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Cancer Research Communications Jun 2024Sipuleucel-T is an autologous cellular immunotherapy that targets prostatic acid phosphatase (PAP) and is available for treatment of men with asymptomatic or minimally...
PURPOSE
Sipuleucel-T is an autologous cellular immunotherapy that targets prostatic acid phosphatase (PAP) and is available for treatment of men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). In this single-arm, two-cohort, multicenter clinical study, potential racial differences in immune responses to sipuleucel-T in men with mCRPC were explored.
PATIENTS AND METHODS
Patients' blood samples were obtained to assess serum cytokines, humoral responses, and cellular immunity markers pre- and post-treatment. Baseline cumulative product parameters (total nucleated and CD54+ cell counts, and CD54 upregulation) were evaluated. IgM titers against the immunogen PA2024, the target antigen PAP, prostate-specific membrane antigen (PSMA) and prostate-specific antigen (PSA) were quantified by ELISA. Cytotoxic T lymphocyte activity was determined by ELISpots, and cytokine and chemokine concentrations by Luminex.
RESULTS
Twenty-nine African Americans (AA) and 28 non-African Americans (non-AA) with mCRPC received sipuleucel-T. Baseline total nucleated cell count, CD54+ cell count, CD54 expression, and cumulative product parameters were higher in non-AA. Although PSA baseline levels were higher in AA, there were no racial differences in IgM antibody and IFN- ELISpots responses against PA2024, PAP, PSA and PSMA pre- and post-treatment. Expression of co-stimulatory receptor ICOS on CD4+ and CD8+ T cells, and the levels of Th1 cytokine granulocyte-macrophage colony-stimulating factor and chemokines CCL4 and CCL5, were significantly higher in AA pre- and/or post-treatment. Despite no difference in the overall survival, PSA changes from baseline were significantly different between the two races.
CONCLUSIONS
The data suggest that immune correlates in blood differ in AA and non-AA with mCRPC pre- and post-sipuleucel-T.
PubMed: 38856749
DOI: 10.1158/2767-9764.CRC-24-0112 -
Translational Andrology and Urology May 2024Small cell neuroendocrine prostate cancer (SCNC) is a rare aggressive type of neuroendocrine prostate cancer (NEPC) characterized by aggressive clinical course and lack...
BACKGROUND
Small cell neuroendocrine prostate cancer (SCNC) is a rare aggressive type of neuroendocrine prostate cancer (NEPC) characterized by aggressive clinical course and lack of response to hormone therapy.
CASE DESCRIPTION
We present a case report of a 60-year-old man diagnosed with a histologically confirmed primary metastatic (bone, lymph nodes and visceral) SCNC with small components of an adenocarcinoma with clinical symptoms mimicking an acute prostatitis. Of note, serum based neuroendocrine markers (carcinoembryonic antigen, chromogranin A) were negative and the patient had a prostate-specific antigen (PSA) elevation. Genetic testing of tumor tissue revealed breast cancer gene 2 () copy number loss and a retinoblastoma gene () mutation reflecting again the aggressiveness of the disease. Germline testing for the copy number loss was unremarkable. After 6 cycles of carboplatin and etoposide in combination with androgen deprivation therapy (ADT) the Eastern Cooperative Oncology Group (ECOG) performance status has improved from 3 to 0, in addition the patient was free of pain. In line with clinical improvement, both prostate-specific membrane antigen (PSMA) and fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) revealed a significant reduction of metastatic load. Currently, the patient is treated with ADT plus apalutamide.
CONCLUSIONS
We demonstrate for the first time a case of a primary metastatic SCNC with adenocarcinoma components successfully treated by the combination of platinum-based chemotherapy plus hormonal therapy. In addition, we provide a literature overview on management of SCNC as there is no standard treatment established for this disease.
PubMed: 38855597
DOI: 10.21037/tau-23-541 -
Translational Andrology and Urology May 2024
PubMed: 38855594
DOI: 10.21037/tau-23-612 -
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