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Current Oncology (Toronto, Ont.) Feb 2022(1) Background: Following radical prostatectomy (RP), the absence of a demonstrable tumor on the specimen of a previously histologically proven malignancy is known as... (Review)
Review
(1) Background: Following radical prostatectomy (RP), the absence of a demonstrable tumor on the specimen of a previously histologically proven malignancy is known as the pT0 stage. The aim of our present study is to perform a narrative review of current literature in order to determine the frequency and oncological outcomes in patients with pT0 disease. (2) Methods: A narrative review of all available literature was performed. (3) Results: The incidence of pT0 ranges between 0.07% and 1.3%. Predictors of the pT0 stage are only a single biopsy core with low-grade cancer, a cancer length not exceeding 2 mm and a high prostate volume. Biochemical recurrence ranges between 0 and 11%. (4) Conclusions: The absence of malignancy in the RP specimen despite a previous positive biopsy is a rare and unpredictable finding. Although the prognosis is considered to be excellent in most of the cases, a continued close follow-up is warranted.
Topics: Carcinoma; Humans; Male; Neoplasm Staging; Prostate; Prostatectomy; Prostatic Neoplasms
PubMed: 35323311
DOI: 10.3390/curroncol29030111 -
International Journal of Molecular... May 2023Prostate specific membrane antigen (PSMA) is an excellent target for imaging and treatment of prostate carcinoma (PCa). Unfortunately, not all PCa cells express PSMA....
Prostate specific membrane antigen (PSMA) is an excellent target for imaging and treatment of prostate carcinoma (PCa). Unfortunately, not all PCa cells express PSMA. Therefore, alternative theranostic targets are required. The membrane protein prostate stem cell antigen (PSCA) is highly overexpressed in most primary prostate carcinoma (PCa) cells and in metastatic and hormone refractory tumor cells. Moreover, PSCA expression positively correlates with tumor progression. Therefore, it represents a potential alternative theranostic target suitable for imaging and/or radioimmunotherapy. In order to support this working hypothesis, we conjugated our previously described anti-PSCA monoclonal antibody (mAb) 7F5 with the bifunctional chelator CHX-A″-DTPA and subsequently radiolabeled it with the theranostic radionuclide Lu. The resulting radiolabeled mAb ([Lu]Lu-CHX-A″-DTPA-7F5) was characterized both in vitro and in vivo. It showed a high radiochemical purity (>95%) and stability. The labelling did not affect its binding capability. Biodistribution studies showed a high specific tumor uptake compared to most non-targeted tissues in mice bearing PSCA-positive tumors. Accordingly, SPECT/CT images revealed a high tumor-to-background ratios from 16 h to 7 days after administration of [Lu]Lu-CHX-A″-DTPA-7F5. Consequently, [Lu]Lu-CHX-A″-DTPA-7F5 represents a promising candidate for imaging and in the future also for radioimmunotherapy.
Topics: Animals; Mice; Male; Pentetic Acid; Tissue Distribution; Prostate; Cell Line, Tumor; Antibodies, Monoclonal; Stem Cells; Carcinoma; Lutetium
PubMed: 37298374
DOI: 10.3390/ijms24119420 -
World Journal of Surgical Oncology Dec 2022Biomarkers of DNA damage repair deficiency provide opportunities for personalized treatment with immunotherapy. However, there is limited research on the immune...
BACKGROUND
Biomarkers of DNA damage repair deficiency provide opportunities for personalized treatment with immunotherapy. However, there is limited research on the immune microenvironment of adeno-neuroendocrine prostate cancer (NEPC). In this study, we aimed to assess and describe the comprehensive clinicopathological manifestations of NEPC to improve diagnosis and predict prognosis.
METHODS
A retrospective medical record review of 66 patients with prostate cancer (PCa) was performed. PCa samples from the 66 patients were analyzed using immunohistochemical staining for the detection of chromogranin, neural cell adhesion molecule 1, and synaptophysin. For tumor-associated immune microenvironment analysis, PD-L1, CD3, and CD8 were labeled in tissue slides. The effect of clinicopathological factors on the survival of patients with Adeno-NEPC was analyzed.
