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Journal of the National Cancer Institute Nov 2023Grade Group 1 (GG1) prostate cancer should be managed with active surveillance (AS). Global uptake of AS remains disappointingly slow and heterogeneous. Removal of...
BACKGROUND
Grade Group 1 (GG1) prostate cancer should be managed with active surveillance (AS). Global uptake of AS remains disappointingly slow and heterogeneous. Removal of cancer labels has been proposed to reduce GG1 overtreatment. We sought to determine the impact of GG1 disease terminology on individual's perceptions and decision making.
METHODS
Discrete choice experiments were conducted on 3 cohorts: healthy men, canonical partners (partners), and patients with GG1 (patients). Participants reported preferences in a series of vignettes with 2 scenarios each, permuting key opinion leader-endorsed descriptors: biopsy (adenocarcinoma, acinar neoplasm, prostatic acinar neoplasm of low malignant potential [PAN-LMP], prostatic acinar neoplasm of uncertain malignant potential), disease (cancer, neoplasm, tumor, growth), management decision (treatment, AS), and recurrence risk (6%, 3%, 1%, <1%). Influence on scenario selection were estimated by conditional logit models and marginal rates of substitution. Two additional validation vignettes with scenarios portraying identical descriptors except the management options were embedded into the discrete choice experiments.
RESULTS
Across cohorts (194 healthy men, 159 partners, and 159 patients), noncancer labels PAN-LMP or prostatic acinar neoplasm of uncertain malignant potential and neoplasm, tumor, or growth were favored over adenocarcinoma and cancer (P < .01), respectively. Switching adenocarcinoma and cancer labels to PAN-LMP and growth, respectively, increased AS choice by up to 17%: healthy men (15%, 95% confidence interval [CI] = 10% to 20%, from 76% to 91%, P < .001), partners (17%, 95% CI = 12% to 24%, from 65% to 82%, P < .001), and patients (7%, 95% CI = 4% to 12%, from 75% to 82%, P = .063). The main limitation is the theoretical nature of questions perhaps leading to less realistic choices.
CONCLUSIONS
"Cancer" labels negatively affect perceptions and decision making regarding GG1. Relabeling (ie, avoiding word "cancer") increases proclivity for AS and would likely improve public health.
Topics: Male; Humans; Prostatic Neoplasms; Prostate; Prostate-Specific Antigen; Adenocarcinoma; Neoplasm Grading; Logistic Models
PubMed: 37285311
DOI: 10.1093/jnci/djad108 -
The Canadian Journal of Urology Apr 2024
Topics: Male; Humans; Prostatic Neoplasms; Gallium Isotopes; Positron-Emission Tomography; Neoplasm Staging
PubMed: 38642457
DOI: No ID Found -
Lakartidningen Apr 2024This article introduces a series of articles covering some of the most important aspects of contemporary prostate cancer care. After the introduction of the... (Review)
Review
This article introduces a series of articles covering some of the most important aspects of contemporary prostate cancer care. After the introduction of the prostate-specific antigen (PSA) blood test and systematic prostate biopsies in the early 1990s, the incidence of localised prostate cancer and the use of radical treatment rose dramatically. Improved diagnostic methods and understanding of the tumour biology now reduce overdiagnosis and pave the way for organised screening. New and more effective treatments, in combination with the stage shift from advanced to localised disease at the time of diagnosis, have reduced the age-standardised prostate cancer specific mortality by half in men under the age of 85 years. The National Prostate Cancer Register of Sweden (NPCR) has evolved over the past 25 years and now comprehensively supports clinical care and is an invaluable research data source. Patients' organisations have emerged as important players on the national arena.
Topics: Humans; Prostatic Neoplasms; Male; Prostate-Specific Antigen; Sweden; Registries; Early Detection of Cancer
PubMed: 38661575
DOI: No ID Found -
International Journal of Molecular... Feb 2024Prostate cancer (PCa) is the second most common cancer and the fifth highest cause of cancer-related death among men in the world [...].
Prostate cancer (PCa) is the second most common cancer and the fifth highest cause of cancer-related death among men in the world [...].
