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Brain metastasis from prostate carcinoma: The M. D. Anderson Cancer Center experience
Cancer
Abstract
The objective of this study was to estimate the incidence and describe distribution, clinical presentation, and prognosis of brain metastases in patients with prostate carcinoma who were seen at The University of Texas M. D. Anderson Cancer Center (MDACC).
The authors reviewed the charts of 16,280 patients with prostate carcinoma in the MDACC patient data base. Of 131 patients with craniospinal metastases confirmed by neuroimaging (n=53 patients) or autopsy (n=78 patients), 103 of 16,280 patients (0.63%) had parenchymal metastases.
The median patient age at diagnosis was 64 years (range, 16-85 years). The median interval from the diagnosis of prostate carcinoma to the detection of brain metastasis was 35 months for patients with adenocarcinoma and 48 months for patients with small cell carcinoma (SCC). Confusion, headache, and memory deficits were the most frequent initial symptoms. Eighty-six percent of patients had single lesions, and 14% of patients had > or = 2 lesions. Metastases were supratentorial in 81 of 103 patients (76%), infratentorial in 22 of 103 patients (21%), and both supratentorial and infratentorial in 3 of 103 patients (3%). SCC and cribriform subtypes were more likely than adenocarcinoma to metastasize to the brain (relative risk, 20.36; 95% confidence interval, 9.91-41.84). Regardless of histology, the median survival in untreated patients was 1 month compared with 3.5 months in patients who were treated with radiotherapy. Patients who underwent stereotactic radiosurgery (n=5 patients) had a longer median survival (9 months). Survival was not affected by supratentorial or infratentorial location of metastases.
Brain metastasis from prostate carcinoma is a rare, terminal event with death in <1 year frequently due to advanced, systemic disease. The majority of metastases were single and supratentorial. The most common clinical presentation was nonfocal neurologic symptoms related to intracranial hypertension. A better understanding of the biology of prostate carcinoma will help clarify the basis for its metastasis to the brain.
... However, considering the epidemiology of malignant lesions in the prostate, small cell carcinoma and cribriform subtypes were more likely than adenocarcinoma to metastasize to the brain. However, the cribriform subtype of which tumor is mentioned here is unclear [13]. All patients in their study have a Table 1 Demographic data and histologic features of metastatic prostatic adenocarcinoma. ...
... The same is true for PSAP, where more than 20% metastatic prostate carcinomas lose staining with it and staining intensity is also reduced in positive staining cases [16]. The most frequent reported initial neurologic symptoms caused by intracranial metastases are confusion, headache, and memory deficits [13]. Symptoms can vary from progressive language difficulties and mixed dysphasia to hemiparesis [6]. ...
... From 1944 to 1998, the median survival in untreated patients with brain metastasis was 1 month compared with 3.5 months in patients who were treated with radiotherapy. Patients who underwent stereotactic radiosurgery had a longer median survival (9 months) [13]. McCutcheon et al., in their study from (1980)(1981)(1982)(1983)(1984)(1985)(1986)(1987)(1988)(1989)(1990)(1991)(1992)(1993)(1994)(1995)(1996)(1997)(1998), had a median survival of 4 months and a mean survival of 6 months if they were treated with radiation therapy [17]. ...
Background
Brain metastasis from prostate adenocarcinoma (PCa) is rare, often leading to death within a year. Its infrequent occurrence and atypical histopathologic features contribute to lower consideration in the differential diagnosis of tumor brain metastasis. This study aims to assess the clinical characteristics and distinctive histopathologic features of metastatic PCa in the brain for timely and enhanced diagnostic accuracy.
Design
A retrospective search spanning 20 years (2003–2022) was conducted on our archives and identified 21 cases diagnosed as “metastatic prostate adenocarcinoma (mPCa)” in brain biopsies and resections. All existing slides were thoroughly reviewed to evaluate the histopathology of the mPCa.
Result
The mean age at presentation for brain metastasis was 70 years. Of 21 cases, 5 were dural-based lesions, 16 were true intraparenchymal metastases, including 2 sellar/suprasellar masses, 3 frontal, 3 temporal, 3 occipital, 1 cerebellum, and 4 involving multiple brain lobes. The average interval between initial diagnosis and brain metastasis was 90.75 months. Notably, brain metastasis was the initial presentation for one patient, while another patient, initially diagnosed with prognostic grade group (GG) 2 PCa in 1/12 cores, presented with isolated brain metastasis two years later. Architecturally, tumor cells were arranged in sheets or nests in most cases; however, four cases showed histologic cribriform patterns, and five displayed papillary architecture. Cytohistology varied from uniform monomorphic to highly pleomorphic cells with prominent nucleoli (8/19) and high mitotic activity. Interestingly, 1 case showed small round blue cell morphology, another had focal areas of rhabdoid and spindle cell differentiation, and 6 had cytoplasmic clearing. Almost half of the cases (47%) showed necrosis.
Conclusion
mPCa to the brain can present with variable histomorphology. Therefore, consideration of mPCa in the differential diagnosis of metastatic brain lesions, even with non-suggestive imaging, is imperative in male patients with or without a history of primary disease. Accurate and prompt diagnosis is crucial, given the recent advancements in treatment that have improved survival rates.
... Prostate cancer is one of the most common malignancies among men worldwide and it usually metastasizes to the bone, lungs, and liver [1][2][3][4][5][6]. Central nervous system (CNS) involvement is rare, and generally manifests as a single lesion, later in the course of the disease [1][2][3][4][5]7]. ...
... Prostate cancer is one of the most common malignancies among men worldwide and it usually metastasizes to the bone, lungs, and liver [1][2][3][4][5][6]. Central nervous system (CNS) involvement is rare, and generally manifests as a single lesion, later in the course of the disease [1][2][3][4][5]7]. Adenocarcinoma is the most frequent histologic subtype based on its incidence rate but the proportion of brain metastasis is higher in other uncommon histologic subtypes such as small cell carcinoma [1][2][3]. ...
... Central nervous system (CNS) involvement is rare, and generally manifests as a single lesion, later in the course of the disease [1][2][3][4][5]7]. Adenocarcinoma is the most frequent histologic subtype based on its incidence rate but the proportion of brain metastasis is higher in other uncommon histologic subtypes such as small cell carcinoma [1][2][3]. The clinical presentation is predominantly non-focal in most cases, either accompanied by headache, dizziness, behavioral alterations, and memory loss or asymptomatic [1,2,7]. ...
Brain metastasis in prostate cancer is quite a rare entity, especially when it manifests at diagnosis. The symptoms are usually non-focal and vary based on the location affected. It is almost always associated with a poor prognosis, with an overall survival of less than a year. The ideal management modality for these patients is not well established but a combination of surgery, radiation, and chemotherapy may be possible options based on the extent and systemic involvement. Brain screening is not done systematically in prostate cancer and more research is needed to understand the outcome this decision would lead to. We report a case of a patient diagnosed with prostate cancer with single metastasis to the brain that manifested as headache and vomiting. The patient was treated with surgery, adjuvant irradiation of the surgical bed, and androgen deprivation therapy. He later underwent intensity-modulated radiation therapy (IMRT) to the prostate and has been remarkably relapse-free for four years.
... In addition, it is common for patients to have concurrent distant metastases. In the Tremont-Lukats et al. series of patients, they reported a median treatment-free survival of 1 month (8). The median survival time of prostate cancer patients with brain metastases has ranged from 1 to 7.7 months (5,(8)(9)(10)(11). ...
... In the Tremont-Lukats et al. series of patients, they reported a median treatment-free survival of 1 month (8). The median survival time of prostate cancer patients with brain metastases has ranged from 1 to 7.7 months (5,(8)(9)(10)(11). ...
... In addition, SRS has shown promise in increasing the overall survival (OS) of patients with intracranial metastases from prostate cancer, with three small studies reporting survivals of between 9 and 13 months (8,22,23). Two studies with larger numbers of patients have recently been published (16,24). ...
Brain metastases in prostate cancer are infrequent. Treatment of brain metastases includes radiotherapy. The aim of this literature review was to study whole brain radiotherapy, radiosurgery, and fractionated stereotactic radiotherapy and its applications in the treatment of prostate brain metastasis. We searched MEDLINE and PUBMED for articles published in the last 5 years and identified 153 articles. After examining them, 31 articles met the selection criteria and were included. Most were retrospective studies. MeSH terms used in the search included: prostate cancer OR prostate brain metastases AND radiotherapy, brain metastases AND radiotherapy AND prostate cancer. English language articles with information on the type of radiotherapy, doses and fractionation, indications, local control, toxicities, and survival of radiotherapy in prostate brain metastasis were included in this review. All articles were assessed for validity and relevant content. The usual treatment of prostate brain metastasis involves whole brain radiotherapy; however, the current trend in the metastases of prostate cancer and of other origins is the use of radiosurgery techniques or stereotactic body radiotherapy.
... However, failed ADT may facilitate such a spread resulting in an advanced metastatic stage of PCa, which carries a poor prognosis. Tis occurs mostly in intracranial sites such as the leptomeninges, cerebrum, and cerebellum, with many of the nonfocal neurologic symptoms being attributed to intracranial hypertension [6,[8][9][10][11][12][13]. It has been demonstrated that patients with nonadenocarcinoma PCa have a higher chance of BMs [10]. ...
... As illustrated in the results, the frst line imaging modality to detect BMs in PCa is a noncontrast CT scan which identifes lethal neurological conditions including hemorrhage, hydrocephaly, or massive compressive lesions [9,29,30,38,41,44,87]. Before using MRI as a diagnostic tool for detecting CNS metastases, imaging modalities lack the sensitivity to identify multiple intraparenchymal metastatic lesions. ...
... Before using MRI as a diagnostic tool for detecting CNS metastases, imaging modalities lack the sensitivity to identify multiple intraparenchymal metastatic lesions. Terefore, most BMs were reported as unifocal [9,73,91]. ...
Aim:
Prostate cancer (PCa) is the second most common nonskin malignancy and the second most common cause of cancer-related deaths in men. The most common site of metastasis in PCa is the axial skeleton which may lead to back pain or pathological fractures. Hematogenous spread to the brain and involvement of the central nervous system (CNS) are a rare occurrence. However, failed androgen deprivation therapy (ADT) may facilitate such a spread resulting in an advanced metastatic stage of PCa, which carries a poor prognosis.
Methods:
In this systematic review, we searched the PubMed, Scopus, and Web of Science online databases based on the PRISMA guideline and used all the medical subject headings (MeSH) in terms of the following search line: ("Brain Neoplasms" OR "Central Nervous System Neoplasms") and ("Prostatic Neoplasms" OR "Prostate"). Related studies were identified and reviewed.
Results:
A total of 59 eligible studies (902 patients) were included in this systematic review. In order to gain a deeper understanding, we extracted and presented the data from included articles based on clinical manifestations, diagnostic methods, therapeutic approaches, and prognostic status of PCa patients having BMs.
Conclusion:
We have demonstrated the current knowledge regarding the mechanism, clinical manifestations, diagnostic methods, therapeutic approaches, and prognosis of BMs in PCa. These data shed more light on the way to help clinicians and physicians to understand, diagnose, and manage BMs in PCa patients better.
... Amongst all metastatic sites from prostate cancer, BM are associated with particularly poor outcome, with the most recent available patient series suggesting a median survival ranging from two to twelve months following diagnosis [4,11,12]. Furthermore, BM from prostate cancer are also associated with a high symptom burden [13,14]. ...
... The manual reference search conducted for each of the 23 selected articles resulted in the selection of an additional four articles. Ultimately, a total of 27 articles were included in this analysis, spanning the period from 1976 to 2021 [4,5,7,[9][10][11][12][13][14][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47]. ...
... Patient data was reported from four possible sources: retrospective chart reviews (n = 13; 48%), administrative healthcare databases (n = 7; 26%), autopsy series (n = 4; 15%), and case series (n = 3; 11%; Table 1; Figure 2C). Publication by patient selection: number of patients per study and assignment of publications to the following sources of information: autopsy reviews, case series, retrospective chart reviews, or administrative database search [4,5,7,[9][10][11][12][13][14][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47]. Publication by patient selection: number of patients per study and assignment of publications to the following sources of information: autopsy reviews, case series, retrospective chart reviews, or administrative database search [4,5,7,[9][10][11][12][13][14][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47]. ...
Brain metastases (BM) are perceived as a rare complication of prostate cancer associated with poor outcome. Due to limited published data, we conducted a literature review regarding incidence, clinical characteristics, treatment options, and outcomes of patients with prostate cancer BM. A literature analysis of the PubMed, MEDLINE, and EMBASE databases was performed for full-text published articles on patients diagnosed with BM from prostate cancer. Eligible studies included four or more patients. Twenty-seven publications were selected and analyzed. The sources of published patient cohorts were retrospective chart reviews, administrative healthcare databases, autopsy records, and case series. BM are rare, with an incidence of 1.14% across publications that mainly focus on intraparenchymal metastases. Synchronous visceral metastasis and rare histological prostate cancer subtypes are associated with an increased rate of BM. Many patients do not receive brain metastasis-directed local therapy and the median survival after BM diagnosis is poor, notably in patients with multiple BM, dural-based metastases, or leptomeningeal dissemination. Overall, prostate cancer BM are rare and associated with poor prognosis. Future research is needed to study the impact of novel prostate cancer therapeutics on BM incidence, to identify patients at risk of BM, and to characterize molecular treatment targets.