RESULTS
Twenty patients presented with adeno-NEPC, whereas 46 presented with adeno-PCa. The median age of patients at PCa diagnosis was 67.86 ± 7.05 years (68.65 ± 7.23 years, adeno-NEPC; 67.52 ± 7.02 years, adeno-PCa). Eleven patients with adeno-NEPC underwent prostatectomy, whereas nine received primary androgen deprivation therapy (ADT). Additionally, 30 patients with adeno-PCa underwent prostatectomy, whereas 16 (34.8%) received primary ADT. There was a significant difference in overall survival between patients with adeno-NEPC and those with adeno-PCa (46.0 months vs. 65.0 months). There was also a significant difference in time from prostatectomy to biochemical recurrence between the groups of patients who underwent prostatectomy. Prostatectomy and normal lactate dehydrogenase levels were clinical factors that were significantly associated with better outcomes in patients with adeno-NEPC. Metastatic adeno-NEPC was associated with a higher programmed death ligand 1 (PD-L1) score (2-4) than localized PCa. The data showed that PD-L1 expression in adeno-NEPC may be negatively associated with that in CD8 T cells.
CONCLUSIONS
Our study revealed clinicopathological manifestations of adeno-NEPC and some possible predictive factors significantly associated with better outcomes in patients with adeno-NEPC. These findings might be beneficial in the development of diagnostic strategies and customized treatment plans.
Topics: Male; Humans; Middle Aged; Aged; Prostatic Neoplasms; B7-H1 Antigen; Retrospective Studies; Androgen Antagonists; CD8-Positive T-Lymphocytes; Prostate; Adenocarcinoma; Tumor Microenvironment
PubMed: 36572885
DOI: 10.1186/s12957-022-02841-6 -
The Prostate May 2023Amphicrine prostate carcinoma (AMPC) is a poorly defined subset of prostate cancer in which cells co-express luminal prostate epithelial and neuroendocrine markers. The...
BACKGROUND
Amphicrine prostate carcinoma (AMPC) is a poorly defined subset of prostate cancer in which cells co-express luminal prostate epithelial and neuroendocrine markers. The optimal treatment strategy is unknown. We sought to further characterize the clinical, histomorphologic, and molecular characteristics of AMPC and to identify areas of potential future treatment investigations.
METHODS
We retrospectively identified 17 cases of AMPC at a single institution, defined as synaptophysin expression in >70% of cells and co-expression of androgen receptor (AR) signaling markers (either AR, PSA, or NKX3.1) in >50% of cells. Clinical and histologic features of AMPC cases as well as response to treatment and clinical outcomes were described.
RESULTS
Five AMPC cases arose de novo in the absence of prior systemic treatment and behaved distinctly from cases that were treatment-emergent. In these de novo cases, despite expression of neuroendocrine markers, prognosis appeared more favorable than high-grade neuroendocrine carcinoma, with two (40%) patients with de novo metastatic disease, universal response to androgen deprivation therapy, and no deaths at a median follow-up of 12.3 months. Treatment-emergent AMPC arose a median of 41.1 months after androgen deprivation therapy initiation and was associated with poor response to therapy.
CONCLUSIONS
We show that amphicrine prostate cancer is a unique entity and differs in clinical and molecular features from high-grade neuroendocrine carcinomas of the prostate. Our study highlights the need to recognize AMPC as a unique molecularly defined subgroup of prostate cancer.
Topics: Male; Humans; Prostatic Neoplasms; Retrospective Studies; Androgen Antagonists; Androgens; Prostate; Carcinoma, Neuroendocrine; Prostatic Neoplasms, Castration-Resistant
PubMed: 36779357
DOI: 10.1002/pros.24497 -
Frontiers in Immunology 2023Cuproptosis plays a crucial role in cancer, and different subtypes of cuproptosis have different immune profiles in prostate adenocarcinoma (PRAD). This study aimed to...
