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1.
Lakartidningen ; 1212024 Apr 22.
Artículo en Sueco | MEDLINE | ID: mdl-38661575

RESUMEN

This article introduces a series of articles covering some of the most important aspects of contemporary prostate cancer care. After the introduction of the prostate-specific antigen (PSA) blood test and systematic prostate biopsies in the early 1990s, the incidence of localised prostate cancer and the use of radical treatment rose dramatically. Improved diagnostic methods and understanding of the tumour biology now reduce overdiagnosis and pave the way for organised screening. New and more effective treatments, in combination with the stage shift from advanced to localised disease at the time of diagnosis, have reduced the age-standardised prostate cancer specific mortality by half in men under the age of 85 years. The National Prostate Cancer Register of Sweden (NPCR) has evolved over the past 25 years and now comprehensively supports clinical care and is an invaluable research data source. Patients' organisations have emerged as important players on the national arena.


Asunto(s)
Antígeno Prostático Específico , Neoplasias de la Próstata , Humanos , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/terapia , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/epidemiología , Masculino , Antígeno Prostático Específico/sangre , Suecia/epidemiología , Sistema de Registros , Detección Precoz del Cáncer
2.
Zhonghua Zhong Liu Za Zhi ; 46(4): 354-364, 2024 Apr 23.
Artículo en Chino | MEDLINE | ID: mdl-38644271

RESUMEN

Objective: To determine the total and age-specific cut-off values of total prostate specific antigen (tPSA) and the ratio of free PSA divided total PSA (fPSA/tPSA) for screening prostate cancer in China. Methods: Based on the Chinese Colorectal, Breast, Lung, Liver, and Stomach cancer Screening Trial (C-BLAST) and the Tianjin Common Cancer Case Cohort (TJ4C), males who were not diagnosed with any cancers at baseline since 2017 and received both tPSA and fPSA testes were selected. Based on Cox regression, the overall and age-specific (<60, 60-<70, and ≥70 years) accuracy and optimal cut-off values of tPSA and fPSA/tPSA ratio for screening prostate cancer were evaluated with time-dependent receiver operating characteristic curve (tdROC) and area under curve (AUC). Bootstrap resampling was used to internally validate the stability of the optimal cut-off value, and the PLCO study was used to externally validate the accuracy under different cut-off values. Results: A total of 5 180 participants were included in the study, and after a median follow-up of 1.48 years, a total of 332 prostate cancer patients were included. In the total population, the tdAUC of tPSA and fPSA/tPSA screening for prostate cancer were 0.852 and 0.748, respectively, with the optimal cut-off values of 5.08 ng/ml and 0.173, respectively. After age stratification, the age specific cut-off values of tPSA in the <60, 60-<70, and ≥70 age groups were 3.13, 4.82, and 11.54 ng/ml, respectively, while the age-specific cut-off values of fPSA/tPSA were 0.153, 0.135, and 0.130, respectively. Under the age-specific cut-off values, the sensitivities of tPSA screening for prostate cancer in males <60, 60-70, and ≥70 years old were 92.3%, 82.0%, and 77.6%, respectively, while the specificities were 84.7%, 81.3%, and 75.4%, respectively. The age-specific sensitivities of fPSA/tPSA for screening prostate cancer were 74.4%, 53.3%, and 55.9%, respectively, while the specificities were 83.8%, 83.7%, and 83.7%, respectively. Both bootstrap's internal validation and PLCO external validation provided similar results. The combination of tPSA and fPSA/tPSA could further improve the accuracy of screening. Conclusion: To improve the screening effects, it is recommended that age-specific cut-off values of tPSA and fPSA/tPSA should be used to screen for prostate cancer in the general risk population.


Asunto(s)
Detección Precoz del Cáncer , Antígeno Prostático Específico , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/sangre , Antígeno Prostático Específico/sangre , Anciano , Persona de Mediana Edad , Detección Precoz del Cáncer/métodos , Factores de Edad , Curva ROC , China , Sensibilidad y Especificidad , Tamizaje Masivo/métodos , Área Bajo la Curva
3.
JCO Precis Oncol ; 8: e2300634, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38662984

