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The Canadian Journal of Urology Jun 2024
Topics: Humans; Digital Rectal Examination; Male; Prostatic Neoplasms
PubMed: 38912935
DOI: No ID Found -
Acta Oncologica (Stockholm, Sweden) Jun 2024The delineation of intraprostatic lesions is vital for correct delivery of focal radiotherapy boost in patients with prostate cancer (PC). Errors in the delineation... (Comparative Study)
Comparative Study
BACKGROUND
The delineation of intraprostatic lesions is vital for correct delivery of focal radiotherapy boost in patients with prostate cancer (PC). Errors in the delineation could translate into reduced tumour control and potentially increase the side effects. The purpose of this study is to compare PET-based delineation methods with histopathology.
MATERIALS AND METHODS
The study population consisted of 15 patients with confirmed high-risk PC intended for prostatectomy. [68Ga]-PSMA-PET/MR was performed prior to surgery. Prostate lesions identified in histopathology were transferred to the in vivo [68Ga]-PSMA-PET/MR coordinate system. Four radiation oncologists manually delineated intraprostatic lesions based on PET data. Various semi-automatic segmentation methods were employed, including absolute and relative thresholds, adaptive threshold, and multi-level Otsu threshold.
RESULTS
The gross tumour volumes (GTVs) delineated by the oncologists showed a moderate level of interobserver agreement with Dice similarity coefficient (DSC) of 0.68. In comparison with histopathology, manual delineations exhibited the highest median DSC and the lowest false discovery rate (FDR) among all approaches. Among semi-automatic approaches, GTVs generated using standardized uptake value (SUV) thresholds above 4 (SUV > 4) demonstrated the highest median DSC (0.41), with 0.51 median lesion coverage ratio, FDR of 0.66 and the 95th percentile of the Hausdorff distance (HD95%) of 8.22 mm.
INTERPRETATION
Manual delineations showed a moderate level of interobserver agreement. Compared to histopathology, manual delineations and SUV > 4 exhibited the highest DSC and the lowest HD95% values. The methods that resulted in a high lesion coverage were associated with a large overestimation of the size of the lesions.
Topics: Humans; Male; Prostatic Neoplasms; Gallium Radioisotopes; Tumor Burden; Gallium Isotopes; Positron-Emission Tomography; Aged; Prostatectomy; Middle Aged; Radiopharmaceuticals; Oligopeptides; Magnetic Resonance Imaging; Edetic Acid
PubMed: 38912830
DOI: 10.2340/1651-226X.2024.39041 -
BMC Urology Jun 2024The incidence of recurrent hernia after radical resection of prostate cancer is high, so this article discusses the incidence and risk factors of inguinal hernia after...
OBJECTIVE
The incidence of recurrent hernia after radical resection of prostate cancer is high, so this article discusses the incidence and risk factors of inguinal hernia after radical resection of prostate cancer.
METHODS
This case control study was conducted in The First People's Hospital of Huzhou clinical data of 251 cases underwent radical resection of prostate cancer in this hospital from March 2019 to May 2021 were retrospectively analyzed. According to the occurrence of inguinal hernia, the subjects were divided into study group and control group, and the clinical data of each group were statistically analyzed, Multivariate Logistic analysis was performed to find independent influencing factors for predicting the occurrence of inguinal hernia. The Kaplan-Meier survival curve was drawn according to the occurrence and time of inguinal hernia.
RESULTS
The overall incidence of inguinal hernia after prostate cancer surgery was 14.7% (37/251), and the mean time was 8.58 ± 4.12 months. The average time of inguinal hernia in patients who received lymph node dissection was 7.61 ± 4.05 (month), and that in patients who did not receive lymph node dissection was 9.16 ± 4.15 (month), and there was no significant difference between them (P > 0.05). There were no statistically significant differences in the incidence of inguinal hernia with age, BMI, hypertension, diabetes, PSA, previous abdominal operations and operative approach (P > 0.05), but there were statistically significant differences with surgical method and pelvic lymph node dissection (P < 0.05). The incidence of pelvic lymph node dissection in the inguinal hernia group was 24.3% (14/57), which was significantly higher than that in the control group 11.8% (23/194). Logistic regression analysis showed that pelvic lymph node dissection was a risk factor for inguinal hernia after prostate cancer surgery (OR = 0.413, 95%Cl: 0.196-0.869, P = 0.02). Kaplan-Meier survival curve showed that the rate of inguinal hernia in the group receiving pelvic lymph node dissection was significantly higher than that in the control group (P < 0.05).