BACKGROUND
Cuproptosis plays a crucial role in cancer, and different subtypes of cuproptosis have different immune profiles in prostate adenocarcinoma (PRAD). This study aimed to investigate immune genes associated with cuproptosis and develop a risk model to predict prognostic characteristics and chemotherapy/immunotherapy responses of patients with PRAD.
METHODS
The CIBERSORT algorithm was used to evaluate the immune and stromal scores of patients with PRAD in The Cancer Genome Atlas (TCGA) cohort. Validation of differentially expressed genes DLAT and DLD in benign and malignant tissues by immunohistochemistry, and the immune-related genes of DLAT and DLD were further screened. Univariable Cox regression were performed to select key genes. Least absolute shrinkage and selection operator (LASSO)-Cox regression analyse was used to develop a risk model based on the selected genes. The model was validated in the TCGA, Memorial Sloan-Kettering Cancer Center (MSKCC) and Gene Expression Omnibus (GEO) datasets, as well as in this study unit cohort. The genes were examined functional enrichment analysis, and the tumor immune features, tumor mutation features and copy number variations (CNVs) of patients with different risk scores were analysed. The response of patients to multiple chemotherapeutic/targeted drugs was assessed using the pRRophetic algorithm, and immunotherapy was inferred by the Tumor Immune Dysfunction and Exclusion (TIDE) and immunophenoscore (IPS).
RESULTS
Cuproptosis-related immune risk scores (CRIRSs) were developed based on PRLR, DES and LECT2. High CRIRSs indicated poor overall survival (OS), disease-free survival (DFS) in the TCGA-PRAD, MSKCC and GEO datasets and higher T stage and Gleason scores in TCGA-PRAD. Similarly, in the sample collected by the study unit, patients with high CRIRS had higher T-stage and Gleason scores. Additionally, higher CRIRSs were negatively correlated with the abundance of activated B cells, activated CD8 T cells and other stromal or immune cells. The expression of some immune checkpoints was negatively correlated with CRIRSs. Tumor mutational burden (TMB), mutant-allele tumor heterogeneity (MATH) and copy number variation (CNV) scores were all higher in the high-CRIRS group. Multiple chemotherapeutic/targeted drugs and immunotherapy had better responsiveness in the low-CRIRS group.
CONCLUSION
Overall, lower CRIRS indicated better response to treatment strategies and better prognostic outcomes.
Topics: Humans; Male; Adenocarcinoma; CD8-Positive T-Lymphocytes; DNA Copy Number Variations; Intercellular Signaling Peptides and Proteins; Prognosis; Prostate; Prostatic Neoplasms; Tumor Microenvironment; Copper; Apoptosis
PubMed: 37600770
DOI: 10.3389/fimmu.2023.1181370 -
Indian Journal of Pathology &... 2022Prostate cancer being the world's leading cause of cancer and also the second most common cancer in men is posing challenges in its diagnosis. Immunohistochemistry with...
Prostate cancer being the world's leading cause of cancer and also the second most common cancer in men is posing challenges in its diagnosis. Immunohistochemistry with markers like high molecular weight cytokeratin, p63 aid in the diagnosis. The absence of p63 and high molecular weight cytokeratin and presence of p504s in the biopsies indicate malignant lesions. Yet, there is a loophole to this too. A rare case of p63-positive prostatic adenocarcinoma in an 87-year-old patient, with immunohistochemistry results showing overexpression of p63 in the nuclei of the malignant glands. This tumor shows high molecular weight cytokeratin negativity, and p504s positivity. Prognosis of this variant of the tumor is mostly favorable. Prompt treatment will halt the progression of this tumor and prevent paraplegia. Radical prostatectomy could be avoided by treatment modalities like androgen blockade and brachytherapy, as morbidity is very high with radical prostatectomy surgery.