RESUMEN

PURPOSE: While 177Lu-PSMA-617 (LuPSMA) is an effective therapy for many patients with metastatic castration-resistant prostate cancer (mCRPC), biomarkers associated with outcomes are not well defined. We hypothesized that prostate cancer mutational profile may associate with clinical activity of LuPSMA. We devised a study to evaluate associations between mCRPC mutational profile with LuPSMA clinical outcomes. METHODS: This was a multicenter retrospective analysis of patients with mCRPC with next-generation sequencing (NGS) who received LuPSMA. PSA50 response (ie, ≥50% decline in prostate-specific antigen [PSA]) rate, PSA progression free survival (PSA PFS), and overall survival (OS) were compared between genetically defined subgroups. RESULTS: One hundred twenty-six patients with NGS results who received at least one cycle of LuPSMA were identified. The median age was 73 (IQR, 68-78) years, 124 (98.4%) received ≥1 prior androgen receptor-signaling inhibitor, and 121 (96%) received ≥1 taxane-based chemotherapy regimen. Fifty-eight (46%) patients with a DNA damage repair gene mutation (DNA damage response group) and 59 (46.8%) with a mutation in TP53, RB1, or PTEN tumor suppressor genes (TSG group) were identified. After adjusting for relevant confounders, the presence of ≥1 TSG mutation was associated with shorter PSA PFS (hazard ratio [HR], 1.93 [95% CI, 1.05 to 3.54]; P = .034) and OS (HR, 2.65 [95% CI, 1.15 to 6.11]; P = .023). There was improved OS favoring the DNA damage response group (HR, 0.37 [95% CI, 0.14 to 0.97]; P = .044) on multivariable analysis. Univariate analysis of patients with ATM mutations had significantly higher rates of PSA50 response, PSA PFS, and OS. CONCLUSION: Outcomes on LuPSMA varied on the basis of mutational profile. Prospective studies to define the clinical activity of LuPSMA in predefined genomic subgroups are justified.


Asunto(s)
Dipéptidos , Lutecio , Neoplasias de la Próstata Resistentes a la Castración , Humanos , Masculino , Estudios Retrospectivos , Anciano , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/patología , Neoplasias de la Próstata Resistentes a la Castración/sangre , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Lutecio/uso terapéutico , Dipéptidos/uso terapéutico , Compuestos Heterocíclicos con 1 Anillo/uso terapéutico , Antígeno Prostático Específico/sangre , Antígenos de Superficie/genética , Estudios de Cohortes , Glutamato Carboxipeptidasa II/genética
4.
Sci Rep ; 14(1): 9494, 2024 04 25.
Artículo en Inglés | MEDLINE | ID: mdl-38664545

RESUMEN

Cancer-directed surgeries (CDS) play a crucial role in prostate cancer (PCa) management along with possible survival and therapeutic benefits. However, barriers such as socioeconomic factors may affect patients' decision of refusing recommended CDS. This study aimed to uncover risk factors and the impact on survival associated with CDS refusal. We retrospectively reviewed the Surveillance, Epidemiology, and End Results database for patients diagnosed with PCa between 2000 and 2019. Multiple sociodemographic and clinical characteristics were extracted to assess predictors for physicians' surgical recommendations and patients' surgical refusal, respectively. Propensity score matching was performed to balance the covariates. The impact of surgical refusal on mortality risk was also investigated. A total of 185,540 patients were included. The physician's recommendation of CDS was significantly influenced by the patient's age, race, income, home location, diagnosis year, Gleason score, prostate-specific antigen (PSA), and TNM stage. About 5.6% PCa patients refused CDS, most of whom were older, non-White race, lack of partners, living outside of metropolitan areas, with higher PSA or lower clinical TNM stage. Patients who refused CDS had an increased risk of cancer-specific mortality and overall mortality than those who performed CDS. Physicians may weigh a host of sociodemographic and clinical factors prior to making a CDS recommendation. Patients' refusal of recommended CDS affected survival and was potentially modifiable by certain sociodemographic factors. Physicians should fully consider the hindrances behind patients' CDS refusal to improve patient-doctor shared decision-making, guide patients toward the best alternative and achieve better outcomes.


