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Translational Andrology and Urology May 2024
PubMed: 38855591
DOI: 10.21037/tau-23-674 -
Theranostics 2024In 1853, the perception of prostate cancer (PCa) as a rare ailment prevailed, was described by the eminent Londoner surgeon John Adams. Rapidly forward to 2018, the... (Review)
Review
In 1853, the perception of prostate cancer (PCa) as a rare ailment prevailed, was described by the eminent Londoner surgeon John Adams. Rapidly forward to 2018, the landscape dramatically altered. Currently, men face a one-in-nine lifetime risk of PCa, accentuated by improved diagnostic methods and an ageing population. With more than three million men in the United States alone grappling with this disease, the overall risk of succumbing to stands at one in 39. The intricate clinical and biological diversity of PCa poses serious challenges in terms of imaging, ongoing monitoring, and disease management. In the field of theranostics, diagnostic and therapeutic approaches that harmoniously merge targeted imaging with treatments are integrated. A pivotal player in this arena is radiotheranostics, employing radionuclides for both imaging and therapy, with prostate-specific membrane antigen (PSMA) at the forefront. Clinical milestones have been reached, including FDA- and/or EMA-approved PSMA-targeted radiodiagnostic agents, such as [F]DCFPyL (PYLARIFY, Lantheus Holdings), [F]rhPSMA-7.3 (POSLUMA, Blue Earth Diagnostics) and [Ga]Ga-PSMA-11 (Locametz, Novartis/ ILLUCCIX, Telix Pharmaceuticals), as well as PSMA-targeted radiotherapeutic agents, such as [Lu]Lu-PSMA-617 (Pluvicto, Novartis). Concurrently, ligand-drug and immune therapies designed to target PSMA are being advanced through rigorous preclinical research and clinical trials. This review delves into the annals of PSMA-targeted radiotheranostics, exploring its historical evolution as a signature molecule in PCa management. We scrutinise its clinical ramifications, acknowledge its limitations, and peer into the avenues that need further exploration. In the crucible of scientific inquiry, we aim to illuminate the path toward a future where the enigma of PCa is deciphered and where its menace is met with precise and effective countermeasures. In the following sections, we discuss the intriguing terrain of PCa radiotheranostics through the lens of PSMA, with the fervent hope of advancing our understanding and enhancing clinical practice.
Topics: Humans; Prostatic Neoplasms; Glutamate Carboxypeptidase II; Male; Antigens, Surface; Radiopharmaceuticals; Nuclear Medicine; Theranostic Nanomedicine; Radioisotopes; History, 21st Century; History, 20th Century
PubMed: 38855174
DOI: 10.7150/thno.92612 -
European Urology Oncology Jun 2024While collagen density has been associated with poor outcomes in various cancers, its role in prostate cancer (PCa) remains elusive. Our aim was to analyze...
BACKGROUND AND OBJECTIVE
While collagen density has been associated with poor outcomes in various cancers, its role in prostate cancer (PCa) remains elusive. Our aim was to analyze collagen-related transcriptomic, proteomic, and urinome alterations in the context of detection of clinically significant PCa (csPCa, International Society of Urological Pathology [ISUP] grade group ≥2).
METHODS
Comprehensive analyses for PCa transcriptome (n = 1393), proteome (n = 104), and urinome (n = 923) data sets focused on 55 collagen-related genes. Investigation of the cellular source of collagen-related transcripts via single-cell RNA sequencing was conducted. Statistical evaluations, clustering, and machine learning models were used for data analysis to identify csPCa signatures.
KEY FINDINGS AND LIMITATIONS
Differential expression of 30 of 55 collagen-related genes and 34 proteins was confirmed in csPCa in comparison to benign prostate tissue or ISUP 1 cancer. A collagen-high cancer cluster exhibited distinct cellular and molecular characteristics, including fibroblast and endothelial cell infiltration, intense extracellular matrix turnover, and enhanced growth factor and inflammatory signaling. Robust collagen-based machine learning models were established to identify csPCa. The models outcompeted prostate-specific antigen (PSA) and age, showing comparable performance to multiparametric magnetic resonance imaging (mpMRI) in predicting csPCa. Of note, the urinome-based collagen model identified four of five csPCa cases among patients with Prostate Imaging-Reporting and Data System (PI-IRADS) 3 lesions, for which the presence of csPCa is considered equivocal. The retrospective character of the study is a limitation.
