Metastatic prostate carcinoma to bone: clinical and pathologic features associated with cancer-specific survival

BACKGROUND: The objective of this study was to examine the clinical and pathologic features of metastatic prostate carcinoma to bone in a large cohort of men, and the associations of these features with outcome. METHODS: Sixty-eight men who underwent surgery for metastatic prostate carcinoma to bone for stabilization of a pathologic fracture or impending fracture were studied. Clinical characteristics included the type of treatment for the primary and metastatic prostate carcinoma, age and serum prostate specific antigen (PSA) at the diagnosis of the metastatic prostate carcinoma, radiographic findings of the metastasis (osteoblastic, osteolytic, or mixed), and the number of metastatic sites at the time of the surgery for the metastasis. Pathologic features examined included Gleason score of the metastatic prostate carcinoma. Immunohistochemical stains for MIB-1, cytokeratin, PSA, synaptophysin, chromogranin A, serotonin, estrogen receptor, progesterone receptor, and androgen receptor were performed for all cases. The Kaplan-Meier method was used to estimate cancer-specific survival. The duration of follow-up was defined as the interval from the date of surgery for the metastasis to the date of death or last follow-up. Univariate and multivariate Cox proportional hazards models were fit to assess the features that were associated with death from prostate carcinoma. RESULTS: The average (standard deviation) time from the surgery for the metastasis to death from prostate carcinoma was 1.5 (1.9) years, ranging from 0 days to 10 years, with a median of 1 year. The estimated cancer-specific survival rates at 1 year, 2 years, and 3 years were 54.3%, 28.8%, and 22.9%, respectively. Median cancer-specific survival occurred at 1.1 years. After 4 years of follow-up, there were only seven patients left at risk for death from prostate carcinoma. Features that were found to be significantly associated with death from prostate carcinoma univariately included the interval between the diagnosis of metastasis and the surgery for metastasis (P < 0.001), androgen deprivation therapy before surgery for the metastasis (P = 0.002), presentation with metastasis (P = 0.003), the number of metastatic sites (P = 0.034), Gleason score of the metastasis (P = 0.002), and tumor positivity for chromogranin A (P = 0.041). On multivariate analysis, the interval between the diagnosis of metastasis and the surgery for metastasis (P < 0.001), Gleason score of the metastasis (P < 0.001), and tumor positivity for chromogranin A (P = 0.009) were associated significantly with death from prostate carcinoma. CONCLUSIONS: Although cancer-specific survival for patients after surgery for prostate carcinoma metastatic to bone is poor, assessments of tumor differentiation of the metastasis and chromogranin A positivity provide prognostic information.     

Brain metastasis from prostate carcinoma: antemortem recognition and outcome after treatment

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. RESULTS: 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. 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.     

Increased expression of apoptosis inhibitor protein XIAP contributes to anoikis resistance of circulating human prostate cancer metastasis precursor cells

Survival in lymph or blood is an essential prerequisite for metastasis of carcinoma cells to distant organs. Recently, we reported isolation and initial biological characterization of circulating metastatic cells in a fluorescent, orthotopic, metastatic nude-mouse model of human prostate cancer. Here we show that the metastatic human prostate carcinoma cells selected for survival in the circulation have increased resistance to anoikis, which is apoptosis induced by cell detachment. Using gene silencing and gene transfer techniques, we show that increased expression of the apoptosis inhibitory protein XIAP contributes to anoikis resistance of the circulating metastatic human prostate carcinoma cells. We also provide initial preclinical data on the antimetastatic efficacy of recently discovered small-molecule antagonists of XIAP.     

Viable circulating metastatic cells produced in orthotopic but not ectopic prostate cancer models

Elucidation of the mechanisms of hormone-independent metastatic prostate cancer remains a significant and highly relevant challenge. We report here that hormone-refractory human prostate carcinoma growing orthotopically efficiently deliver viable metastatic cells in the host circulation. This is in contrast to the ectopic tumors of the same lineage, which do not deliver live cells into the circulation. To investigate the malignant potential of viable circulating carcinoma cells, we developed a novel dual-color orthotopic coimplantation model of human prostate cancer metastasis in nude mice. This model is comprised of coinjection of an equivalent mixture of isolated and cultured circulating green fluorescent protein-expressing clones and parental red fluorescent protein-expressing human prostate carcinoma cells. In the dual-color model, the selected green fluorescent protein-labeled viable circulating cells have an increased metastatic propensity relative to the red fluorescent protein-labeled parental cells. The identification and isolation of highly malignant viable circulating human prostate carcinoma cells from orthotopic but not ectopic models will enable important new insights into the metastatic process including the role of the tumor microenvironment.     

