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1.
Int Braz J Urol ; 50(4): 450-458, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38743063

RESUMEN

PURPOSE: We assessed the prognostic impact of the 2012 Briganti nomogram on prostate cancer (PCa) progression in intermediate-risk (IR) patients presenting with PSA <10ng/mL, ISUP grade group 3, and clinical stage up to cT2b treated with robot assisted radical prostatectomy eventually associated with extended pelvic lymph node dissection. MATERIALS AND METHODS: From January 2013 to December 2021, data of surgically treated IR PCa patients were retrospectively evaluated. Only patients presenting with the above-mentioned features were considered. The 2012 Briganti nomogram was assessed either as a continuous and a categorical variable (up to the median, which was detected as 6%, vs. above the median). The association with PCa progression, defined as biochemical recurrence, and/or metastatic progression, was evaluated by Cox proportional hazard regression models. RESULTS: Overall, 147 patients were included. Compared to subjects with a nomogram score up to 6%, those presenting with a score above 6% were more likely to be younger, had larger/palpable tumors, presented with higher PSA, underwent tumor upgrading, harbored non-organ confined disease, and had positive surgical margins at final pathology. PCa progression, which occurred in 32 (21.7%) cases, was independently predicted by the 2012 Briganti nomogram both considered as a continuous (Hazard Ratio [HR]:1.04, 95% Confidence Interval [CI]:1.01-1.08;p=0.021), and a categorical variable (HR:2.32; 95%CI:1.11-4.87;p=0.026), even after adjustment for tumor upgrading. CONCLUSIONS: In IR PCa patients with PSA <10ng/mL, ISUP grade group 3, and clinical stage up to cT2b, the 2012 Briganti nomogram independently predicts PCa progression. In this challenging subset of patients, this tool can identify prognostic subgroups, independently by upgrading issues.


Asunto(s)
Progresión de la Enfermedad , Clasificación del Tumor , Estadificación de Neoplasias , Nomogramas , Antígeno Prostático Específico , Prostatectomía , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/sangre , Anciano , Persona de Mediana Edad , Estudios Retrospectivos , Prostatectomía/métodos , Antígeno Prostático Específico/sangre , Metástasis Linfática/patología , Escisión del Ganglio Linfático , Pronóstico , Factores de Riesgo , Medición de Riesgo/métodos , Ganglios Linfáticos/patología
2.
Clin Transl Oncol ; 26(10): 2444-2456, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-38744755

RESUMEN

Prostate cancer (PCa) is the second most prevalent cancer in men. In 2020, approximately 1,414,259 new cases were reported that accounted for 3,75,324 deaths (Sung et al. in CA 71:209-249, 2021). PCa is often asymptomatic at early stages; hence, routine screening and monitoring based on reliable biomarkers is crucial for early detection and assessment of cancer progression. Early diagnosis of disease is key step in reducing PCa-induced mortality. Biomarkers such as PSA have played vital role in reducing recent PCa deaths. Recent research has identified many other biomarkers and also refined PSA-based tests for non-invasive diagnosis of PCa in patients. Despite progress in screening methods, an important issue that influences treatment is heterogeneity of the cancer in different individuals, necessitating personalized treatment. Currently, focus is to identify biomarkers that can accurately diagnose PCa at early stage, indicate the stage of the disease, metastatic nature and chances of survival based on individual patient profile (Fig. 1). Fig. 1 Graphical abstract.


Asunto(s)
Biomarcadores de Tumor , Detección Precoz del Cáncer , Medicina de Precisión , Neoplasias de la Próstata , Humanos , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/terapia , Biomarcadores de Tumor/sangre , Detección Precoz del Cáncer/métodos , Masculino , Antígeno Prostático Específico/sangre
3.
Clin Transl Oncol ; 26(9): 2369-2379, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38602643

RESUMEN

PURPOSE: Machine learning (ML) models presented an excellent performance in the prognosis prediction. However, the black box characteristic of ML models limited the clinical applications. Here, we aimed to establish explainable and visualizable ML models to predict biochemical recurrence (BCR) of prostate cancer (PCa). MATERIALS AND METHODS: A total of 647 PCa patients were retrospectively evaluated. Clinical parameters were identified using LASSO regression. Then, cohort was split into training and validation datasets with a ratio of 0.75:0.25 and BCR-related features were included in Cox regression and five ML algorithm to construct BCR prediction models. The clinical utility of each model was evaluated by concordance index (C-index) values and decision curve analyses (DCA). Besides, Shapley Additive Explanation (SHAP) values were used to explain the features in the models. RESULTS: We identified 11 BCR-related features using LASSO regression, then establishing five ML-based models, including random survival forest (RSF), survival support vector machine (SSVM), survival Tree (sTree), gradient boosting decision tree (GBDT), extreme gradient boosting (XGBoost), and a Cox regression model, C-index were 0.846 (95%CI 0.796-0.894), 0.774 (95%CI 0.712-0.834), 0.757 (95%CI 0.694-0.818), 0.820 (95%CI 0.765-0.869), 0.793 (95%CI 0.735-0.852), and 0.807 (95%CI 0.753-0.858), respectively. The DCA showed that RSF model had significant advantages over all models. In interpretability of ML models, the SHAP value demonstrated the tangible contribution of each feature in RSF model. CONCLUSIONS: Our score system provide reference for the identification for BCR, and the crafting of a framework for making therapeutic decisions for PCa on a personalized basis.


