2516

Brain Stem Metastasis as the Only Site of Spread in Prostate Carcinoma A Case Report

A n u Gupta, M.D., Said Baidas, M.D., and Richard K. Cumberlin, M.D.

Metastasis to the brain from prostate carcinoma is a rare event, having been reported in less than 5% of postmor- tem examinations. The incidence of cases detected ante- mortem is even smaller, and the incidence of brain me- tastasis as the only site of metastasis has been reported in only one other case. The authors present a second such case of a patient with a Stage C adenocarcinoma of the prostate that metastasized to the brain stem; this was the only site of spread. Cancer 1994;74:2516-9.

Key words: prostate neoplasm, adenocarcinoma, brain metastasis, prostate specific antigen.

Parenchymal, nonosseous intracranial metastases from prostate adenocarcinoma are rare, having been reported in fewer than 5% of some large autopsy series.' The most recently reported number of cases of brain metas- tases at autopsy has been 25, with an additional 15 case reports of such metastases diagnosed antemortern.' In addition, patients with autopsy evidence of intracranial metastases are likely to have widespread, advanced dis- ease in other sites. We report a patient with a solitary brain stem metastasis as the isolated site of spread from adenocarcinoma of the prostate and present a review of the literature. In the rare instances of antemortem diagnosis of brain metastases, patients have had pre- viously known metastatic disease for several years before manifestation in the brain. This is the second reported case of an isolated brain metastases from pros- tate carcinoma.

Case Report

In November 1991, a 55-year-old man experienced rectal pain for which he sought medical attention. On rectal examination,

From Georgetown University Hospital, Washington, DC. Address for reprints: Anu Gupta, M.D., Resident, Department

of Radiation Medicine, LL Bles Building, 3800 Reservoir Road, Wash- ington, DC 20007.

Received April 5,1994; revision received June 17,1994; accepted July 5, 1994.

the patient's prostate was tender, and he was referred to an urologist. He specifically denied symptoms of dysuria, pyuria, hematuria, or difficulty with his urinary stream. A prostate specific antigen (PSA) was drawn at that time and noted to be 11.5 ng/ml (normal range, 0-4 ng/ml). The patient un- derwent a transrectal ultrasound with biopsy, which revealed adenocarcinoma, Gleason's Grade 7 (4 + 3). A bone scan, computed tomography scans of the abdomen and pelvis, and chest X-ray were negative. The patient subsequently un- derwent a modified radical nerve-sparing prostatectomy.

Pathologic review of the surgical specimen showed diffuse penetration of the posterior and posterolateral capsule on the right side and the posterior capsule on the left side. The tumor focally extended to the right posterior margin and involved the proximal urethral margin and the right and left seminal vesicles. Surgical margins were noted to be positive. The pathologic report was consistent with well differentiated adenocarcinoma. Nodal sampling was negative. A postopera- tive PSA was 0.1 ng/ml.

The patient underwent a course of radiation therapy to 6120 cGy using a 360-degree rotational arc technique to 4500 cGy in 25 fractions and a dose of 1620 cGy using bilateral 120-degree arcs. Thc patient completed radiation therapy in September 1992,9 months after his initial symptoms. His PSA at the beginning of radiation therapy was 0.03 ng/ml, and 2 months after completion of therapy, it was 0.02 ng/ml.

He did well until November 1993, at which time he noted he had a tendency to "lean to the right," felt a fullness in his face, and had headaches that were ill defined. Physical exam- ination at that time was unremarkable. Notably, cranial nerves were grossly intact, reflexes were normal, gait was in- tact, and there was no evidence of papilledema. No bony ten- derness was noted. He underwent a magnetic resonance im- aging scan (Fig. I), which showed an enhancing mass mea- suring 2 cm X 3 cm in the left pons/left cerebral peduncle. The patient underwent a stereotactic biopsy at that time, which showed poorly differentiated adenocarcinoma. Computed to- mography scans of the abdomen, pelvis, and lung were nega- tive. A bone scan also was negative. A serum PSA at this time was 1 .OO ng/ml. lmmunohistochemical staining of the biopsy specimen was strongly positive for PSA.