CONCLUSIONS AND CLINICAL IMPLICATIONS
Collagen-related transcriptome, proteome, and urinome signatures exhibited superior accuracy in detecting csPCa in comparison to PSA and age. The collagen signatures, especially in cases of ambiguous lesions on mpMRI, successfully identified csPCa and could potentially reduce unnecessary biopsies. The urinome-based collagen signature represents a promising liquid biopsy tool that requires prospective evaluation to improve the potential of this collagen-based approach to enhance diagnostic precision in PCa for risk stratification and guiding personalized interventions.
PATIENT SUMMARY
In our study, collagen-related alterations in tissue, and urine were able to predict the presence of clinically significant prostate cancer at primary diagnosis.
PubMed: 38851995
DOI: 10.1016/j.euo.2024.05.014 -
Frontiers in Public Health 2024This study aims to investigate the impact of depression and urinary metals on Prostate-Specific Antigen (PSA).
OBJECTIVE
This study aims to investigate the impact of depression and urinary metals on Prostate-Specific Antigen (PSA).
METHODS
Analysis was conducted on 1901 samples collected from the National Health and Nutrition Examination Survey (NHANES) database between 2001 and 2010. Analytical methods included stepwise multiple linear regression (MLR) analysis of the overall population's urinary metals and PSA relationship, analysis of urinary metals and PSA relationship in older adults and BMI subgroups, analysis of urinary metals and PSA relationship in the depressed population, and restricted cubic spline (RCS) analysis. A significance level of < 0.05 was considered statistically significant.
RESULTS
In the stepwise multiple linear regression, beryllium (Be) showed a dose-response association with PSA (third quartile: β = 0.05, 95%CI (0.02, 0.09); fourth quartile: β = 0.07, 95%CI (0.02, 0.12), trend = 0.048). Subgroup analysis indicated that in individuals aged >60, Be at Q4 level [β = 0.09, 95%CI (0.05, 0.21)] exhibited a dose-response correlation with PSA. In the population with 25 ≤ BMI < 30, Be might more significantly elevate PSA, with Q4 level having a pronounced impact on PSA levels [β = 0.03, 95%CI (0.02, 1.27)]. In the depressed population, urinary cadmium (Cd) levels showed a significant positive dose-response relationship, with Q4 level of Cd having the maximum impact on PSA [β = 0.3, 95%CI (0.09, 0.49)].
CONCLUSION
Individuals exposed to beryllium (Be), especially the older adults and overweight, should monitor their PSA levels. In depressed patients, cadmium (Cd) levels may further elevate PSA levels, necessitating increased monitoring of PSA levels among males.
Topics: Humans; Male; Cross-Sectional Studies; Prostate-Specific Antigen; Middle Aged; Nutrition Surveys; Depression; Aged; Female; Metals; Adult; Body Mass Index; Aging
PubMed: 38846601
DOI: 10.3389/fpubh.2024.1401072 -
BJR Case Reports May 2024Granular cell tumour is a rare, mostly benign, soft tissue, neuroectodermal tumour, most commonly seen in the skin and peripheral soft tissue. There are no publications...
Granular cell tumour is a rare, mostly benign, soft tissue, neuroectodermal tumour, most commonly seen in the skin and peripheral soft tissue. There are no publications to date of PSMA-PET avidity in a granular cell tumour. In this 60 year old male, staging PSMA-PET for a localized intermediate risk prostate cancer incidentally identified a PSMA-avid left supraspinatus lesion, which was subsequently biopsy-proven as a granular cell tumour. We present the first case of PSMA-avid granular cell tumour and add to the growing literature documenting PSMA-PET avidity in benign and malignant lesions apart from prostate cancer.
PubMed: 38846270
DOI: 10.1093/bjrcr/uaae015 -
HGG Advances Jun 2024Deciphering the genetic basis of prostate-specific antigen (PSA) levels may improve their utility for prostate cancer (PCa) screening. Using genome-wide association...
