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1.
J Cancer Res Clin Oncol ; 150(9): 414, 2024 Sep 09.
Article in English | MEDLINE | ID: mdl-39249593

ABSTRACT

PURPOSE: Apalutamide plus androgen-deprivation therapy (ADT) improved outcomes in patients with non-metastatic castration-resistant prostate cancer (nmCRPC). Nevertheless real-world data are limited. The aim of this multicenter study was to generate real-world data from nmCRPC patients treated with ADT plus apalutamide. METHODS: In this observational cohort based investigator initiated trial data of nmCRPC patients receiving apalutamide plus ADT were collected focusing on patient demographic data, prostate-specific antigen (PSA) declines, safety profile including dose modification/discontinuation as well as subsequent therapy and metastasis-free survival (MFS). RESULTS: Data from a total of 31 nmCRPC patients were documented. Compared to the Phase III study Spartan real-world patients are older, showed a higher ECOG-PS and more aggressive tumors. In the cohort PSA decreased about 98.1%, 74% of patients showed a PSA decrease over 90% and 54.8% reached a PSA-level < 0.2ng/ml. Apalutamide was well tolerated in real world patients: adverse events occurred in 67.7% but were in the majority mild (≥ grade 3: 6.5%). Dose reduction was necessary in 38.7% and 32.2% discontinued apalutamide treatment. MFS was 43 months and majority of patients were subsequently treated with abiraterone. CONCLUSION: In real world more comorbid nmCRPC patients with a higher ECOG-PS and more aggressive tumors are treated with apalutamide plus ADT. Nevertheless efficacy results as well as side effects are similar in real-world compared to Spartan trial showing also a rapid, durable and deep PSA response with a median MFS of 43 months.


Subject(s)
Prostatic Neoplasms, Castration-Resistant , Thiohydantoins , Humans , Male , Thiohydantoins/therapeutic use , Thiohydantoins/administration & dosage , Thiohydantoins/adverse effects , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/pathology , Prostatic Neoplasms, Castration-Resistant/mortality , Aged , Middle Aged , Aged, 80 and over , Prostate-Specific Antigen/blood , Androgen Antagonists/administration & dosage , Androgen Antagonists/therapeutic use , Androgen Antagonists/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cohort Studies
2.
Theranostics ; 14(12): 4555-4569, 2024.
Article in English | MEDLINE | ID: mdl-39239510

ABSTRACT

Rationale: PSMA-targeting radioligand therapy (PSMA-RLT) has shown promise in metastatic castration-resistant prostate cancer (mCRPC), particularly in PSMA-avid tumours. However, predicting response remains challenging. Preclinical data suggests aberrant p53-signalling as a predictor of poor response. Methods: The patient population of this pre-planned retrospective cohort study consists of 96 patients with mCRPC who underwent treatment with PSMA-RLT and were molecularly profiled by whole-genome sequencing and or targeted next-generation sequencing. Response to PSMA-RLT was assessed per molecular subtype, including TP53-mutational status. Results: Patients with TP53 loss-of-function alterations had a shorter median progression-free survival (3.7 versus 6.2 months, P<0.001), a lower median PSA change (-55% vs. -75%, P=0.012) and shorter overall survival from initiation of PMSA-RLT (7.6 vs. 13.9 months, P=0.003) compared to TP53-wildtype patients. Pathogenic alterations in AR, MYC, BRCA1, or BRCA2 as well as in genes linked to the PI3K or MAPK pathways or genes involved in homologous recombination repair, were not associated with response. Only lactate dehydrogenase was, alongside TP53-status, significantly associated with response. Transcriptome analysis of 21 patients, identified six p53 signalling genes whose low expression was associated to a shorter progression-free survival (P<0.05). Conclusion: TP53 loss-of-function may serve as a prognostic factor for PSMA-RLT outcomes in patients with mCRPC.


Subject(s)
Glutamate Carboxypeptidase II , Prostatic Neoplasms, Castration-Resistant , Tumor Suppressor Protein p53 , Humans , Male , Prostatic Neoplasms, Castration-Resistant/radiotherapy , Prostatic Neoplasms, Castration-Resistant/genetics , Prostatic Neoplasms, Castration-Resistant/pathology , Prostatic Neoplasms, Castration-Resistant/metabolism , Aged , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , Retrospective Studies , Middle Aged , Glutamate Carboxypeptidase II/metabolism , Glutamate Carboxypeptidase II/genetics , Aged, 80 and over , Antigens, Surface/metabolism , Antigens, Surface/genetics , Mutation , Prostate-Specific Antigen/metabolism , Progression-Free Survival , Radiopharmaceuticals/therapeutic use , Treatment Outcome , Whole Genome Sequencing
3.
J Nucl Med Technol ; 52(3): 208-211, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-39237335

ABSTRACT

Although guidelines for the use of 177Lu-PSMA-617 published by various organizations are important, they do not include all the essential, practical points necessary for a complete institutional protocol. Therefore, a brief survey was performed to assess key components of the 177Lu-PSMA-617 protocol before, during, and after delivery of therapy. This survey demonstrated the wide variability in many aspects of institutional protocols regarding determination of eligibility for and administration of 177Lu-PSMA-617 therapy. The real-world protocol details provided here from a variety of institutions may help new and established theranostic programs.