Thus, this is a patient with a Stage C adenocarcinoma

Solitary Brain Stem Metastasis in Prostate Cancer/Gupta et al. 2517

Figure 1. MRI showing a 2 cm mass in the left pons/left cerebral peduncle.

of the prostate who, 1 year after radical prostatectomy and external beam radiation, has a solitary brain stem metastasis as the only site of spread. Because of the location of the lesion, surgical intervention was not an option. He was treated with a palliative course of external beam radiation therapy to the whole brain and brain stem with reduced fields. The patient is considering the use of hormonal therapy. His most recent PSA, drawn 2 months after external beam radiation therapy, was 2.9 ng/ml. He has no residual neurologic symptoms but has nonspecific gastrointestinal symptoms.

Discussion

Symptomatic brain metastasis from adenocarcinoma of the prostate is rare. The signs and symptoms of brain metastases are similar to those of vascular obstruction, and mistakes in the diagnosis may occur.’ Symptoms cannot be differentiated from metastatic lesions attrib- utable to other causes. Sarma and Godeau3 report the most common symptoms associated with metastatic prostate carcinoma to be motor dysfunction, headache, and seizure. Leptomeninges are the most common site of intracranial involvement (67%), but until significant growth has occurred to cause increased intracranial pressure, the involvement may remain silent. The next most common site is the cerebrum (25%), followed by cerebellum (8%). Cerebellar metastasis has been re- ported in only five patients. In contrast, cancer from other sites usually spreads to the cerebrum (84%), the cerebellum (9”/0), dura (6%), and pituitary (l?’~). Spe- cifically, brain stem metastases from various primary sites were seen in approximately 3% of brain metasta-

ses, as noted by Posner and Chernik.4 One also must differentiate skull-based lesions extending into the brain parenchyma from a nonosseous, parenchymal le- sion, which is the more common route of intracranial spread in prostate carcinoma.

Taylor et al.5 reported results from 126 autopsy cases of prostate carcinoma. Fourteen cases showed in- tracranial metastases. Nine of the 14 cases had Stage C or D disease, suggesting that patients with advanced or poorly differentiated malignancies may have intracran- ial metastases more often than has been suspected. Ta- ble 1 is modified from Lynes et a1.’ and shows the inci- dence of brain metastases in autopsy series of prostatic adenocarcinoma.

No study has examined the clinical significance of isolated brain metastases from prostate cancer. The treatment options for brain metastasis from any malig- nancy include external beam radiation therapy surgery for a few, small lesions, or radiosurgery. However, the clinical significance of lung metastases in prostate can- cer has been examined in a report by Varkarakis et a1.6 The course of lung metastases in prostatic carcinoma does not appear to be dependent on the clinical staging of the primary prostatic lesions or on the interval be- tween the first diagnosis of the disease and its detection. However, most patients with lung metastases also have bone involvement. Whether one can extrapolate this to brain metastases is unclear. Thus, brain metastasis from adenocarcinoma of the prostate is a rare event, and a brain stem metastasis as the sole area of spread is more unusual.

From the small number of reported patients, one would anticipate this patient to have a poor prognosis despite treatment. There are little data on the best treat- ment for metastatic brain lesions. Patients who undergo

Table 1. Parenchymal Brain Metastases in Autospy Series of PC

No. of autopsy No. of cases of Series patients with PC PC brain mets

Krasting 18 1 Rao 23 0 Mintz and Smith 100 1 Earle 159 0 Earle 89 0

Franks 53 0 France 51 2 Catane 211 4 Sarma and Godeau 121 2

Totals 841 11 (1.3%)

Lesse and Netsky 16 1

PC: urostatic adenocarcinoma

2518 CANCER November 1,1994, Volume 74, No. 9

a craniotomy appear to have a better survival, but the data are scant. In an examination of 101 surgically treated patients with brain metastases from various sites, Kishi et aL7 found an overall 1-year survival of 18%. Chung and Thannikkary' reported survival after brain metastasis was short (7.6 months), but two of four patients who receive whole brain external beam radia- tion therapy survived more than 1.5 years. This rela- tively long survival may be attributable to the slow pro- gression of the disease.

