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International Journal of Molecular... Oct 2019Despite its name, prostate-specific membrane antigen (PSMA) has been shown using immunohistochemistry (IHC) to also be over-expressed in the tumor neovasculature of a... (Review)
Review
Despite its name, prostate-specific membrane antigen (PSMA) has been shown using immunohistochemistry (IHC) to also be over-expressed in the tumor neovasculature of a wide variety of solid tumors other than prostate carcinoma. Accordingly, positron-emitting radiolabeled small molecules targeting PSMA, initially developed for positron emission tomography in prostate carcinomas, are currently being explored for their staging and restaging potential as an alternative imaging modality in other solid tumor types where 18-F-fluorodeoxyglucose (FDG)-PET imaging has low diagnostic accuracy. In this paper, the currently available literature in this field is reviewed. Preliminary, mainly retrospective studies are encouraging, with evidence of improved diagnostic sensitivity and specificity in clear cell renal carcinoma, glioma, and hepatocellular carcinoma, leading to a change in patient management in several patients. However, the results published thus far warrant confirmation by larger prospective studies additionally assessing the longitudinal impact on patient outcomes.
Topics: Animals; Antigens, Surface; Diagnosis, Differential; Fluorodeoxyglucose F18; Glutamate Carboxypeptidase II; Humans; Neoplasms; Positron-Emission Tomography; Radiopharmaceuticals
PubMed: 31581638
DOI: 10.3390/ijms20194886 -
Frontiers in Oncology 2024Large cell neuroendocrine carcinoma (LCNEC) is a rare subtype of prostate cancer. The pathogenesis, clinical manifestation, treatment options, and prognosis are...
BACKGROUND
Large cell neuroendocrine carcinoma (LCNEC) is a rare subtype of prostate cancer. The pathogenesis, clinical manifestation, treatment options, and prognosis are uncertain and underreported.
MATERIALS AND METHODS
A systematic search was conducted in April 2022 through PubMed, Embase, and Cochrane. We reviewed cases of LCNEC developed either from or transformation from prostate adenocarcinoma and summarized the relevant pathophysiological course, treatment options, and outcomes.
RESULTS
A total of 25 patients with a mean age of 70.4 (range 43 87 years old) from 18 studies were included in this review. 13 patients were diagnosed with LCNEC of the prostate. 12 patients were from the transformation of adenocarcinoma post-hormonal therapy treatment. Upon initial diagnosis, patients diagnosed with prostatic LCNEC had a mean serum PSA value of 24.6 ng/ml (range: 0.09-170 ng/ml, median 5.5 ng/ml), while transformation cases were significantly lower at 3.3 ng/ml (range: 0-9.3 ng/ml, median 0.05 ng/ml). The pattern of metastasis closely resembles prostate adenocarcinoma. Six out of twenty-three cases displayed brain metastasis matching the correlation between neuroendocrine tumors and brain metastasis. Three notable paraneoplastic syndromes included Cushings syndrome, dermatomyositis, and polycythemia. Most patients with advanced metastatic disease received conventional platinum-based chemotherapy with a mean survival of 5 months. There was one exception in the transformation cohort with a somatic BRCA2 mutation who was treated with a combination of M6620 and platinum-based chemotherapy with an impressive PFS of 20 months. Patients with pure LCNEC phenotype have worse survival outcomes when compared to those with mixed LCNEC and adenocarcinoma phenotypes. It is unclear whether there is a survival benefit to administering ADT in pure pathologies.
CONCLUSION
LCNEC of the prostate is a rare disease that can occur or transformation from prostatic adenocarcinoma. Most patients present at an advanced stage with poor prognosis and are treated with conventional chemotherapy regimens. Patients who had better outcomes were those who were diagnosed at an early stage and received treatment with surgery or radiation and androgen deprivation therapy (ADT). There was one case with an exceptional outcome that included a treatment regimen of M6620 and chemotherapy.