... Prostate cancer is one of the most common types of cancer with almost 1,500,000 new cases worldwide (1). Cranial metastases are rare with an estimated 0.16-0.7% of all prostate cancer patients developing parenchymal or meningeal metastases during the course of their disease (2,3). Brain metastases occur late in the course of treatment with an estimated median time from first diagnosis of prostate cancer to the first diagnosis of brain metastases of 29-82 months (3)(4)(5)(6). ...
... Cranial metastases are rare with an estimated 0.16-0.7% of all prostate cancer patients developing parenchymal or meningeal metastases during the course of their disease (2,3). Brain metastases occur late in the course of treatment with an estimated median time from first diagnosis of prostate cancer to the first diagnosis of brain metastases of 29-82 months (3)(4)(5)(6). ...
... Survival after the diagnosis of brain metastases is poor with a median survival from radiotherapy of 1-4 months (2,3,7) and only few case series of selected patients reporting a longer median survival of 10-16 months (4,8,9). In those case series, patients were treated with stereotactic radiotherapy or a combination of whole brain radiotherapy, stereotactic radiotherapy, surgery or further systemic therapy. ...
Background/aim:
To evaluate patients and treatment characteristics as well as clinical outcome in patients with intracranial metastases from prostate cancer (PCA) treated with palliative radiotherapy.
Patients and methods:
Fifteen patients treated for intracranial metastases of PCA were identified. The median age of patients was 69 years. 80% of patients received whole brain radiotherapy and 20% received partial brain radiotherapy. Clinical outcome was assessed. Univariate analysis was performed to analyze the impact of patient specific parameters on survival.
Results:
There was no >G2 acute or any late toxicity. Median time from the first diagnosis of PCA to first diagnosis of intracranial metastases was 62 months (range=15-160 months). Median survival from first diagnosis of intracranial metastases was 14 weeks (range=0-126 weeks) and 6 weeks (range=0-47 weeks) from the start of radiotherapy. In univariate analysis, survival was significantly better for patients with an Eastern Cooperative Oncology Group (ECOG) performance status 1 compared to ECOG 2-3 [18 weeks (range=5-47 weeks) vs. 3 weeks (range=0-21 weeks), p=0.030] and Recursive Partitioning Analysis (RPA) class 2 compared to RPA class 3 [18 weeks (range=5-47 weeks) vs. 6 weeks (range=0-21 weeks), p=0.045].
Conclusion:
Overall survival of the patients with wide-spread intracranial metastases from PCA was poor. The decision for a radiotherapy should be done on individual patient basis.
... 2,3 Intracranial dissemination is considered a rare event, estimated to occur in 0.63% of prostate cancer patients. 4 However, with the introduction of new therapies, an increase in the frequency of prostate cancer brain metastases from 0.8% to 2.8% has been reported. 5 This increase was postulated to be related to increasing survival of those with advanced cancer 5 and the inability of new therapies like docetaxel to cross the blood-brain barrier. ...
... 5 This increase was postulated to be related to increasing survival of those with advanced cancer 5 and the inability of new therapies like docetaxel to cross the blood-brain barrier. 6,7 Historically, patients with intracranial prostate metastases have been treated with whole-brain radiation therapy (WBRT) alone, 4,8,9 resulting in a median survival of 4-9 months, 4,9 or resection and WBRT, with a mean survival of 9.2 months reported. 10 Nevertheless, intracranial dissemination of prostate cancer usually occurs late in the disease, and resection of a brain metastasis in prostate cancer patients may not convey a favorable benefit-to-risk profile for many such patients. ...
... 5 This increase was postulated to be related to increasing survival of those with advanced cancer 5 and the inability of new therapies like docetaxel to cross the blood-brain barrier. 6,7 Historically, patients with intracranial prostate metastases have been treated with whole-brain radiation therapy (WBRT) alone, 4,8,9 resulting in a median survival of 4-9 months, 4,9 or resection and WBRT, with a mean survival of 9.2 months reported. 10 Nevertheless, intracranial dissemination of prostate cancer usually occurs late in the disease, and resection of a brain metastasis in prostate cancer patients may not convey a favorable benefit-to-risk profile for many such patients. ...
OBJECTIVE
As novel therapies improve survival for men with prostate cancer, intracranial metastatic disease has become more common. The purpose of this multicenter study was to evaluate the safety and efficacy of stereotactic radiosurgery (SRS) in the management of intracranial prostate cancer metastases.
METHODS
Demographic data, primary tumor characteristics, SRS treatment parameters, and clinical and imaging follow-up data of patients from nine institutions treated with SRS from July 2005 to June 2020 for cerebral metastases from prostate carcinoma were collected and analyzed.
RESULTS
Forty-six patients were treated in 51 SRS procedures for 120 prostate cancer intracranial metastases. At SRS, the mean patient age was 68.04 ± 9.05 years, the mean time interval from prostate cancer diagnosis to SRS was 4.82 ± 4.89 years, and extracranial dissemination was noted in 34 (73.9%) patients. The median patient Karnofsky Performance Scale (KPS) score at SRS was 80, and neurological symptoms attributed to intracranial involvement were present prior to 39 (76%) SRS procedures. Single-fraction SRS was used in 49 procedures. Stereotactic radiotherapy using 6 Gy in five sessions was utilized in 2 procedures. The median margin dose was 18 (range 6–28) Gy, and the median tumor volume was 2.45 (range 0.04–45) ml. At a median radiological follow-up of 6 (range 0–156) months, local progression was seen with 14 lesions. The median survival following SRS was 15.18 months, and the 1-year overall intracranial progression-free survival was 44%. The KPS score at SRS was noted to be associated with improved overall (p = 0.02) and progression-free survival (p = 0.03). Age ≥ 65 years at SRS was associated with decreased overall survival (p = 0.04). There were no serious grade 3–5 toxicities noted.
CONCLUSIONS
SRS appears to be a safe, well-tolerated, and effective management option for patients with prostate cancer intracranial metastases.
... The diagnosis of prostate cancer is based on elevated prostate-specific antigen (PSA) levels and tissue biopsy. Metastatic prostate cancer presenting with aphasia is rare (3%) and not commonly seen [7]. We report a 60-year-old male patient who developed aphasia with nonspecific magnetic resonance imaging (MRI) findings concerning for diffuse irregular dural/ pachymeningeal thickening and enhancement, suspicious for prostate cancer metastasis. ...
... In a study of 16,280 patients with prostate carcinoma, only 131 patients had craniospinal metastasis, which was then further divided into Fig. 1 a Computed tomography unremarkable for evidence of acute ischemic or hemorrhagic stroke. b Computed tomography angiogram unremarkable for vessel occlusion intraparenchymal metastasis (103 or 79%), dural metastasis (28 or 21%), and leptomeningeal disease (5, or 4%) [7]. Of these 131 patients, the most common symptom or finding was headaches (36%), delirium (51%), memory deficits (17%), asymptomatic (11%), and cranial nerve VII or other lower cranial nerve neuropathies (9%). ...
Background
Leptomeningeal metastasis occurs in 5% of patients with prostate cancer and indicates a very poor prognosis.
Case presentation
A 60-year-old Caucasian male patient diagnosed with metastatic castration-resistant prostate cancer with sclerotic bone metastases and soft tissue metastases underwent multiple courses of chemotherapy and hormone therapy. The diagnosis of prostate cancer is based on elevated prostate-specific antigen levels and tissue biopsy. He subsequently presented with expressive aphasia. Nonspecific, diffuse irregular dural/pachymeningeal thickening enhancement was noted on magnetic resonance imaging. Upon evaluation by neurology, electroencephalogram was negative for an epileptiform correlate. The workup included a lumbar puncture to rule out infectious etiology. The patient’s neurological status stabilized, and he was discharged home with a plan for continued therapy with abiraterone and prednisone. Due to advanced malignancy, the patient enrolled in hospice and died 3 weeks after hospital discharge.
Conclusions
Central nervous system metastasis occurs very rarely in prostate cancer. With the increase in life expectancy and advances in oncologic therapy for prostate cancer, physicians should be aware of and consider central nervous system metastasis in men aged 50 years and above.
... По данным аутопсий частота метастатического поражения ГМ при РПЖ превосходит клинические, составляя 1-6% [16,17]. ...
... По данным других авторов, стереотаксическая радиохирургия увеличивает выживаемость до 9 мес [16]. ...
Background. Intracranial metastases, as the first clinical symptom of prostate cancer (PC), are extremely rare, with only anecdotal case reports in the literature. Aim. To present a case of multiple brain metastases (MCI) as the first clinical manifestation of PC with isolated facial nerve injury (FNI). Materials and methods. A 66-year-old patient with PC and multiple brain and bone metastases was observed. Results. The patient considered himself sick for 4 months when weakness in the left arm, headache, dizziness, facial asymmetry, staggering when walking, and memory loss appeared. He received non-surgical treatment prescribed by a neurologist. A clinical examination revealed a neurological deficit in the form of FN central palsy of grade 3 according to the House-Brackmann score. Magnetic resonance imaging of the brain showed masses in the right insular, left temporal lobes, and left cerebellar hemisphere of 3.7×3.3×2.9, 1.1×0.8 and 0.5×0.6 cm, respectively, with marked perifocal edema. According to the magnetic resonance imaging of the pelvis in the right half of the prostate gland, a tumor of 2.2×1.0×2.7 cm and PI-RADS 5 score was detected, and a metastatic lesion of the left ilium was found. Bone scintigraphy showed metastases in the thoracic and lumbar spine. A core biopsy of the prostate was performed. Histological and immunohistochemical studies revealed acinar adenocarcinoma with a Gleason score of 6 (3+3) points. The level of total prostate-specific antigen was 8.6 ng/mL. A final diagnosis was made: stage IV prostate cancer, T2aN0M1c, with brain and bone metastases. Given the neurological symptoms, radiation therapy was performed on the brain with a total radiation dose of 30 Gy, followed by androgen deprivation and monochemotherapy with docetaxel and bisphosphonates. Conclusion. Multiple brain lesions as the first clinical manifestation of PC are extremely rare. An isolated lesion of FN with neurological deficit in the form of central palsy indicates an advanced metastatic process. The primary method of treatment is palliative radiation therapy with a total radiation dose of 30 Gy, followed by androgen deprivation and chemotherapy.
... However, brain metastasis from prostatic cancer (PC), especially prostate adenocarcinomas is very rare, in contrast to lung, breast, melanoma, colon, and kidney malignancies, which are more commonly associated with brain metastasis [4]. It only occurs in 0.04 % to 2 % of cases of prostate adenocarcinoma [5,6]. Previously, it was long believed that the brain parenchyma could resist the growth of metastatic tumor from prostate cancer cells [5]. ...
... It only occurs in 0.04 % to 2 % of cases of prostate adenocarcinoma [5,6]. Previously, it was long believed that the brain parenchyma could resist the growth of metastatic tumor from prostate cancer cells [5]. ...
... (and higher in some autopsy studies), of which fully 2/3 are in the dura or other leptomeninges, with the remaining lesions identified in the cerebral or cerebellar parenchyma. [9][10][11][12] Furthermore, PSMA radioligand uptake has also been observed in lesions of benign etiology creating potential pitfalls when interpreting images [13,14]. This may introduce uncertainty as to diagnosis when parenchymal lesions are identified. ...
... Nevertheless, incidentally detected foci of PSMA uptake in the brain may disease. In a study of 16,280 patients with prostate cancer at a single institution over a 54-year timespan, Tremont-Lukats et al. reported a 0.12% incidence of intracranial dural metastases and 0.63% incidence of parenchymal brain metastases, representing 1.6% of all metastases for the prostate cancer population [10]. More recently however, brain metastases have been more commonly seen, likely related to improving prostate cancer survival. ...
Purpose
Brain metastases are rare in patients with prostate cancer and portend poor outcome. Prostate-specific membrane antigen positron emission tomography (PSMA PET)/CT scans including the brain have identified incidental tumors. We sought to identify the incidental brain tumor detection rate of PSMA PET/CT performed at initial diagnosis or in the setting of biochemical recurrence.
Methods
An institutional database was queried for patients who underwent ⁶⁸Ga-PSMA-11 or ¹⁸F-DCFPyL (¹⁸F-piflufolastat) PET/CT imaging at an NCI-designated Comprehensive Cancer Center from 1/2018 to 12/2022. Imaging reports and clinical courses were reviewed to identify brain lesions and describe clinical and pathologic features.
Results
Two-thousand seven hundred and sixty-three patients underwent 3363 PSMA PET/CT scans in the absence of neurologic symptoms. Forty-four brain lesions were identified, including 33 PSMA-avid lesions: 10 intraparenchymal metastases (30%), 4 dural-based metastases (12%), 16 meningiomas (48%), 2 pituitary macroadenomas (6%), and 1 epidermal inclusion cyst (3%) (incidences of 0.36, 0.14, 0.58, 0.07, and 0.04%). The mean parenchymal metastasis diameter and mean SUVmax were 1.99 cm (95%CI:1.25–2.73) and 4.49 (95%CI:2.41–6.57), respectively. At the time of parenchymal brain metastasis detection, 57% of patients had no concurrent extracranial disease, 14% had localized prostate disease only, and 29% had extracranial metastases. Seven of 8 patients with parenchymal brain metastases remain alive at a median 8.8 months follow-up.