CONCLUSION
Pelvic lymph node dissection is a risk factor for inguinal hernia after radical resection of prostate cancer.
Topics: Humans; Male; Hernia, Inguinal; Prostatic Neoplasms; Risk Factors; Incidence; Case-Control Studies; Aged; Middle Aged; Prostatectomy; Postoperative Complications; Retrospective Studies; Lymph Node Excision; Correlation of Data
PubMed: 38909202
DOI: 10.1186/s12894-024-01493-w -
Diagnostic Pathology Jun 2024Catenin (Cadherin-Associated Protein), Beta 1 (CTNNB1) genomic alterations are rare in prostate cancer (PCa). Gain-of-function mutations lead to overexpression of...
BACKGROUND
Catenin (Cadherin-Associated Protein), Beta 1 (CTNNB1) genomic alterations are rare in prostate cancer (PCa). Gain-of-function mutations lead to overexpression of β-catenin, with consequent hyperactivation of the Wnt/β-catenin signaling pathway, implicated in PCa progression and treatment resistance. To date, successful targeted treatment options for Wnt/β-catenin - driven PCa are lacking.
METHODS
We report a rare histologic transformation of a CTNNB1 (β-catenin) mutated metastatic castration resistant prostate cancer (mCRPC), clinically characterized by highly aggressive disease course. We histologically and molecularly characterized the liver metastatic tumor samples, as well as successfully generated patient-derived organoids (PDOs) and patient-derived xenograft (PDX) from a liver metastasis. We used the generated cell models for further molecular characterization and drug response assays.
RESULTS
Immunohistochemistry of liver metastatic biopsies and PDX tumor showed lack of expression of typical PCa (e.g., AR, PSA, PSAP, ERG) or neuroendocrine markers (synaptophysin), compatible with double-negative CRPC, but was positive for nuclear β-catenin expression, keratin 7 and 34βE12. ERG rearrangement was confirmed by fluorescent in situ hybridization (FISH). Drug response assays confirmed, in line with the clinical disease course, lack of sensitivity to common drugs used in mCRPC (e.g., enzalutamide, docetaxel). The casein kinase 1 (CK1) inhibitor IC261 and the tankyrase 1/2 inhibitor G700-LK showed modest activity. Moreover, despite harbouring a CTNNB1 mutation, PDOs were largely insensitive to SMARCA2/4- targeting PROTAC degraders and inhibitor.
CONCLUSIONS
The reported CTNNB1-mutated mCRPC case highlights the potential challenges of double-negative CRPC diagnosis and underlines the relevance of further translational research to enable successful targeted treatment of rare molecular subtypes of mCRPC.