PubMed: 38515575
DOI: 10.3389/fonc.2024.1341794 -
Cancer Cell International 2020Accumulating evidence suggests androgen receptor splice variant 7 (AR-V7) may be associated with the prognosis of castration-resistant prostate cancer (CRPC) received... (Review)
Review
BACKGROUND
Accumulating evidence suggests androgen receptor splice variant 7 (AR-V7) may be associated with the prognosis of castration-resistant prostate cancer (CRPC) received novel hormonal therapy while its characteristic and prognosis value in hormonal sensitive prostate cancer is unclear.
METHODS
We aimed to evaluate the prognostic role of AR-V7 by progression free survival (PFS) and overall survival (OS) in hormonal sensitive prostate cancer (HSPC), and the AR-V7-positive-proportion difference in HSPC and CRPC. A search of PubMed, Embase, and the Web of Science was performed using the keywords prostate cancer, prostate tumor, prostate neoplasm, prostate carcinoma; AR-V7, AR3, androgen receptor splicing variant-7, or androgen receptor-3. Seventeen trials published due December 2019 were enrolled.
RESULTS
AR-V7-positive proportion in CRPC was significantly larger than newly diagnosed prostate cancer (PCa) (odds ratio [OR] 7.06, 95% confidence interval [CI] 2.52-19.83, P < 0.001). Subgroup analyses indicated significantly higher AR-V7-positive proportion in CRPC derived from RNA in situ hybridization (OR 65.23, 95% CI 1.34-3171.43, P = 0.04), exosome RNA (OR 3.88, 95% CI 0.98-15.39, P = 0.05) and tissue RNA (OR 10.89, 95% CI 4.13-28.73, P < 0.001). AR-V7-positive patients had a significantly shorter PFS than those who were AR-V7-negative treated with first-line hormonal therapy (hazard ratio [HR] 3.63, 95% CI 1.85-7.10, P < 0.001) and prostatectomy (HR 2.49, 95% CI 1.33-4.64, P = 0.004). OS (HR 5.59, 95% CI 2.89-10.80, P < 0.001) were better in AR-V7-negative than AR-V7-positive HSPC patients treated with first-line hormonal therapy. The limitations of our meta-analysis were differences in study sample size and design, AR-V7 detection assay, and disease characteristics.
CONCLUSION
AR-V7-positive proportion was significantly higher in CRPC than that in newly diagnosed PCa. AR-V7 positive HSPC patients portend worse prognosis of first-line hormonal therapy and prostatectomy. Additional studies are warranted to confirm these findings.
PubMed: 32390764
DOI: 10.1186/s12935-020-01229-4 -
World Journal of Gastroenterology Dec 2015To summarize the current knowledge about the potential relationship between hepatitis C virus (HCV) infection and the risk of several extra-liver cancers. (Review)
Review
AIM
To summarize the current knowledge about the potential relationship between hepatitis C virus (HCV) infection and the risk of several extra-liver cancers.
METHODS
We performed a systematic review of the literature, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) Statement. We extracted the pertinent articles, published in MEDLINE and the Cochrane Library, using the following search terms: neoplasm/cancer/malignancy/tumor/carcinoma/adeno-carcinoma and non-Hodgkin lymphomas, kidney/renal-, cholangio-, pancreatic-, thyroid-, breast-,oral-, skin-, prostate-, lung-, colon-, stomach-, haematologic. Case series, case-series with control-group, case-control, cohort-studies as well as meta-analyses, written in English were collected. Some of the main characteristics of retrieved trials, which were designed to investigate the prevalence of HCV infection in each type of the above-mentioned human malignancies were summarised. A main table was defined and included a short description in the text for each of these tumours, whether at least five studies about a specific neoplasm, meeting inclusion criteria, were available in literature. According to these criteria, we created the following sections and the corresponding tables and we indicated the number of included or excluded articles, as well as of meta-analyses and reviews: (1) HCV and haematopoietic malignancies; (2) HCV and cholangiocarcinoma; (3) HCV and pancreatic cancer; (4) HCV and breast cancer; (5) HCV and kidney cancer; (6) HCV and skin or oral cancer; and (7) HCV and thyroid cancer.