Conclusion
Prostate cancer brain metastases are rare, especially in the absence of widespread metastatic disease. Nevertheless, incidentally detected brain foci of PSMA uptake may represent previously unknown prostate cancer metastases, even in small lesions and in the absence of systemic disease.
... Metastasis to brain is an extremely rare phenomenon. A retrospective study showed only 1.6% of prostate tumors metastasized to brain [2] . There are different histologic types of prostatic cancer: adenocarcinoma, small cell carcinoma, squamous cell carcinoma, cribriform type, and few others. ...
... Most common histologic subtype of prostate cancer is adenocarcinoma accounting for about 99% of cases. It is interesting to note that despite adenocarcinoma being the most common type of prostate cancer, it is not the most common histologic type of prostate cancer to metastasize to the brain [2][3][4] . Brain metastasis from prostate cancer presenting as a cystic tumor as seen in our patient is also a rarity. ...
Carcinoma prostate is the second most common cancer in men after skin cancer. It is the most common visceral malignancy in the United States of America. Like any other cancerous lesion, it has the propensity to metastasize to any part of the body; the most common locations being bones, lymph nodes, liver, and thoracic organs. However, it rarely metastasizes to the brain. It is even rarer for brain metastases to manifest as cystic lesions. We describe an unusual case of a metastatic prostate carcinoma presenting as a cystic brain mass.
... 4 The most common neurological manifestations of brain metastases from prostate cancer are non-focal neurologic symptoms related to the intracranial hypertension. 5 In some cases, patient do not complain any symptoms. 6 Commonly brain metastases occur in the frontal lobes (86% of patients). ...
... 6 Commonly brain metastases occur in the frontal lobes (86% of patients). 5,7 Prostate-specific membrane antigen (PSMA) is a glycoprotein, a membrane-bound metallopeptidase, that is overexpressed in over 90% of PCa cells. This molecular target is a suitable tissue biomarker for PCa functional imaging. ...
Brain metastases from prostate cancer typically occur in the more advanced stages of the disease. Clinically, the early diagnosis of visceral disease is crucial, impacting on patient’s management and prognosis. Although magnetic resonance imaging (MRI) is the modality of choice for the detection of brain metastases, it is not routinely performed in the surveillance of prostate cancer patients unless neurological manifestations appear. Prostate-specific membrane antigen (PSMA) is a glycoprotein, a membrane-bound metallopeptidase, overexpressed in more than 90% of prostate cancer cells. This molecular target is a suitable tissue biomarker for prostate cancer functional imaging. We present a case of a 73-year gentleman diagnosed with prostate adenocarcinoma and surgically treated (pT3bN1Mx, Gleason Score of 9) in February 2016. Subsequently, he underwent androgen deprivation therapy because of the occurrence of a bone metastasis. Between 2016 and January 2019 PSA levels were maintained under control. Starting from September 2019, it progressively raised up to 0.85 ng/mL with a doubling time of 3.3 months. Therefore, he performed a [⁶⁸Ga]Ga-PSMA-11 PET/CT which showed a focal radiopharmaceutical uptake in the right temporal lobe corresponding to the presence of a rounded cystic lesion on brain MRI. The subsequent excisional biopsy diagnosed a prostate adenocarcinoma metastasis. PSMA expression has been reported in brain parenchyma after ischemic strokes and in some brain tumors including gliomas, meningiomas, and neurofibromas. In our case, the lack of symptoms and the relatively low PSA level raised questions about the nature of the lesion, posing the differential diagnosis between brain metastases and primary brain tumor. Finally, our case shows the capability of [⁶⁸Ga]Ga-PSMA-11 PET/CT to detect metachronous distant brain metastases in a low biochemical recurrent asymptomatic prostate cancer patient, indicating that proper acquisition – from the vertex to thigh – should be always considered, regardless of the PSA level.
... However, underreporting could remain an issue because current staging strategies do not routinely include CNS imaging without neurologic symptoms [30]. Conversely, despite an estimated post-mortem BMETS diagnosis frequency of 1%-6% from an autopsy series [31], it is unlikely that the presence of undiagnosed occult BMETS is an unidentified risk factor for mortality in aPC [5]. ...
Background
Brain metastases (BMETS) from prostate cancer are rare. Hence, brain imaging in neurologically asymptomatic patients with advanced prostate cancer (aPC) is not routinely performed. Prostate‐specific membrane antigen (PSMA) PET/CT uses a radiotracer that binds to prostate cancer epithelial cells and is FDA‐approved for initial staging for high‐risk prostate cancer, detecting prostate cancer recurrence, and determining eligibility for radionuclide therapy.
Methods
We report six patients with asymptomatic BMETS from aPC found on staging PSMA PET/CT or MRI. Along with cranial MRI, PSMA PET/CT may be useful for detecting asymptomatic intracranial metastasis in select patients with prostate cancer.
Results
Brain metastases were diagnosed in four patients by staging PSMA PET/CT scan—three after systemic disease progression and one during routine surveillance. In two other patients, BMETS were detected using MRI despite negative PSMA PET/CT for brain lesions. All were neurologically asymptomatic. Three patients had undetectable serum prostate‐specific antigen (PSA) concentrations; one had neuroendocrine differentiation on histology.
Conclusion
In patients with poorly differentiated or neuroendocrine aPC, BMETS may occur without neurologic symptoms and stable PSA. PSMA PET/CT may complement brain MRI for identifying BMETS in these patients.
... Only up to 0.6% of all metastases of prostate cancer and, according to autopsy cases, 3% of brain parenchyma metastases were reported to occur from prostate cancer. 2 The spread of cranial or leptomeningeal metastases of prostate cancer has been demonstrated to occur through the connection of prostatic venous plexus and cerebrospinal venous system (CSVS) within the extradural neuraxis compartment which is described as an intricate, extradural, neuraxial continuum consisting of adipovenous tissue, epidural veins, and traversing neurovascular structures between the orbit and the coccyx ( Figure 1). Hence, prostate cancer metastasis may involve all skull base fossae via this anatomic continuum provided by the CSVS and mimic a variety of central nervous system (CNS) tumours at the skull base. ...
Prostate adenocarcinoma metastasis to brain has been reported to occur only up to 0.6% of patients and these are mostly diagnosed in autopsy series. In the setting of biochemical recurrence of prostate cancer, a suspected PSMA-avid lesion in the brain is still strongly suggestive of an intracranial metastasis of prostate cancer. This needs, however, a thoroughly recurrency work-up due to other potentially PSMA-avid cranial lesions, as PSMA initially was developed for the imaging of primary CNS tumors. We report of a challenging clinical case of a 71-year-old-patient with a strongly PSMA-avid lesion at the skull base. Given the medical history of a meningioma at the skull base, the further diagnostic work-up with MRI could still not rule out a malignancy, so that the patient needed to undergo a surgical excision of the tumor mass. The histological and immunohistochemical examinations revealed a relapsed CNS WHO grade 1 meningioma. From the aspect of molecular imaging and critical analysis of regular clinical care in a third-level university hospital, we consider this result very intriguing. Hence, we analyze the decision-making process and clinical course of this case in the light of molecular imaging findings.
... BM incidence in our study (Table 1) was comparable to that reported in the literature, with ranges in the following intervals: 0.5-2.6% for GCT [8,9], 0.25-7% for UCC [10][11][12][13], 0.07-2% for PrCa [14][15][16][17][18], and 1.48-11% for RCC [19][20][21][22]. ...
Simple Summary
Incidence of brain metastases from genito-urinary cancers has increased over the last years due to improved imaging techniques and better survival outcomes for patients even at an advanced metastatic stage thanks to therapeutic advances. However, no clear consensus exists on their management, and every case ought to be discussed in a multidisciplinary panel. We perform a single-centre retrospective study to report on incidence, patient demographics, clinicopathological characteristics, and treatment modalities. We also manage to identify predictive factors of outcome.
Abstract
Background: Incidence of brain metastases is precisely unknown and there is no clear consensus on their management. We aimed to determine the incidence of brain metastases among patients with genito-urinary primaries, present patients’ characteristics and identify prognostic factors. Method: We identified 51 patients treated in Geneva University Hospitals between January 1992 and December 2019. We retrospectively correlated their overall survival with 23 variables. We repeated a multivariate analysis with significant variables. Results: Overall incidence of Brain Metastases (BMs) among Genito-Urinary (GU) patients is estimated to be 1.76% (range per primary GU tumour type: 0.00–6.65%). BMs originate from germ cell tumours in two cases (3.92%), from urothelial cell carcinoma in 15 cases (29.41%), from prostate cancer in 13 cases (25.49%), and from renal cell carcinoma in 21 cases (41.18%); there are no BMs from penile cancer in our cohort. The median age at BM diagnosis is 67 years old (range: 25–92). Most patients (54%) have a stage IV disease at initial diagnosis and 11 patients (22%) have BM at initial diagnosis. Only six patients (12%) are asymptomatic at BM diagnosis. The median Overall Survival (OS) from BM diagnosis is 3 months (range: 0–127). Five patients (10%) are long survivors (OS > 24 months). OS is significantly influenced by patient performance status and administration of systemic treatment. In the absence of meningeal carcinomatosis, OS is influenced by systemic treatment and stereotactic radiosurgery. We also apply the Graded Prognostic Assessment (GPA) score to our cohort and note significant differences between groups. Conclusion: Brain metastases from solid tumours is not a uniform disease, with a prognosis varying a lot among patients. The optimal management for patients with genito-urinary malignancies with brain metastases remain unclear and further research is needed.
... Metastasis to the axial skeleton and the lymph nodes is the most typical pattern of spread for prostate cancer [2][3][4]. Brain metastatic prostate cancer is a rare phenomenon, accounting for 0.2-2.0% of all prostate cancer metastases, and nonadenocarcinoma histologies have been shown to have a higher likelihood of brain metastases than adenocarcinomas [4][5][6][7]. Brain metastatic prostate cancer most frequently occurs in the setting of widely disseminated bone and soft tissue disease, making solitary parenchymal metastases without intervening nodal or osseous metastases particularly rare [4]. Here, we present a case of exclusively brain metastatic prostate cancer, identified on 68 Gallium prostate-specific membrane antigen PET-CT ([ 68 Ga]PSMA PET/CT) and successfully managed with surgical resection and adjuvant stereotactic Gamma Knife radiosurgery (GKRS), followed by androgen deprivation therapy (ADT). ...
Brain metastatic carcinoma is a rare occurrence among prostate cancer metastases. ⁶⁸Gallium prostate-specific membrane antigen PET-CT ([⁶⁸Ga]PSMA PET/CT) is commonly used for prostate cancer staging and detection of biochemical recurrences. However, various CNS tumors exhibit activity on [⁶⁸Ga]PSMA PET/CT and may often be included in the differential diagnosis. Herein, we present a case of brain metastatic prostate cancer successfully treated with surgical resection and adjuvant stereotactic Gamma Knife radiosurgery (GKRS) followed by androgen deprivation therapy (ADT) to emphasize the need for histologic confirmation. A 70-year-old male with a history of very high-risk prostatic adenocarcinoma presented with biochemical recurrence following radical prostatectomy and irradiation of the prostatic fossa. [⁶⁸Ga]PSMA PET/CT and MRI identified a solitary lesion in the left occipital lobe; differential diagnosis included prostate metastasis, meningioma, or a new metastatic primary lesion. The patient underwent surgical resection, and immunohistochemical staining confirmed the lesion as brain metastatic prostate adenocarcinoma. One month after resection, the patient underwent GKRS to the tumor bed and two additional metastases, followed by ADT. Repeated imaging 15 months after GKRS revealed stable posttreatment changes with no evidence of new metastases, thus demonstrating durable, effective local and systemic control. Brain metastatic prostate adenocarcinoma without nodal or osseous metastases is a rare phenomenon. The affinity of [⁶⁸Ga]PSMA PET/CT for non-prostate histologies such as meningioma introduces uncertainty into the diagnostic process. This case demonstrates the durable local control conferred by GKRS toward these lesions and emphasizes the need for clinical, radiographic, and histopathologic data to identify disease presentations and facilitate appropriate treatment regimens.
... Several rare mutations, including splice variants in the androgen receptor (e.g., AR-V7) and known oncogenic mutations (e.g., P53, PTEN, BRCA2), promote treatment resistance in select patients, potentially predisposing them to the development of metastases [14]. Other risk-associated patient demographics include age of presentation around 65 years, concurrent metastases to bone, and classic neurologic symptoms (confusion, headache, memory deficits) [15,16]. Yet, the association of these known clinical features and prostate cancer grading scales with risk of mortality is unknown. ...
Simple Summary
Brain metastases from systemic cancer are the most common tumors of the central nervous system. For prostate metastases to the brain, the clinical progression is poorly understood. This retrospective study aims to elucidate clinical risk factors associated with overall survival (OS; months post-diagnosis) in prostate metastases to the brain, and then develop a nomogram to aid in clinical decision making for this vulnerable population. We identified several factors associated with survival, including race, tumor size, and the presence of additional metastases. This study should serve as a clinical framework for prognostication in metastatic prostate cancer to the brain.