Asunto(s)
Aprendizaje Automático , Recurrencia Local de Neoplasia , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/patología , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/patología , Estudios Retrospectivos , Anciano , Persona de Mediana Edad , Pronóstico , Árboles de Decisión , Modelos de Riesgos Proporcionales , Algoritmos , Máquina de Vectores de Soporte , Antígeno Prostático Específico/sangre
5.
Cancer Med ; 13(4): e7012, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38457188

RESUMEN

BACKGROUND: We previously reported that outcomes after radical prostatectomy (RP) were similar among non-Hispanic Black, non-Hispanic White, and Hispanic White Veterans Affairs (VA) patients. However, prostate cancer (PC) mortality in Puerto Rican Hispanics (PRH) may be higher than in other Hispanic groups. Data focused on PRH patients is sparse; thus, we tested the association between PR ethnicity and outcomes after RP. METHODS: Analysis included men in SEARCH cohort who underwent RP (1988-2020, n = 8311). PRH patients (n = 642) were treated at the PR VA, and outcomes were compared to patients treated in the Continental US regardless of race. Logistic regression was used to test the associations between PRH and PC aggressiveness, adjusting for demographic and clinicopathological features. Multivariable Cox models were used to investigate PRH versus Continental differences in biochemical recurrence (BCR), metastases, castration-resistant PC (CRPC), and PC-specific mortality (PCSM). RESULTS: Compared to Continental patients, PRH patients had lower adjusted odds of pathological grade group ≥2 (p < 0.001), lymph node metastasis (p < 0.001), and positive margins (p < 0.001). In contrast, PRH patients had higher odds of extracapsular extension (p < 0.001). In Cox models, PRH patients had a higher risk for BCR (HR = 1.27, p < 0.001), metastases (HR = 1.49, p = 0.014), CRPC (HR = 1.80, p = 0.001), and PCSM (HR = 1.74, p = 0.011). Further adjustment for extracapsular extension and other pathological variables strengthened these findings. CONCLUSIONS: In an equal access setting, PRH RP patients generally had better pathological features, but despite this, they had significantly worse post-treatment outcomes than men from the Continental US, regardless of race. The reasons for the poorer prognosis among PRH men require further research.


Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración , Neoplasias de la Próstata , Masculino , Humanos , Extensión Extranodal , Neoplasias de la Próstata/patología , Prostatectomía/métodos , Resultado del Tratamiento , Antígeno Prostático Específico , Hispánicos o Latinos , Recurrencia Local de Neoplasia/cirugía , Estudios Retrospectivos
6.
Clin Transl Oncol ; 26(8): 1998-2005, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38472559

RESUMEN

OBJECTIVE: To clarify the composition of lesions in different magnetic resonance imaging (MRI) partitions of positive surgical margins (PSM) after laparoscopic radical prostatectomy, explore the influence of lesion location on PSM, and construct a clinical prediction model to predict the risk of PSM. MATERIALS AND METHODS: This retrospective cohort study included 309 patients who underwent laparoscopic radical prostatectomy from 2018 to 2021 in our center was performed. 129 patients who met the same criteria from January to September 2022 were external validation cohorts. RESULTS: The incidence of PSM in transition zone (TZ) lesions was higher than that in peripheral zone (PZ) lesions. The incidence of PSM in the middle PZ was lower than that in other regions. Prostate specific antigen (PSA), clinical T-stage, the number of positive cores, international society of urological pathology (ISUP) grade (biopsy), MRI lesion location, extracapsular extension, seminal vesicle invasion (SVI), pseudo-capsule invasion (PCI), long diameter of lesions, lesion volume, lesion volume ratio, PSA density were related to PSM. MRI lesion location and PCI were independent risk factors for PSM. Least absolute shrinkage and selection operator (LASSO) regression was used to construct a clinical prediction model for PSM, including five variables: the number of positive cores, SVI, MRI lesion location, long diameter of lesions, and PSA. CONCLUSION: The positive rate of surgical margin in middle PZ was significantly lower than that in other regions, and MRI lesion location was an independent risk factor for PSM.