Asunto(s)
Puntaje de Propensión , Neoplasias de la Próstata , Negativa del Paciente al Tratamiento , Humanos , Masculino , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/mortalidad , Anciano , Factores de Riesgo , Persona de Mediana Edad , Estudios Retrospectivos , Negativa del Paciente al Tratamiento/estadística & datos numéricos , Programa de VERF , Prostatectomía , Antígeno Prostático Específico/sangre , Clasificación del Tumor , Estadificación de Neoplasias , Factores Socioeconómicos
5.
World J Urol ; 42(1): 217, 2024 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-38581590

RESUMEN

PURPOSE: Prostate cancer (PCa) histology, particularly the Gleason score, is an independent prognostic predictor in PCa. Little is known about the inter-reader variability in grading of targeted prostate biopsy based on magnetic resonance imaging (MRI). The aim of this study was to assess inter-reader variability in Gleason grading of MRI-targeted biopsy among uropathologists and its potential impact on a population-based randomized PCa screening trial (ProScreen). METHODS: From June 2014 to May 2018, 100 men with clinically suspected PCa were retrospectively selected. All men underwent prostate MRI and 86 underwent targeted prostate of the prostate. Six pathologists individually reviewed the pathology slides of the prostate biopsies. The five-tier ISUP (The International Society of Urological Pathology) grade grouping (GG) system was used. Fleiss' weighted kappa (κ) and Model-based kappa for associations were computed to estimate the combined agreement between individual pathologists. RESULTS: GG reporting of targeted prostate was highly consistent among the trial pathologists. Inter-reader agreement for cancer (GG1-5) vs. benign was excellent (Model-based kappa 0.90, Fleiss' kappa κ = 0.90) and for clinically significant prostate cancer (csPCa) (GG2-5 vs. GG0 vs. GG1), it was good (Model-based kappa 0.70, Fleiss' kappa κ 0.67). CONCLUSIONS: Inter-reader agreement in grading of MRI-targeted biopsy was good to excellent, while it was fair to moderate for MRI in the same cohort, as previously shown. Importantly, there was wide consensus by pathologists in assigning the contemporary GG on MRI-targeted biopsy suggesting high reproducibility of pathology reporting in the ProScreen trial.


Asunto(s)
Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Detección Precoz del Cáncer , Reproducibilidad de los Resultados , Estudios Retrospectivos , Antígeno Prostático Específico , Biopsia , Imagen por Resonancia Magnética/métodos , Clasificación del Tumor , Biopsia Guiada por Imagen
8.
Urol Pract ; 11(3): 557, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38560923
9.
Urol Pract ; 11(3): 547-556, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38564816

RESUMEN

INTRODUCTION: Cigarette smoking is associated with higher-risk prostate cancer at the time of diagnosis and increased overall and prostate cancer‒specific mortality. Previous studies indicate smokers are less likely to undergo PSA screening. Herein we investigate the association between smoking and PSA screening using a nationally representative US survey. We hypothesize that smokers are less likely to undergo guideline-concordant PSA screening. METHODS: We performed a cross-sectional analysis of men aged 55 to 69 who responded to the cigarette smoking and PSA screening questions of the 2018 Behavioral Risk Factor Surveillance System survey. Adjusted prevalence and adjusted risk differences were calculated using complex weighted multivariable Poisson regression modeling. RESULTS: We identified 58,996 individuals who qualified for analysis. PSA screening prevalence was 39% (95% CI: 39%-40%) nationally, 42% (95% CI: 41%-44%) for never smokers, 42% (95% CI: 39%-40%) for former smokers, and 27% (95% CI: 25%-29%) for current smokers, including 27% (95% CI: 24%-29%) for daily smokers and 29% (95% CI: 24%-33%) for nondaily smokers. Compared to never smokers, the adjusted relative risk for undergoing PSA screening was 0.81 for current smokers (95% CI: 0.75-0.88, P < .01) and 0.99 for former smokers (95% CI: 0.94-1.03, P = .53). CONCLUSIONS: Current smokers are less likely to undergo recommended PSA screening, but former smokers are screened at similar rates as never smokers. As delays in diagnosis may substantially contribute to worse prostate cancer outcomes, targeted interventions to increase screening in this population may yield significant effects.