Brain metastasis from prostate cancer. Report of 13 cases and critical analysis of the literature

Brain metastasis from prostate carcinoma occurs very rarely. We describe 13 patients with single brain metastasis from prostatic cancer. Total removal of the lesions was performed in ten patients. Three patients underwent stereotactic biopsy. All patients were treated with postoperative whole brain radiotherapy (WBRT). Eight patients died for systemic disease after a mean time of 9.2 months with a diagnosis of metastasis. Five patients are still alive at 20, 14, 11, 7 and 6 months, respectively. Even if brain metastasis from prostate cancer is often a terminal event with death occurring within few months from diagnosis, we suggest the same protocol (surgery and/or radiosurgery plus postoperative WBRT) usually adopted to treat brain metastasis from other primitive tumours. A non specific neurological symptomatology and a possible normal dosage of serum specific antigen may contribute to a delay in diagnosis. However, considering the rarity of brain metastasis from prostate carcinoma, standard brain MRI follow-up in men with prostatic cancer does not seem to be necessary yet.     

Prostate cancer and spinal cord compression

Prostate cancer metastasis to the spine is an extremely difficult clinical problem to treat. However, it occurs commonly, and all clinicians--not only oncologists--should undertake to understand its pathogenesis, diagnosis, clinical presentation, and current treatment options. This review emphasizes the surgical treatment of prostate cancer metastasis to the spine. The goals of this article are to (1) present an overview of the pathophysiology of this disease, with an emphasis on the mechanisms of metastasis and invasion, (2) provide a general overview of the clinical presentation and diagnosis of metastatic prostate carcinoma, and (3) discuss currently available treatment options. Such options include best medical management, nonsurgical treatments (radiation, chemotherapy), and surgical treatment of newly diagnosed and previously irradiated metastatic prostate carcinoma to the spine. Algorithms for the treatment of this disease are presented.     

Iris metastasis from prostate carcinoma: A case report and review of the literature

Despite the high incidence of prostate carcinoma, metastases of the uvea are very rare and the iris localization is even more. Only a few cases worldwide have been described so far. We report here the case of a 66-year-old man diagnosed with a metastatic prostate carcinoma. Nine months later, he developed brain and skin metastases. A couple of weeks later, the metastatic lesion appeared on his left iris. He has received whole brain radiation therapy including the iris lesion in the radiation fields. Through this case report and a literature review, we discuss the incidence, the different clinical presentations and the impact on the survival prognosis of this uncommon metastatic site.     

不同骨转移潜能人前列腺癌细胞亚株的筛选

背景与目的:前列腺癌具有很高的骨转移率,是导致患者死亡的主要原因,但是其机制仍不清楚。利用裸鼠肿瘤转移模型筛选人前列腺癌不同骨转移潜能的细胞亚株,通过分析其细胞生物学特性,将为今后探索前列腺癌骨转移机制提供模型。方法:采用人前列腺癌细胞系PC-3左心室注射法制作裸鼠肿瘤转移模型,分别获取骨和淋巴结转移灶内的肿瘤细胞,经体外培养及造模,筛选高、低骨转移潜能的细胞亚株。结果:筛选出具有高、低骨转移潜能的细胞亚株T3B和P24,其裸鼠体内骨转移率分别为8/10(80%)、1/10(10%),与母系PC-3细胞6/15(40%)比较差异有显著性(P<0.05);细胞生物学特性分析显示T3B、P24和PC-3的体外黏附率分别为112%±8%、80.3%±2.7%和77%±4%,侵袭能力分别为53±6个/视野、31±3个/视野和24±5个/视野,T3B的细胞黏附和侵袭能力均显著高于P24和PC-3(P<0.01),三者体外细胞增殖率、软琼脂克隆形成率、裸鼠皮下成瘤率及瘤体大小的差异无显著性(P>0.05)。结论:运用裸鼠肿瘤转移模型反复筛选,获得高(T3B)、低(P24)骨转移潜能的人前列腺癌PC-3细胞系亚株。     