Topics: Male; Humans; Prostatic Neoplasms; Disease Progression
PubMed: 38473699
DOI: 10.3390/ijms25052451 -
European Journal of Medicinal Chemistry Jan 2024Prostate specific membrane antigen (PSMA) has been the subject of several studies in recent decades as a promising molecular target for prostate cancer (PCa), in fact it... (Review)
Review
Prostate specific membrane antigen (PSMA) has been the subject of several studies in recent decades as a promising molecular target for prostate cancer (PCa), in fact it is considered an excellent molecular target for both PCa imaging (both for staging and follow-up), by means of PET/CT and for radioligand therapy. Its interesting molecular features have enabled the development of a new diagnostic and therapeutic approach for PCa, called "theranostics." Considering the abundance of PSMA-based probes that have appeared so far in the literature, the present work focuses the attention on radiopharmaceuticals with increasing clinical application, highlighting advantages and disadvantages in terms of different metabolization and excretion processes, pharmacokinetic, binding affinity and variable internalization rate, tumor-to-background ratio, residence times and toxicity profile.
Topics: Male; Humans; Positron Emission Tomography Computed Tomography; Prostatic Neoplasms; Radiopharmaceuticals; Precision Medicine; Gallium Radioisotopes
PubMed: 37992520
DOI: 10.1016/j.ejmech.2023.115966 -
Journal of Translational Medicine Apr 2024Loss of AZGP1 expression is a biomarker associated with progression to castration resistance, development of metastasis, and poor disease-specific survival in prostate...
BACKGROUND
Loss of AZGP1 expression is a biomarker associated with progression to castration resistance, development of metastasis, and poor disease-specific survival in prostate cancer. However, high expression of AZGP1 cells in prostate cancer has been reported to increase proliferation and invasion. The exact role of AZGP1 in prostate cancer progression remains elusive.
METHOD
AZGP1 knockout and overexpressing prostate cancer cells were generated using a lentiviral system. The effects of AZGP1 under- or over-expression in prostate cancer cells were evaluated by in vitro cell proliferation, migration, and invasion assays. Heterozygous AZGP1 mice were obtained from European Mouse Mutant Archive (EMMA), and prostate tissues from homozygous knockout male mice were collected at 2, 6 and 10 months for histological analysis. In vivo xenografts generated from AZGP1 under- or over-expressing prostate cancer cells were used to determine the role of AZGP1 in prostate cancer tumor growth, and subsequent proteomics analysis was conducted to elucidate the mechanisms of AZGP1 action in prostate cancer progression. AZGP1 expression and microvessel density were measured in human prostate cancer samples on a tissue microarray of 215 independent patient samples.
RESULT
Neither the knockout nor overexpression of AZGP1 exhibited significant effects on prostate cancer cell proliferation, clonal growth, migration, or invasion in vitro. The prostates of AZGP1 mice initially appeared to have grossly normal morphology; however, we observed fibrosis in the periglandular stroma and higher blood vessel density in the mouse prostate by 6 months. In PC3 and DU145 mouse xenografts, over-expression of AZGP1 did not affect tumor growth. Instead, these tumors displayed decreased microvessel density compared to xenografts derived from PC3 and DU145 control cells, suggesting that AZGP1 functions to inhibit angiogenesis in prostate cancer. Proteomics profiling further indicated that, compared to control xenografts, AZGP1 overexpressing PC3 xenografts are enriched with angiogenesis pathway proteins, including YWHAZ, EPHA2, SERPINE1, and PDCD6, MMP9, GPX1, HSPB1, COL18A1, RNH1, and ANXA1. In vitro functional studies show that AZGP1 inhibits human umbilical vein endothelial cell proliferation, migration, tubular formation and branching. Additionally, tumor microarray analysis shows that AZGP1 expression is negatively correlated with blood vessel density in human prostate cancer tissues.
CONCLUSION
AZGP1 is a negative regulator of angiogenesis, such that loss of AZGP1 promotes angiogenesis in prostate cancer. AZGP1 likely exerts heterotypical effects on cells in the tumor microenvironment, such as stromal and endothelial cells. This study sheds light on the anti-angiogenic characteristics of AZGP1 in the prostate and provides a rationale to target AZGP1 to inhibit prostate cancer progression.
Topics: Male; Animals; Prostatic Neoplasms; Humans; Neovascularization, Pathologic; Cell Line, Tumor; Cell Proliferation; Cell Movement; Mice, Knockout; Glycoproteins; Neoplasm Invasiveness; Mice; Gene Expression Regulation, Neoplastic; Angiogenesis; Zn-Alpha-2-Glycoprotein
PubMed: 38659028
DOI: 10.1186/s12967-024-05183-x -
Genome Medicine Oct 2023Prostate cancer (PrCa) genomic heterogeneity causes resistance to therapies such as androgen deprivation. Such heterogeneity can be deciphered in the context of...