Asunto(s)
Fumar Cigarrillos , Neoplasias de la Próstata , Masculino , Humanos , Fumadores , Antígeno Prostático Específico , Estudios Transversales , Neoplasias de la Próstata/diagnóstico , Fumar Cigarrillos/epidemiología
10.
Eur Rev Med Pharmacol Sci ; 28(6): 2372-2386, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38567600

RESUMEN

OBJECTIVE: Prostate cancer (PCa) is the most common malignant tumor in the male genitourinary system. Once PCa has metastasized, it is very difficult to cure. The purpose of this study was to investigate the prognostic risk factor analysis of patients with different prostate-specific antigen (PSA) levels in distant metastatic PCa. At the same time, we construct effective models for predicting the survival rate of prostate cancer patients. PATIENTS AND METHODS: Data on prostate cancer patients with the presence of distant metastases were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. PCa patients with distant metastases were categorized into two groups based on PSA levels, one with PSA <20 ng/mL and the other with PSA ≥20 ng/mL. Univariate and multivariate COX regression analyses were used to identify independent factors affecting the prognosis of the patients. A nomogram was constructed using the independent prognostic factors, and the results were evaluated using calibration curves, timeROC curves, and Kaplan-Meier curves. RESULTS: In the PSA <20 ng/mL group, there were a total of 1,832 patients. COX regression analysis showed that age, marital status, N stage, grade, Gleason score, and medical household income inflation were independent prognostic factors for overall survival (OS) in patients. In addition, we found that age, marital status, N stage, bone metastasis, grade, and Gleason score were independent prognostic factors for cancer-specific survival (CSS) in patients. In the PSA ≥20 ng/mL group, there were a total of 5,314 patients. It was found that age, ethnicity, marital status, bone metastasis, first malignant primary indicator, grade, Gleason score, and medical household income inflation were patients' independent prognostic factors for OS. For CSS, we found that age, ethnicity, marital status, T stage, radiotherapy, bone metastasis, Gleason score, and Median household income inflation were independent prognostic factors. Constructing a nomogram can accurately predict the prognosis of this group of patients. CONCLUSIONS: We found different independent prognostic factors for different PSA levels in patients with distant metastatic PCa. A new nomogram was constructed to predict OS and CSS in patients, which helps in clinical-assisted decision-making.


Asunto(s)
Nomogramas , Neoplasias de la Próstata , Humanos , Masculino , Antígeno Prostático Específico , Próstata , Factores de Riesgo , Pronóstico
11.
J Robot Surg ; 18(1): 158, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38568342

RESUMEN

Prior history of transurethral resection of the prostate (TURP) can complicate Robot-assisted radical prostatectomy (RARP). Very few studies analyse the outcomes of RARP in men with a prior history of TURP. We analysed the oncological and functional outcomes of RARP in post-TURP men from our prospectively maintained database. We included the RARP data from January 2016 to January 2022. Thirty men who had RARP with a prior history of TURP were identified (Group 2). They were matched using R software and propensity score matching to 90 men with no previous TURP (Group-1). The groups were matched for age, body mass index (BMI), Gleason score, stage, PSA and D'Amico risk category in a 1:3 ratio. The two-year oncological and functional outcomes were compared. Overall, the study found no significant difference between the groups in the preoperative parameters, such as BMI, age, Gleason grade, clinical stage, PSA, prostate volume, and D'amico risk grouping. There was no difference in the estimated blood loss. The TURP group had a lower chance of having a nerve spare (p = 0.03). The median console time was longer in the TURP group (140 min (120,180) versus 168 (129,190) p = 0.058). The postoperative complications (Clavien-Dindo 3a 2% versus 6.7%) and hospital stay (median of 2 days), positive surgical margins, continence, and biochemical recurrence rates at 3, 12, and 24 months were not statistically different between the groups. In high-volume centres, the oncological and continence outcomes of RARP post-TURP are not inferior to that of men without prior TURP.


Asunto(s)
Procedimientos Quirúrgicos Robotizados , Robótica , Resección Transuretral de la Próstata , Masculino , Humanos , Próstata/cirugía , Procedimientos Quirúrgicos Robotizados/métodos , Resección Transuretral de la Próstata/efectos adversos , Análisis por Apareamiento , Antígeno Prostático Específico , Prostatectomía/efectos adversos
12.
BMC Urol ; 24(1): 76, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38566091