The diagnosis of brain metastases is made, on the average, 60 months after the prostatic primary. This generally is preceded by metastatic disease elsewhere. In contrast, bone metastases are noted 19 months after diagnosis and lung metastases at 35 months.

Metastatic spread from any type of malignancy occurs from direct extension (the one-step process) or from cells that have grown in metastatic sites (the multistep or cascade process). Batson' suggested that retrograde blood flow in the system of epidural and vertebral veins and their extensive anastomotic com- munication with the veins of the thoracic and abdom- inal cavities may be a route of central nervous system metastasis. He stated that the pressure in these veins was low and that a Valsalva maneuver might increase the pressure enough to reverse flow from the inferior vena cava to the vertebral venous plexus. This plexus could allow metastatic cells to reach the central ner- vous system without first passing through the lungs. Cancer cells may reach the central nervous system via the arterial circulation. Three other explanations of spread are given by Baker.'" First, tumor emboli might pass via the wide capillaries of the lung directly to the left side of the heart for arterial distribution. Second, pulmonary lesions might be so small that they would be overlooked even on microscopic sections. Finally, Baker describes "paradoxical embolism," whereby tumor cells might pass through a patent foramen ovale to the left side of the heart.

Since the early 1940s, endocrine manipulation and androgen deprivation have become the accepted meth- ods of treating patients with metastatic disease. Since their discovery, the treatment for advanced prostate cancer has been predicated on modalities that inhibit the production or action of testosterone. Bilateral orchi- ectomy removes more than 95% of the circulating tes- tosterone and is considered the gold standard to which other forms of treatment are compared. Estrogen, in the form of diethylstilbestrol (DES), also has been used to produce castration levels of testosterone. However, DES is associated with numerous well known side effects, such as thrombosis, pulmonary embolus, and myocardial infarction.

Luteinizing hormone releasing hormone (LHRH) was isolated in 1971. Long-term administration of LHRH agonist will desensitize the pituitary, with sub- sequent suppression of luteinizing hormone (LH). Sup- pression of LH causes a decrease of testosterone pro- duction to castrate levels. Leuprolide and goserelin are the two LHRH analogues approved for use in the United States.

Numerous studies have been completed world- wide, and most support the conclusion that the LHRH analogues are comparable to, but not superior to, or- chiectomy or estrogen administration. For example, the Leuprolide Study Group" conducted a random- ized, unblinded, prospective trial of 199 patients with carcinoma of the prostate with bone metastases, lymph node metastases, or metastases to other soft tissue. Ninety-eight patients were assigned to leu- prolide therapy and 10 1 to DES therapy. The results showed progression and survival to be similar in both groups, but more side effects were seen in the group receiving DES.

More recently, flutamide, a nonsteroidal antiandro- gen that inhibits the binding of androgens to the cell nucleus, has been used with leuprolide to provide max- imum androgen blockade. Current data suggest that flutamide has substantial antitumor activity when ap- plied as a first-line treatment for patients with meta- static cancer of the prostate.12 In a recent double- blinded study by Crawford et al.,I3 leuprolide alone and leuprolide with flutamide were compared in 603 pa- tients with Stage D2 carcinoma of the prostate who were randomized to receive leuprolide and flutamide or leuprolide only. The results showed an increase in pro- gression free survival and overall survival by 27% in the leuprolide and flutamide group.

In conclusion, the failure of patients to benefit from treatment underscores the importance of understand- ing mechanisms of dissemination. For the rare patient with brain metastasis from prostate cancer, the outlook appears to be poor. Radiation therapy and surgery are standard treatment options for brain metastases. Whether or not the use of hormonal therapy will benefit these patients is uncertain.

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