his spine when he had evidence of metastatic cancer on bone scan, even though the initial prostate biopsy was negative. Needle biopsy is always subject to sampling error and a negative biopsy does no rule out cancer.(4)

Spinal cord compromise is a common but infrequent complication of metastatic prostate cancer. The presence of back pain should immediately raise a physician's level of suspicion and lead to prompt diagnostic intervention with immediate treatment if the suspicion is confirmed. Immediate treatment, as opposed to watchful waiting, is warranted even in an asymptomatic patient.(5)

Spinal cord compression is an oncologic emergency requiring immediate imaging of the spine (MRI or CT-myelogram) and consideration of either radiation or neurosurgical intervention. In this case, radiation was preferred due to the multiple sites of extradural extension. The initial management includes high-dose dexamethasone up to 100 mg IV stat and 10 mg IV every 6 hours. The use of high-dose steroids should be accompanied by the use of an H₂-blocker (e.g., ranitidine or famotidine).

Medical treatment may be started immediately. However, a luteinizing-releasing hormone agonist (LHRH-agonist) may be detrimental if there is spinal cord compression or urinary obstruction since there can be an initial flare of the disease. Therefore, androgen ablation with an antiandrogen (flutamide) and ketoconazole can be instituted, initially, which will not produce disease flare. Ketoconazole is an antifungal agent, which, at high doses, effectively blocks both testicular and adrenal androgenesis.

Once radiation therapy has been instituted and neurologic improvement noted, then medical suppression of testicular function can be considered with an LHRH-agonist (with or without the addition of an antiandrogen). However, the simplest, least expensive and most definitive way to achieve androgen ablation is still surgical castration. For patients with metastatic disease, treated with orchiectomy, a reasonable guideline for follow-up is a history, physical examination and PSA analysis every three months.(6)