Subject(s)
Clinical Protocols , Dipeptides , Heterocyclic Compounds, 1-Ring , Lutetium , Dipeptides/therapeutic use , Humans , United States , Surveys and Questionnaires , Prostatic Neoplasms/radiotherapy , Prostate-Specific Antigen
4.
BMJ ; 386: e077738, 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-39231588

ABSTRACT

OBJECTIVE: To provide a baseline comparative assessment of the main epidemiological features of prostate cancer in European populations as background for the proposed EU screening initiatives. DESIGN: Population based study. SETTING: 26 European countries, 19 in the EU, 1980-2017. National or subnational incidence data were extracted from population based cancer registries from the International Agency for Research on Cancer's Global Cancer Observatory, and mortality data from the World Health Organization. POPULATION: Men aged 35-84 years from 26 eligible countries. RESULTS: Over the past decades, incidence rates for prostate cancer varied markedly in both magnitude and rate of change, in parallel with temporal variations in prostate specific antigen testing. The variation in incidence across countries was largest around the mid-2000s, with rates spanning from 46 (Ukraine) to 336 (France) per 100 000 men. Thereafter, incidence started to decline in several countries, but with the latest rates nevertheless remaining raised and increasing again in the most recent quinquennium in several countries. Mortality rates during 1980-2020 were much lower and less variable than incidence rates, with steady declines in most countries and lesser temporal differences between countries. Overall, the up to 20-fold variation in prostate cancer incidence contrasts with a corresponding fivefold variation in mortality. Also, the inverse U-shape of the age specific curves for incidence contrasted with the mortality pattern, which increased progressively with age. The difference between the highest and lowest incidence rates across countries ranged from 89.6 per 100 000 men in 1985 to 385.8 per 100 000 men in 2007, while mortality rates across countries ranged from 23.7 per 100 000 men in 1983 to 35.6 per 100 000 men in 2006. CONCLUSIONS: The epidemiological features of prostate cancer presented here are indicative of overdiagnosis varying over time and across populations. Although the results are ecological in nature and must be interpreted with caution, they do support previous recommendations that any future implementation of prostate cancer screening must be carefully designed with an emphasis on minimising the harms of overdiagnosis.


Subject(s)
Early Detection of Cancer , Prostate-Specific Antigen , Prostatic Neoplasms , Humans , Prostatic Neoplasms/epidemiology , Prostatic Neoplasms/mortality , Prostatic Neoplasms/diagnosis , Male , Aged , Incidence , Middle Aged , Europe/epidemiology , Adult , Aged, 80 and over , Early Detection of Cancer/statistics & numerical data , Prostate-Specific Antigen/blood , Registries , Mass Screening/statistics & numerical data , Mass Screening/methods
6.
Pan Afr Med J ; 48: 30, 2024.
Article in English | MEDLINE | ID: mdl-39220559

ABSTRACT

Introduction: prostate cancer recurrence after definitive therapy for organ-confined disease often manifests as rising prostate-specific antigen (PSA) levels without clinically overt disease. 68Gallium prostate-specific membrane antigen, positron emission tomography/computed tomography (68GaPSMA PET/CT) imaging plays a major role in the management of recurrent prostate cancer. The purpose of this study was to assess the positivity rate of 68Ga PSMA PET/CT scans in cases of prostate cancer recurrence, and to compare the results with existing international literature. Methods: a retrospective analysis of 177 68Ga PSMA PET/CT scans of patients with biochemically proven disease recurrence was performed. The possible association of a positive PSMA PET/CT with the PSA level and Gleason score were analyzed. Results: a total of 177 68Ga PSMA PET/CT scans were performed in 163 patients (median age 66 years). Of these, 117 (66%) scans detected the site of disease recurrence. Among patients with PSA 0.2-0.99 ng/ml, 23/49 (47%, p<0.0001) were positive, and 20/35 (57%, p<0.0005) were positive in the group of patients with PSA 1.00-1.99. When PSA values were further categorized into PSA <2 ng/ml and PSA ≥2 ng/ml, detection rates were 49% and 86% respectively (p <0.0001). The scans were positive in 65% of patients with Gleason score of <7, 62% with Gleason score of =7 and 68% with Gleason score >7 (p=0.745). Conclusion: there was an increase in the detection rate with an increase in the PSA. Gleason score was not a predictor of a positive 68Ga PSMA PET/CT scan. 68Ga-PSMA PET/CT should be prioritized in patients with biochemical recurrence with PSA levels >0.2 ng/ml.