RESUMEN

BACKGROUND: To develop a risk model including clinical and radiological characteristics to predict false-positive The Prostate Imaging Reporting and Data System (PI-RADS) 5 lesions. METHODS: Data of 612 biopsy-naïve patients who had undergone multiparametric magnetic resonance imaging (mpMRI) before prostate biopsy were collected. Clinical variables and radiological variables on mpMRI were adopted. Lesions were divided into the training and validation cohort randomly. Stepwise multivariate logistic regression analysis with backward elimination was performed to screen out variables with significant difference. A diagnostic nomogram was developed in the training cohort and further validated in the validation cohort. Calibration curve and receiver operating characteristic (ROC) analysis were also performed. RESULTS: 296 PI-RADS 5 lesions in 294 patients were randomly divided into the training and validation cohort (208 : 88). 132 and 56 lesions were confirmed to be clinically significant prostate cancer in the training and validation cohort respectively. The diagnostic nomogram was developed based on prostate specific antigen density, the maximum diameter of lesion, zonality of lesion, apparent diffusion coefficient minimum value and apparent diffusion coefficient minimum value ratio. The C-index of the model was 0.821 in the training cohort and 0.871 in the validation cohort. The calibration curve showed good agreement between the estimation and observation in the two cohorts. When the optimal cutoff values of ROC were 0.288 in the validation cohort, the sensitivity, specificity, PPV, and NPV were 90.6%, 67.9%, 61.7%, and 92.7% in the validation cohort, potentially avoiding 9.7% unnecessary prostate biopsies. CONCLUSIONS: We developed and validated a diagnostic nomogram by including 5 factors. False positive PI-RADS 5 lesions could be distinguished from clinically significant ones, thus avoiding unnecessary prostate biopsy.


Asunto(s)
Imágenes de Resonancia Magnética Multiparamétrica , Neoplasias de la Próstata , Masculino , Humanos , Próstata/diagnóstico por imagen , Próstata/patología , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Nomogramas , Imagen por Resonancia Magnética/métodos , Antígeno Prostático Específico , Estudios Retrospectivos , Biopsia Guiada por Imagen/métodos
14.
Appl Clin Inform ; 15(2): 274-281, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38599618

RESUMEN

OBJECTIVES: Our objective was to pilot test an electronic health record-embedded decision support tool to facilitate prostate-specific antigen (PSA) screening discussions in the primary care setting. METHODS: We pilot-tested a novel decision support tool that was used by 10 primary care physicians (PCPs) for 6 months, followed by a survey. The tool comprised (1) a risk-stratified algorithm, (2) a tool for facilitating shared decision-making (Simple Schema), (3) three best practice advisories (BPAs: <45, 45-75, and >75 years), and (4) a health maintenance module for scheduling automated reminders about PSA rescreening. RESULTS: All PCPs found the tool feasible, acceptable, and clear to use. Eight out of ten PCPs reported that the tool made PSA screening conversations somewhat or much easier. Before using the tool, 70% of PCPs felt confident in their ability to discuss PSA screening with their patient, and this improved to 100% after the tool was used by PCPs for 6 months. PCPs found the BPAs for eligible (45-75 years) and older men (>75 years) more useful than the BPA for younger men (<45 years). Among the 10 PCPs, 60% found the Simple Schema to be very useful, and 50% found the health maintenance module to be extremely or very useful. Most PCPs reported the components of the tool to be at least somewhat useful, with 10% finding them to be very burdensome. CONCLUSION: We demonstrated the feasibility and acceptability of the tool, which is notable given the marked low acceptance of existing tools. All PCPs reported that they would consider continuing to use the tool in their clinic and were likely or very likely to recommend the tool to a colleague.


Asunto(s)
Médicos de Atención Primaria , Neoplasias de la Próstata , Masculino , Humanos , Anciano , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/prevención & control , Antígeno Prostático Específico , Proyectos Piloto , Detección Precoz del Cáncer , Toma de Decisiones , Atención Primaria de Salud , Tamizaje Masivo
15.
BMC Cancer ; 24(1): 482, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38627648