Topics: Humans; Male; beta Catenin; Mutation; Prostatic Neoplasms, Castration-Resistant; Liver Neoplasms; Animals; Biomarkers, Tumor; Aged; Disease Progression
PubMed: 38907236
DOI: 10.1186/s13000-024-01511-3 -
Scientific Reports Jun 2024Previous research has produced inconsistent findings concerning the connection between metabolic syndrome and prostate cancer. It is challenging for observational... (Meta-Analysis)
Meta-Analysis
Previous research has produced inconsistent findings concerning the connection between metabolic syndrome and prostate cancer. It is challenging for observational studies to establish a conclusive causal relationship between the two. However, Mendelian randomization can provide stronger evidence of causality in this context. To examine the causal link between a metabolic composite and its components with prostate cancer, we performed a two-sample Mendelian randomization (MR) study utilizing aggregated data from genome-wide association studies, followed by meta-analyses. In our study, we employed inverse variance weighting as the primary method for MR analysis. Additionally, we assessed potential sources of heterogeneity and horizontal pleiotropy through the Cochran's Q test and MR-Egger regression. Moreover, we used multivariate MR to determine whether smoking versus alcohol consumption had an effect on the outcomes. We found no causal relationship between metabolic syndrome and its components and prostate cancer(MetS, odds ratio [OR] = 0.95, 95% confidence interval [CI] = 0.738-1.223, p = 0.691; TG, [OR] = 1.02, 95%[CI] = 0.96-1.08, p = 0.59); HDL, [OR] = 1.02, 95% [CI] = 0.97-1.07, p = 0.47; DBP, [OR] = 1.00, 95%[CI] = 0.99-1.01, p = 0.87; SBP, [OR] = 1.00, 95%[CI] = 0.99-1.00, p = 0.26; FBG [OR] = 0.92, 95%[CI] = 0.81-1.05, p = 0.23; WC, [OR] = 0.93, 95%[CI] = 0.84-1.03, p = 0.16). Finally, the MVMR confirms that the metabolic syndrome and its components are independent of smoking and alcohol consumption in prostate cancer. We didn't find significant evidence to determine a causal relationship between the metabolic syndrome and its components and prostate cancer through MR analysis. Further research is necessary to explore the potential pathogenesis between the two diseases.
Topics: Humans; Male; Metabolic Syndrome; Prostatic Neoplasms; Mendelian Randomization Analysis; Genome-Wide Association Study; Risk Factors; Alcohol Drinking; Odds Ratio; Smoking; Polymorphism, Single Nucleotide
PubMed: 38906920
DOI: 10.1038/s41598-024-65310-y -
Science Advances Jun 2024Androgen deprivation therapy (ADT) for prostate cancer is associated with an increased risk of dementia, including Alzheimer's disease (AD). The mechanistic connection...
Androgen deprivation therapy (ADT) for prostate cancer is associated with an increased risk of dementia, including Alzheimer's disease (AD). The mechanistic connection between ADT and AD-related cognitive impairment in patients with prostate cancer remains elusive. We established a clinically relevant prostate cancer-bearing AD mouse model to explore this. Both tumor-bearing and ADT induce complex changes in immune and inflammatory responses in peripheral blood and in the brain. ADT disrupts the integrity of the blood-brain barrier (BBB) and promotes immune cell infiltration into the brain, enhancing neuroinflammation and gliosis without affecting the amyloid plaque load. Moreover, treatment with natalizumab, an FDA-approved drug targeting peripheral immune cell infiltration, reduces neuroinflammation and improves cognitive function in this model. Our study uncovers an inflammatory mechanism, extending beyond amyloid pathology, that underlies ADT-exacerbated cognitive deficits, and suggests natalizumab as a potentially effective treatment in alleviating the detrimental effects of ADT on cognition.
Topics: Animals; Alzheimer Disease; Male; Cognitive Dysfunction; Mice; Brain; Humans; Blood-Brain Barrier; Disease Models, Animal; Androgen Antagonists; Prostatic Neoplasms; Natalizumab; Plaque, Amyloid
PubMed: 38905345
DOI: 10.1126/sciadv.adn8709 -
Frontiers in Endocrinology 2024The relationship between cathepsins and prostate cancer (PCa) has been reported. However, there is a lack of research on cathepsins and benign prostate diseases (BPDs)....
OBJECTIVES
The relationship between cathepsins and prostate cancer (PCa) has been reported. However, there is a lack of research on cathepsins and benign prostate diseases (BPDs). This study investigated the potential genetic link between cathepsins and BPDs through the utilization of Mendelian randomization (MR) analysis to determine if a causal relationship exists.
METHODS
Publicly accessible summary statistics on BPDs were obtained from FinnGen Biobank. The data comprised 149,363 individuals, with 30,066 cases and 119,297 controls for BPH, and 123,057 individuals, with 3,760 cases and 119,297 controls for prostatitis. The IEU OpenGWAS provided the Genome-wide association data on ten cathepsins. To evaluate the causal relationship between BPDs and cathepsins, five distinct MR analyses were employed, with the primary method being the inverse variance weighted (IVW) approach. Additionally, sensitivity analyses were conducted to examine the horizontal pleiotropy and heterogeneity of the findings.