Subject(s)
Gallium Isotopes , Gallium Radioisotopes , Neoplasm Grading , Neoplasm Recurrence, Local , Positron Emission Tomography Computed Tomography , Prostate-Specific Antigen , Prostatic Neoplasms , Humans , Male , Positron Emission Tomography Computed Tomography/methods , Retrospective Studies , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Aged , Prostate-Specific Antigen/blood , Middle Aged , Aged, 80 and over , Edetic Acid/analogs & derivatives , Edetic Acid/administration & dosage , Radiopharmaceuticals/administration & dosage , Radiopharmaceuticals/pharmacology
7.
Zhonghua Bing Li Xue Za Zhi ; 53(8): 803-808, 2024 Aug 08.
Article in Chinese | MEDLINE | ID: mdl-39103261

ABSTRACT

Objective: To study the clinicopathological features, immunohistochemical phenotypes, molecular changes, differential diagnosis and prognosis of isolated intraductal carcinoma of the prostate (iIDC-P). Methods: Three iIDC-P cases were collected retrospectively from 2016 to 2022 at Ningbo Clinical Pathology Diagnosis Center, Ningbo, China. The clinicopathologic features and immunophenotypic profiles were studied using light microscopy and immunohistochemistry. A targeted next-generation sequencing panel was used to analyze cancer-associated mutations. Follow-up and literature review were also performed. Results: The patients' ages were 61, 67 and 77 years, and their preoperative prostate specific antigen (PSA) levels were 7.99, 7.99 and 4.86 µg/L, respectively. Case 1 and 2 were diagnosed on needle biopsy and radical prostatectomy (RP) specimens, and case 3 was diagnosed on a specimen of transurethral resection of the prostate (TURP). The RP specimen was entirely submitted for histologic examination. In the case 1, iIDC-P was found in one tissue core (involving two ducts) in the biopsy specimen, and in 6 sections (diameter, 0.3-1.1 cm) from the radical prostatectomy specimen, and one section had separate foci of low-grade acinar adenocarcinoma (diameter, 0.05 cm). In the case 2, 6 tissue sections from the biopsy specimens showed iIDC-P, and 13 sections from RP specimen showed iIDC-P (diameter, 0.5-1.6 cm), and the other 3 sections had separate low grade acinar adenocarcinoma (diameter, 0.6 cm). In the case 3, 5 tissue blocks from the TURP specimen showed iIDC-P. The case 1 and 2 showed solid architecture with expansile proliferation of neoplastic cells in native ducts and acini. The case 3 showed dense or loose cribriform pattern, with marked cytological atypia, and frequent mitotic figures. Comedonecrosis was found in solid or dense cribriform glands in the case 2. Immunohistochemically, surrounding basal cells were highlighted using high-molecular-weight cytokeratin (34ßE12 and CK5/6) and p63, while P504s was positive in the tumor cells. The tumor cells were also positive for AR and prostate markers (NKX3.1, PSA and PSAP), and negative for GATA3. The iIDC-P and acinar adenocarcinoma both showed weak PTEN expression and no ERG (nuclear) expression. In case 2 and 3, targeted sequencing revealed activated oncogenic driver mutations in MAPK and PI3K pathway genes (KRAS, MTOR and PTEN). In addition, pathogenic mutation in TP53 and FOXA1 mutation were found in the case 2 and 3, respectively. No case demonstrated TMPRSS2::ERG translocation. All cases were microsatellite stable and had lower tumor mutation burdens (range, 2.1-3.1 muts/Mb). The patients showed no biochemical recurrence or metastasis after follow-up of 16-91 months. Conclusions: iIDC-P is a special type of intraductal carcinoma of the prostate and differs from intraductal carcinoma within high-grade prostate cancer. iIDC-P has unique molecular characteristics and may represent as a molecularly unique in situ tumor of prostate cancer.