Asunto(s)
Laparoscopía , Imagen por Resonancia Magnética , Márgenes de Escisión , Prostatectomía , Neoplasias de la Próstata , Humanos , Masculino , Prostatectomía/métodos , Laparoscopía/métodos , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/diagnóstico por imagen , Estudios Retrospectivos , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Anciano , Antígeno Prostático Específico/sangre , Factores de Riesgo , Medición de Riesgo/métodos , Clasificación del Tumor , Estadificación de Neoplasias
7.
Braz J Microbiol ; 55(1): 447-454, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38308684

RESUMEN

The aim of this study was to investigate multi-drug-resistant (MDR) Escherichia coli in urine of adult male patients with enlarged prostate. Three hundred and sixty-eight samples of urine and blood were collected. Escherichia coli was isolated, purified, and identified and prostate-specific antigen (PSA) was determined. Multi-drug resistance test and specific drug resistance genes were assessed. Prevalence of Escherichia coli was high (38.5%) in patients with PSA of 60-79 ng ml-1 and 60% were MDR. The isolates showed highest resistance to tetracycline (53.3.0%) and least to cephalosporins (5%). They had intL and gyrA genes, which are integron, and quinolone resistance genes and sul1 and sul2 which are sulphonamide resistance-associated genes. Levofloxacin, ertapenem, and Augmentin (100% susceptibilities) were considered choice drugs for treatment of Escherichia coli infection in patients with elevated PSA.


Asunto(s)
Infecciones por Escherichia coli , Hospitales Generales , Adulto , Humanos , Masculino , Próstata , Antígeno Prostático Específico , Escherichia coli/genética , Infecciones por Escherichia coli/epidemiología , Infecciones por Escherichia coli/microbiología , Antibacterianos/farmacología , Levofloxacino , Pruebas de Sensibilidad Microbiana , Farmacorresistencia Bacteriana Múltiple/genética
9.
Int Braz J Urol ; 50(1): 65-79, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38166224

RESUMEN

OBJECTIVE: In the following years after the United States Preventive Service Task Force (USPSTF) recommendation against prostate cancer screening with PSA in 2012, several authors worldwide described an increase in higher grades and aggressive prostate tumors. In this scenario, we aim to evaluate the potential impacts of USPSTF recommendations on the functional and oncological outcomes in patients undergoing robotic-assisted radical prostatectomy (RARP) in a referral center. MATERIAL AND METHODS: We included 11396 patients who underwent RARP between 2008 and 2021. Each patient had at least a 12-month follow-up. The cohort was divided into two groups based on an inflection point in the outcomes at the end of 2012 and the beginning of 2013. The inflection point period was detected by Bayesian regression with multiple change points and regression with unknown breakpoints. We reported continuous variables as median and interquartile range (IQR) and categorical variables as absolute and relative percent frequencies. RESULTS: Group 1 had 4760 patients, and Group 2 had 6636 patients, with a median follow-up of 109 and 38 months, respectively. In the final pathology, Group 2 had 9.5% increase in tumor volume, 24% increase on Gleason ≥ 4+3 (ISUP 3) , and 18% increase on ≥ pT3. This translated to a 6% increase in positive surgical margins and 24% reduction in full nerve sparing in response to the worsening pathology. There was a significant decline in post-operative outcomes in Group 2, including a 12-month continence reduction of 9%, reduction in potency by 27%, and reduction of trifecta by 22%. CONCLUSIONS: The increasing number of high-risk patients has led to worse functional and oncologic outcomes. The initial rapid rise in PSM was leveled by the move towards more partial nerve sparing. Among some historical changes in prostate cancer diagnosis and management in the period of our study, the USPSTF recommendation coincided with worse outcomes of prostate cancer treatment in a population who could benefit from PSA screening at the appropriate time.


Asunto(s)
Prostatectomía , Neoplasias de la Próstata , Procedimientos Quirúrgicos Robotizados , Humanos , Masculino , Teorema de Bayes , Detección Precoz del Cáncer , Antígeno Prostático Específico , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Resultado del Tratamiento
10.
Clin Transl Oncol ; 26(4): 872-879, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37672205

RESUMEN

PURPOSE: Local recurrence of prostate cancer after low-dose rate brachytherapy is a clinical problem with limited salvage treatment options. This prospective study evaluated the tolerability and outcome of salvage external beam radiation therapy (S-EBRT) for locally recurrent prostate cancer after primary low-dose rate prostate brachytherapy (LDR-BT). MATERIALS AND METHODS: Between October 2012 and 2022, 18 patients with biopsy-proven locally recurrent prostate cancer after primary LDR-BT and received S-EBRT. We evaluated biochemical failure (BF), overall survival (OS) and acute/late gastrointestinal and urinary toxicities (CTCAE v5.0 or CTCAE v4, only before 2017). RESULTS: Median follow-up was 32 months (range, 5-124). The median age was at S-EBRT 68 years (range 59-79). 34% (6/18) were low risk, 44% (8/18) intermediate risk, 5% (1/18) high risk, and 17% (3/18) not specified. All patients were treated with IMRT/VMAT and received 60 Gy (2.5 Gy/fraction) to the prostate and 40% (7/18) 55.2 Gy (2,3 Gy/fx) to the seminal vesicles. 56% received ADT The 3-year OS and biochemical relapse-free survival after S-EBRT were 100% and 89%, respectively, with a median PSA nadir 0,035 ng/mL (0,01-0,34). Acute cystitis was present in 72% (13/18) of patients (27% of Grade > 2). Urethritis was present in 78% (14/18) patients (16% of cases Grade > 3), and acute rectitis occurred in 22% (4/18) of patients (no cases Grade > 3). CONCLUSIONS: Our data suggest that the treatment of locally recurrent prostate cancer with S-EBRT could provide adequate disease control safely and be used as an additional treatment in the natural history of prostate cancer patients. However, the results are still early and the sample is small; larger studies with longer follow-up would be mandatory.