RESULTS
The examination of IVW MR findings showed that cathepsin O had a beneficial effect on BPH (IVW OR=0.94, 95% CI 0.89-0.98, P=0.0055), while cathepsin X posed a threat to prostatitis (IVW OR=1.08, 95% CI 1.00-1.16, P=0.047). Through reverse MR analysis, it was revealed that prostatitis had an adverse impact on cathepsin V (IVW OR=0.89, 95% CI 0.80-0.99, P=0.035), while no favorable association was observed between BPH and cathepsins. The results obtained from MR-Egger, weighted median, simple mode, and weighted mode methods were consistent with the findings of the IVW approach. Based on sensitivity analyses, heterogeneity, and horizontal pleiotropy are unlikely to distort the results.
CONCLUSION
This study offers the initial evidence of a genetic causal link between cathepsins and BPDs. Our findings revealed that cathepsin O was beneficial in preventing BPH, whereas cathepsin X posed a potential threat to prostatitis. Additionally, prostatitis negatively affected cathepsin V level. These three cathepsins could be targets of diagnosis and treatment for BPDs, which need further research.
Topics: Humans; Male; Mendelian Randomization Analysis; Cathepsins; Prostatic Hyperplasia; Genome-Wide Association Study; Polymorphism, Single Nucleotide; Case-Control Studies; Genetic Predisposition to Disease; Prostatic Neoplasms; Prostatitis; Prostatic Diseases
PubMed: 38904040
DOI: 10.3389/fendo.2024.1348310 -
Journal of Health, Population, and... Jun 2024According to our knowledge, the relationship between dietary patterns such as pro-healthy, pro-vegetarian, and non-healthy dietary patterns and prostate cancer risk has...
INTRODUCTION
According to our knowledge, the relationship between dietary patterns such as pro-healthy, pro-vegetarian, and non-healthy dietary patterns and prostate cancer risk has not been clearly investigated in Iranian men. Therefore, we aimed to investigate the relationship between adherence to a pro-healthy (PHDI), pro-vegetarian (PDP), and non-healthy dietary indices (NHDI) and the risk of prostate cancer.
METHOD
In this matched case-control study, 125 participants (62 cases and 63 hospital-based controls) were enrolled from April to September 2015. Participants' dietary intakes were evaluated using a valid and reliable 160-item semi-quantitative food frequency questionnaire. Dietary indices calculated based on previous studies. The relationship between dietary indices (PHDI, NHDI and PDP) and prostate cancer risk was assessed using binary regression models.
RESULTS
According to adjusted model, significant negative correlations were found between PHDI and PDP with prostate cancer (PHDI: OR = 0.31; 95% CI; 0.11-0.85; P = 0.023 - PDP: OR = 0.34; 95% CI; 0.15-0.75; P = 0.008). Also, a positive association was seen between NHDI and prostate cancer (OR = 3.01; 95% CI; 1.20-7.57; P = 0.019).
CONCLUSION
We found that adherence to healthy dietary indices which includes high amounts of fruits, vegetables, and whole grains reduces the risk of prostate cancer. While adherence to a dietary pattern high in red and processed meat, refined grains, and sweetened beverages increases the risk of prostate cancer.
Topics: Humans; Male; Prostatic Neoplasms; Case-Control Studies; Iran; Middle Aged; Diet, Healthy; Risk Factors; Aged; Diet; Diet, Vegetarian; Feeding Behavior; Adult; Diet Surveys
PubMed: 38902815
DOI: 10.1186/s41043-024-00578-4 -
Journal of Experimental & Clinical... Jun 2024The androgen receptor (AR) is a drug target used to inhibit AR and prostate cancer (PCa) growth. Surprisingly, treatment with supraphysiological androgen level (SAL),...