Raf kinase inhibitor protein: a prostate cancer metastasis suppressor gene

Defining the mechanisms that confer metastatic ability on cancer cells is an important goal towards prevention of metastasis. A gene array screen between a non-metastatic prostate cancer cell and its metastatic derivative line revealed decreased expression of Raf kinase inhibitor protein (RKIP) in the metastatic cell line. This finding is consistent with the possibility that loss of RKIP is associated with metastasis. RKIP is expressed in many tissues including brain, lung, and liver. RKIP blocks Raf-induced phosphorylation of MEK. In addition to its modulation of Raf signaling, RKIP modulates both G-protein signaling and NF-kappaB activity. The impact that RKIP has on multiple signaling pathways grants it the ability to play a role in several cellular functions including membrane biosynthesis, spermatogenesis, and neural signaling. Novel cellular functions for RKIP continue to be identified, several of which contribute to cancer biology. For example, RKIP promotes apoptosis of cancer cells, which suggests that loss of RKIP in cancer will protect cancer cells against cell death. Additionally, restoration of RKIP expression ina metastatic prostate cancer cell line does not effect primary tumor growth, but it does inhibit prostate cancer metastasis. These parameters identify RKIP as a metastasis suppressor gene, which suggest that it or proteins it interacts with are putative molecular targets to control metastasis. These findings are supported by the observation that RKIP expression is decreased in metastases of prostate cancer patients, compared to normal prostate or the primary prostate tumor. In this review, RKIP biology and its role in cancer will be described.     

Brain metastases from prostate adenocarcinoma

Brain metastases of prostate adenocarcinoma are rare. We report a case of brain metastases from prostate adenocarcinoma 15 months after the diagnosis of the primary tumour. The patient had headache and one solitary metastasis upon magnetic resonance imaging (MRI). The biopsy performed showed metastatic prostate adenocarcinoma. He was treated with surgery and cranial irradiation.     

Long-term survival after brain metastasis from endometrial cancer

A case is reported of prolonged survival after radical hysterectomy for poorly differentiated adenocarcinoma of the endometrium and resection of metastatic carcinoma of the brain followed by radiation therapy. The 43-year-old patient has survived for seven years after hysterectomy and six years 10 months after excision of the brain metastasis. Our results show that the surgical excision of a single metastatic lesion of the brain with postoperative irradiation offers hope of prolonged survival in patients with a solitary brain metastasis and no evident systemic disease.     

Isolated Peritoneal Metastasis of Prostate Cancer Presenting with Massive Ascites: A Case Report

The peritoneal carcinomatosis of prostate cancer without bone or other visceral organ involvement is extremely rare. We report a case of an isolated peritoneal metastasis of prostate cancer in a patient without other metastatic sites and a history of prostate surgery. A 63-year-old male with locally advanced prostate cancer without known distant metastasis on androgen deprivation therapy presented with abdominal distension that had persisted for a month. Abdominopelvic computed tomography (CT) showed gastric wall thickening and a moderate amount of ascites. The gastroscopy showed hyperemic mucosal patches on the antrum body. A cytological examination of the ascites fluid was negative for malignant cells. Diagnostic laparoscopy showed multiple nodules in the peritoneum. A biopsy was performed. Histological findings were compatible with metastatic carcinoma of the prostate, which was immunohistochemically positive for pan-cytokeratin, the androgen receptor, and prostate-specific antigen (PSA). The patient was then treated with abiraterone acetate. After 1 month of treatment, both ascites and the PSA value decreased. We describe an extremely rare case of isolated peritoneal carcinomatosis from prostate cancer without any organ metastasis or history of surgery. Clinicians should be aware of these very rare metastases of prostate cancer. Hormonal therapy may be helpful for such cases.     

Prostate Cancer: Cases of Rare Presentation and Rare Metastasis

Prostate cancer is the second most common cancer in men. Diagnosis of early disease is based on prostate biopsy which is carried out because of symptoms of prostatism or asymptomatic rise in PSA. On the other side, advanced disease can locally invade and metastasise to lymph nodes, bones, lungs, etc. Initial presentation of prostate cancer in form of brain metastasis is extremely seldom. Similarly, prostate cancer, which metastasised to the breast, is very rare too. Here, we discuss two unique cases of prostate cancer, one of them had an initial presentation of brain metastasis from prostate adenocarcinoma and the other case had an established diagnosis of prostate cancer metastasised to the breast. In theory, cancer can cause metastatic spread to any part of the body; however diversity into such presentation or progression from prostate cancer has not been frequently noticed.Key Words: Prostate cancer, Rare presentation, Metastasis     

An unusual variant of prostatic adenocarcinoma with metastasis to testis.A case report