Abstract
Brain metastases are an uncommon yet life-limiting manifestation of prostate cancer. However, there is limited insight into the natural progression, therapeutics, and patient outcomes for prostate cancer once metastasized to the brain. This is a retrospective study of 461 patients with metastatic prostate cancer to the brain with a primary outcome of median overall survival (OS). The Surveillance, Epidemiology, and End Results (SEER) database was examined using Cox regression univariate and multivariable analyses, and a corresponding nomogram was developed. The median overall survival was 15 months. In the multivariable analysis, Hispanic patients had significantly increased OS (median OS 17 months, p = 0.005). Patients with tumor sizes greater than three centimeters exhibited significantly reduced OS (median OS 19 months, p = 0.014). Patients with additional metastases to the liver exhibited significantly reduced OS (median OS 3.5 months, p < 0.001). Increased survival was demonstrated in patients treated with chemotherapy or systemic treatment (median OS 19 months, p = 0.039), in addition to radiation and chemotherapy (median OS 25 months, p = 0.002). The nomogram had a C-index of 0.641. For patients with prostate metastases to the brain, median OS is influenced by race, tumor size, presence of additional metastases, and treatment. The lack of an association between traditional prostate cancer prognosis metrics, including Gleason and ISUP grading, and mortality highlights the need for individualized, metastasis-specific prognosis metrics. This prognostic nomogram for prostate metastases to the brain can be used to guide the management of affected patients.
... 4 This is in contrast to older reports, such as a study conducted at MD Anderson in 1999, where the incidence of central nervous system metastases was reported as low as 0.7% in a cohort of 7994 patients over an 18-year period. 5 It has even been suggested that the discrepancy between the systemic effectiveness of docetaxel and its low CNS penetration may also contribute to the potential rise in prostate cancer CNS involvement. leptomeningeal seeding is gadolinium-enhanced T1-weighted MR imaging which has sensitivity and specificity of 70% and 77%-100%, respectively. ...
Background
Prostate cancer is the second most common cancer in men. Central nervous system (CNS) involvement in prostate cancer which manifests as cerebral, leptomeningeal, or dural involvement is uncommon and occurs late in the course of disease.
Case
A 60‐year‐old patient with castration resistant prostate cancer (CRPC) presented with headache and fatigue. Evaluation revealed bone marrow and leptomeningeal involvement. The patient treated by whole brain radiotherapy, leuprolide, weekly docetaxel and daily 1000 mg abiraterone. Complete blood count (CBC) and CNS symptoms improved and the patient is alive after 11 months with excellent performance status.
Conclusion
Leptomeningeal involvement in prostate cancer is rare and is associated with a poor prognosis but the possibility of such event should be considered in patients with new onset progressive CNS symptoms. New treatment strategies such as combination of docetaxel and abiraterone added to androgen deprivation therapy (triplet therapy) might improve outcome in these patients.
... Рак предстательной железы характеризуется определенным паттерном метастазирования, включающим лимфогенное распространение в тазовые и забрюшинные лимфатические узлы, а также гематогенное распространение в кости и внутренние органы. Стоит отметить, что кости являются преимущественной локализацией отдаленных метастазов, а наличие висцеральных метастазов обычно ассоциировано с генерализацией процесса, быстрым прогрессированием и смертью [11][12][13]. Солитарные висцеральные метастатические очаги -редкое явление при РПЖ, а в контексте поражения головного мозга (без дальнейшей генерализации процесса) встречаются крайне редко [14]. В связи с этим такие случаи требуют особого внимания со стороны врачей-специалистов, занимающихся диагностикой и лечением пациентов с РПЖ. ...
It is established that prostate-specific membrane antigen (PSMA), despite its name, is expressed in many tissues other than the prostate gland, both within physiological conditions and in various pathological processes. Additionally, apart from prostate cancer, other malignant tumors are characterized by increased PSMA expression which, according to many authors, is associated with neoangiogenesis. These factors are reflected in the results of PSMA-radioligand imaging and require comprehensive approach to image interpretation including evaluation of computed tomography and magnetic resonance semiotics. In addition, rare cases of distant visceral prostate cancer metastasis in the form of solitary lesions also should be considered during interpretation of the results of radiologic imaging including positron emission tomography/computed tomography.
We present two clinical cases in which positron emission tomography/computed tomography revealed solitary foci of pathological 18F-PSMA-1007 uptake outside the areas of typical metastatic spread (with exception of advanced disease) of prostate cancer, specifically in the stomach wall and the left cerebellar hemisphere. In the first case histological examination results revealed a metachronous low grade neuroendocrine tumor of the stomach, in the second case a metastatic lesion of the cerebellum was diagnosed as part of the underlying disease.
... The clinical presentation of dural metastasis was rare, which contrasted with autopsy findings that reported a much higher incidence. In 2003, a review of 16,280 prostate cancer cases at MD Anderson revealed only 19 cases diagnosed with dural metastases [20]. Before 2008, patients diagnosed with dural metastases were usually heavily pre-treated, had significantly higher PSA with heavy disease burden and clear progression of disease at other sites [1]. ...
Introduction
Spinal epidural metastases (SEM) are an uncommon phenomenon and traditionally occur as a preterminal event in heavily pre-treated patients. The introduction of novel anti-androgen therapies, such as enzalutamide and abiraterone acetate, has greatly improved the survival of patients with metastatic prostate cancer but may be changing the pattern of disease.
Case Presentation
Four patients diagnosed with metastatic castrate-resistant prostate cancer (CRPC) were commenced on enzalutamide prior to chemotherapy. Baseline scans in all patients demonstrated extensive bony disease and lymph node involvement. All patients experienced a moderate initial PSA response to treatment (median PSA at baseline 53.5 ng/mL to median nadir 24.5 ng/mL). In all four cases, clinical presentation of spinal cord compression was unexpected with no prodromal neurological symptoms, PSA levels either stable or slowly rising, and CT scans and whole-body bone scans showing stable disease at other metastatic sites. Whole-spine MRI on presentation of neurological deficits showed epidural and dural metastases on the background of stable bone disease. Spinal cord compression occurred at a median of 11.4 months after starting enzalutamide.
Conclusion
Clinicians should be aware of this change in the pattern of CRPC in patients treated with novel anti-androgen therapy. Onset of “silent” spinal cord compression due to SEM rather than bone metastases, can occur relatively early with minimal warning despite stable disease on PSA and standard imaging. Differential progression in nontraditional sites suggests that research into the androgen microenvironment in a wide range of tissue sites should be undertaken, and may explain why prostate cancer metastasizes preferentially to bone and lymph nodes.
... The optimal treatment is not yet clear, and the mortality rate is high [3]. PCA occurs most frequently in the axial bone, pelvic lymph nodes, and lungs; PCA in the bladder and brain is extremely uncommon [4,5]. We describe a rare case of AVPC that had both uncommon brain and bladder metastases in addition to the fatal clinical presentation of the disease. ...
BACKGROUND
Aggressive variant prostate cancer (AVPC) is a rare disease that progresses rapidly. The first-line treatment for AVPC is currently unknown. We examined a rare case of AVPC with rare brain and bladder metastases. A summary review of the mechanism of development, clinicopathological manifestations, associated treatments and prognosis of this disease is presented.
CASE SUMMARY
The patient was diagnosed with prostate cancer (PCA), and was actively treated with endocrine therapy, radiotherapy, chemotherapy, and traditional Chinese medicine. Unfortunately, he was insensitive to treatment, and the disease progressed rapidly. He died five years after being diagnosed with PCA.
CONCLUSION
We should reach consensus definitions of the AVPC and other androgen receptor-independent subtypes of PCA and develop new biomarkers to identify groups of high-risk variants. It is crucial to complete a puncture biopsy of the tumor or metastatic lesion as soon as possible in patients with advanced PCA who exhibit clinical features such as low Prostate-specific antigen levels, high carcinoembryonic antigen levels, and insensitivity to hormones to determine the pathological histological type and to create a more aggressive monitoring and treatment regimens.
... Isolated lung metastases from prostate cancer are found in <1% of cases [2]. Brain metastasis is even rarer, with incidence ranging from 0.04% to 2% among prostate adenocarcinoma cases [3]. Here, we present a 60-year-old Gleason high-grade prostate cancer with initially negative PSA (Prostate-speci c antigen) with metastases to both lung and brain without bone involvement. ...
Background:
Prostate cancer is a prevalent malignancy in males, particularly in older individuals and non-Hispanic Black men. Adenocarcinomas represent most prostate cancers, while other histological types are less common. Metastases from prostate cancer primarily involve bones and lymph nodes, with isolated lung and brain metastases being extremely uncommon. Understanding prostate cancer's clinical characteristics and behavior with atypical metastatic patterns is crucial for accurate diagnosis and optimal treatment strategies.
Case Presentation:
We present a case of a 60-year-old patient with high-grade Gleason prostate cancer, initially presenting with negative PSA levels. Despite the absence of bone involvement, the patient developed metastases to both the lung and brain, representing an unusual spread pattern. Detailed clinical features, imaging findings, diagnostic workup, and treatment interventions are described to provide a comprehensive understanding of this exceptional case.
Conclusion:
This case report highlights the rarity and clinical significance of prostate cancer metastases to the lung and brain without bone involvement. Isolated lung and brain metastases from prostate cancer are infrequent occurrences, and their diagnosis and management pose considerable challenges. Clinicians should be aware of these potential metastatic patterns, especially when encountering unusual clinical presentations or imaging findings in prostate cancer patients. Further research and case reports are warranted to enhance our knowledge of these rare metastatic events and optimize treatment approaches for patients with prostate cancer and atypical metastases.
... 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. ...
Prostate cancer is a common malignancy affecting elderly males. Generally, prostate cancer metastases to lymph nodes and skeletal lesions. Brain metastasis from prostate cancer is an uncommon phenomenon. When occurs, it affects the liver and lungs. Less than 1% of the cases show brain metastases, with isolated brain metastases being even more rare. We present the case of a 67-year-old male patient who was diagnosed to have prostate carcinoma and maintained on hormonal therapy. Later, the patient presented with raising serum-68 prostate-specific antigen (PSA) levels. Gallium-68 prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) scan revealed isolated cerebellar metastasis. He was later treated with whole brain radiotherapy.
... CNS metastasis from metastatic prostate carcinoma was noted in 131 of 6282 (2.1%) patients with prostate carcinoma. [8] However, when prostate carcinoma metastasizes to the CNS, it is characterized by a high proportion of dural metastases and is the most common primary tumor of dural metastasis in men. [3,6] Dural metastasis from prostate carcinoma can look like meningioma on imaging, and there have been several reports of dural metastasis from prostate carcinoma that was difficult to differentiate preoperatively from meningioma. ...
Background
Prostate carcinoma rarely metastasizes to the central nervous system. However, when it does, a dural lesion is a common and possible misdiagnosis of meningioma. Here, we describe a case of a 77-year-old man with dural metastasis from prostate carcinoma of the tuberculum sellae.
Case Description
The patient was diagnosed with prostate carcinoma 7 years previously and was well-controlled by hormone therapy. He was incidentally found to have a suprasellar tumor and underwent endoscopic endonasal transsphenoidal surgery because of rapid tumor growth and worsening visual impairment. Since his serum prostate-specific antigen (PSA) level was within the normal range, malignant meningioma was suspected based on the magnetic resonance imaging (MRI) and the course. However, the pathological findings revealed dural metastasis from prostate carcinoma. He received radiation therapy, and the tumor disappeared on MRI. His visual impairment improved without recurrence. This case report highlights that dural metastasis of the tuberculum sellae arose despite the patient’s PSA level being within the normal range, and a single metastasis to the dura was found.
Conclusion
In patients with a history of prostate carcinoma or older men, careful follow-up considering the possibility of metastasis is required when a dural lesion is found.
... The proportion of brain metastasis in SCCP was 10-16%, whereas that of prostate adenocarcinoma was 0.8%. 8,9 Leptomeningeal carcinomatosis in prostate cancer is also rare (<5%), which is usually observed in patients with end-stage disease. 10 Additionally, the prognosis of leptomeningeal carcinomatosis from solid tumors is extremely poor, as the median overall survival periods are approximately 4 weeks without treatment and 2-4 months even with intensive treatment. ...
Introduction:
Leptomeningeal carcinomatosis in small cell carcinoma of the prostate is rare.
Case presentation:
A 69-year-old man visited our hospital due to dysuria and edema. Bilateral hydronephrosis and lymph node metastases due to a pelvic tumor were observed. Although the prostate-specific antigen level was normal, the tumor was suspected to originate from the prostate. He underwent percutaneous nephrostomy and prostate biopsy. Histopathology revealed small cell carcinoma accompanied by increased pro-gastrin-releasing peptide and neuron-specific enolase levels. After receiving systemic chemotherapy with carboplatin and etoposide and radiation therapy for prostate, these lesions gradually decreased in size, and tumor markers normalized. Ten months after the initial diagnosis, he developed consciousness disorder and seizure. Magnetic resonance imaging revealed leptomeningeal carcinomatosis without any other recurrences and elevated tumor markers. He died 4 weeks after these symptoms appeared.
Conclusion:
Careful monitoring of the central nervous system should be considered in small cell carcinoma of the prostate patients.
... Dural metastasis is known to mimic a subdural hematoma or an abscess, and interesting case reports of metastatic spread to the membranes of a true chronic subdural hematoma have been described. 4 Thus, in the differential diagnosis of subdural collections, without any history of recent head injuries, prostatic metastasis needs to be considered. The osteoblastic changes induced on the dural layers can at times mimic a meningioma too. 3 Pure parenchymal intra-axial metastatic lesions especially in the cerebellum are extremely uncommon. ...