RESULTS
According to available data, a clear correlation between regions of HCV prevalence and risk of extra-liver cancers has emerged only for a very small group of types and histological subtypes of malignancies. In particular, HCV infection has been associated with: (1) a higher incidence of some B-cell Non-Hodgkin-Lymphoma types, in countries, where an elevated prevalence of this pathogen is detectable, accounting to a percentage of about 10%; (2) an increased risk of intra-hepatic cholangiocarcinoma; and (3) a correlation between HCV prevalence and pancreatic cancer (PAC) incidence.
CONCLUSION
To date no definitive conclusions may be obtained from the analysis of relationship between HCV and extra-hepatic cancers. Further studies, recruiting an adequate number of patients are required to confirm or deny this association.
Topics: Carcinoma, Hepatocellular; Hepacivirus; Hepatitis C; Humans; Liver Neoplasms; Neoplasms; Risk Assessment; Risk Factors
PubMed: 26668515
DOI: 10.3748/wjg.v21.i45.12896 -
Journal of Clinical Medicine Dec 2023Lower urinary tract symptoms (LUTS) and hematuria are common symptoms in men with neoplasms, mainly affecting the elderly population. Prostatic arterial embolization... (Review)
Review
Lower urinary tract symptoms (LUTS) and hematuria are common symptoms in men with neoplasms, mainly affecting the elderly population. Prostatic arterial embolization (PAE) is a minimally invasive procedure that has shown promising results in managing LUTS and massive intractable prostatic hematuria in patients with benign prostatic hyperplasia (BPH) and prostate cancer (PCa). A few studies, however, have provided valuable insights into the durability and efficacy of PAE focusing on the long-term effectiveness, quality of life, and cancer-specific control of hemostasis and urinary symptoms. As a result of concomitant cardiovascular conditions, these patients often take anticoagulants or antithrombotics, which can worsen their hematuria and clinical status. Transurethral resection of the prostate (TURP) is considered a very high-risk procedure, even without massive bleeding, and requires discontinuation of vitamin K antagonists and antiplatelet therapies. Such patients usually have their surgery postponed, and PAE should be considered a safe alternative treatment. We aimed to report a narrative review from 1976 to June 2023 of the current state of PAE for massive and intractable hematuria, highlighting recent developments in this technique, including prospective cohort studies, and focusing on long-term outcome, safety, and complication management of patients with prostatic neoplasms who develop significant hemorrhagic symptoms. Additionally, we present a case report and a simple algorithm for treating intractable bleeding in a 92-year-old man with PCa and massive hematuria.
PubMed: 38202072
DOI: 10.3390/jcm13010065 -
Frontiers in Endocrinology 2022Prostate cancer is a common malignancy affecting men worldwide. While the vast majority of newly diagnosed prostate cancers are categorized as adenocarcinomas, a...
Prostate cancer is a common malignancy affecting men worldwide. While the vast majority of newly diagnosed prostate cancers are categorized as adenocarcinomas, a spectrum of uncommon tumor types occur including those with small cell and neuroendocrine cell features. Benign neuroendocrine cells exist in the normal prostate microenvironment, and these cells may give rise to primary neuroendocrine carcinomas. However, the more common development of neuroendocrine prostate cancer is observed after therapeutics designed to repress the signaling program regulated by the androgen receptor which is active in the majority of localized and metastatic adenocarcinomas. Neuroendocrine tumors are identified through immunohistochemical staining for common markers including chromogranin A/B, synaptophysin and neuron specific enolase (NSE). These markers are also common to neuroendocrine tumors that arise in other tissues and organs such as the gastrointestinal tract, pancreas, lung and skin. Notably, neuroendocrine prostate cancer shares biochemical features with nerve cells, particularly functions involving the secretion of a variety of peptides and proteins. These secreted factors have the potential to exert local paracrine effects, and distant endocrine effects that may modulate tumor progression, invasion, and resistance to therapy. This review discusses the spectrum of factors derived from neuroendocrine prostate cancers and their potential to influence the pathophysiology of localized and metastatic prostate cancer.