RESUMEN

BACKGROUND: Therapies for metastatic castration-resistant prostate cancer (mCRPC) include targeting the androgen receptor (AR) with androgen receptor inhibitors (ARIs) and prostate-specific membrane antigen (PSMA). Having the ability to detect AR, AR splice variant 7 (AR-V7), or PSMA in circulating tumor cells (CTCs) or circulating exosomal cell-free RNA (cfRNA) could be helpful to guide selection of the appropriate therapy for each individual patient. The Vortex Biosciences VTX-1 system is a label-free CTC isolation system that enables the detection of the expression of multiple genes in both CTCs and exosomal cfRNA from the same blood sample in patients with mCRPC. Detection of both AR-V7 and PSMA gene expression in both CTCs and cfRNA simultaneously has not yet been reported. METHODS: To characterize the combined VTX-1-AdnaDetect workflow, 22Rv1 cancer cells were spiked into blood from healthy donors and processed with the VTX-1 to mimic patient samples and assess performances (capture efficiency, purity, AR and AR-V7 expression). Then, we collected 19 blood samples from 16 patients with mCRPC and therapeutic resistance to androgen receptor inhibitors (ARIs). Plasma was separated and the plasma-depleted blood was processed further with the VTX-1 to collect CTCs. Both plasma exosomal cfRNA and CTCs were subsequently analyzed for AR, AR-V7, PSMA, and prostate-specific antigen (PSA) mRNA expression using the AdnaTest ProstateCancerPanel AR-V7 assay. RESULTS: AR-V7 expression could be detected in 22Rv1 cells spiked into blood from healthy volunteers as well as in CTCs and plasma-derived exosomal cfRNA from patients with mCRPC by processing blood with the VTX-1 CTC isolation system followed by the AdnaTest ProstateCancerPanel AR-V7 assay. 94.7% of patient blood samples (18/19) had detectable AR expression in either CTCs or exosomal cfRNA (16 in CTCs, 12 in cfRNA). 15.8% of the 19 patient blood samples (3/19) were found to have AR-V7-positive (AR-V7+) CTCs, one of which was also AR-V7+ in the exosomal cfRNA analysis. 42.1% of patient blood samples (8/19) were found to be PSMA positive (PSMA+): 26.3% (5/19) were PSMA+ in the CTC analysis and 31.6% (6/19) were PSMA+ in the exosomal cfRNA analysis. Of those 8 PSMA+ samples, 2 had detectable PSMA only in CTCs, and 3 had detectable PSMA only in exosomal cfRNA. CONCLUSION: VTX-1 enables isolation of CTCs and plasma exosomes from a single blood draw and can be used for detecting AR-V7 and PSMA mRNA in both CTCs and cfRNA in patients with mCRPC and resistance to ARIs. This technology facilitates combining RNA measurements in CTCs and exosomal cfRNA for future studies to develop potentially clinically relevant cancer biomarker detection in blood.


Asunto(s)
Ácidos Nucleicos Libres de Células , Exosomas , Células Neoplásicas Circulantes , Neoplasias de la Próstata Resistentes a la Castración , Humanos , Masculino , Antagonistas de Receptores Androgénicos/farmacología , Antagonistas de Receptores Androgénicos/uso terapéutico , Biomarcadores de Tumor/genética , Ácidos Nucleicos Libres de Células/genética , Ácidos Nucleicos Libres de Células/metabolismo , Exosomas/genética , Exosomas/metabolismo , Células Neoplásicas Circulantes/patología , Próstata/patología , Antígeno Prostático Específico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Isoformas de Proteínas/genética , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , ARN Mensajero/genética
16.
Technol Cancer Res Treat ; 23: 15330338241246636, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38629205

RESUMEN

OBJECTIVE: This study intends to examine the anticipatory power of clinical and radiological parameters in detecting clinically significant prostate cancer in patients demonstrating Prostate Imaging Reporting and Data System 3 lesions. METHODS: This was a retrospective study. The study included participation from 453 patients at the First Affiliated Hospital of Soochow University, sampled between September 2017 through August 2022. Each patient underwent a routine 12-core prostate biopsy followed by a 2 to 5 core fusion-targeted biopsy. We utilized both univariate and multivariate logistic regression analyses to identify the parameters that have a correlation with clinically significant prostate cancer. The predictive ability of these parameters was assessed using the receiver operating characteristic curve, leading to the creation of a nomogram. RESULTS: Clinically significant prostate cancer was detected in 68 out of 453 patients with Prostate Imaging Reporting and Data System 3 lesions (15.01%). Among Prostate Imaging Reporting and Data System 3a and 3b patients, 4.78% (3.09% of the total) and 33.75% (11.92% of the total), respectively, had clinically significant prostate cancer. Systematic biopsy improved prostate cancer and clinically significant prostate cancer detection rates by 7.72% and 3.09%, respectively, compared to targeted biopsy. Without systematic biopsy, there would be an undetected rate of 15% for prostate cancer and 8.13% for clinically significant prostate cancer in Prostate Imaging Reporting and Data System 3b patients. Several clinical parameters, including age, prostate-specific antigen density, lesion volume, apparent diffusion coefficient, and digital rectal examination, were statistically significant in the logistic regression analysis for clinically significant prostate cancer. The individual diagnostic accuracies of these parameters for clinically significant prostate cancer were 0.648, 0.645, 0.75, 0.763, and 0.7, respectively, but their combined accuracy improved to 0.866. A well-fit nomogram based on the identified risk factors was constructed (χ2 = 10.254, P = .248). CONCLUSION: The combination of age, prostate-specific antigen density, lesion volume, apparent diffusion coefficient, and digital rectal examination presented a higher diagnostic value for clinically significant prostate cancer than any single parameter in patients with Prostate Imaging Reporting and Data System 3 lesions. Systematic biopsy proved crucial for biopsy-naive patients with Prostate Imaging Reporting and Data System 3 lesions and should not be omitted.