Deciphering the genetic basis of prostate-specific antigen (PSA) levels may improve their utility for prostate cancer (PCa) screening. Using genome-wide association study (GWAS) summary statistics from 95,768 PCa-free men, we conducted a transcriptome-wide association study (TWAS) to examine impacts of genetically predicted gene expression on PSA. Analyses identified 41 statistically significant (p < 0.05/12,192 = 4.10 × 10) associations in whole blood and 39 statistically significant (p < 0.05/13,844 = 3.61 × 10) associations in prostate tissue, with 18 genes associated in both tissues. Cross-tissue analyses identified 155 statistically significantly (p < 0.05/22,249 = 2.25 × 10) genes. Out of 173 unique PSA-associated genes across analyses, we replicated 151 (87.3%) in a TWAS of 209,318 PCa-free individuals from the Million Veteran Program. Based on conditional analyses, we found 20 genes (11 single tissue, nine cross-tissue) that were associated with PSA levels in the discovery TWAS that were not attributable to a lead variant from a GWAS. Ten of these 20 genes replicated, and two of the replicated genes had colocalization probability of >0.5: CCNA2 and HIST1H2BN. Six of the 20 identified genes are not known to impact PCa risk. Fine-mapping based on whole blood and prostate tissue revealed five protein-coding genes with evidence of causal relationships with PSA levels. Of these five genes, four exhibited evidence of colocalization and one was conditionally independent of previous GWAS findings. These results yield hypotheses that should be further explored to improve understanding of genetic factors underlying PSA levels.
PubMed: 38845201
DOI: 10.1016/j.xhgg.2024.100315 -
Nigerian Journal of Clinical Practice May 2024Organ-confined prostate cancer is curable through surgical treatment by radical prostatectomy.
BACKGROUND
Organ-confined prostate cancer is curable through surgical treatment by radical prostatectomy.
AIM
To report initial outcomes of open radical prostatectomy in Nigeria from 2014 to 2019.
METHODS
Open radical prostatectomy in private hospital settings. Thirty-five patients underwent open radical prostatectomy in private hospital settings from 2014 to 2019. A retrospective study of the case notes was undertaken.
RESULTS
The age range was 56-77 years (mean: 67.7 ± 5.6 years); presenting total PSA 7.3-32.0 ng/ml (mean: 16.2 ± 6.4); Gleason score range 6-10 and clinical stage T2c. Mean operation duration 192.4 ± 52.0 min. All patients received blood transfusion (average blood transfusion 4.58 ± 1.9 pints). The median length of hospital stay was 7 days and the catheterization duration was 16.6 days. The Gleason score ranges from 6 to 10. Biopsy and specimen histology Gleason scores correlated in all cases. Biochemical relapse within 1 year occurred in 12 (34.3%) patients. Adequate PSA control was achieved in 23 (65.7%) patients. Two cancer-related deaths occurred within 2 years of surgery. All patients voided well following removal of the catheter; persisting mild stress urinary incontinence resolved on conservative measures within 3-6 months. Anastomotic stricture occurred in one patient 1 (2.9%) in this present. Information on preoperative potency rate was unavailable; however, postoperation, 11 (31.4%) patients achieved erections sufficient for intercourse with oral therapy. All surviving 33 (94.3%) patients reported satisfactory performance status.
CONCLUSIONS
Open radical prostatectomy was successfully performed in all the patients. Reasonable, comparative functional, and oncological outcomes were achieved during the study period.
Topics: Humans; Male; Prostatectomy; Middle Aged; Nigeria; Aged; Prostatic Neoplasms; Retrospective Studies; Treatment Outcome; Neoplasm Grading; Length of Stay; Prostate-Specific Antigen
PubMed: 38842705
DOI: 10.4103/njcp.njcp_453_23 -
Cureus May 2024This case report documents the diagnosis of multiple myeloma (MM) in a 74-year-old man following treatment for locally advanced prostate cancer. It is important to...
This case report documents the diagnosis of multiple myeloma (MM) in a 74-year-old man following treatment for locally advanced prostate cancer. It is important to include MM in the differential diagnosis when the patient presents with nonspecific symptoms such as back pain, anemia, and renal impairment in the absence of a prominent increase in prostate-specific antigen (PSA). The present case was diagnosed as IgE MM with a poor prognosis. Prompt diagnosis and intervention of MM is necessary to avoid complications, including renal impairment.
PubMed: 38841024
DOI: 10.7759/cureus.59732 -
Archivos Espanoles de Urologia May 2024Radical prostatectomy (RP) is one of the most effective methods used to cure localised prostate cancer, but the risk of postoperative biochemical recurrence persists....