Subject(s)
Prostate-Specific Antigen , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/pathology , Prostatic Neoplasms/genetics , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/surgery , Aged , Middle Aged , Retrospective Studies , Prostate-Specific Antigen/metabolism , Receptors, Androgen/metabolism , Receptors, Androgen/genetics , Diagnosis, Differential , Transcription Factors/metabolism , Transcription Factors/genetics , Carcinoma, Intraductal, Noninfiltrating/pathology , Carcinoma, Intraductal, Noninfiltrating/genetics , Carcinoma, Intraductal, Noninfiltrating/metabolism , Homeodomain Proteins/metabolism , Homeodomain Proteins/genetics , Carcinoma, Ductal/pathology , Carcinoma, Ductal/genetics , Carcinoma, Ductal/metabolism , Carcinoma, Ductal/surgery , Transurethral Resection of Prostate , Racemases and Epimerases/metabolism , Racemases and Epimerases/genetics , High-Throughput Nucleotide Sequencing , Prognosis , Keratins , Membrane Proteins
8.
Cancer Med ; 13(15): e70085, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39119746

ABSTRACT

BACKGROUND: Anticipating the postoperative pathological stage and potential for adverse features of prostate cancer (PCa) patients before radical prostatectomy (RP) is crucial for guiding perioperative treatment. METHODS: A cohort consisting of three sub-cohorts with a total of 709 patients has been enlisted from two major tertiary medical centres in China. The primary assessment parameters for adverse pathological features in this study are the pathological T stage, the AJCC prognostic stage groups and perineural invasion (PNI). Logistic regression analyses were performed to investigate the relationship between prostate specific antigen (PSA), its derivatives (incluing Prostate Health Index, phi and phi density, phiD), and the pathological outcomes after RP. RESULTS: Both phi and phiD showed a significant association with pathologic T stage of pT3 or above (phi, adjusted OR, AOR = 2.82, 95% confidence interval, 95% CI: 1.88-4.23, p < 0.001; phiD, AOR = 2.47, 95% CI: 1.76-3.48, p < 0.001) and PNI (phi, AOR = 2.15, 95% CI: 1.39-3.32, p < 0.001; phiD, AOR = 1.94, 95% CI: 1.38-2.73, p < 0.001). In a subgroup analysis with a total PSA value <10 ng/mL, phi and phiD continued to show a significant correlation with pT3 or above (phi, AOR = 4.70, 95% CI: 1.29-17.12, p = 0.019; phiD, AOR = 3.44, 95% CI: 1.51-7.85, p = 0.003), and phiD also maintained its predictive capability for PNI in this subgroup (AOR = 2.10, 95% CI: 1.17-3.80, p = 0.014). Sensitivity analysis indicated that the findings in the combined cohort are mainly influenced by one of the sub-cohorts, partially attributable to disparities in sample sizes between sub-cohorts. Combined analysis of phi(D) and multiparametric MRI (mpMRI) data yielded similar results. CONCLUSIONS: Preoperative measurement of serum phi and phiD is valuable for predicting the occurrence of adverse pathological features in Chinese PCa patients after RP.


Subject(s)
Neoplasm Staging , Prostatectomy , Prostatic Neoplasms , Humans , Male , Prostatectomy/methods , Prostatic Neoplasms/surgery , Prostatic Neoplasms/pathology , Prostatic Neoplasms/blood , Middle Aged , China/epidemiology , Aged , Prognosis , Prostate-Specific Antigen/blood , East Asian People
9.
Int J Mol Sci ; 25(15)2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39125581

ABSTRACT

There is a significant unmet need for clinical reflex tests that increase the specificity of prostate-specific antigen blood testing, the longstanding but imperfect tool for prostate cancer diagnosis. Towards this endpoint, we present the results from a discovery study that identifies new prostate-specific antigen reflex markers in a large-scale patient serum cohort using differentiating technologies for deep proteomic interrogation. We detect known prostate cancer blood markers as well as novel candidates. Through bioinformatic pathway enrichment and network analysis, we reveal associations of differentially abundant proteins with cytoskeletal, metabolic, and ribosomal activities, all of which have been previously associated with prostate cancer progression. Additionally, optimized machine learning classifier analysis reveals proteomic signatures capable of detecting the disease prior to biopsy, performing on par with an accepted clinical risk calculator benchmark.


Subject(s)
Biomarkers, Tumor , Prostatic Neoplasms , Proteomics , Humans , Male , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/blood , Biomarkers, Tumor/blood , Proteomics/methods , Ion Mobility Spectrometry/methods , Prostate-Specific Antigen/blood , Aged , Machine Learning , Middle Aged
10.
Aging Male ; 27(1): 2391380, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39140708