Asunto(s)
Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Antígeno Prostático Específico , Imagen por Resonancia Magnética/métodos , Estudios Retrospectivos , Biopsia Guiada por Imagen/métodos
17.
Theranostics ; 14(6): 2560-2572, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38646643

RESUMEN

Management of prostate cancer (PC) might be improved by combining external beam radiotherapy (EBRT) and prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) with lutetium-177 (177Lu)-labeled PSMA inhibitors. We hypothesized a higher efficacy of the combination due to augmentation of the radiation dose to the tumor and interactions of EBRT with PSMA expression potentially increasing radiopharmaceutical uptake. Therefore, this study analyzed the influence of radiation on PSMA expression levels in vitro. The results were translated to evaluate the efficacy of the combination of photon EBRT and [177Lu]Lu-PSMA-617 in a murine PC xenograft model. Finally, a clinical case report on a combined elective field EBRT with RLT dose escalation illustrates a proof-of-concept. Methods: PSMA gene and protein expression were assessed in human PSMA-overexpressing LNCaP cells after irradiation using reverse transcription quantitative polymerase chain reaction (RT-qPCR), flow cytometry and On-Cell Western assays. In the in vivo therapy study, LNCaP tumor-bearing BALB/c nu/nu mice were irradiated once with 2 Gy X-ray EBRT and injected with 40 MBq [177Lu]Lu-PSMA-617 after 4 h or received single or no treatment (n = 10 each). Tumor-absorbed doses by [177Lu]Lu-PSMA-617 were calculated according to the Medical Internal Radiation Dosimetry (MIRD) formalism after deriving time-activity curves using a gamma probe. An exemplified patient case is demonstrated where fractionated EBRT (54 Gy to prostate; 45 Gy to pelvic lymphatics) and three cycles of [177Lu]Lu-PSMA-617 (3.4-6.0 GBq per cycle) were sequentially combined under concurrent androgen deprivation for treating locally advanced PC. Results: At 4 h following irradiation with 2-8 Gy, LNCaP cells displayed a PSMA protein upregulation by around 18% relative to non-irradiated cells, and a stronger upregulation on mRNA level (up to 2.6-fold). This effect was reversed by 24 h when PSMA protein levels were downregulated by up to 22%. Mice treated with the combination therapy showed significantly improved outcomes regarding tumor control and median survival (p < 0.0001) as compared to single or no treatment. Relative to monotherapy with PSMA-RLT or EBRT, the tumor doubling time was prolonged 1.7- or 2.7-fold and the median survival was extended by 24% or 60% with the combination, respectively. Additionally, tumors treated with EBRT exhibited a 14% higher uptake of the radiopharmaceutical as evident from the calculated tumor-absorbed dose, albeit with high variability in the data. Concerning the patient case, the tri-modality treatment was well tolerated and the patient responded with a long-lasting complete biochemical remission for five years following end of PSMA-RLT. The patient then developed a biochemical relapse with oligo-recurrent disease on follow-up imaging. Conclusion: The present preclinical and clinical data demonstrate that the combination of EBRT with dose escalation by PSMA-RLT improves tumor control and potentially prolongs survival. This may pave the way for further clinical investigations of this approach to explore the curative potential of the combination therapy.


