Keywords
brain metastases - carcinoma prostate -
68Ga PSMA PET/CT scan - hormonal therapy
Introduction
Prostate cancer (PC) is primarily a disease of the elderly with more than three quarters
of the cases occurring in men older than 65 years. The most common metastatic sites
for PC are the bones (84%), distant lymph nodes (10.6%), liver (10.2%), and lungs.
Brain parenchymal metastases from PC are uncommon probably because of the blood–brain
barrier that acts as a protective mechanism. The majority of intracranial prostatic
metastases involve the dura mater.[1]
Studies have shown the incidence of brain metastases in PC to be 0.16%.[2] Here, we present the case of a 67-year-old man with PC, who underwent radiotherapy,
maintained on hormonal therapy, with raising serum prostate-specific antigen (Sr PSA)
levels and underwent gallium-68 prostate-specific membrane antigen positron emission
tomography/computed tomography (68Ga PSMA PET/CT) scan for evaluation.
Case Report
A 67-year-old gentleman, who was nondiabetic and nonhypertensive, presented with increased
frequency of urination. On evaluation, the patient was found to have adenocarcinoma
prostate (Gleason score: 4 + 5 = 9). He later underwent radical RT, and was maintained
on hormonal therapy with abiraterone. The patient was treated with multiple lines
of chemotherapy, initially with six cycles of docetaxel and later bicalutamide with
leuprolide. This progressed to leuprolide too, so he was started on enzalutamide.
The Sr. PSA levels increased from 2.59 to 3.5 ng/mL on enzalutamide and later to 5.8
ng/mL. Also, the patient had complaints of occasional diffuse headache. The patient
was advised 68Ga PSMA PET/CT scan in view of rising Sr. PSA levels and complaints of headache.
Imaging Studies
68Ga PSMA PET/CT scan revealed enhancing lesions in the left cerebellar hemisphere,
largest approximately 20 × 16 mm, with perilesional edema and minimal PSMA uptake.
Also, the prostate gland was measured 29 × 22 mm with focal intense PSMA uptake in
the seminal vesicle at midline corresponding to subtle enhancing lesion abutting the
posterior wall of the urinary bladder (∼ 10 × 9 mm; [Fig. 1]).
Fig. 1 F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) computed tomography
(CT) maximum intensity projection (MIP) image (A) and axial CT (B,C,F) and fused PET CT (D,E,G) images showing mildly prostate-specific membrane antigen (PSMA) avid enhancing metastatic
lesions in the left cerebellum (yellow arrows) and PSMA avid enhancing soft-tissue density in the primary lesion in the prostate
gland (black arrows).
Three days later, the patient underwent magnetic resonance imaging (MRI) of the brain
with contrast that revealed ill-defined heterogeneously enhancing T1-weighted hypointense
with T2-weighted/fluid attenuated inversion recovery (FLAIR) hyperintense lesions
with mild perilesional edema in the left cerebellar hemisphere, the largest measuring
18 × 10 × 9 mm. Magnetic resonance spectroscopy (MRS) also suggested cerebellar metastases.
Mild enhancement was noted along the right cerebellar folia, suggestive of leptomeningeal
carcinomatosis ([Fig. 2]).
Fig. 2 Axial magnetic resonance (MR) images of (A,B) T1, (C,D) T2, and (E,F) fluid attenuated inversion recovery (FLAIR) sequences showing ill-defined heterogeneously
enhancing T1-weighted hypointense with T2-weighted/FLAIR hyperintense lesions with
mild perilesional edema in the left cerebellar hemisphere.
The patient later underwent palliative whole brain radiotherapy (WBRT) of 10 fractions
and total dose of 30 Gy. On follow-up, the Sr. PSA levels came down to 0.1 ng/mL.