ABSTRACT

BACKGROUND: Direct evidence for the relationship between a large prostate (≥80 ml) and androgen receptor/PSA signal remains lacking in benign prostatic hyperplasia (BPH). Our aim is to identify whether the cause of a large prostate is related to progesterone receptor (PGR) androgen receptor (AR), oestrogen receptor α, ß (ERα,ß) and prostate-specific antigen (PSA). MATERIALS AND METHODS: Surgical specimens of BPH in plasmakinetic resection of the prostate (PKRP) with three groups of different prostate-sizes with mean volumes of 25.97 ml, 63.80 ml, and 122.37 ml were collected for immunohistochemical analysis of the tissue microarray with PGR, AR, PSA and ERs. Rats were castrated and treated with testosterone replacement to explore androgen and PGR, AR and ERs expression levels in the prostate. Quantitative real-time reverse transcription polymerase chain reaction (Rt-PCR) for mRNA detection of above genes was conducted. RESULTS: Immunoblotting, Rt-PCR and immunohistochemistry assays showed that PGR, PSA, AR, ERα expression levels were positively correlated with prostate size and that ERß expression levels were negatively correlated with prostate volume. Animal experiments have shown that prostate volume is decreased in castrated rats with decreased PGR, AR, ERα and increased ERß expression levels. CONCLUSION: PGR, AR, ERs signals can be regarded as important factors for large-sized prostates in BPH patients (≥100 ml).


Subject(s)
Disease Models, Animal , Estrogen Receptor alpha , Prostate-Specific Antigen , Prostate , Prostatic Hyperplasia , Receptors, Androgen , Receptors, Progesterone , Male , Prostatic Hyperplasia/metabolism , Prostatic Hyperplasia/pathology , Animals , Receptors, Androgen/metabolism , Receptors, Progesterone/metabolism , Receptors, Progesterone/analysis , Rats , Humans , Prostate-Specific Antigen/blood , Aged , Estrogen Receptor alpha/metabolism , Estrogen Receptor alpha/analysis , Prostate/metabolism , Prostate/pathology , Rats, Sprague-Dawley , Middle Aged , Receptors, Estrogen/metabolism , Receptors, Estrogen/analysis , Estrogen Receptor beta/metabolism , Estrogen Receptor beta/analysis , Organ Size
11.
World J Urol ; 42(1): 495, 2024 Aug 23.
Article in English | MEDLINE | ID: mdl-39177844

ABSTRACT

OBJECTIVES: To develop and validate a prediction model for identifying non-prostate cancer (non-PCa) in biopsy-naive patients with PI-RADS category ≥ 4 lesions and PSA ≤ 20 ng/ml to avoid unnecessary biopsy. PATIENTS AND METHODS: Eligible patients who underwent transperineal biopsies at West China Hospital between 2018 and 2022 were included. The patients were randomly divided into training cohort (70%) and validation cohort (30%). Logistic regression was used to screen for independent predictors of non-PCa, and a nomogram was constructed based on the regression coefficients. The discrimination and calibration were assessed by the C-index and calibration plots, respectively. Decision curve analysis (DCA) and clinical impact curves (CIC) were applied to measure the clinical net benefit. RESULTS: A total of 1580 patients were included, with 634 non-PCa. Age, prostate volume, prostate-specific antigen density (PSAD), apparent diffusion coefficient (ADC) and lesion zone were independent predictors incorporated into the optimal prediction model, and a corresponding nomogram was constructed ( https://nomogramscu.shinyapps.io/PI-RADS-4-5/ ). The model achieved a C-index of 0.931 (95% CI, 0.910-0.953) in the validation cohort. The DCA and CIC demonstrated an increased net benefit over a wide range of threshold probabilities. At biopsy-free thresholds of 60%, 70%, and 80%, the nomogram was able to avoid 74.0%, 65.8%, and 55.6% of unnecessary biopsies against 9.0%, 5.0%, and 3.6% of missed PCa (or 35.9%, 30.2% and 25.1% of foregone biopsies, respectively). CONCLUSION: The developed nomogram has favorable predictive capability and clinical utility can help identify non-PCa to support clinical decision-making and reduce unnecessary prostate biopsies.


Subject(s)
Nomograms , Prostate-Specific Antigen , Prostate , Unnecessary Procedures , Humans , Male , Middle Aged , Prostate-Specific Antigen/blood , Aged , Unnecessary Procedures/statistics & numerical data , Biopsy , Prostate/pathology , Prostate/diagnostic imaging , Retrospective Studies , Prostatic Neoplasms/pathology , Prostatic Neoplasms/blood
12.
Tidsskr Nor Laegeforen ; 144(9)2024 Aug 20.
Article in English, Norwegian | MEDLINE | ID: mdl-39166985