Topics: Male; Humans; Prostate; Prostatic Neoplasms; Carcinoma, Neuroendocrine; Adenocarcinoma; Neuroendocrine Tumors; Tumor Microenvironment
PubMed: 36440195
DOI: 10.3389/fendo.2022.1012005 -
Therapeutic Advances in Medical Oncology 2022Cabozantinib is approved, in various settings, for the treatment of renal cell carcinoma, medullary thyroid cancer, and hepatocellular carcinoma, and it has been... (Review)
Review
BACKGROUND
Cabozantinib is approved, in various settings, for the treatment of renal cell carcinoma, medullary thyroid cancer, and hepatocellular carcinoma, and it has been investigated for the treatment of other cancers. With the available evidence and the real-world performance of cabozantinib compared with clinical trial data, we performed a systematic review of cabozantinib monotherapy as treatment for solid tumors in adults.
METHODS
This study was designed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and registered with PROSPERO (CRD42020144680). We searched for clinical and observational studies of cabozantinib monotherapy for solid tumors using Embase, MEDLINE, and Cochrane databases (October 2020), and screened relevant congress abstracts. Eligible studies reported clinical or safety outcomes, or biomarker data. Small studies ( < 25) and studies of cabozantinib combination therapies were excluded. Quality was assessed using National Institute for Health and Care Excellence methodology, and study characteristics were described qualitatively.
RESULTS
Of 2888 citations, 114 were included (52 randomized studies, 29 observational studies, 32 nonrandomized phase I or II studies or pilot trials, and 1 analysis of data from a randomized study and a nonrandomized study). Beyond approved indications, other tumors studied were castration-resistant prostate cancer, urothelial carcinoma, Ewing sarcoma, osteosarcoma, uveal melanoma, non-small-cell lung cancer, Merkel cell carcinoma, glioblastoma, pheochromocytomas and paragangliomas, cholangiocarcinoma, gastrointestinal stromal tumor, colorectal cancer, salivary gland cancer, carcinoid and pancreatic neuroendocrine tumors, and breast, endometrial and ovarian cancers. The most common adverse events were hypertension, diarrhea, and fatigue.
CONCLUSION
The identified evidence demonstrates the positive efficacy/effectiveness of cabozantinib monotherapy in various solid tumor types, with safety findings being consistent with those observed with other VEGFR-targeting tyrosine kinase inhibitors. When available, real-world findings were consistent with the data reported from clinical trials. A limitation of this review is the high proportion of abstracts; however, this allowed us to capture the most up-to-date findings.
PubMed: 35847482
DOI: 10.1177/17588359221107112 -
Histopathology Sep 2023Cribriform architecture has been recognised as an independent parameter for prostate cancer outcome. Little is yet known on the added value of individual Gleason 5... (Review)
Review
Cribriform architecture has been recognised as an independent parameter for prostate cancer outcome. Little is yet known on the added value of individual Gleason 5 growth patterns. Comedonecrosis is assigned Gleason pattern 5 and can occur in both invasive and intraductal carcinoma. The aim of this study is to systematically review the literature for the prognostic value of comedonecrosis in prostate cancer. A systematic literature search of Medline, Web of Science, Cochrane library and Google scholar was performed according to the Preferred reporting items for systematic reviews and meta-analysis (PRISMA)guidelines. After identification and screening of all relevant studies published up to July 2022, 12 manuscripts were included. Clinicopathological data were extracted and the presence of comedonecrosis in either invasive, intraductal or ductal carcinoma was associated with at least one clinical outcome measure. No meta-analysis was performed. Eight of 11 studies showed that comedonecrosis was significantly associated with biochemical recurrence and two studies with metastasis or death. The only studies using metastasis-free and disease specific-free survival as an endpoint both found comedonecrosis to be an independent prognostic parameter in multivariate analysis. The studies were all retrospective and demonstrated considerable heterogeneity with regard to clinical specimen, tumour type, grade group, correction for confounding factors and endpoints. This systematic review demonstrates weak evidence for comedonecrosis to be associated with adverse prostate cancer outcome. Study heterogeneity and lack of correction for confounding factors prohibit drawing of definitive conclusions.