Intracranial metastases from prostate carcinoma are uncommon and usually manifest as dural secondaries in the supratentorial compartment. We present an unusual case of intra-parenchymal posterior fossa prostatic metastasis in a 61-year-old gentleman and discuss the diagnostic and management challenges involved. A 61-year-old hypertensive, diabetic man presented with gait unsteadiness for 1-month duration and no other neurological deficits. He had previously undergone bilateral orchiectomy for prostate carcinoma with multiple osseous metastases. Magnetic resonance imaging showed a well-defined lobulated, intraventricular, peripherally enhancing lesion in the fourth ventricle with obstructive hydrocephalus. He underwent sub-occipital craniectomy and decompression, and histological examination was consistent with metastatic prostate adenocarcinoma. Although cerebellar secondaries are atypical, a suspicion of metastasis should be upheld in all patients with the history of prostate carcinoma, regardless of their location and radiological characteristics of the intracranial lesion.
... The cytological examination of the cerebrospinal fluid can also lead to the diagnosis although it is normal in 5 to 10% of cases. In the M.D. Anderson Cancer Center review of 16'280 patients with prostate cancer between 1944 and 1998, 131 patients had craniospinal metastases, 52 were diagnosed with CT or MRI and 78 postmortems; of these only 19 had intracranial meningeal carcinomatosis [11]. The present study was motivated by the unexpected increase of meningeal carcinomatosis cases from prostate cancer observed in our institution starting from 2012, with the aim to explore the associated factors. ...
... Metastases to the central nervous system (CNS) are rare. A retrospective study of patients with prostate cancer seen at MD Anderson Cancer Center from 1944 to 1998 estimated the incidence of brain metastases to be 0.6% (Tremont-Lukats et al. 2003). Even among men who die from prostate cancer, the rate of brain metastases has been reported to be in the range of 2-4% in autopsy studies (Catane et al. 1976;Saitoh et al. 1984). ...
Parenchymal brain metastases from prostate cancer are unusual and are associated with poor prognosis. Given the rarity of this entity, little is known about its molecular and histologic characteristics. Here we describe a patient with metastatic castration-resistant, mismatch repair-deficient (dMMR) prostate cancer with parenchymal brain metastases. Analysis of a brain metastasis revealed MLH1 loss consistent with dMMR, yet few tumor-infiltrating lymphocytes (TILs). He was treated with immune checkpoint blockade (ICB) and exhibited an extra-central nervous system (CNS) systemic response but CNS progression. Subsequent assessment of a brain metastasis following ICB treatment surprisingly showed increased TIL density and depletion of macrophages, suggestive of an enhanced antitumor immune response. Post-treatment tumoral DNA sequencing did not reveal acquired mutations that might confer resistance to ICB. This is the first description of ICB therapy for a patient with prostate cancer with parenchymal brain metastases, with pre- and post-treatment immunogenomic analyses.
Background
Prostate carcinoma (PC) is the most common cancer in men worldwide. However, brain metastases (BM) from prostate cancer are extremely rare events, usually in the later course of the disease. There is no established standard of care treatment for this situation. The efficacy of androgen synthesis inhibitor abiraterone in BM from PC is unknown.
Case
We herein report the case of an 83-year-old patient with metastatic hormone-sensitive PC who had multiple BM at primary diagnosis, clinically manifesting with dizziness, ataxia, and unsteady gait. Combination of abiraterone and androgen deprivation therapy showed exceptional sustained cerebral tumor response. After 12 months of treatment, the patient is asymptomatic with an excellent performance status.
Conclusion
Symptomatic BM from PC is a rarity but can show sustained response to abiraterone and androgen deprivation therapy. After comprehensive literature search, there is no comparable case published to date.
Mục tiêu: Nghiên cứu nhằm đánh giá kết quả sau phẫu thuật nội soi qua niệu đạo cắt ung thư tuyến tiền liệt giai đoạn tiến triển kèm cắt hai tinh hoàn tại bệnh viện Hữu Nghị Việt Đức giai đoạn 1/2018 - 12/2022. Phương pháp nghiên cứu: hồi cứu theo dõi dọc trên 217 bệnh nhân có chẩn đoán ung thư tuyến tiền liệt giai đoạn tiến triển được phẫu thuật nội soi cắt u kèm cắt hai tinh hoàn. Kết quả: Phần lớn các bệnh nhân đều ở giai đoạn T3, T4 chiếm 82.9%, giai đoạn sớm T2 chỉ chiếm 17.1%.Trong số 217 BN có 118 BN còn sống (54,4%), tử vong 99 BN (45,6%). Tỷ lệ sống sót giảm dần theo thời gian theo dõi trong các nhóm từ 24 đến 72 tháng sau phẫu thuật tương ứng với 67,1% đến 36,8%. Nguyên nhân tử vong chủ yếu là ung thư di căn các cơ quan khác. Các yếu tố ảnh hưởng đến tỷ lệ sống còn là điểm Gleason, nhóm tuổi và giai đoạn UTTTL (p<0,05). Khả năng tiểu tiện, chất lượng cuộc sống của bệnh nhân cải thiện rõ rệt sau phẫu thuật: theo thang điểm IPSS phần lớn các bệnh nhân sau mổ tại thời điểm khám lại – phỏng vấn có rối loạn tiểu tiện ở mức độ nhẹ và trung bình chiếm 94,1%, tăng hơn nhiều so với thời điểm trước mổ là 36,5% (p<0.001). Chất lượng cuộc sống (QoL) của bệnh nhân sau mổ ở mức độ chấp nhận được và hài lòng có tỷ lệ 90,6% cao hơn mức trước phẫu thuật là 18,5% (p<0.001)
In an age characterized by an influx of information, access to comprehensive volumes on uro-oncology is becoming increasingly practical. This publication endeavors to present contemporary insights into the management of metastatic prostate cancer. The integration of new imaging methodolo-gies and therapeutic interventions signifies a transformative phase in prostate cancer management. Authored with contributions from esteemed professionals possessing both national and international expertise, this text offers a com-prehensive discourse on the holistic management of meta-static prostate cancer. By facilitating interdisciplinary collab-oration among fields such as urology, radiology, pathology, nuclear medicine and oncology, it serves as a guiding beacon amidst the complexities of contemporary clinical practice and scholarly pursuits.
El edema del disco óptico es resultado de una amplia gama de procesos patológicos secundarios a presiónintracraneal elevada. Conlleva etiologías específicas dentro de las cuales se encuentran lesiones expansivasdel parénquima cerebral y alteraciones óseas craneales. Otros mecanismos infrecuentes son síndromes paraneoplásicos neurológicos, contando con muy poca información de este fenómeno. Se presenta el casode paciente masculino joven con diagnóstico de cáncer de próstata metastásico sin afección a parénquimaencefálico que desarrolló neuropatía óptica como síndrome paraneoplásico.
Dural metastases of prostate adenocarcinoma are an extremely rare complication and may mimic intracranial hematoma. Preoperatively diagnosis may be difficult due to similarities in symptoms and radiological appearance. We present a 65-year-old man admitted to the ED with a history of headache, nausea, vomiting, vertigo, diplopia, as well as numbness of his left lower extremity. Past medical history confirmed metastatic prostate cancer disease. After computed tomography and contrast computed tomography, the consulting radiologist diagnosed a chronic subdural hematoma. After burr hole trephination and dural opening, tumorous mass was detected. Histopathologic samples were taken. Histopathological examination was consistent with metastatic adenocarcinoma of the prostate. Although rare, dural metastases need to be included in oncological patients presenting in the ED with symptoms and radiological imaging suggesting hematoma. Both neurooncological and neurosurgical consultations are essential in order to apply the best treatment strategy.
Background
Prostate cancer (PCa) parenchymal brain metastases are uncommon and troubling observations in the course of the disease. Our study aims to evaluate the prevalence of brain metastases among PCa patients while reporting various therapeutic modalities, clinical features, and oncological outcomes.
Methods
We retrospectively identified 34 patients with parenchymal brain metastasis out of 4575 patients using a prospectively maintained database that contains clinicopathologic characteristics of PCa patients between January 2012 and December 2021. Based on the three treatment modalities used, the patients were divided into three groups: stereotactic radiosurgery (SRS), whole brain radiotherapy (WBRT), and systemic therapy alone. The Kaplan–Meier curve was used to calculate overall survival [OS] probability and the Cox proportional hazards regression model was used to compare between groups.
Results
At the time of brain metastasis diagnosis, the median age was 66 years, the median (interquartile range [IQR]) prostate‐specific antigen (PSA) was 2.2 (0.1–26.6) ng/ml and the median (IQR) months from initial PCa diagnosis to brain metastasis development was 70.8 (27.6–100.9). The median (IQR) primary Gleason score was 8 (7–9) and over a median (IQR) follow‐up time of 2.2 (1.2–16.5) months, 76.5% ( n = 26) of the patients died. Thirteen (38.2%) patients had solitary lesion, whereas 21 (61.8%) had ≥2 lesions. The lesions were supratentorial in 19 (55.9%) patients, infratentorial in six (17.6%), and both sides in nine (26.5%). Among all 34 patients, 10 (29.4%) were treated with SRS, seven (20.6%) with WBRT, and 17 (50%) with systemic therapy alone. OS varied greatly between the three treatment modalities (log‐rank test, p = 0.049). Those who were treated with SRS and WBRT had better OS compared with patients who were treated with systemic therapy alone (hazard ratio: 0.37, 95% confidence interval: 0.16–0.86, p = 0.022).
Conclusions
In our single‐institutional study, we confirmed that PCa brain metastasis is associated with poor survival outcomes and more advanced metastatic disease. Furthermore, we found that SRS and WBRT for brain metastasis in patients with recurrent PCa appear to be associated with improved OS as compared with systemic therapy alone and are likely secondary to selection bias.
Intracranial metastases in prostate cancer are uncommon but clinically aggressive. A detailed molecular characterization of prostate cancer intracranial metastases would improve our understanding of their pathogenesis and the search for new treatment strategies. We evaluated the clinical and molecular characteristics of 36 patients with metastatic prostate cancer to either the dura or brain parenchyma. We performed whole genome sequencing (WGS) of 10 intracranial prostate cancer metastases, as well as WGS of primary prostate tumors from men who later developed metastatic disease ( n = 6) and nonbrain prostate cancer metastases ( n = 36). This first whole genome sequencing study of prostate intracranial metastases led to several new insights. First, there was a higher diversity of complex structural alterations in prostate cancer intracranial metastases compared to primary tumor tissues. Chromothripsis and chromoplexy events seemed to dominate, yet there were few enrichments of specific categories of structural variants compared with non-brain metastases. Second, aberrations involving the AR gene, including AR enhancer gain were observed in 7/10 (70%) of intracranial metastases, as well as recurrent loss of function aberrations involving TP53 in 8/10 (80%), RB1 in 2/10 (20%), BRCA2 in 2/10 (20%), and activation of the PI3K/AKT/PTEN pathway in 8/10 (80%). These alterations were frequently present in tumor tissues from other sites of disease obtained concurrently or sequentially from the same individuals. Third, clonality analysis points to genomic factors and evolutionary bottlenecks that contribute to metastatic spread in patients with prostate cancer. These results describe the aggressive molecular features underlying intracranial metastasis that may inform future diagnostic and treatment approaches.
Brain metastasis in prostate adenocarcinoma is extremely rare and usually arises in the setting of widespread osseous and visceral metastases. Surgical resection and radiation therapy, including stereotactic radiosurgery, are the mainstays of treatment for brain metastasis. Radiation necrosis is a common complication of radiotherapy for brain metastasis, and distinguishing it from tumor recurrence by MRI is difficult because of overlapping findings. We present a 73-year-old man with prostate cancer with a solitary brain metastasis where PET with 18F-piflufolostat helped detect disease recurrence in the setting of ambiguous MRI findings.
Background
Prostate cancer (PC) rarely metastasizes to the central nervous system (CNS). In this retrospective single-institution study at a tertiary cancer center, we aimed to evaluate the clinical and genetic characteristics of advanced PC patients with CNS metastases.
Patients and Methods
Between January 2010 and March 2020, 12 out of 579 patients with extracranial metastatic PC were identified to have CNS metastases based on imaging, including 6 patients with brain metastases (BMs), 5 patients with dural metastases, and 1 unknown. These patients were followed up through March 2022. Clinical data were compared to the overall cohort of patients evaluated at our cancer center during that decade. Genetics information was also analyzed for the patients with available data via cell-free DNA (cfDNA) blood samples.
Results
Median time from development of extracranial metastatic disease to development of CNS metastases was 5.5 years (95% CI, 1.8-7.0). Median overall survival (mOS) from diagnosis of CNS metastases was 6.1 months (95% CI, 5.8-8.2). Notably, there was no significant difference in mOS after development of extracranial metastases in patients with CNS metastases (6.4 years; 95% CI, 4.6-7.9) compared to the patients without known CNS metastases (5.2 years; 95% CI, 4.6-5.7) (p=0.91). For the cohort with CNS metastases, nine patients had germline testing and seven patients had somatic testing via cfDNA.
Conclusions
PC patients with CNS metastases did not often die from a neurologic cause. With advancing therapies, the overall prognosis of metastatic PC continues to improve, and CNS metastases will become more common.
Introduction
: The overall survival (OS) of metastatic castration-resistant prostate cancer (mCRPC) patients has improved since 2011 with the use of novel hormonal agents (NHAs). The incidence of brain metastases (mets) has been reported to increase since 2004 with the use of docetaxel, but not the incidence of visceral mets. Our objective was to study whether the use of NHAs increases the risk of developing visceral or brain mets (VBMs).