Asunto(s)
Braquiterapia , Neoplasias de la Próstata , Reirradiación , Masculino , Humanos , Persona de Mediana Edad , Anciano , Braquiterapia/efectos adversos , Braquiterapia/métodos , Estudios Prospectivos , Dosificación Radioterapéutica , Antígeno Prostático Específico , Terapia Recuperativa/métodos , Estudios Retrospectivos
11.
Prostate ; 84(2): 166-176, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37839045

RESUMEN

PURPOSE: Prostate cancer (PCa) is the leading cause of death among men in 48 countries. Genetic alterations play a significant role in PCa carcinogenesis. For the hypothesis of this research, five unique polymorphisms (SNP) were investigated in different genes that showed to be associated in different ways with PCa: rs4430796, rs2735839, rs4792311, rs12329760, and rs28931588, respectively for the genes HNF1B, KLK3, ELAC2, TMPRSS2-ERG, and CTNNB1. PATIENTS AND METHODS: Blood samples from 426 subjects were evaluated: 290 controls (161 females and 129 males) and 136 PCa patients. SNP were determined by real-time polymerase chain reaction. TaqMan SNP genotyping assay. In the control samples, the SNPs were defined in association with the self-reported ethnicity, and in 218 control samples with markers with ancestry indicators. The genes were in Hardy-Weinberg equilibrium. One hundred and seventy control samples were matched by ethnicity for comparison with the PCa samples. RESULTS: The G allele at rs28931588 was monomorphic in both patients and controls studied. Significant differences were observed in allelic and genotypic frequencies between the control and Pca samples in rs2735839 (KLK3; p = 0.002 and χ2 = 8.73 and p = 0.01, respectively), by the global frequency and in the dominant model rs2735839_GG (odds ratio [OR] = 0.51, p = 0.02). AA and GA genotypes at rs4792311 (ELAC2) were more frequent in patients with Gleason 7(4 + 3), 8, and 9 (n = 37%-59.7%) compared to patients with Gleason 6 and 7(3 + 4) (n = 26%-40.0%) conferring a protective effect on the GG genotype (OR = 0.45, p = 0.02). The same genotype showed an OR = 2.71 (p = 0.01) for patients with low severity. The HNF1B-KLK3-ELAC2-TMPRSS2-ERG haplotypes: GAAT, AAAT, GAGT, and AAGT were more frequent in patients with Pca with OR ranging from 4.65 to 2.48. CONCLUSIONS: Higher frequencies of risk alleles were confirmed in the SNPs, KLK3 rs2735839_A, ELAC2 rs4792311_A, and TMPRSS2 rs12329760_T in patients with Pca. Rs2735839_A was associated with risk of Pca and rs4792311_A with severity and Gleason score of 7(4 + 3) or greater. There is a need for careful observation of rs2735839 and rs4792311 in association with the prostatic biopsy due to the increased risk of Pca.


Asunto(s)
Antígeno Prostático Específico , Neoplasias de la Próstata , Masculino , Humanos , Calicreínas/genética , Predisposición Genética a la Enfermedad , Neoplasias de la Próstata/patología , Genotipo , Polimorfismo de Nucleótido Simple , Regulador Transcripcional ERG/genética , Factor Nuclear 1-beta del Hepatocito/genética , Proteínas de Neoplasias , beta Catenina/genética
12.
Clin Genitourin Cancer ; 22(1): e148-e155.e1, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-37903669