Topics: Male; Humans; Retrospective Studies; Prostatic Neoplasms; Prognosis; Neoplasm Grading; Carcinoma, Ductal, Breast; Breast Neoplasms
PubMed: 37195595
DOI: 10.1111/his.14945 -
Clinical Genitourinary Cancer Aug 2014Radical prostatectomy (RP) is one of the treatment options for localized, high-risk prostate cancer (PC), but it has never been compared with external beam radiotherapy... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Radical prostatectomy (RP) is one of the treatment options for localized, high-risk prostate cancer (PC), but it has never been compared with external beam radiotherapy (RT), which is an alternative approach, in a large randomized trial. To compare the outcomes of patients treated with surgery versus RT, we performed a metaanalysis of available studies on this topic.
MATERIALS AND METHODS
We performed a search of MEDLINE, EMBASE, Web of Science, SCOPUS, and The Cochrane Central Register of Controlled Trials (CENTRAL) for randomized or observational studies that investigated overall survival (OS) and PC-specific mortality (PCSM) risks in relation to use of surgery or RT in patients with high-risk PC. Fixed- and random-effect models were fitted to estimate the summary odds ratio (OR). Between-study heterogeneity was tested using χ(2) statistics and measured using the I(2) statistic. Publication bias was evaluated using a funnel plot and Egger regression asymmetry test.
RESULTS
Seventeen studies were included (1 randomized and 16 retrospective). RP was associated with improved OS (OR, 0.51; 95% confidence interval [CI], 0.38-0.68; P < .00001), PCSM (OR, 0.56; 95% CI, 0.37-0.85; P = .007), and non-PCSM (OR, 0.53; 95% CI, 0.35-0.8; P = .002) compared with RT. Biochemical relapse-free survival rates were similar to those of RT.
CONCLUSION
Overall and cancer-specific mortality rates appear to be better with RP compared with RT in localized, high-risk PC. Surgery is also associated with a 50% decreased risk of non-PCSM compared with RT.
Topics: Humans; Male; Prognosis; Prostatectomy; Prostatic Neoplasms; Radiotherapy; Risk Factors
PubMed: 24589471
DOI: 10.1016/j.clgc.2014.01.010 -
Journal of Personalized Medicine Jun 2023Prostatic adenocarcinoma (PA) is the second most common malignancy in men globally. Signet-ring cell-like adenocarcinoma (SRCC) is a very rare PA subtype, with around... (Review)
Review
A Case of Prostatic Signet-Ring Cell-like Carcinoma with Pagetoid Spread and Intraductal Carcinoma and Long-Term Survival: PD-L1 and Mismatch Repair System Proteins (MMR) Immunohistochemical Evaluation with Systematic Literature Review.
Prostatic adenocarcinoma (PA) is the second most common malignancy in men globally. Signet-ring cell-like adenocarcinoma (SRCC) is a very rare PA subtype, with around 200 cases reported in the English literature. Histologically, the tumor cells show a vacuole compressing the nucleus to the periphery. Pagetoid spread in acini and ducts is usually related to metastases from urothelial or colorectal carcinomas, less commonly associated with intraductal carcinoma (IC); histologically, the tumor cells grow between the acinar secretory and basal cell layers. To our knowledge, we report the first prostatic SRCC (Gleason score 10, stage pT3b) associated with IC and pagetoid spread to prostatic acini and seminal vesicles. To our systematic literature review (PRISMA guidelines), it is the first tested case for both PD-L1 (<1% of positive tumor cells, clone 22C3) and mismatch repair system proteins (MMR) (MLH1+/MSH2+/PMS2+/MSH6+). We found no SRCC previously tested for MMR, while only four previous cases showed high expression of another PD-L1 clone (28-8). Finally, we discussed the differential diagnoses of prostatic SRCC.
PubMed: 37374005
DOI: 10.3390/jpm13061016