Patients and methods
: mCRPC patients with mets limited to bone (bmCRPC), treated at Tours University Hospital between 2007 and 2015, were included retrospectively. The primary endpoint was to determine whether treatment with NHAs was associated with an increased incidence of VBMs. Secondary endpoints included the search for putative predictive factors to develop VBMs.
Results
: On 187 bmCRPC patients included, 65 developed VBMs. VBM incidence increased in bmCRPC patients alive after 2011, compared to patients who died before (39.7 vs 24.6%, p = 0.04). Meanwhile, their median OS increased from 16.3 months to 28.5 months (p = 0.01). The longer was the treatment with NHAs, the lower was the risk of VBMs (HR = 0.96, 95%CI [0.94; 0.99]), whereas age < 70 years (HR = 3.33, 95%CI [1.50; 7.40]) and low PSA level at diagnosis (HR = 1.58, 95%CI [1.16; 2.15]) increased this risk.
Conclusion
: Though retrospective, our results showed an increased incidence of VBMs in bmCRPC patients after 2011. However, this was not associated with NHA exposure duration. The role of NHA exposure remains unclear and needs further investigation.
MicroAbstract
: We aimed to study whether the use of novel hormonal agents (NHAs) increases the risk of developing visceral or brain metastases (VBMs) in bone metastatic castration-resistant prostate cancer (bmCRPC). Among the 187 bmCRPC patients included, VBMs incidence increased after 2011 (p = 0.04). Yet, the longer was the treatment with NHAs, the lower was the risk of VBMs.
CT images of a 56‐year‐old man with headache showed a meningioma‐like mass in the occipital region. The tumor was well‐defined and non‐uniform with bone thickening and no internal calcification. Eventually, he was diagnosed on the basis of histopathology and immunostaining findings as having a dural metastasis from a prostate cancer. In men, brain tumors that resemble meningiomas on CT images and are associated with bone thickening and rapid growth should be strongly suspected of being dural metastases from prostate cancer and therefore be evaluated quickly.
Background/aim:
Neuroendocrine prostate cancer (NEPC) is rare and has a poor prognosis; its clinical course and treatment outcomes are also unclear. This study investigated the clinical characteristics, clinical course, and treatment outcomes of patients with NEPC.
Patients and methods:
This retrospective study investigated 14 patients histologically diagnosed with NEPC at Kanazawa University Hospital between 2000 and 2019. Overall survival (OS) and progression-free survival (PFS) were retrospectively analyzed using the Kaplan-Meier method. Additionally, log-rank tests were used to compare survival distributions.
Results:
We included 14 patients histologically diagnosed with NEPC among 1,845 patients with prostate cancer. Four patients (0.22%) were diagnosed with de novo NEPC, and ten patients were diagnosed with NEPC during treatment. First-line platinum-based therapy's objective response rate (ORR) was 66.7%, and disease control rate was 91.7%; median PFS was 7.5 months. The median OS from NEPC diagnosis was 20.3 months. The median OS of the liver metastasis (-) group was 31.6 months, and that of the (+) group was 9.4 months (p=0.03, hazard ratio=0.24). The median OS of the somatostatin receptor scintigraphy (SRS)-positive group was 31.6 months, and that of the SRS-negative group was 10.6 months (p=0.04, hazard ratio=0.14).
Conclusion:
Platinum-based chemotherapy is effective to some extent, but the duration of response is not sufficient; therefore, new treatment options are needed. This is the first study to show that SRS findings and the presence of liver metastases might be prognostic predictors of NEPC.
During disease progression from primary towards metastatic prostate cancer (PCa), and in particular bone metastases, the tumor microenvironment (TME) evolves in parallel with the cancer clones, altering extracellular matrix composition, vasculature architecture, and recruiting specialized tumor-supporting cells that favor tumor spread and colonization at distant sites. We introduce the clinical profile of advanced metastatic PCa in terms of common genetic alterations. Findings from recently developed models of PCa metastatic spread are discussed, focusing mainly on the role of the TME (mainly matrix and fibroblast cell types), at distinct stages: premetastatic niche orchestrated by the primary tumor towards the metastatic site and bone metastasis. We report evidence of premetastatic niche formation, such as the mechanisms of distant site conditioning by extracellular vesicles, chemokines and other tumor-derived mechanisms, including altered cancer cell-ECM interactions. Furthermore, evidence supporting the similarities of stroma alterations among the primary PCa and bone metastasis, and contribution of TME to androgen deprivation therapy resistance are also discussed. We summarize the available bone metastasis transgenic mouse models of PCa from a perspective of pro-metastatic TME alterations during disease progression and give an update on the current diagnostic and therapeutic radiological strategies for bone metastasis clinical management.
Althought it may vary between countries, since the prostate specific antigen screening era, metastasic prostate cancer at diagnosis accounts for approximately 10% of cases. Intracranial dural metastases are uncommon, but when present they may lead to an increase in intracranial pressure that can subsequently damage intracranial structures, such as the cranial nerves. Prolonged intracranial hypertension can cause optic nerve ischemia, leading to progressive and irreversible vision loss if untreated, hence the importance of anamnesis, complete physical examination, and clinical suspicion.
Background
Intracranial metastases from prostate adenocarcinoma are very unusual and typically occur late in the course of the disease, and initial presentation with symptomatic brain involvement, especially vision loss is very rare (with this being only the sixth such reported case to the best of our knowledge). The present case elucidates how a diagnosis was reached in such a scenario and the management provided.
Case presentation
A 66-year-old gentleman presented with loss of vision and headache with no other ocular or neurological complaint. Computed tomography (CT) of his head revealed a destructive lesion involving the clivus and a space-occupying lesion (SOL) in occipito-parietal region. Detailed inquiry regarding the possible primary source of suspected the metastatic lesion revealed an increased frequency of urination, nocturia, and significant weight loss. His serum prostate-specific antigen (PSA) levels were raised. He was treated by surgical hormonal therapy and his visual symptoms improved.
Conclusion
Awareness of such a presentation can lead to an accurate diagnosis. Initiation of appropriate therapy can successfully alleviate the neurologic deficits.
Background
While it has been suspected that different primary cancers have varying predilections for metastasis in certain brain regions, recent advances in neuro-imaging and spatial modeling analytics have facilitated further exploration into this field.
Methods
A systematic electronic database search for studies analyzing the distribution of brain metastases (BM) from any primary systematic cancer published January 1990-July 2020 was conducted using PRISMA guidelines.
Results
Two authors independently reviewed 1,957 abstracts, 46 of which underwent full-text analysis. A third author arbitrated both lists; 13 studies met inclusion/exclusion criteria. All were retrospective single- or multi-institution database reviews analyzing over 8,227 BMs from 2,599 patients with breast (8 studies), lung (7 studies), melanoma (5 studies), gastrointestinal (4 studies), renal (3 studies), and prostate (1 study) cancers. Breast, lung, and colorectal tended to metastasize to more posterior/caudal topographic and vascular neuroanatomical regions, particularly the cerebellum, with notable differences based on subtype and receptor expression. HER-2 positive breast cancers were less likely to arise in the frontal lobes or subcortical region, while ER-positive and PR-positive breast metastases were less likely to arise in the occipital lobe or cerebellum. BM from lung adenocarcinoma tended to arise in the frontal lobes, and squamous cell carcinoma in the cerebellum. Melanoma metastasized more to the frontal and temporal lobes.
Conclusion
The observed topographical distribution of BM likely develops based on primary cancer type, molecular subtype, and genetic profile. Further studies analyzing this association and relationships to vascular distribution are merited to potentially improve patient treatment and outcomes.
Introduction and importance
Brain metastasis of prostatic cancer is highly a rare condition. Its intracranial metastatic process and presentation are poorly understood and limited to case reports, making it challenging to detect and diagnose. We aim to highlight the rare case, brain metastasis of prostate cancer, and review the literature regarding the progress and therapies of prostatic cancer in the current era. The case of a prostate adenocarcinoma patient who acquired brain metastasis was outlined. In addition, we review the literature to discuss the main aspects of brain metastasis in prostate cancer.
Case presentation
Herein, the patient was a 62-year-old male with metastatic prostate adenocarcinoma into the brain, which suffered from progressive language difficulties, mixed dysphasia, and right hemiparesis.
Clinical Discussion
Brain magnetic resonance imaging revealed a left frontoparietal mass, confirmed with an elevated PSA level. The group was resected, and after that, the patient was discharged with noticeable language and neurological improvement. Upon follow-up, after six months, a new asymptomatic left temporal lesion was observed and successfully treated with chemotherapy and radiotherapy. This case confirms that prostatic adenocarcinoma's possibility to spread into the brain.
Conclusion
This report reviews the literature about prostate cancer brain metastasis, highlighting that although rare, it does occur and shouldn't be neglected, especially with the current progress in prostatic cancer therapies, which prolongs the patient's survival time, so those brain metastases out of prostatic cancer are expected to be a frequent clinical scenario. Therefore, follow-up of prostatic cancer male patients of 50 years old or more is necessary.
"Prostate cancer is the second most frequent malignancy worldwide, with an increased incidence over the last two decades. Most patients are asymptomatic at diagnosis due to widespread opportunistic prostate-specific antigen-based screening. Cerebral metastases originating from prostatic tumors are rare, occurring in 0.16% to 0.63% of prostate cancer cases, and generally developing in the setting of widespread disease. We report the case of a 62-year-old male with symptomatic isolated brain metastasis as an early clinical presentation of prostate adenocarcinoma in the setting of a normal PSA and digital rectal examination. Next-generation sequencing panel revealed a mutation in the PALB2 gene. Germline mutation in genes involved in homologous recombination repair complex, such as BRCA1, BRCA2, and PALB2 increase the incidence and the aggressiveness of multiple cancer types including prostate cancer, yet can provide alternative treatment options using PARP inhibitors after disease progression for patients previously treated with enzalutamide or abiraterone."
A 61-year-old man visited our hospital with a headache and left visual field defect. A head MRI showed an intracranial dural tumor with cerebral compression, which was suspected to be metastatic. Analysis of the tumor markers revealed an increase in prostate-specific antigen (PSA) levels (172.8 ng/mL), and therefore prostate cancer was suspected as the primary tumor. Histological diagnosis of a prostatic tissue sample using a transrectal needle biopsy gave a prostate carcinoma with Gleason score of 5+4=9. Additional imaging examinations revealed metastatic lesions in the intra-pelvic lymph node and bones. These data indicated to us that curative surgery was unlikely to be successful, but finally we decided to perform a craniotomy for tumor resection for the intracranial dural tumor to remove his neurological symptoms. After surgery, his headache and visual field defect improved. The pathological finding was intracranial dural metastasis from prostate cancer and the clinical stage was diagnosed as T3bN1M1c in the UICC criteria (ver. 8). Endocrine therapy with degarelix and bicalutamide was started for the primary and residual metastatic prostate cancers. After one year of initial treatment, bicalutamide was changed to enzalutamide because of a tendency towards increased plasma PSA levels. The patient has survived for two and a half years after surgery with no new metastatic tumors or intracranial tumors. Our experience indicates that combined modality therapy with surgery can provide long-term survival with no cranial nerve disorders for patients who have prostate cancer with intracranial dural metastasis.
Prostatic cancer in 1885 autopsy cases was classified according to the number of organs involved in metastasis, and a comparison was made concerning the frequency of metastasis to the various organs. The frequencies of metastasis to the lungs and para-aortic lymph nodes were low in cases with single-organ involvement (4.6% and 2.3%, respectively), but increased rectilinearly in accordance with the number of organs involved and became high in cases with metastasis to three or more organs (49.1% and 21.8% in total, respectively). On the other hand, the frequencies of local extension to the bladder and invasion of the pelvic lymph nodes were high even in cases with single-organ involvement (34.5% and 9.2%, respectively) and were not significantly changed regardless of the number of organs involved. No significant correlation was seen between pelvic and para-aortic lymph node involvement. In cases with single-organ involvement, metastasis to the lumbar spine occurred frequently, but those to the ribs, sternum, and ilium occurred less frequently. There may be multiple metastases in cases with metastases to the para-aortic lymph nodes, sternum, and ilium. The number of metastatically involved organs is useful in analyzing the mode of metastasis.
BACKGROUND
With the advent of new therapies for metastatic carcinoma to the brain, patterns of intracranial disease and factors influencing survival become important considerations when examining potential treatment options.METHODS
The records of 729 patients with metastases to the brain treated during the period between 1973 to 1993 were reviewed.RESULTSPrimary tumor histologic type in order of descending frequency included nonsmall cell lung carcinoma (NSCLC), breast carcinoma, small cell lung carcinoma (SCLC), malignant melanoma, renal cell carcinoma, gastrointestinal carcinoma, uterine/vulvar carcinoma, and unknown primary carcinoma. There were 384 patients (53%) with a single brain metastasis, which was encountered most commonly in patients with prostate carcinoma and least often in patients with SCLC. Multiple metastases were present in 345 patients (47%). The median duration from diagnosis to presentation with a brain metastasis was 12 months, ranging from 3 months for patients with NSCLC to 53 months for patients with breast carcinoma. The median duration from presentation with brain metastases to death was 4 months, ranging from 3 months for patients with SCLC to 13 months for patients with prostate carcinoma. Median survival from presentation with brain metastases to death was 5 months for patients with single lesions and 3 months for patients with multifocal disease (P = 0.0001). Median survival for patients with a single lesion was 11 months with surgery and 3 months without surgery (P = 0.0001). Surgery did not significantly influence survival in patients with multiple metastases.CONCLUSIONS
Dissemination of systemic carcinoma to the brain continues to carry a poor prognosis. Knowledge of the metastatic patterns and limited survival associated with specific tumor types may be useful for guiding future therapeutic intervention. Cancer 1996;1781-8.