Topics: Aged, 80 and over; Biomarkers, Tumor; Carcinoma; Humans; Keratins; Male; Membrane Proteins; Prostate; Prostatic Neoplasms
PubMed: 35435392
DOI: 10.4103/0377-4929.343157 -
Modern Pathology : An Official Journal... Jan 2018Prostatic adenocarcinoma remains the most common cancer affecting men. A substantial majority of patients have the diagnosis made on thin needle biopsies, most often in... (Review)
Review
Prostatic adenocarcinoma remains the most common cancer affecting men. A substantial majority of patients have the diagnosis made on thin needle biopsies, most often in the absence of a palpable abnormality. Treatment choices ranging from surveillance to radical prostatectomy or radiation therapy are largely driven by the pathologic findings in the biopsy specimen. The first part of this review focuses on important morphologic parameters in needle biopsy specimens that are not covered in the accompanying articles. This includes tumor quantification as well as other parameters such a extraprostatic extension, seminal vesicle invasion, perineural invasion, and lymphovascular invasion. For those men who undergo radical prostatectomy, pathologic stage and other parameters are critical in prognostication and in determining the appropriateness of adjuvant therapy. Staging parameters, including extraprostatic extension, seminal vesicle invasion, and lymph node status are discussed here. Surgical margin status is also an important parameter and definitions and reporting of this feature are detailed. Throughout the article the current reporting guidelines published by the College of American Pathologists and the International Collaboration on Cancer Reporting are highlighted.
Topics: Adenocarcinoma; Biopsy, Needle; Ejaculatory Ducts; Guidelines as Topic; Humans; Male; Margins of Excision; Neoplasm Invasiveness; Neoplasm Staging; Prostate; Prostatectomy; Prostatic Neoplasms; Seminal Vesicles; Specimen Handling
PubMed: 29297497
DOI: 10.1038/modpathol.2017.167 -
Journal of Cancer Research and... 2019The purpose of the study is to assess the clinical value of magnetic resonance imaging (MRI)-guided transperineal prostate biopsy in the diagnosis of prostate disease.
PURPOSE
The purpose of the study is to assess the clinical value of magnetic resonance imaging (MRI)-guided transperineal prostate biopsy in the diagnosis of prostate disease.
MATERIALS AND METHODS
The institutional ethics committee approved this study. MRI-guided transperineal prostate biopsy was performed on 78 patients who had presented to our hospital with a prostate-specific antigen level >4 ng/mL or with MRI scans suggesting prostate cancer between January 2015 and August 2017. Written informed consent was obtained from all patients.
RESULTS
Of the 78 patients, pathological diagnosis could not be carried out in one because insufficient prostate tissue was obtained during biopsy. Prostate adenocarcinoma was confirmed in 34 patients, small-cell neuroendocrine carcinoma in 1 patient, prostatic tuberculosis in 1 patient, and benign prostatic hyperplasia in 41 patients. These diagnoses were confirmed by surgical pathology in 31 patients, and all results were consistent with the biopsy pathology, with no false positives. Postoperative urinary tract infection occurred in one patient, and mild postoperative hemorrhage around the prostate gland was seen in 65 patients, without the need for further clinical treatment.
CONCLUSION
MRI-guided transperineal prostate biopsy is helpful in the diagnosis and treatment of prostatic disease.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Humans; Image-Guided Biopsy; Magnetic Resonance Imaging; Male; Middle Aged; Prostate; Prostatic Neoplasms
PubMed: 30964117
DOI: 10.4103/jcrt.JCRT_725_18 -
BMC Cancer Jan 2023Cuproptosis, an emerging form of programmed cell death, has recently been identified. However, the association between cuproptosis-related long non-coding RNA (lncRNA)... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Cuproptosis, an emerging form of programmed cell death, has recently been identified. However, the association between cuproptosis-related long non-coding RNA (lncRNA) signature and the prognosis in prostate carcinoma remains elusive. This study aims to develop the novel cuproptosis-related lncRNA signature in prostate cancer and explore its latent molecular function.