BACKGROUND
Prostate cancer (PrCa) genomic heterogeneity causes resistance to therapies such as androgen deprivation. Such heterogeneity can be deciphered in the context of evolutionary principles, but current clinical trials do not include evolution as an essential feature. Whether or not analysis of genomic data in an evolutionary context in primary prostate cancer can provide unique added value in the research and clinical domains remains an open question.
METHODS
We used novel processing techniques to obtain whole genome data together with 3D anatomic and histomorphologic analysis in two men (GP5 and GP12) with high-risk PrCa undergoing radical prostatectomy. A total of 22 whole genome-sequenced sites (16 primary cancer foci and 6 lymph node metastatic) were analyzed using evolutionary reconstruction tools and spatio-evolutionary models. Probability models were used to trace spatial and chronological origins of the primary tumor and metastases, chart their genetic drivers, and distinguish metastatic and non-metastatic subclones.
RESULTS
In patient GP5, CDK12 inactivation was among the first mutations, leading to a PrCa tandem duplicator phenotype and initiating the cancer around age 50, followed by rapid cancer evolution after age 57, and metastasis around age 59, 5 years prior to prostatectomy. In patient GP12, accelerated cancer progression was detected after age 54, and metastasis occurred around age 56, 3 years prior to prostatectomy. Multiple metastasis-originating events were identified in each patient and tracked anatomically. Metastasis from prostate to lymph nodes occurred strictly ipsilaterally in all 12 detected events. In this pilot, metastatic subclone content analysis appears to substantially enhance the identification of key drivers. Evolutionary analysis' potential impact on therapy selection appears positive in these pilot cases.
CONCLUSIONS
PrCa evolutionary analysis allows tracking of anatomic site of origin, timing of cancer origin and spread, and distinction of metastatic-capable from non-metastatic subclones. This enables better identification of actionable targets for therapy. If extended to larger cohorts, it appears likely that similar analyses could add substantial biological insight and clinically relevant value.
Topics: Male; Humans; Middle Aged; Prostatic Neoplasms; Androgen Antagonists; Precision Medicine; Prostatectomy; Oncogenes
PubMed: 37828555
DOI: 10.1186/s13073-023-01242-y -
Cell Reports Apr 2024Attachment of circulating tumor cells to the endothelial cells (ECs) lining blood vessels is a critical step in cancer metastatic colonization, which leads to metastatic...
Attachment of circulating tumor cells to the endothelial cells (ECs) lining blood vessels is a critical step in cancer metastatic colonization, which leads to metastatic outgrowth. Breast and prostate cancers are common malignancies in women and men, respectively. Here, we observe that β1-integrin is required for human prostate and breast cancer cell adhesion to ECs under shear-stress conditions in vitro and to lung blood vessel ECs in vivo. We identify IQGAP1 and neural Wiskott-Aldrich syndrome protein (NWASP) as regulators of β1-integrin transcription and protein expression in prostate and breast cancer cells. IQGAP1 and NWASP depletion in cancer cells decreases adhesion to ECs in vitro and retention in the lung vasculature and metastatic lung nodule formation in vivo. Mechanistically, NWASP and IQGAP1 act downstream of Cdc42 to increase β1-integrin expression both via extracellular signal-regulated kinase (ERK)/focal adhesion kinase signaling at the protein level and by myocardin-related transcription factor/serum response factor (SRF) transcriptionally. Our results identify IQGAP1 and NWASP as potential therapeutic targets to reduce early metastatic dissemination.
Topics: Humans; Integrin beta1; ras GTPase-Activating Proteins; Neoplasm Metastasis; Cell Line, Tumor; Serum Response Factor; Male; Female; Prostatic Neoplasms; Animals; Trans-Activators; Cell Adhesion; Wiskott-Aldrich Syndrome Protein, Neuronal; Breast Neoplasms; Mice; Focal Adhesion Kinase 1; Gene Expression Regulation, Neoplastic; cdc42 GTP-Binding Protein
PubMed: 38536816
DOI: 10.1016/j.celrep.2024.113989 -
JAMA Network Open Jun 2024Prostate cancer is a prevalent disease among men worldwide, exhibiting substantial heterogeneity in presentation and outcomes influenced by various factors, including... (Observational Study)
Observational Study
IMPORTANCE
Prostate cancer is a prevalent disease among men worldwide, exhibiting substantial heterogeneity in presentation and outcomes influenced by various factors, including race and ethnicity. Disparities in incidence, stage at diagnosis, and survival rates have been observed between Black men and those of other races and ethnicities.