RESUMEN

INTRODUCTION: Among Hispanic-American (HA) men, prostatic cancer (PCa) accounts for nearly one-quarter of the total cancer burden. We sought to identify differences in PCa presentation and treatment status for HA subgroups based on country/region of origin. MATERIAL AND METHODS: Using the National Cancer Database, we identified patients with histologically confirmed prostate adenocarcinoma with reported race/ethnicity, clinical staging, Gleason score ≥ 6, and PSA level at diagnosis from 2010 to 2016. HAs were divided into 4 subgroups: Mexican, Puerto Ricans, Cubans, and Central/South Americans. Non-Hispanic White (NHW) men were used as a reference group. Statistical analysis was derived from the Kruskal-Wallis test for continuous variables and χ2 test for categorical variables. Models were constructed to evaluate the association of Hispanic country of origin with metastatic presentation and treatment status. RESULTS: A total of 428,829 patients were included, with 5625 (1.3%) classified as HA. Within the Hispanic group, 2880 (51.2%) were Mexican, 999 (17.8%) Puerto Rican, 477 (8.5%) Cuban, and 1269 (22.6%) South/Central American. Mexican men presented with higher median PSA, more Gleason 8 to 10 disease, and higher rates of metastatic presentation compared to NHW and other HA subgroups (all, p < .01). Metastatic rates over the study period for Mexican, Puerto Rican, Cuban, and South/Central Americans were 6.4 (±1.2), 5.3 (±3.0), 3.2 (±2.0), and 4.6% (±1.7), respectively (p = .01). Treatment rates were 89.1, 89.6, 92.4, and 89.3% for Mexican, Puerto Rican, Cuban, and South/Central Americans, respectively (p = .19). Mexican men had higher odds of initial metastatic presentation (OR: 1.32; 95%CI: 1.07-1.63, p = .01) but lower odds of receiving treatment (0.68; 0.55-0.85, p < .01). CONCLUSION: Men of Mexican origin presented with more advanced PCa when compared to NHW and other Hispanic subgroups. Our results warrant further investigation into potential biological factors affecting Hispanic patients as well as the identification of treatment barriers for this vulnerable population.


Asunto(s)
Pueblos Caribeños , Etnicidad , Neoplasias de la Próstata , Humanos , Masculino , Hispánicos o Latinos , Antígeno Prostático Específico , Neoplasias de la Próstata/terapia , Neoplasias de la Próstata/epidemiología , Estados Unidos/epidemiología , Blanco
13.
Prostate ; 84(3): 285-291, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37961000

RESUMEN

BACKGROUND: The urinary microbiota of patients with benign prostatic hyperplasia (BPH) has been associated with lower urinary tract symptoms (LUTS), however, little is known about urinary microbiota correlations with clinicopathological parameters associated with BPH. Here, we investigate associations between the urinary microbiota and clinical parameters of patients with BPH undergoing surgery. METHODS: Forty-one patients with BPH undergoing surgery were recruited from two medical centers. Catheterized urine specimens were collected and the microbiota was characterized by 16S rRNA gene sequencing. Patients were segregated into two groups according to each clinical parameter and differences in urinary microbiota diversity and composition were evaluated. RESULTS: Higher prostate weight and prostate-specific antigen (PSA) levels were associated with higher alpha diversity in the urinary microbiota of BPH patients. At the specific microbe level, we found that the greater the prostatic weight, the lower the relative abundance of Streptococcus, while the greater the PSA levels, the higher the abundance of Lactobacillus. Treatment with 5-α-reductase inhibitor was associated with overall urinary microbiota composition, in part due to a higher abundance of Corynebacterium and Anaerococcus in this group. CONCLUSIONS: We demonstrated that the urinary microbiota of BPH patients is associated with clinicopathological features, paving the way for larger studies in which causality between urinary microbiota and BPH can be appropriately explored.


Asunto(s)
Síntomas del Sistema Urinario Inferior , Hiperplasia Prostática , Masculino , Humanos , Hiperplasia Prostática/tratamiento farmacológico , Antígeno Prostático Específico/uso terapéutico , ARN Ribosómico 16S/genética , Próstata , Síntomas del Sistema Urinario Inferior/etiología
14.
BMC Urol ; 23(1): 208, 2023 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-38082337

RESUMEN

BACKGROUND: Prostate cancer exhibits a very diverse behaviour, with some patients dying from the disease and others never needing treatment. Active surveillance (AS) consists of periodic PSA assessment (prostate-specific antigen), DRE (digital rectal examination) and periodic prostate biopsies. According to the main guidelines, AS is the preferred strategy for low-risk patients, to avoid or delay definitive treatment. However, concerns remain regarding its applicability in certain patient subgroups, such as African American men, who were underrepresented in the main cohorts. Brazil has a very racially diverse population, with 56.1% self-reporting as brown or black. The aim of this study is to evaluate and validate the AS strategy in low-risk prostate cancer patients following an AS protocol in the Brazilian public health system. METHODS: This is a multicentre AS prospective cohort study that will include 200 patients from all regions of Brazil in the public health system. Patients with prostate adenocarcinoma and low-risk criteria, defined as clinical staging T1-T2a, Gleason score ≤ 6, and PSA < 10 ng/ml, will be enrolled. Archival prostate cancer tissue will be centrally reviewed. Patients enrolled in the study will follow the AS strategy, which involves PSA and physical examination every 6 months as well as multiparametric MRI (mpMRI) every two years and prostate biopsy at month 12 and then every two years. The primary objective is to evaluate the reclassification rate at 12 months, and secondary objectives include determining the treatment-free survival rate, metastasis-free survival, and specific and overall survival. Exploratory objectives include the evaluation of quality of life and anxiety, the impact of PTEN loss and the economic impact of AS on the Brazilian public health system. DISCUSSION: This is the first Brazilian prospective study of patients with low-risk prostate cancer under AS. To our knowledge, this is one of the largest AS study cohort with a majority of nonwhite patients. We believe that this study is an opportunity to better understand the outcomes of AS in populations underrepresented in studies. Based on these data, an AS national clinical guideline will be developed, which may have a beneficial impact on the quality of life of patients and on public health. TRIAL REGISTRATION: Clinicaltrials registration is NCT05343936.