Asunto(s)
Dipéptidos , Compuestos Heterocíclicos con 1 Anillo , Lutecio , Antígeno Prostático Específico , Neoplasias de la Próstata , Radioisótopos , Radiofármacos , Animales , Masculino , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/metabolismo , Humanos , Lutecio/uso terapéutico , Lutecio/farmacología , Compuestos Heterocíclicos con 1 Anillo/uso terapéutico , Compuestos Heterocíclicos con 1 Anillo/farmacología , Dipéptidos/farmacología , Dipéptidos/uso terapéutico , Línea Celular Tumoral , Ratones , Radiofármacos/uso terapéutico , Radiofármacos/farmacología , Radiofármacos/farmacocinética , Radioisótopos/uso terapéutico , Radioisótopos/farmacología , Ratones Endogámicos BALB C , Ratones Desnudos , Glutamato Carboxipeptidasa II/metabolismo , Glutamato Carboxipeptidasa II/genética , Ensayos Antitumor por Modelo de Xenoinjerto , Antígenos de Superficie/metabolismo , Antígenos de Superficie/genética
18.
Appl Clin Inform ; 15(2): 282-294, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38599619

RESUMEN

OBJECTIVES: We conducted a focus group to assess the attitudes of primary care physicians (PCPs) toward prostate-specific antigen (PSA)-screening algorithms, perceptions of using decision support tools, and features that would make such tools feasible to implement. METHODS: A multidisciplinary team (primary care, urology, behavioral sciences, bioinformatics) developed the decision support tool that was presented to a focus group of 10 PCPs who also filled out a survey. Notes and audio-recorded transcripts were analyzed using Thematic Content Analysis. RESULTS: The survey showed that PCPs followed different guidelines. In total, 7/10 PCPs agreed that engaging in shared decision-making about PSA screening was burdensome. The majority (9/10) had never used a decision aid for PSA screening. Although 70% of PCPs felt confident about their ability to discuss PSA screening, 90% still felt a need for a provider-facing platform to assist in these discussions. Three major themes emerged: (1) confirmatory reactions regarding the importance, innovation, and unmet need for a decision support tool embedded in the electronic health record; (2) issues around implementation and application of the tool in clinic workflow and PCPs' own clinical bias; and (3) attitudes/reflections regarding discrepant recommendations from various guideline groups that cause confusion. CONCLUSION: There was overwhelmingly positive support for the need for a provider-facing decision support tool to assist with PSA-screening decisions in the primary care setting. PCPs appreciated that the tool would allow flexibility for clinical judgment and documentation of shared decision-making. Incorporation of suggestions from this focus group into a second version of the tool will be used in subsequent pilot testing.


Asunto(s)
Médicos de Atención Primaria , Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/diagnóstico , Antígeno Prostático Específico , Detección Precoz del Cáncer , Registros Electrónicos de Salud , Pautas de la Práctica en Medicina , Tamizaje Masivo
19.
20.
J Urol ; 211(5): 648-655, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38591703

RESUMEN

PURPOSE: Benefits of docetaxel-based neoadjuvant chemohormonal therapy (NCHT) before radical prostatectomy (RP) remain largely unknown. We explored whether docetaxel-based NCHT would bring pathological benefits and improve biochemical progression-free survival (bPFS) over neoadjuvant hormonal therapy (NHT) in locally advanced prostate cancer. MATERIALS AND METHODS: A randomized trial was designed recruiting 141 locally advanced, high-risk prostate cancer patients who were randomly assigned at the ratio of 2:1 to the NCHT group (75 mg/m2 body surface area every 3 weeks plus androgen deprivation therapy for 6 cycles) and the NHT group (androgen deprivation therapy for 24 weeks). The primary end point was 3-year bPFS. Secondary end points were pathological response including pathological downstaging and minimal residual disease rates. RESULTS: The NCHT group showed significant benefits in 3-year bPFS compared to the NHT group (29% vs 9.5%, P = .002). At a median follow-up of 53 months, the NCHT group achieved a significantly longer median bPFS time than the NHT group (17 months vs 14 months). No significant differences were found between the 2 groups in pathological downstaging and minimal residual disease rates. CONCLUSIONS: NCHT plus RP achieved significant bPFS benefits when compared with NHT plus RP in high-risk, locally advanced prostate cancer. A larger cohort with longer follow-up duration is essential in further investigation.


Asunto(s)
Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/cirugía , Docetaxel , Terapia Neoadyuvante , Antagonistas de Andrógenos/uso terapéutico , Estudios Prospectivos , Andrógenos , Neoplasia Residual/cirugía , Prostatectomía , Antígeno Prostático Específico
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