BACKGROUND
The androgen receptor (AR) is a drug target used to inhibit AR and prostate cancer (PCa) growth. Surprisingly, treatment with supraphysiological androgen level (SAL), used in bipolar androgen therapy, inhibits growth of PCa suggesting a tumor-suppressive activity by SAL. SAL was shown to induce cellular senescence in PCa.
METHODS
RNA-seq and transcriptome analysis, ChIP-seq, human 3D PCa spheroids, mouse xenografted castration-resistant PCa, knockdown and overexpression, Co-immunoprecipitation (Co-IP), translocation analysis, immune detection, qRT-PCR, protein-protein interaction modelling.
RESULTS
Here, mice xenografts with castration-resistant PCa tumors show that SAL inhibits cancer growth in vivo suggesting that SAL activates a tumor-suppressive mechanism. RNA-seq and ChIP-seq revealed the clock gene BHLHE40 is a novel direct AR target. Compared to adjacent human prostate tissues, the expression of BHLHE40 is reduced in PCa tumors and associated with reduced survival. Knockdown suggests that BHLHE40 mediates SAL-induced cellular senescence including tumor spheroids. Interestingly, a large overlap of differentially expressed gene sets was identified between BHLHE40 and SAL leading to the identification of four classes of SAL-BHLHE40 transcriptome landscapes. Co-IP and modelling suggest binding of BHLHE40 to AR and their co-translocation into nucleus by SAL treatment. Further, RNA-seq and ChIP-seq analysis indicate that the atypical tumor suppressive cyclin G2 emerged as a novel downstream target of BHLHE40 and a mediator of SAL-induced cellular senescence.
CONCLUSIONS
The data provide evidence of the tumor suppressive activity of SAL and a novel signaling by the AR-BHLHE40-CCNG2 axis for androgen-induced cellular senescence, linking circadian rhythm factor to androgen signaling as a novel tumor suppressive pathway.
Topics: Male; Humans; Cellular Senescence; Mice; Animals; Prostatic Neoplasms; Basic Helix-Loop-Helix Transcription Factors; Androgens; Cell Line, Tumor; Homeodomain Proteins; Receptors, Androgen; Gene Expression Regulation, Neoplastic; Xenograft Model Antitumor Assays
PubMed: 38902772
DOI: 10.1186/s13046-024-03097-6 -
JCO Clinical Cancer Informatics Jun 2024Prostate cancer (PCa) represents a highly heterogeneous disease that requires tools to assess oncologic risk and guide patient management and treatment planning. Current...
PURPOSE
Prostate cancer (PCa) represents a highly heterogeneous disease that requires tools to assess oncologic risk and guide patient management and treatment planning. Current models are based on various clinical and pathologic parameters including Gleason grading, which suffers from a high interobserver variability. In this study, we determine whether objective machine learning (ML)-driven histopathology image analysis would aid us in better risk stratification of PCa.
MATERIALS AND METHODS
We propose a deep learning, histopathology image-based risk stratification model that combines clinicopathologic data along with hematoxylin and eosin- and Ki-67-stained histopathology images. We train and test our model, using a five-fold cross-validation strategy, on a data set from 502 treatment-naïve PCa patients who underwent radical prostatectomy (RP) between 2000 and 2012.
RESULTS
We used the concordance index as a measure to evaluate the performance of various risk stratification models. Our risk stratification model on the basis of convolutional neural networks demonstrated superior performance compared with Gleason grading and the Cancer of the Prostate Risk Assessment Post-Surgical risk stratification models. Using our model, 3.9% of the low-risk patients were correctly reclassified to be high-risk and 21.3% of the high-risk patients were correctly reclassified as low-risk.
CONCLUSION
These findings highlight the importance of ML as an objective tool for histopathology image assessment and patient risk stratification. With further validation on large cohorts, the digital pathology risk classification we propose may be helpful in guiding administration of adjuvant therapy including radiotherapy after RP.
Topics: Humans; Prostatic Neoplasms; Male; Deep Learning; Neoplasm Grading; Risk Assessment; Prostatectomy; Aged; Middle Aged; Image Processing, Computer-Assisted
PubMed: 38900978
DOI: 10.1200/CCI.23.00184