ABSTRACT

Background: Treatment of castration-resistant metastatic prostate cancer with [¹77Lu]PSMA radioligand. Case presentation: A man in his seventies with metastatic prostate cancer received castration therapy for four years, developing castration-resistant disease. PET/CT with [68Ga]PSMA-11 showed high uptake in metastatic lymph nodes. The patient received 7.4 GBq [¹77Lu]PSMA-I&T (Curium, Finland) as five treatments at five-week intervals. Five weeks after the first treatment, p-PSA dropped from 154 to 53 µg/L. Five weeks after the fifth treatment, p-PSA was 1.8 µg/L. [68Ga]PSMA-11 PET/CT showed significant reduction in the size of metastases, with the largest decreasing in diameter from 10 to 4 mm. Seven months after the fifth treatment, p-PSA increased to 14.3 µg/L, and [68Ga]PSMA-11 PET/ CT revealed additional skeletal metastases, while the lymph node metastases remained unchanged. Thus, the treatment had a good but temporary effect on the metastases. Interpretation: Treatment with [¹77Lu]PSMA radioligand resulted in a temporary regression of the metastases.


Subject(s)
Gallium Radioisotopes , Lutetium , Positron Emission Tomography Computed Tomography , Prostate-Specific Antigen , Prostatic Neoplasms, Castration-Resistant , Radiopharmaceuticals , Humans , Male , Prostatic Neoplasms, Castration-Resistant/radiotherapy , Prostatic Neoplasms, Castration-Resistant/pathology , Radiopharmaceuticals/therapeutic use , Radiopharmaceuticals/pharmacokinetics , Prostate-Specific Antigen/blood , Lutetium/therapeutic use , Aged , Lymphatic Metastasis , Dipeptides/therapeutic use , Dipeptides/pharmacokinetics , Oligopeptides , Gallium Isotopes
13.
J Public Health Policy ; 45(3): 552-561, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39090221

ABSTRACT

In 1994, the United States approved the Prostate-Specific Antigen (PSA) test as a screening tool for prostate cancer. It did so despite the test's inherent weakness: not being prostate cancer specific. Subsequent randomized trials yielded conflicting results as to its benefits. Medical guideline organizations are concerned that PSA screening results in the diagnosis and treatment of clinically indolent prostate cancer. Nevertheless, PSA screening is prevalent in North America and Europe with PSA screening increasing in other regions. We provide a critical review of the major factors that led to the prevalence of PSA screening in the United States despite the debate about its benefits. Public advocacy in favor of the test and failure of the medical community to appreciate its inherent weakness led to widespread adoption. These factors persist today. Other countries need to carefully analyze the utility of the PSA test before adopting it.


Subject(s)
Early Detection of Cancer , Prostate-Specific Antigen , Prostatic Neoplasms , Humans , Prostate-Specific Antigen/blood , Male , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/blood , Prostatic Neoplasms/epidemiology , United States/epidemiology , Early Detection of Cancer/methods , Mass Screening/methods
14.
Clin Chim Acta ; 563: 119902, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-39111647

ABSTRACT

Tumor markers should be measured regularly and accurately to prevent, diagnose, and monitor cancers efficiently. We aimed to characterize the pre-analytical factors effecting on the analytical performance of point-of-care test (POCT) platform IchromaTM II (Boditech Med Inc., Gangwon-do, Korea) for alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and prostate specific antigen (PSA) and evaluate their consequences in clinical practice. Based on comprehensive evaluation for the analytical performance of IchromaTM II including precision, linearity, and method comparison performed according to CLSI guidelines, pre-analytical factors of sample types and conditions were extensively analyzed. A total of five sample types [serum, plasma (PL) and whole blood (WB) from EDTA tube, PL and WB from sodium heparin tube] from 40 patients were used for comparing among specimen types. Additionally, stability was assessed up to 21 h at room temperature, refrigerated for 8 days, and frozen for 16 weeks by using 4 levels of pooled patient samples which were measured in triplicate. Precision, linearity and correlation with central laboratory analyzers observed in all three tumor markers were within acceptable criteria. However, variable degrees of percent deviations were observed according to sample type and storage conditions. Only EDTA PL samples presented clinically acceptable percentage biases for all three tumor markers when stored at room temperature or refrigerated condition. Positive bias of CEA and PSA in storage duration until 16 weeks were observed when stored in frozen condition. While IchromaTM II showed an adequate analytical performance as a POCT platform with simple operating procedures for the measurement of tumor markers, clinical laboratories should be aware of stability issues when different types of blood specimens are practically utilized.