Asunto(s)
Antígeno Prostático Específico , Neoplasias de la Próstata , Masculino , Humanos , Estudios Prospectivos , Brasil/epidemiología , Espera Vigilante/métodos , Calidad de Vida , Salud Pública , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/terapia
15.
Technol Cancer Res Treat ; 22: 15330338231207318, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37828833

RESUMEN

BACKGROUND AND AIMS: A gonadotropin-releasing hormone (GnRH)-based therapeutic vaccine candidate against hormone-sensitive prostate cancer has demonstrated its safety and signs of efficacy in phase I/II trials. In this study, we characterized the isotype/subclass profiles of the anti-GnRH humoral response generated by the vaccination and analyzed its association with patients' clinical outcomes. METHODS: The immunoglobulin isotypes and IgG subclasses of the antibody responses of 34 patients included in a randomized, open, prospective phase I/II clinical trial were characterized. Every patient included in the study had a diagnosis of locally advanced prostate adenocarcinoma at stages 3 and 4 and received immunization with the vaccine candidate. Additionally, serum testosterone and prostate specific antigen (PSA) concentrations, serving as indicators of tumor response, were determined. The type of anti-GnRH antibody response was correlated to the time elapsed until the first biochemical recurrence in patients and the outcome of the disease. RESULTS: All patients developed strong and prolonged anti-GnRH antibody responses, resulting in a short- to mid-term decrease in serum testosterone and PSA levels. Following immunizations, anti-GnRH antibodies of the IgM/IgG and IgG1/IgG3 subclasses were observed. Following radiotherapy, the humoral response switched to IgG (IgG1/IgG4). Patients who experienced a short-term biochemical relapse were characterized by significantly higher levels of anti-GnRH IgG titers, particularly IgG1 and IgG4 subclasses. These characteristics, along with a high response of specific IgM antibodies at the end of immunizations and the development of anti-GnRH IgA antibody responses following radiotherapy, were observed in patients whose disease progressed, compared to those with controlled disease. CONCLUSION: The nature of the humoral response against anti-GnRH, induced by vaccination may play a key role in activating additional immunological mechanisms. Collectively, these mechanisms could contribute significantly to the regulation of tumor growth.


Asunto(s)
Adenocarcinoma , Neoplasias de la Próstata , Vacunas , Masculino , Humanos , Hormona Liberadora de Gonadotropina , Antígeno Prostático Específico , Estudios Prospectivos , Próstata , Recurrencia Local de Neoplasia , Inmunización , Neoplasias de la Próstata/terapia , Vacunación , Inmunoglobulina G , Testosterona , Castración , Adenocarcinoma/terapia , Inmunoglobulina M
16.
Sci Rep ; 13(1): 10144, 2023 06 22.
Artículo en Inglés | MEDLINE | ID: mdl-37349324

RESUMEN

Due to its complexity, much effort has been devoted to the development of biomarkers for prostate cancer that have acquired the utmost clinical relevance for diagnosis and grading. However, all of these advances are limited due to the relatively large percentage of biochemical recurrence (BCR) and the limited strategies for follow up. This work proposes a methodology that uses discretization to predict prostate cancer BCR while optimizing the necessary variables. We used discretization of RNA-seq data to increase the prediction of biochemical recurrence and retrieve a subset of ten genes functionally known to be related to the tissue structure. Equal width and equal frequency data discretization methods were compared to isolate the contribution of the genes and their interval of action, simultaneously. Adding a robust clinical biomarker such as prostate specific antigen (PSA) improved the prediction of BCR. Discretization allowed classifying the cancer patients with an accuracy of 82% on testing datasets, and 75% on a validation dataset when a five-bin discretization by equal width was used. After data pre-processing, feature selection and classification, our predictions had a precision of 71% (testing dataset: MSKCC and GSE54460) and 69% (Validation dataset: GSE70769) should the patients present BCR up to 24 months after their final treatment. These results emphasize the use of equal width discretization as a pre-processing step to improve classification for a limited number of genes in the signature. Functionally, many of these genes have a direct or expected role in tissue structure and extracellular matrix organization. The processing steps presented in this study are also applicable to other cancer types to increase the speed and accuracy of the models in diverse datasets.