BACKGROUND
Brain metastases are diagnosed in 15% of patients with metastatic breast carcinoma. Most patients are treated with whole-brain radiotherapy (WBRT) and/or chemotherapy. The information on surgical results is sparse.METHODS
Among 709 patients with tumors metastatic to the brain who underwent craniotomy at Memorial Hospital, New York, New York, between January 1974 and December 1993, 70 (10%) had a primary breast carcinoma. Their treatment outcomes were analyzed retrospectively.RESULTSThe median age at diagnosis of primary breast carcinoma and brain metastasis was 46 and 50 years, respectively. All but two patients had metachronous diagnoses of breast carcinoma and brain metastasis. The median interval between both diagnoses in this subgroup was 28 months. In all 70 patients, the overall median survival was 54 months after diagnosis of the primary breast tumor and 16.2 months after diagnosis of the brain tumor. Only 5 patients (7%) were alive at last follow-up. The overall median survival after brain surgery was 14 months. Four patients died within 30 days of craniotomy. Twelve patients had a solitary cerebellar metastasis and 16 had multiple metastases; their median survival was 10.9 months and 14.8 months, respectively. There was no statistical difference in survival for patients who had single or multiple lesions. The median survival of 22 patients with positive hormonal receptor (estrogen receptor [ER] or progesterone receptor [PR]) was significantly longer than the median survival of 20 patients with negative ER/PR (21.9 vs. 12.5 months, P < 0.05). For 35 patients (50%) who had brain lesions ≥4 cm, the median survival was 11 months, compared with 16.3 months for patients with smaller lesions (P = 0.16, not significant [NS]). Patients age ≤50 years versus >50 years had survival of 17.3 and 11.1 months, respectively (P = NS). Neurologic deficit prior to craniotomy shortened survival for 24 patients to 11.5 months, compared with 17.4 months for patients without deficit (P = NS). Fifteen patients experienced failure with WBRT prior to undergoing craniotomy, and their median survival was shorter than for those who underwent craniotomy as the initial treatment (6.3 vs. 15.8 months, P < 0.03). However, their survival after diagnosis of brain metastasis was not significantly different (19.2 vs. 16.1). Forty-seven patients received WBRT postoperatively, and 9 patients did not receive adjuvant radiation therapy. Subsequent relapse in the brain was diagnosed in 27 patients, and 8 of them underwent reresection. One-year, 2-year, 3-year, and 5-year survival rates were 53%, 25.7%, 18.6%, and 7%, respectively. In multivariate analysis, the adjuvant WBRT after craniotomy and the absence of meningeal carcinomatosis were the only significant predictive variables for longer survival.CONCLUSIONS
In a subset of selected patients, craniotomy followed by WBRT can positively impact survival. Cancer 1997; 80:1746-54. © 1997 American Cancer Society.
Brain metastasis from prostatic carcinoma is considered rare and usually is diagnosed at postmortem examination. The authors reviewed the tumor registry of 1314 patients with proven diagnosis of prostatic carcinoma seen at Hines VA Hospital from January 1963 to December 1978 and found that 8 of the 1314 patients (0.6%) had brain metastasis. Six of eight patients (75%) were diagnosed having brain metastasis at premortem and of these, two patients presented with brain metastasis before diagnosis of prostatic carcinoma was made. Two of four patients who received palliative whole brain irradiation survived more than 1.5 years. It is our belief that patients with prostatic carcinoma who have symptoms of brain metastasis should be worked up and given palliative whole brain irradiation.
BACKGROUND
In patients with prostate carcinoma, brain metastasis has most commonly been reported in autopsy series. Symptomatic brain metastasis from prostate carcinoma has occasionally been detected.METHODS
The authors retrospectively studied a series of 38 patients with antemortem intracerebral metastasis found on review of 7994 patients treated over an 18-year period at the University of Texas M. D. Anderson Cancer Center.RESULTSThe mean time from diagnosis of prostate carcinoma to discovery of brain metastasis was 28 months, with a mean survival of 9.2 months after the discovery of the brain metastasis. The brain metastasis was treated only with whole brain irradiation in 29 patients, with craniotomy and irradiation in 8 patients, and with surgery alone in 1 patient. Small cell carcinomas and primary transitional cell carcinomas of the prostate were much more likely to produce brain metastasis than were adenocarcinomas. Also noted among the overall prostate carcinoma cohort was a second group of 16 patients with prostate carcinoma and brain metastasis that had developed from a second primary tumor, which in all was either lung carcinoma or melanoma.CONCLUSIONS
The occurrence of brain metastasis in prostate carcinoma patients is rare, usually signifies a late stage of the disease, and may in some patients be produced by a tandem extraprostatic tumor. Cancer 1999;86:2301–11. © 1999 American Cancer Society.
Between 1959 and 1971 there were 91 patients with clinically diagnosed prostatic carcinoma who were autopsied at Roswell Park Memorial Institute. In four of these 91 (4.4%) intracerebral metastasis were found at autopsy, but only in one of these four was the diagnosis arrived at pre-mortem. This report describes the diagnosis and management of intracerebral metastasis from prostate carcinoma. It appears, on the basis of our initial experience, that the clinical diagnosis of this entity deserves more frequent consideration.
A total of 21 patients with metastatic small cell carcinoma of the prostate was treated with combination chemotherapy, either following initial hormonal therapy (15) or as initial therapy (6). Of the patients 13 (62%) had pure small cell carcinoma, whereas 8 (38%) had mixed histology of small cell carcinoma and adenocarcinoma. Patients presented with a characteristic clinical picture of a large primary mass (16 cases) with a high frequency of visceral metastases to the liver (9), lungs (7) and brain (2). The majority of the patients did not have an elevated serum prostate specific antigen (1 of 14, 7%) or prostatic acid phosphatase (2 of 21, 10%). Serum carcinoembryonic antigen was elevated in 13 patients (62%). Of the 21 patients 13 (62%) responded to chemotherapy. Survival after the diagnosis of small cell carcinoma of the prostate resulted in a median of 9.4 months with a range of 1 to 25 months. The regimens used were those considered active in the treatment of small cell carcinoma of the lung (vincristine, doxorubicin and cyclophosphamide, or etoposide and cisplatin with or without doxorubicin). Small cell carcinoma of the prostate has a characteristic clinical picture and a high response rate to cytotoxic therapy. Early introduction of chemotherapy in the treatment of small cell carcinoma of the prostate may increase the survival rate.
The number and site of brain metastases were identified on the computed tomographic scans of 288 patients. There was one brain metastasis in 49%, two in 21%, three in 13%, four in 6%, and five or more in 11% of scans. In patients with one metastasis, the posterior fossa was involved in 50% of patients when the primary tumor was pelvic (prostate or uterus) or gastrointestinal, but it was involved in only 10% of patients with other primary tumors. Hemispheral metastases preferred the anatomic "watershed areas" (29% of the brain surface contained 37% of the metastases), indicating that tumoral microemboli tend to lodge in the capillaries of the distal parts of the superficial arteries. The charts of 134 patients with brain metastases from a primary tumor originating outside the lung revealed that the incidence of lung and spine metastases was the same, whether the primary tumor was pelvic or gastrointestinal or from another site. These data suggest that the high incidence of subtentorial lesions in patients with pelvic and gastrointestinal primary tumors cannot be explained by arterial embolization alone, and that this peculiar distribution is probably not explained by seeding of the brain through Batson's plexus.
Two patients with parenchymal brain metastases from adenocarcinoma of the prostate (CaP) are presented. Both patients had the diagnosis made antemortem by biopsy, and tumor immunoreactivity for prostatic phosphatase and prostate specific antigen confirmed prostatic origin. Brain metastases from prostatic adenocarcinoma are unusual, occurring in only 0.2 per cent of all patients with CaP. Patients present with symptoms of motor dysfunction, headache, and seizures. The mean age at presentation of brain metastases from CaP is fifty-nine years old, which is younger than most patients with CaP. The majority of patients die within weeks after diagnosis. Craniotomy with tumor debulking, radiation therapy, and androgen deprivation may be useful in prolonging survival. All reported cases of CaP metastatic to brain have been histologically moderately differentiated or poorly differentiated. The periprostatic venous plexus is considered the most likely route of tumor spread to the brain.
A report is presented on 12 patients with extrapulmonary small cell carcinoma. In 9 patients the primary tumor could be localized (cervix in 3, esophagus in 3, prostate in 2, pancreas in 1) whereas no primary was found in 3. Seven of 12 patients presented with distant metastases and four developed metastases later. Five of 12 had CNS metastases (brain metastases in 4, spinal cord compression in 1). Six patients were initially treated by surgery or radiotherapy (2 and 4 respectively). All six developed distant metastases during or shortly after local treatment. Five of 6 patients initially treated with chemotherapy responded to the treatment. Three of 12 patients are surviving 18+, 80+ and 81+ months after the initial diagnosis without evidence of disease. The biology and clinical course of extrapulmonary small cell carcinoma are similar to those of its pulmonary counterpart. In planning therapy for extrapulmonary small cell carcinoma, particular importance should be attached to systemic treatment.
Prostatic cancer in 1885 autopsy cases was classified according to the number of organs involved in metastasis, and a comparison was made concerning the frequency of metastasis to the various organs. The frequencies of metastasis to the lungs and para-aortic lymph nodes were low in cases with single-organ involvement (4.6% and 2.3%, respectively), but increased rectilinearly in accordance with the number of organs involved and became high in cases with metastasis to three or more organs (49.1% and 21.8% in total, respectively). On the other hand, the frequencies of local extension to the bladder and invasion of the pelvic lymph nodes were high even in cases with single-organ involvement (34.5% and 9.2%, respectively) and were not significantly changed regardless of the number of organs involved. No significant correlation was seen between pelvic and para-aortic lymph node involvement. In cases with single-organ involvement, metastasis to the lumbar spine occurred frequently, but those to the ribs, sternum, and ilium occurred less frequently. There may be multiple metastases in cases with metastases to the para-aortic lymph nodes, sternum, and ilium. The number of metastatically involved organs is useful in analyzing the mode of metastasis.
In a clinicopathologic review of 126 autopsied cases with prostate cancer, 14 demonstrated intracranial metastases. Only two of nine symptomatic patients were evaluated for suspected central nervous system metastases prior to death, and five asymptomatic patients were incidentally found to have metastases at autopsy. Intracranial metastases in prostate cancer occur in the setting of widespread disease, and tissue pathology may reveal moderately to poorly differentiated tumor (11 of 14 cases).
In Geneva at autopsies, 4.8% of the cranial cavities contained metastasis of any origin (872 cases in 19 years), which in 21 cases was prostatic (2.4%). During 7 years, 7592 autopsies were performed, and 159 prostatic cancers discovered (2.1%), among them 10 had intracranial metastasis, in each case in association with other localisations. Multiple localisations were present in 70 cases (44%), unique localisation in 26 cases; no metastasis were discovered in 63 cases (40%). The most frequent localisation was bone. The mean age was 70.5 years when an intracranial localisation was present, 78.3 years when not. Only 3 cases out of 21 were admitted in a neurological or neurosurgical ward and no intracranial operation was performed. This can explain why intracranial mestastasis of prostatic carcinoma is usually considered as a rare condition.
The authors reviewed the records of 231 patients who underwent resection of brain metastases from nonsmall-cell lung cancer between 1976 and 1991. Data regarding the primary disease and the characteristics of brain metastasis were retrospectively collected. Median survival in the group from the time of first craniotomy was 11 months; post-operative mortality was 3%. Survival rates of 1, 2, 3, and 5 years were 46.3%, 24.2%, 14.7%, and 12.5%, respectively. One hundred twelve women survived significantly longer than 119 men (13.8 vs. 9.5 months, p < 0.02). Patients with single metastatic lesions (200 patients) survived longer than those (31 patients) with multiple metastases (11.1 vs. 8.5 months, p < 0.02). Patients with supratentorial tumors survived longer than patients with cerebellar lesions. A high Karnofsky performance scale score before surgery also indicated increased survival. In multivariate analyses, incomplete resection or no resection of primary lung tumor, male gender, infratentorial location, presence of systemic metastases, and age older than 60 years were significantly correlated with shorter survival. Approximately one-third of the patients died of neurological causes, one-third of systemic disease, and one-third of a combination of both. The results of this series confirm that the overall prognosis for patients with even a single resectable brain metastasis is poor, but that aggressive therapy can prolong life with quality of life preserved and can occasionally permit long-term survival.
Metastases are frequently diagnosed among patients with renal cell carcinoma (RCC). Of 709 patients with brain metastases (BMET) who were operated on at our institution between 1974 and 1993, 50 (7%) were of renal origin.
Medical records were reviewed retrospectively. Survival time was calculated by the Kaplan-Meier method and Cox proportional hazards model.