Subject(s)
Biomarkers, Tumor , Humans , Biomarkers, Tumor/blood , Prostate-Specific Antigen/blood , Prostate-Specific Antigen/analysis , Carcinoembryonic Antigen/blood , Carcinoembryonic Antigen/analysis , Point-of-Care Systems/standards , alpha-Fetoproteins/analysis , Specimen Handling , Pre-Analytical Phase
15.
J Extracell Vesicles ; 13(8): e12491, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39175282

ABSTRACT

In the quest for efficient tumor diagnosis via liquid biopsy, extracellular vesicles (EVs) have shown promise as a source of potential biomarkers. This study addresses the gap in biomarker efficacy for predicting clinically significant prostate cancer (csPCa) between the Western and Chinese populations. We developed a urinary extracellular vesicles-based prostate score (EPS) model, utilizing the EXODUS technique for EV isolation from 598 patients and incorporating gene expressions of FOXA1, PCA3, and KLK3. Our findings reveal that the EPS model surpasses prostate-specific antigen (PSA) testing in diagnostic accuracy within a training cohort of 234 patients, achieving an area under the curve (AUC) of 0.730 compared to 0.659 for PSA (p = 0.018). Similarly, in a validation cohort of 101 men, the EPS model achieved an AUC of 0.749, which was significantly better than PSA's 0.577 (p < 0.001). Our model has demonstrated a potential reduction in unnecessary prostate biopsies by 26%, with only a 3% miss rate for csPCa cases, indicating its effectiveness in the Chinese population.


Subject(s)
Biomarkers, Tumor , Extracellular Vesicles , Prostate-Specific Antigen , Prostatic Neoplasms , Male , Humans , Prostatic Neoplasms/urine , Prostatic Neoplasms/diagnosis , Extracellular Vesicles/metabolism , Middle Aged , Aged , Biomarkers, Tumor/urine , Risk Assessment/methods , Hepatocyte Nuclear Factor 3-alpha/metabolism , Hepatocyte Nuclear Factor 3-alpha/genetics , Kallikreins/urine , Antigens, Neoplasm/urine , Liquid Biopsy/methods
16.
JCO Clin Cancer Inform ; 8: e2400094, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39159422

ABSTRACT

PURPOSE: No consensus about the effectiveness of prostate-specific antigen (PSA) screening exists among clinical guidelines, especially for the elderly. Randomized trials of PSA screening have yielded different results, partly because of variations in adherence, and it is unlikely that new trials will be conducted. Our objective was to estimate the effect of annual PSA screening on prostate cancer (PC) mortality in Medicare beneficiaries age 67-84 years. METHODS: This is a large-scale, population-based, observational study of two screening strategies: annual PSA screening and no screening. We used data from 537,599 US Medicare (2001-2008) beneficiaries age 67-84 years who had a good life expectancy, no previous PC, and no PSA test in the 2 years before baseline. We estimated the 8-year PC mortality and incidence, treatments for PC, and treatment complications of PSA screening. RESULTS: In men age 67-74 years, the estimated difference in 8-year risk of PC death between PSA screening and no screening was -2.3 (95% CI, -4.1 to -1.1) deaths per 1,000 men (a negative risk difference favors screening). Treatment complications were more frequent under PSA screening than under no screening. In men age 75-84 years, risk difference estimates were closer to zero. CONCLUSION: Our estimates suggest that under conventional statistical criteria, annual PSA screening for 8 years is highly compatible with reductions of PC mortality from four to one fewer PC deaths per 1,000 screened men age 67-74 years. As with any study using real-world data, the estimates could be affected by residual confounding.


Subject(s)
Early Detection of Cancer , Medicare , Prostate-Specific Antigen , Prostatic Neoplasms , Humans , Male , Aged , Prostate-Specific Antigen/blood , United States/epidemiology , Prostatic Neoplasms/mortality , Prostatic Neoplasms/diagnosis , Aged, 80 and over , Early Detection of Cancer/methods , Mass Screening/methods , Incidence
17.
J Med Case Rep ; 18(1): 371, 2024 Aug 17.
Article in English | MEDLINE | ID: mdl-39152479

ABSTRACT

BACKGROUND: Prostate ductal adenocarcinoma, a rare histology observed in 0.4-0.8% of all prostate cancers, is treated similarly to acinar adenocarcinoma but tends to have a higher likelihood of metastasis, recurrence, and poorer prognosis. CASE PRESENTATION: A 73-year-old Asian-Japanese male presented with gross hematuria, with investigations revealing a prostate ductal adenocarcinoma. Subsequent radical prostatectomy indicated a Gleason score of 8 with no lymph node metastasis. Despite initial prostate-specific antigen level reductions post-prostatectomy and salvage radiation therapy due to recurring elevated prostate-specific antigen levels, no recurrence was evident until 13 years later. A tumor in the anterior urethra was identified as metastasis of his prostate ductal adenocarcinoma. CONCLUSION: This report presents an uncommon case of prostate ductal adenocarcinoma exhibiting a late recurrence in the anterior urethra 13 years post-radical prostatectomy.