METHODS
RNA-seq data and clinical information were downloaded from the TCGA datasets. Then, cuproptosis-related gene was identified from the previous literature and further applied to screen the cuproptosis-related differentially expressed lncRNAs. Patients were randomly assigned to the training cohort or the validation cohort with a 1:1 ratio. Subsequently, the machine learning algorithms (Lasso and stepwise Cox (direction = both)) were used to construct a novel prognostic signature in the training cohorts, which was validated by the validation and the entire TCGA cohorts. The nomogram base on the lncRNA signature and several clinicopathological traits were constructed to predict the prognosis. Functional enrichment and immune analysis were performed to evaluate its potential mechanism. Furthermore, differences in the landscape of gene mutation, tumour mutational burden (TMB), microsatellite instability (MSI), drug sensitivity between both risk groups were also assessed to explicit their relationships.
RESULTS
The cuproptosis-related lncRNA signature was constructed based on the differentially expressed cuproptosis-related lncRNAs, including AC005790.1, AC011472.4, AC099791.2, AC144450.1, LIPE-AS1, and STPG3-AS1. Kaplan-Meier survival and ROC curves demonstrate that the prognosis signature as an independent risk indicator had excellent potential to predict the prognosis in prostate cancer. The signature was closely associated with age, T stage, N stage, and the Gleason score. Immune analysis shows that the high-risk group was in an immunosuppressive microenvironment. Additionally, the significant difference in landscape of gene mutation, tumour mutational burden, microsatellite instability, and drug sensitivity between both risk groups was observed.
CONCLUSIONS
A novel cuproptosis-related lncRNA signature was constructed using machine learning algorithms to predict the prognosis of prostate cancer. It was closely with associated with several common clinical traits, immune cell infiltration, immune-related functions, immune checkpoints, gene mutation, TMB, MSI, and the drug sensitivity, which may be useful to improve the clinical outcome.
Topics: Humans; Male; Carcinoma; Microsatellite Instability; Prognosis; Prostate; Prostatic Neoplasms; RNA, Long Noncoding; Tumor Microenvironment; Copper; Apoptosis
PubMed: 36717792
DOI: 10.1186/s12885-023-10584-0 -
Archivos Espanoles de Urologia Jun 2022The presence of intraductal carcinoma of the prostate (IDC-P) in radical prostatectomy (RP) specimens correlates with adverse prognostic factors such as worse...
AIM
The presence of intraductal carcinoma of the prostate (IDC-P) in radical prostatectomy (RP) specimens correlates with adverse prognostic factors such as worse biochemical recurrence-free survival, higher grade and stage disease. This study aimed to investigate the effect of IDC-P in radical prostatectomy specimens on short-term oncological outcomes.
MATERIALS AND METHODS
Patients who underwent RP at our clinic for prostate cancer between May 2016 and November 2019 were included in the study. They were divided into two groups based on the presence of IDC-P in RP specimens. Their clinical, pathological, and oncologic data were evaluated retrospectively.
RESULTS
A total of 98 patients underwent RP with a mean age of 65.5 years (50-83) and a mean follow-up time of 31.2 months (6-52). Seventy and 28 patients were evaluated in the group without IDC-P and group with IDC-P, respectively. Surgical margin positivity (p=0.307) and lymph node metastasis (p=0.017) rates were higher in the group with IDC-P. Although there were no statistical differences between the groups, at follow-up biochemical recurrence rate (p=0.052) was higher, and mean time to biochemical recurrence rates were lower (p=0.057) in the group with IDC-P. The group with IDC-P was associated with a 3-fold increase in prostate cancer-specific mortality to the group without IDC-P (p=0.037).
CONCLUSIONS
Patients with IDC-P at RP specimens have more advanced disease, shorter biochemical recurrence-free, and cancerspecific survival than those without IDC-P. Defining the presence of IDC-P in RP specimens is critical in choosing the appropriate treatment strategy and predicting the prognosis.
Topics: Aged; Carcinoma, Intraductal, Noninfiltrating; Humans; Male; Neoplasm Grading; Prostate; Prostatectomy; Prostatic Neoplasms; Retrospective Studies
PubMed: 35983810
DOI: 10.37554/en-j.arch.esp.urol-20210522-3503-23