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The Canadian Journal of Urology Jun 2024Prostate cancer is the second most common cancer in men across the world. Prior to PSA testing, men usually presented with locally advanced disease detected on digital...
Prostate cancer is the second most common cancer in men across the world. Prior to PSA testing, men usually presented with locally advanced disease detected on digital rectal exam or with metastatic disease. PSA ushered in the era of serum biomarkers for prostate cancer. It has taken over three decades to refine the role of PSA in prostate cancer detection. The lack of specificity has spurred research into finding better, readily obtainable biomarkers with high sensitivity and specificity. The trick is to find the prostate cancers that are a threat, not the ones that aren't. Over the last decade and more, many biomarkers have been proposed and tested (HK-2, Pro-PSA, PCA3, TMPRSS2:ERG fusion transcripts, miRNA, just to name a few) but we still await that magical combination of a readily available, reproducible, and hopefully inexpensive biomarker with high sensitivity and specificity. The authors describe the use of a peptide labeled fluorophore for the VPAC1 receptors that are expressed on malignant prostate cancer cells shed in the urine. After initial feasibility work, the authors collected urine from 318 men with lower urinary tract symptoms and a PSA > 4. The patients underwent prostate biopsy yielding Grade Group 2 or higher prostate cancer in 158 patients. One hundred fifty-four or those patients with cancer had a positive result for the biomarker. The sensitivity of the test was 100%, the specificity was 97.56%, positive predictive value was 97.47%, and negative predictive value was 100%.1 These are impressive numbers for a urine biomarker (or any biomarker). This work is certainly promising, BUT, we have seen promising early data on many biomarkers. In this study, the mean PSA in the cancer group was 34.53 ng/mL versus 9.41 in the control (negative) group. Since patients with infection were excluded, the significantly different PSA levels seemed to be selecting the cancers as well. Time and follow up will determine if the "negative biopsy" controls were truly negative. Can the technique and these results be reproduced? The true test will be how this biomarker consistently performs across a broader population of men with a lower, more homogenous PSA elevation. I will eagerly await results of continued study of this promising biomarker for prostate cancer.
Topics: Humans; Male; Prostatic Neoplasms; Biomarkers, Tumor; Sensitivity and Specificity; Prostate-Specific Antigen; Aged; Middle Aged
PubMed: 38912943
DOI: No ID Found -
The Canadian Journal of Urology Jun 2024Prostate cancer is the second most common malignancy in men worldwide. Genomic VPAC receptors are expressed on malignant prostate cancer cells and can be targeted and...
INTRODUCTION
Prostate cancer is the second most common malignancy in men worldwide. Genomic VPAC receptors are expressed on malignant prostate cancer cells and can be targeted and imaged optically by a peptide labeled fluorophore. The objective of our study was to assess the feasibility of detecting cancer of the prostate using a voided urine sample.
MATERIALS AND METHODS
Patients ≥ 40 years old, with lower urinary tract symptoms and serum PSA > 4 ng/mL formed the study group. The first 50 mL of voided urine sample was collected and processed. The cells that were shed in the voided urine were fixed and stained with a peptide TP4303 and incubated. The slide was then stained with DAPI which binds with the DNA in the nucleus. All patients underwent a standard 12-core TRUS-guided prostate biopsy.
RESULTS
A total of 318 patients were included in the study, of these 158 were histologically confirmed cancers. Voided urine samples were positive for VPAC receptors in 154 (97.46%) of these. The remaining 160 patients had no cancer on the HPR examination and none of these patients were positive for VPAC receptors.
CONCLUSIONS
This study validates our belief that patients with prostate cancer shed malignant cells in the urine that can be identified by targeting the VPAC receptors. If these results are further validated by multicentric studies, then this could form the basis for indications for a preliminary prostate biopsy in patients with elevated serum PSA but normal digital examination or in patients needing a repeat biopsy.
Topics: Humans; Male; Prostatic Neoplasms; Middle Aged; Aged; Feasibility Studies; Adult; Lower Urinary Tract Symptoms; Aged, 80 and over
PubMed: 38912942
DOI: No ID Found -
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 -
The Tokai Journal of Experimental and... Jul 2024Recently, effectiveness of local treatment for oncological outcomes for patients with metastatic prostate cancer (PC) has been reported. We performed hemi-ablation with...
Recently, effectiveness of local treatment for oncological outcomes for patients with metastatic prostate cancer (PC) has been reported. We performed hemi-ablation with high-intensity focused ultrasound (HIFU) for a patient with a localized reducted solitary lesion in the prostate, which was diagnosed with magnetic resonance imaging (MRI)-transrectal ultrasound fusion image-guided target biopsy with PSA level of 0.24 ng/mL, after androgen receptor signaling inhibitors (ARSIs) and chemotherapy for metastatic PC. Prostate specific antigen levels decreased to 0.01ng/mL at 1 month after the treatment, and cancer suspicious lesion disappeared on MRI. During the follow-up of 24 months, there was no elevation of PSA level with no severe complication related to the treatment. HIFU has possibility to be an effective and minimally invasive treatment as a local treatment for the localized reducted solitary lesion in the prostate after ARSIs and chemotherapy for metastatic PC.
Topics: Humans; Male; Prostatic Neoplasms; Treatment Outcome; Prostate-Specific Antigen; Magnetic Resonance Imaging; Aged; High-Intensity Focused Ultrasound Ablation; Image-Guided Biopsy; Androgen Receptor Antagonists; Prostate
PubMed: 38904239
DOI: No ID Found -
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