Discussion
Brain metastasis is seen in 30% of solid cancer cases during the course of the disease
in their lifetime.[3]
[4] They are commonly seen in cancers of the lung, breast, colon, kidney, and melanoma,
and brain metastasis from prostatic cancer, especially adenocarcinomas, is extremely
rare.[5]
PC is the second most common cancer in males. Approximately 99% of PC cases are prostate
adenocarcinomas, while other rare subtypes include squamous cell carcinoma, small
cell carcinoma, stromal neoplasms, and neuroendocrine carcinoma, and lymphomas.6 PC primarily metastasized into the bone and lymph node. The incidence of brain metastasis
from prostate carcinoma was found to be 0.16%.[2] In the cases with systemic metastases, it was 0.38%. Interestingly, rare subtypes
of PC metastasize into atypical sites, and the incidence of brain metastasis is much
higher than adenocarcinoma.[6] In spite of this, it is still uncommon. A retrospective study conducted by Tremont-Lukats
et al in 15,397 PC patients revealed that intracranial metastasis from prostate adenocarcinoma
occurred in 0.7% of patients and in 15.8% patients in case of prostate small cell
carcinoma (6/38).[7]
Unlike other cancers, which present more likely as intraparenchymal metastases, dural
metastasis is the most common site in case of PC. Because of the tendency to penetrate
the dura mater and extend in the extradural or subdural space, these lesions could
be mistaken for meningiomas, subdural hematomas, or abscesses on imaging.[5]
The incidence of ante mortem diagnosed isolated brain metastases is extremely rare
with less than 17 cases documented. Only one of these cases had isolated cerebellar
metastases. Our case shows a lesion on 68Ga PSMA PET/CT in the left cerebellar hemisphere, which was suspected to be metastases
based on the MRI characteristics.[8]
Differentiating primary brain lesions from metastatic PC can be challenging, especially
when a solitary lesion is present. Specific MRI characteristics from metastatic PC
have not been well established in the literature; however, some reports describe hemorrhagic
brain metastasis, mixed cystic, solid, or ringlike appearances on MRI. Hemorrhagic
brain metastasis is more consistent with renal cell carcinoma, melanoma, choriocarcinoma,
breast cancer, or thyroid cancer.[9]
Symptoms and Treatment of Brain Metastasis in Prostate Cancer
Symptoms and Treatment of Brain Metastasis in Prostate Cancer
Metastasis to the brain is rare and is usually associated with vague symptomatology
depending on the extent and location of the lesion. Most of the patients with brain
metastases in PC are generally asymptomatic, making it even more difficult to diagnose,
unless the patient experiences neurological manifestations. Symptomatic patients show
clinical manifestations that vary with the site of the metastatic focus, including
headache, seizures, and focal neurological deficits, in addition to some frequent
nonfocal manifestations such as confusion and memory deficits. Isolated brain metastasis
is generally treated with craniotomy and resection, followed by radiation therapy
with WBRT.[10] Similarly, WBRT was given in our case.
Prognosis
The median overall survival of our patients with brain metastases originating in PC
was 2.8 months after the diagnosis of brain metastases by imaging, with a 1 year overall
survival rate of 9.5%. After detecting brain metastasis among published PC cases,
the survival time was reported to range between 2.8 and 4.5 months. Treatment approaches
used for PC brain metastasis are the same as other brain metastases, including corticosteroids
use, surgery, and radiotherapy, in addition to stereotactic radiosurgery in case of
recurrent cases. Such approaches prolong the patient's survival time.[5] Bhambhavni et al conducted a retrospective 10-year study of 31 brain metastatic
PC patients. They found that patients who were treated with stereotactic radiosurgery
versus radiotherapy plus surgical resection had a median survival time of 4.6 vs.
13 months, respectively.[10]
Conclusion
Brain metastases in PC is rare. Isolated brain metastases are even more sparse. Gadolinium
contrast MRI helps in diagnosing brain metastases and differentiating similar conditions
that mimic metastases. The prognosis of these patients appears poor. However, with
the advancement in management techniques, a better survival may be possible. In spite
of newer radiotracers and imaging modalities, reporting of brain metastases in PC
is less, and is required for further discussion and understanding the disease process
and management.