Subject(s)
Neoplasm Recurrence, Local , Prostatectomy , Prostatic Neoplasms , Urethral Neoplasms , Humans , Male , Aged , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgery , Urethral Neoplasms/pathology , Urethral Neoplasms/surgery , Prostate-Specific Antigen/blood , Carcinoma, Ductal/surgery , Carcinoma, Ductal/pathology , Adenocarcinoma/surgery , Adenocarcinoma/pathology
18.
Ann Intern Med ; 177(8): JC94, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39102726

ABSTRACT

SOURCE CITATION: Fazekas T, Shim SR, Basile G, et al. Magnetic resonance imaging in prostate cancer screening: a systematic review and meta-analysis. JAMA Oncol. 2024;10:745-754. 38576242.


Subject(s)
Early Detection of Cancer , Magnetic Resonance Imaging , Prostate-Specific Antigen , Prostatic Neoplasms , Humans , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Prostatic Neoplasms/diagnosis , Male , Prostate-Specific Antigen/blood , Overdiagnosis , Biopsy , Mass Screening/methods
19.
Anal Chem ; 96(33): 13636-13643, 2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39110483

ABSTRACT

In recent years, optical tweezers have become an effective bioassay tool due to their unique advantages, especially in combination with suspension beads, which can be applied to develop a high-performance analysis platform capable of high-quality imaging and stable signal output. However, the optical tweezer-assisted bead analysis is still at the early stage, and further development of different favorable methods is in need. Herein, we have first developed the optical tweezer-assisted immuno-rolling circle amplification (immuno-RCA) on beads for protein detection. Prostate-specific antigen was selected as the model analyte, and the immunosandwich structure on beads was built by the high affinity of "antibody-antigen". The "protein-nucleic acid" signals were effectively converted through the covalent coupling procedure of antibodies and oligonucleotides, further initiating the RCA reaction to achieve signal amplification. The individual beads with the strong irregular Brownian motion in a fluid environment were eventually trapped by the optical tweezers to acquire the accurate and high-quality signal. Compared with the conventional immunoassay on beads, the sensitivity of the developed strategy was increased by 587 times with a limit of detection of 4.29 pg/mL (0.13 pM), as well as excellent specificity, stability, and reproducibility. This study developed the new optical tweezer-assisted beads imaging strategy for protein targets, which has great potential for being applied to clinical serology research and expands the application of optical tweezers in the bioassays.


Subject(s)
Optical Tweezers , Prostate-Specific Antigen , Prostate-Specific Antigen/analysis , Humans , Nucleic Acid Amplification Techniques , Immunoassay/methods , Limit of Detection , Microspheres , Biosensing Techniques/methods
20.
PLoS One ; 19(8): e0306900, 2024.
Article in English | MEDLINE | ID: mdl-39110673

ABSTRACT

BACKGROUND: Non-metastatic castration-resistant prostate cancer (nmCRPC) is an asymptomatic condition with the potential to progress to metastasis. Novel hormonal agents (NHAs) are currently considered the gold standard treatment for nmCRPC, offering significant survival benefits. However, further evidence is needed to determine whether there are differences in the performance of these drugs among Asian populations. METHODS: This retrospective analysis of nmCRPC patients aims to compare the efficacy and safety of three NHAs-apalutamide, darolutamide, and enzalutamide. Data were collected from two prominent prostate care centers in Taichung, Taiwan. Patient characteristics, treatment details, PSA responses, and adverse events were analyzed. Statistical comparisons were performed, and the study received Institutional Review Board approval. RESULTS: Total of 64 patients were recruited in this study, including 29 darolutamide, 26 apalutamide, and 9 enzalutamide patients. Baseline characteristics varied between the three patient groups, but the treatment response still revealed similar results. The apalutamide group experienced more adverse events, notably skin rash. Discontinuation rates due to adverse events differed among the groups, and patients receiving darolutamide were less likely to discontinue treatment. CONCLUSION: This real-world study provides insights into NHA utilization in nmCRPC within the Taiwanese population. Adverse event profiles varied, emphasizing the need for individualized treatment decisions. The study underscores the importance of regional considerations and contributes valuable data for optimizing treatment outcomes in nmCRPC.


Subject(s)
Benzamides , Nitriles , Phenylthiohydantoin , Prostatic Neoplasms, Castration-Resistant , Thiohydantoins , Humans , Male , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/pathology , Aged , Phenylthiohydantoin/therapeutic use , Taiwan , Benzamides/therapeutic use , Nitriles/therapeutic use , Retrospective Studies , Middle Aged , Thiohydantoins/therapeutic use , Thiohydantoins/adverse effects , Aged, 80 and over , Pyrazoles/therapeutic use , Pyrazoles/adverse effects , Antineoplastic Agents, Hormonal/therapeutic use , Treatment Outcome , Prostate-Specific Antigen/blood
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