Asunto(s)
Recurrencia Local de Neoplasia , Neoplasias de la Próstata , Masculino , Humanos , Recurrencia Local de Neoplasia/genética , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/cirugía , Próstata , Antígeno Prostático Específico , Prostatectomía/métodos
17.
World J Urol ; 41(8): 2149-2154, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37326653

RESUMEN

OBJECTIVE: To determine the factors that may be associated with a 2-month high baseline level of Total Prostatic Specific Antigen (PSA) after endoscopic enucleation of the prostate with Holmium Laser (HoLEP). MATERIALS AND METHODS: Retrospective study of a prospectively collected database of adult males undergoing HoLEP at a single tertiary institution from September 2015 to February 2021. Pre-operative epidemiological, clinical characteristics and post-operative factors were analyzed and a multivariate analysis was performed to determine factors independently related to PSA decline. RESULTS: A total of 175 men aged 49-92 years with a prostate size ranging from 25 to 450 cc underwent HoLEP, and after excluding data from patients due to loss of follow-up or incomplete data, 126 patients were included in the final analysis. The patients were divided into group A (n = 84), which included patients with postoperative PSA nadir lower than 1 ng/ml, and group B(n = 42), with postoperative PSA levels greater than 1 ng/ml. In the univariate analysis there was a correlation between the variation of the PSA value and the percentage of resected tissue (p = 0.028), for each 1 g of resected prostate there was a reduction of 0.104 ng/mL, furthermore there was a difference between the means of age of group A (71.56 years) and group B (68.17 years) (p = 0.042). In the multivariate analysis, the use of statins and lower postoperative PSA levels (p = 0.024; HR = 3.71) were correlated. CONCLUSIONS: Our results indicate that PSA after HoLEP is correlated with patient's age, the presence of incidental prostate cancer, and the use of statins.


Asunto(s)
Inhibidores de Hidroximetilglutaril-CoA Reductasas , Terapia por Láser , Láseres de Estado Sólido , Hiperplasia Prostática , Resección Transuretral de la Próstata , Masculino , Adulto , Humanos , Próstata/cirugía , Antígeno Prostático Específico , Hiperplasia Prostática/cirugía , Hiperplasia Prostática/complicaciones , Láseres de Estado Sólido/uso terapéutico , Estudios Retrospectivos , Terapia por Láser/métodos , Resección Transuretral de la Próstata/métodos , Holmio , Resultado del Tratamiento
18.
Rev. méd. Chile ; 151(6): 711-716, jun. 2023. tab, ilus
Artículo en Español | LILACS | ID: biblio-1560230

RESUMEN

INTRODUCCIÓN: El cáncer prostático (CaP) es una patología de alta prevalencia e incidencia mundial. El tamizaje ha perseguido el diagnóstico precoz de esta enfermedad para otorgar tratamientos oportunos. Nosotros buscamos caracterizar los pacientes de un hospital local respecto al diagnóstico y etapificación, y comparar estos resultados con datos previamente reportados. MATERIAL Y MÉTODO: Análisis retrospectivo de pacientes diagnosticados con CaP en un hospital institucional. Se recolectaron variables clínicas al momento del diagnóstico, los métodos de etapificación, el estadío según TNM y grado histológico. RESULTADOS: Se incluyeron 129 pacientes en el análisis. La mediana de APE (ng/mL) al diagnóstico fue de 7,29. El grado histológico fue clasificado como ISUP 1 en 37,5%. Se realizó una resonancia magnética multiparamétrica de próstata (RMmp) en el 42,19% de los pacientes, siendo clasificados como PIRADS 4 en mayor proporción (21,09%). La etapificación con PET-CT PSMA se utilizó principalmente en el grupo de alto riesgo y ante dudas frente a etapificación con medios convencionales. Se prefirió la Tomografía computada (TC) contrastada y la cintigrafía ósea en los otros grupos. 6,25% fue catalogado N1 y 9,37% M1. CONCLUSIÓN: La etapa al diagnóstico de nuestra serie es algo mayor a lo reportado por países desarrollados, pero considerablemente menor a lo publicado por otros países de Latinoamérica e inclusive de otros hospitales de nuestro país. Pareciera ser de gran relevancia nacional contar con protocolos claros de tamizaje y acceso a APE con el fin de disminuir los casos diagnosticados en etapas avanzadas.


INTRODUCTION: Prostate cancer (PCa) is a disease with a high prevalence and incidence worldwide. Screening has pursued the early diagnosis of this disease to provide early treatment. We sought to characterize patients from a local hospital with respect to diagnosis and staging and to compare these results with previously reported data. METHODS: We conducted a retrospective analysis of patients diagnosed with PCa at an institutional hospital. Clinical variables were collected at the time of diagnosis, staging methods, TNM stage, and histological grade. RESULTS: 129 patients were included in the analysis. The median PSA (ng/mL) at diagnosis was 7.29. The histological grade was classified as ISUP 1 in 37.5%. An MRI was performed in 42.19% of the patients, being classified mostly as PIRADS 4 (21.09%). PET-CT PSMA staging was used mainly in the high-risk group, preferring contrast-enhanced CT and bone scintigraphy in the other groups. 6.25% were classified as N1 and 9.37% as M1. CONCLUSION: The stage at diagnosis in our series is somewhat higher than that reported by developed countries but considerably lower than that published by other Latin American countries and even from other hospitals in our country. It is of great national relevance to have clear protocols for screening and access to PSA to reduce the cases diagnosed in advanced stages.