OBJECTIVE
To compare prostate cancer outcomes between Black men and men with other race (Asian, Hispanic, Indigenous, Middle Eastern, White, Multiracial, and Other) in a universal health care system, with race and ethnicity self-reported.
DESIGN, SETTING, AND PARTICIPANTS
This was a prospective, observational cohort study of men diagnosed with prostate cancer between June 1, 2014, and August 28, 2023, who self-identified race and ethnicity. Participants included men who had been prospectively enrolled in the Alberta Prostate Cancer Research Initiative from the 2 major urology referral centers in Alberta (University of Alberta and University of Calgary). All men with prostate cancer enrolled in the initiative were included.
EXPOSURE
Race and ethnicity.
MAIN OUTCOMES AND MEASURES
The primary outcome was the stage and grade of prostate cancer at diagnosis. Further outcomes included age and prostate-specific antigen level at diagnosis, initial treatment modality, time from diagnosis to initial treatment, and prostate cancer-specific, metastasis-free, and overall survivals.
RESULTS
A total of 6534 men were included; 177 (2.7%) were Black, and 6357 (97.3%) had another race or ethnicity. Men who identified as Black were diagnosed with prostate cancer at an earlier age (mean [SD], 62.0 [8.2] compared with 64.6 [7.7] years; P < .001) and had a lower Charlson Comorbidity Index rating (14% compared with 7% ≤ 1; P < .001) compared with men of other races. Men who identified as Black had similar prostate-specific antigen levels at diagnosis, TNM category (74% vs 74% with T1-T2; P = .83) and Gleason Grade Group (34% compared with 35% Gleason Grade Group 1; P = .63). Black men had similar rates of prostate cancer-specific (hazard ratio [HR], 1.10; 95% CI, 0.41-2.97; P = .85), metastasis-free (HR, 0.88; 95% CI, 0.42-1.46; P = .44), and overall (HR, 0.55; 95% CI, 0.25-1.24; P = .15) survival.
CONCLUSIONS AND RELEVANCE
The findings of this cohort study suggest that Black men, despite being diagnosed at a younger age, experience comparable prostate cancer outcomes compared with men of other races.
Topics: Male; Humans; Prostatic Neoplasms; Aged; Middle Aged; Prospective Studies; Alberta; Canada; Black or African American; Neoplasm Grading; Black People; Neoplasm Staging; Prostate-Specific Antigen
PubMed: 38916889
DOI: 10.1001/jamanetworkopen.2024.18475 -
Scientific Data May 2024Infra-fraction motion of the prostate was recorded during 3.423 fractions of image guided radiotherapy (IGRT) in 191 patients, 14 of which were treated by intensity...
Infra-fraction motion of the prostate was recorded during 3.423 fractions of image guided radiotherapy (IGRT) in 191 patients, 14 of which were treated by intensity modulated radiation therapy (IMRT), and 177 of which were treated by volumetric arc therapy (VMAT). The prostate was imaged by three-dimensional and time-resolved transperineal ultrasound (4D-US) of type Clarity by Elekta AB, Stockholm, Sweden. The prostate volume was registered and the prostate position (center of volume) was recorded at a frequency of 2.0 samples per second. This raw data set contains a total of 1.985.392 prostate and patient couch positions over a time span of 272 hours, 52 minutes and 34 seconds of life radiotherapy as exported by the instrument software. This data set has been used for the validation of models of prostate intra-fraction motion and for the estimation of the dosimetric impact of actual intra-fraction motion on treatment quality and side effects. We hope that this data set may be reused by other groups for similar purposes.
Topics: Humans; Male; Movement; Prostate; Prostatic Neoplasms; Radiotherapy, Image-Guided; Radiotherapy, Intensity-Modulated; Ultrasonography
PubMed: 38755158
DOI: 10.1038/s41597-024-03365-2