Ductal adenocarcinoma of the prostate is considered to be a rare variant of prostatic adenocarcinoma when compared to the more common acinar adenocarcinoma. We report here a case of ductal adenocarcinoma of the prostate in a 68-year old man who presented with complaints of abdominal pain, retention of urine and hematuria of one month duration. Clinical examination showed prostatomegaly. The serum Prostate Specific Antigen (PSA) value was raised to 79ng/mL. Histopathological and immunohistochemical evaluation of resected specimen of prostate revealed ductal adenocarcinoma of the prostate. The patient was lost to follow up and presented four years after the initial diagnosis with metastasis to the bone and testis. Though prostatic cancers have the ability for wide spread dissemination, metastasis to testis is rare. Immunohistochemical staining with PSA and Prostatic Acid Phosphatase (PAP) can help in establishing prostatic nature of the neoplasm. We are reporting this case because of the rarity of metastasis of prostatic carcinoma to testis and for stressing the need for keeping in mind the possibility of metastatic carcinoma also while dealing with testicular tumors. Keywords: Prostate, ductal adenocarcinoma, metastasis, testis.     

Long-term survival after brain metastasis from lung cancer

A case is reported of prolonged survival after lobectomy for large cell undifferentiated carcinoma of the lung and resection of metastatic carcinoma of the brain. The patient had survived 11 years 5 months after lung resection and 10 years 4 months after excision of brain metastasis. A review of the reports of another 12 patients who survived 5 years or longer after craniotomy, shows that the surgical excision of a single metastatic lesion of the brain with or without postoperative irradiation offers the best hope for prolonged survival.     

A case of ovarian carcinoma preceded by intracranial metastasis

A 28-year-old woman with primary ovarian carcinoma which was found with intracranial metastasis is reported. The patient was operated on because of metastatic brain tumor with unknown primary lesion. Subsequently, left ovarian tumor was found, and left salpingo-oophorectomy was performed. The histological diagnosis was endometrioid carcinoma. A review of the literature shows that intracranial metastasis by ovarian carcinoma is very rare. The incidence is lower than 2.1%. The present case in which intracranial metastasis manifested itself before primary ovarian carcinoma seems to be extremely rare.     

Identification of leukocyte E-selectin ligands, P-selectin glycoprotein ligand-1 and E-selectin ligand-1, on human metastatic prostate tumor cells

Prostate tumor cells, which characteristically metastasize to bone, initiate binding interactions with bone marrow endothelium under blood flow conditions through binding interactions with E-selectin. We hypothesized that E-selectin ligands on prostate tumor cells are directly associated with bone-metastatic potential. In this report, we elucidate the identity of E-selectin ligands on human metastatic prostate tumor cells and examine their association with prostate tumor progression and metastasis in vivo. To our surprise, we found that the E-selectin-binding form of P-selectin glycoprotein ligand-1 (PSGL-1) is expressed on the human bone-metastatic prostate tumor MDA PCa 2b cell line. Interestingly, we also found that human prostate tumor cells derived from bone, lymph node, and brain metastases expressed another leukocyte E-selectin ligand, E-selectin ligand-1 (ESL-1). Immunohistochemical analysis of PSGL-1 and ESL-1 in normal prostate tissue and in localized and metastatic prostate tumors revealed that ESL-1 was principally localized to intracellular cell membrane and expressed on all normal and malignant prostate tissue, whereas PSGL-1 was notably detected on the surfaces of bone-metastatic prostate tumor cells. These findings implicate a functional role of PSGL-1 in the bone tropism of prostate tumor cells and establish a new perspective into the molecular mechanism of human prostate tumor metastasis.     

Cerebral tumor staging in patients with bronchial carcinoma by computed tomography

Computerized tomographic (CT) scans of 271 patients with histologically proven bronchial carcinoma accomplished for initial tumor staging were retrospectively evaluated for signs of cerebral metastasis. The results for the histologic subtypes were quite different. In 13.8% of patients with small cell carcinoma and limited disease the authors found signs of brain metastasis. However, routine cerebral staging in these patients did not seem to be useful because of lack of therapeutic consequences. On the other hand, no patient with non-small cell carcinoma (N-SCC) and tumor Stage I or II had brain metastases. All patients with brain metastasis from N-SCC had been classified as tumor Stage III before cerebral imaging. Among these patients, however, the authors found brain metastasis in 17.5% of those without known distant metastatic disease (III/M0), especially in large cell carcinoma and in adenocarcinoma. Stage III/M0 patients should undergo routine cerebral imaging if their tumor is surgically resectable and thoracotomy is planned.