Asunto(s)
Humanos , Masculino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/diagnóstico por imagen , Antígeno Prostático Específico/sangre , Estadificación de Neoplasias , Imagen por Resonancia Magnética , Chile/epidemiología , Estudios Retrospectivos , Clasificación del Tumor
19.
Clin Genitourin Cancer ; 21(4): 483-490, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37193610

RESUMEN

BACKGROUND: De novo neuroendocrine prostate cancer (NEPC) and treatment-emergent neuroendocrine prostate cancer (T-NEPC) are rare diseases with a poor prognosis. After first-line platinum chemotherapy, there is no consensus on second-line treatments. PATIENTS AND METHODS: Patients with a pathologic diagnosis of de novo NEPC or T-NEPC between 2000 and 2020 who received first-line platinum and any second-line systemic therapy were selected and standardized clinical data was collected via the electronic health record at each institution. The primary endpoint was overall survival (OS) based on second-line therapy. Secondary endpoints included objective response rate (ORR) to second-line therapy, PSA response, and time on treatment. RESULTS: Fifty-eight patients (32 de novo NEPC, 26 T-NEPC) from 8 institutions were included. At de novo NEPC or T-NEPC diagnosis, the overall cohort had a median age of 65.0 years (IQR 59.2-70.3) and median PSA of 3.0 ng/dL (IQR 0.6-17.9). Following first-line platinum chemotherapy, 21 patients (36.2%) received platinum chemotherapy, 10 (17.2%) taxane monotherapy, 11 (19.0%) immunotherapy, 10 (17.2%) other chemotherapy, and 6 (16.2%) other systemic therapy. Among 41 evaluable patients, the ORR was 23.5%. The mOS after start of second-line therapy was 7.4 months (95% CI 6.1-11.9). CONCLUSIONS: In this retrospective study, patients with de novo NEPC or T-NEPC who received second-line therapy were treated with wide variety of treatment regimens, reflecting the lack of consensus in this setting. Most patients received chemotherapy-based treatments. Overall prognosis was poor and ORR was low in the second line regardless of treatment choice.


Asunto(s)
Antígeno Prostático Específico , Neoplasias de la Próstata , Masculino , Humanos , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Platino (Metal) , Neoplasias de la Próstata/patología , Pronóstico
20.
Int Braz J Urol ; 49(3): 359-371, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37115180

RESUMEN

PURPOSE: Targeted biopsy (TB) combined with systematic biopsy (SB) is an optimized mode of prostate biopsy but can often lead to oversampling and overdiagnosis accompanied by potential biopsy-related complications and patient discomfort. Here, we attempted to reasonably stratify the patient population based on multi-parameter indicators with the aim of avoiding unnecessary SB. METHODS: In total, 340 biopsy-naïve men with suspected lesions, prostate-specific antigen (PSA) < 20 ng/mL and prostate imaging-reporting and data system (PI-RADS) ≥ 3 enrolled for study underwent both TB and SB. The primary outcome was to determine independent predictors for a valid diagnosis, assuming that only TB was performed and SB omitted (defined as mono-TB), taking TB + SB as the reference standard. The secondary outcomes were exploration of the predictive factors of mono-TB and TB + SB in detection of prostate cancer (PCa) and clinically significant PCa (csPCa). RESULTS: The mean PSA density (PSAD) of patient group was 0.27 ng/mL/mL. Multiparametric MRI PI-RADS scores were 3-5 in 146 (42.94%), 105 (30.88%), and 89 (26.18%) cases, respectively. PCa and csPCa were detected in 178/340 (52.35%) and 162/340 (47.65%) patients, respectively. Overall, 116/178 (65.17%) patients diagnosed with PCa displayed pathological consistencies between mono-TB and TB + SB modes. PSAD and PI-RADS were independent predictors of valid diagnosis using mono-TB. CONCLUSIONS: PSAD combined with PI-RADS showed utility in guiding optimization of the prostate biopsy mode. Higher PSAD and PI-RADS values were associated with greater confidence in implementing mono-TB and safely omitting SB, thus effectively balancing the benefits and risks.


Asunto(s)
Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/patología , Imagen por Resonancia Magnética , Antígeno Prostático Específico , Biopsia Guiada por Imagen , Próstata/diagnóstico por imagen , Próstata/patología , Estudios Retrospectivos
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