OBJECTIVE
Radical prostatectomy (RP) is one of the most effective methods used to cure localised prostate cancer, but the risk of postoperative biochemical recurrence persists. This study aims to analyse the effect of continuous nursing based on Internet technology on mental health and quality of life in patients undergoing RP.
METHODS
The medical records of patients undergoing RP in our hospital from February 2021 to February 2023 were retrospectively analysed. From February 2021 to January 2022, 89 patients received routine postoperative nursing, and 85 cases were included in the reference group after excluding 4 patients who had missing clinical data. From February 2022 to February 2023, 86 patients received continuous nursing based on Internet technology, and 80 patients were classified as the observation group after 6 patients (5 patients with incomplete clinical data and 1 patient with cognitive impairment) were excluded. The Hospital Anxiety and Depression Scale (HADS) data were collected, and urinary control, incidence of complications, nursing satisfaction and 36-item short-form health survey (SF-36) were compared between the two groups.
RESULTS
After management, patients in the observation group had lower Hospital Anxiety and Depression Scale-Anxiety (HADS-A) score, Hospital Anxiety and Depression Scale-Depression (HADS-D) score and postvoid residual (PVR) and higher maximum flow rate (Q) and detrusor pressure at the maximum flow rate (P-Q) ( < 0.001) than those in the reference group. The observation group also had significantly lower incidence of complications ( < 0.05), higher scores of physiological function, physiological role, physical pain, general health, vitality, social function, emotional function and mental health ( < 0.01) and significantly higher total nursing satisfaction ( < 0.05). Prostate specific antigen (PSA) level was not significantly different between the two groups after management ( > 0.05).
CONCLUSIONS
Continuous nursing based on Internet technology improves the psychological status and quality of life, reduces the occurrence of postoperative complications and obtains high clinical satisfaction for patients receiving RP.
Topics: Humans; Male; Prostatectomy; Retrospective Studies; Quality of Life; Mental Health; Middle Aged; Aged; Prostatic Neoplasms; Internet; Postoperative Care; Postoperative Complications
PubMed: 38840284
DOI: 10.56434/j.arch.esp.urol.20247704.55 -
Archivos Espanoles de Urologia May 2024High intensity focused ultrasound (HIFU), also referred to as focused ultrasound surgery (FUS), has garnered recent attention as a non-invasive therapeutic strategy for... (Review)
Review
High intensity focused ultrasound (HIFU), also referred to as focused ultrasound surgery (FUS), has garnered recent attention as a non-invasive therapeutic strategy for prostate cancer. It utilizes focused acoustic energy to achieve localized thermal ablation, while also potentially exerting immunomodulatory effects. This review aims to elucidate the mechanisms underlying how HIFU influences tumor-specific immune responses in prostate cancer. These mechanisms include the release of tumor-associated antigens and damage-associated molecular patterns, the activation of innate immune cells, the facilitation of antigen presentation to adaptive immune cells, the enhancement of activation and proliferation of tumor-specific cytotoxic T lymphocytes, and the attenuation of the immunosuppressive tumor microenvironment by reducing the activity of regulatory T cells and myeloid-derived suppressor cells. Both preclinical investigations and emerging clinical data in prostate cancer models highlight HIFU's potential to modulate the immune system, as evidenced by increased infiltration of effector immune cells, elevated levels of pro-inflammatory cytokines, and improved responsiveness to immune checkpoint inhibitors. HIFU induces immunogenic cell death, leading to the release of tumor antigens and danger signals that activate dendritic cells and facilitate cross-presentation to cytotoxic T cells. Additionally, FUS ablation reduces immunosuppressive cells and increases infiltration of CD8 T cells into the tumor, reshaping the tumor microenvironment. By priming the immune system while overcoming immunosuppression, combining FUS with other immunotherapies like checkpoint inhibitors and cancer vaccines holds promise for synergistic anti-tumor effects. Despite challenges in optimizing parameters and identifying suitable patients, FUS represents a novel frontier by modulating the tumor microenvironment and enhancing anti-tumor immunity through a non-invasive approach.
Topics: Prostatic Neoplasms; Male; Humans; High-Intensity Focused Ultrasound Ablation; Tumor Microenvironment
PubMed: 38840273
DOI: 10.56434/j.arch.esp.urol.20247704.44