There were 38 men and 12 women. The median age was 60 years. The primary RCC was resected in 47 patients. Forty patients had a metachronous diagnosis of RCC and BMET. Median interval between the diagnosis of RCC and BMET was 17 months. In all 50 patients overall median survival (MS) from diagnosis of primary RCC was 31.4 months and from craniotomy was 12.6 months. Postoperative mortality was 10% (5 patients). In patients with primary RCC in the left kidney (n=25) versus right kidney (n=25) median survival from craniotomy was longer; 21.3 versus 7.4 months (P<0.014). Twenty-three patients (46%) had intratumoral hemorrhage. Eight patients had cerebellar metastasis (MS, 3.0 months) and 9 had multiple metastases resected (MS, 7.6 months). Thirty-eight patients had both brain and pulmonary metastases, and 16 of them had pulmonary resection (MS, 18.6 versus 8.0 months; P<0.03). Twenty-two patients received whole-brain radiation therapy (WBRT) after craniotomy and 18 did not receive WBRT (MS, 13.3 versus 14.5 months; P<0.62). The 1-year, 2-year, 3-year, and 5-year survival was 51%, 24%, 22%, and 8.5% respectively.
Only the resection of lung metastasis, supratentorial location of BMET, left-sided localization of primary RCC, and lack of neurologic deficit before craniotomy were statistically significant prognostic factors in Cox regression analysis. In the absence of effective systemic treatment, we suggest that patients with BMET from RCC be considered for operative resection for treatment and palliation.
With the advent of new therapies for metastatic carcinoma to the brain, patterns of intracranial disease and factors influencing survival become important considerations when examining potential treatment options.
The records of 729 patients with metastases to the brain treated during the period between 1973 to 1993 were reviewed.
Primary tumor histologic type in order of descending frequency included nonsmall cell lung carcinoma (NSCLC), breast carcinoma, small cell lung carcinoma (SCLC), malignant melanoma, renal cell carcinoma, gastrointestinal carcinoma, uterine/vulvar carcinoma, and unknown primary carcinoma. There were 384 patients (53%) with a single brain metastasis, which was encountered most commonly in patients with prostate carcinoma and least often in patients with SCLC. Multiple metastases were present in 345 patients (47%). The median duration from diagnosis to presentation with a brain metastasis was 12 months, ranging from 3 months for patients with NSCLC to 53 months for patients with breast carcinoma. The median duration from presentation with brain metastases to death was 4 months, ranging from 3 months for patients with SCLC to 13 months for patients with prostate carcinoma. Median survival from presentation with brain metastases to death was 5 months for patients with single lesions and 3 months for patients with multifocal disease (P = 0.0001). Median survival for patients with a single lesion was 11 months with surgery and 3 months without surgery (P = 0.0001). Surgery did not significantly influence survival in patients with multiple metastases.
Dissemination of systemic carcinoma to the brain continues to carry a poor prognosis. Knowledge of the metastatic patterns and limited survival associated with specific tumor types may be useful for guiding future therapeutic intervention.
Brain metastases are diagnosed in 15% of patients with metastatic breast carcinoma. Most patients are treated with whole-brain radiotherapy (WBRT) and/or chemotherapy. The information on surgical results is sparse.
Among 709 patients with tumors metastatic to the brain who underwent craniotomy at Memorial Hospital, New York, New York, between January 1974 and December 1993, 70 (10%) had a primary breast carcinoma. Their treatment outcomes were analyzed retrospectively.
The median age at diagnosis of primary breast carcinoma and brain metastasis was 46 and 50 years, respectively. All but two patients had metachronous diagnoses of breast carcinoma and brain metastasis. The median interval between both diagnoses in this subgroup was 28 months. In all 70 patients, the overall median survival was 54 months after diagnosis of the primary breast tumor and 16.2 months after diagnosis of the brain tumor. Only 5 patients (7%) were alive at last follow-up. The overall median survival after brain surgery was 14 months. Four patients died within 30 days of craniotomy. Twelve patients had a solitary cerebellar metastasis and 16 had multiple metastases; their median survival was 10.9 months and 14.8 months, respectively. There was no statistical difference in survival for patients who had single or multiple lesions. The median survival of 22 patients with positive hormonal receptor (estrogen receptor [ER] or progesterone receptor [PR]) was significantly longer than the median survival of 20 patients with negative ER/PR (21.9 vs. 12.5 months, P < 0.05). For 35 patients (50%) who had brain lesions > or =4 cm, the median survival was 11 months, compared with 16.3 months for patients with smaller lesions (P = 0.16, not significant [NS]). Patients age < or =50 years versus >50 years had survival of 17.3 and 11.1 months, respectively (P = NS). Neurologic deficit prior to craniotomy shortened survival for 24 patients to 11.5 months, compared with 17.4 months for patients without deficit (P = NS). Fifteen patients experienced failure with WBRT prior to undergoing craniotomy, and their median survival was shorter than for those who underwent craniotomy as the initial treatment (6.3 vs. 15.8 months, P < 0.03). However, their survival after diagnosis of brain metastasis was not significantly different (19.2 vs. 16.1). Forty-seven patients received WBRT postoperatively, and 9 patients did not receive adjuvant radiation therapy. Subsequent relapse in the brain was diagnosed in 27 patients, and 8 of them underwent reresection. One-year, 2-year, 3-year, and 5-year survival rates were 53%, 25.7%, 18.6%, and 7%, respectively. In multivariate analysis, the adjuvant WBRT after craniotomy and the absence of meningeal carcinomatosis were the only significant predictive variables for longer survival.
In a subset of selected patients, craniotomy followed by WBRT can positively impact survival.
At the time of diagnosis of colorectal carcinoma, 2-3% of patients are likely to be harboring brain metastases, and another 10% of patients will develop brain lesions during the course of their disease. The purpose of this study was to examine the clinical course of a group of patients with metastatic brain disease who underwent surgical resection in a single institution. The authors believe this information will be useful for establishing prognostic factors and for clinical decision making.
Between 1974 and 1993, 709 consecutive patients underwent surgical resection of brain metastases at Memorial Sloan-Kettering Cancer Center. Seventy-three patients had histologically confirmed colorectal carcinoma. The medical records of these patients were reviewed retrospectively, and the data were analyzed by univariate and multivariate analysis.
The median age of the 43 women and 30 men was 61.5 years. The median interval from the time of diagnosis of the primary tumor and the development of brain metastases was 27.6 months. The primary colorectal tumor was resected in all patients, and the median survival from the day of surgery was 38 months. The median survival from the time of craniotomy was 8.3 months. The 1-year and 2-year survival rates were 31.5% and 6.8%, respectively. Postoperative mortality was 4%. Gender, presence of multiple metastases, presence of lung lesions, and adjuvant brain radiation after craniotomy appeared to have no impact on survival as determined by multivariate Cox analysis. Only the presence of cerebellar brain metastases was associated with decreased survival.
The results of this series, which the authors believe is the largest series of resected brain metastases from colorectal carcinoma published to date, indicate that surgical resection may increase the survival of these patients. Analysis of prognostic factors shows that infratentorial tumor location is associated with a poorer survival compared with supratentorial tumor location (5.1 months vs. 9.1 months; P < 0.002). In patients with recurrent brain disease, repeated resection is a worthwhile consideration because it may prolong survival compared with patients who do not undergo re-resection.
In patients with prostate carcinoma, brain metastasis has most commonly been reported in autopsy series. Symptomatic brain metastasis from prostate carcinoma has occasionally been detected.
The authors retrospectively studied a series of 38 patients with antemortem intracerebral metastasis found on review of 7994 patients treated over an 18-year period at the University of Texas M. D. Anderson Cancer Center.
The mean time from diagnosis of prostate carcinoma to discovery of brain metastasis was 28 months, with a mean survival of 9.2 months after the discovery of the brain metastasis. The brain metastasis was treated only with whole brain irradiation in 29 patients, with craniotomy and irradiation in 8 patients, and with surgery alone in 1 patient. Small cell carcinomas and primary transitional cell carcinomas of the prostate were much more likely to produce brain metastasis than were adenocarcinomas. Also noted among the overall prostate carcinoma cohort was a second group of 16 patients with prostate carcinoma and brain metastasis that had developed from a second primary tumor, which in all was either lung carcinoma or melanoma.
The occurrence of brain metastasis in prostate carcinoma patients is rare, usually signifies a late stage of the disease, and may in some patients be produced by a tandem extraprostatic tumor.
Three male patients with extrapulmonary small-cell carcinoma originating from esophagus, pancreas and prostate are described. The patient with the esophagus tumor had a combined small-cell and undifferentiated carcinoma. The other two patients had a pure small-cell carcinoma. All patients were treated with primary combination chemotherapy consisting of etoposide and cisplatin followed in one patient by locoregional radiotherapy. The patients with the esophagus and the pancreas tumor showed a partial response; the patient with the prostate tumor achieved a complete remission but relapsed with brain metastasis. All patients are alive 7, 13 and 19 months, respectively after initiation of the therapy. As in pulmonary small-cell carcinoma, primary chemotherapy is the treatment of choice in extrapulmonary small-cell carcinoma.
The Radiation Therapy Oncology Group (RTOG) previously developed three prognostic classes for brain metastases using recursive partitioning analysis (RPA) of a large database. These classes were based on Karnofsky performance status (KPS), primary tumor status, presence of extracranial system metastases, and age. An analysis of RTOG 91-04, a randomized study comparing two dose-fractionation schemes with a comparison to the established RTOG database, was considered important to validate the RPA classes.
A total of 445 patients were randomized on RTOG 91-04, a Phase III study of accelerated hyperfractionation versus accelerated fractionation. No difference was observed between the two treatment arms with respect to survival. Four hundred thirty-two patients were included in this analysis. The majority of the patients were under age 65, had KPS 70-80, primary tumor controlled, and brain-only metastases. The initial RPA had three classes, but only patients in RPA Classes I and II were eligible for RTOG 91-04.
For RPA Class I, the median survival time was 6. 2 months and 7.1 months for 91-04 and the database, respectively. The 1-year survival was 29% for 91-04 versus 32% for the database. There was no significant difference in the two survival distributions (p = 0.72). For RPA Class II, the median survival time was 3.8 months for 91-04 versus 4.2 months for the database. The 1-year survival was 12% and 16% for 91-04 and the database, respectively (p = 0.22).
This analysis indicates that the RPA classes are valid and reliable for historical comparisons. Both the RTOG and other clinical trial organizers should currently utilize this RPA classification as a stratification factor for clinical trials.
Reports on the surgical treatment of brain metastases from melanoma in a large group of patients are sparse. The goal of this paper is to review the surgical experience in a series of 91 patients with brain metastases from primary melanoma treated at a single institution.
Seven hundred eighty patients underwent resection of brain metastases at Memorial Sloan-Kettering Cancer Center between 1974 and 1994. The records of 91 (11.7%) of these patients who had melanoma were retrospectively reviewed. The median time from diagnosis of the primary melanoma to diagnosis of the brain lesion was 14.1 months. The overall median length of survival following craniotomy was 6.7 months. Fifteen patients with resected multiple metastases had shorter median survival times than 76 patients with a single lesion (5.4 months compared with 7.8 months, p = 0.12). In eight patients with cerebellar metastases the median length of survival was significantly shorter than that found in patients with supratentorial lesions (2 compared with 7 months, p = 0.03). There was no difference in length of survival between 49 patients who underwent postoperative whole-brain radiation therapy (WBRT) and 29 patients who did not (9.5 compared with 8.3 months, p = 0.67). The incidence of brain metastasis recurrences in WBRT-treated and untreated patients was similar (56% and 45.7%, respectively). Only the presence of infratentorial metastases (p = 0.0013) and unresected recurrence of brain metastases (p = 0.0003) had an impact on outcome according to a Cox regression analysis. Five patients (5.5%) died within 31 days of surgery. Overall survival rates at 1, 2, 3, and 5 years were 36.3, 18.7, 13.2, and 6.6%, respectively.
Although melanoma metastatic to the brain carries a foreboding prognosis, patients who do not display preoperative neurological deficits, harbor a single lesion situated supratentorially, and have no lung or visceral metastases may derive significant palliative benefit from surgical resection of brain metastases.
Brain metastases are a common complication of systemic cancer and a significant cause of morbidity. For patients whose brain metastases remain untreated, the prognosis is poor. The advent of contrast-enhanced magnetic resonance imaging has made accurate diagnosis of brain metastases among symptomatic patients a much more manageable task. However, approximately one-third of patients with intracranial metastases are asymptomatic, and therefore, greater awareness of the risk factors for developing brain metastases may permit better targeting of "at risk" patients for further evaluation. Advances in technology and surgical techniques have created more options for the management of brain metastases via the use of various combinations of surgery, irradiation, and stereotactic radiosurgery. However, successful application of these therapies has redefined the potential for long-term morbidity associated with radiation therapy. Thus, considerable effort is now being directed toward finding a balance between the use of whole-brain radiotherapy, surgery, and radiosurgery, and tailoring those treatment modalities to the unique needs of the patient. Although more prospective, randomized studies are needed before an informed consensus regarding the optimal means for managing brain metastases can be established, this article provides an overview of some of the advantages and disadvantages of therapeutic approaches recently under study.
Validation of the RTOG recursive partitioning analysis (RPA) classification for brain metastases
- L E Gaspar
- C Scott
- K Murray
- W Curran
Gaspar LE, Scott C, Murray K, Curran W. Validation of the RTOG
recursive partitioning analysis (RPA) classification for brain metastases. Int J Radiat Oncol Biol Phys. 2000;47:1001-1006.
- Wronski
- Catane
- Taylor