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1.
Anticancer Res ; 41(9): 4443-4446, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475067

RESUMO

BACKGROUND: Androgen deprivation therapy (ADT) is one of the most effective treatments for advanced prostate cancer (PCa). However, it has been reported that the use of ADT is significantly associated with an increased risk of acute kidney injury (AKI) among patients with newly diagnosed non-metastatic PCa. We investigated changes in renal function that occurred in Japanese patients with PCa after ADT was discontinued. PATIENTS AND METHODS: Among 121 patients who underwent prostate biopsies, were pathologically diagnosed with PCa, and received ADT for ≥6 months at our Institution between 2009 and 2014, 60 patients who underwent radiotherapy for stage B or C PCa were eligible for inclusion in this retrospective study. Renal function was assessed using the estimated glomerular filtration rate (eGFR) before treatment and at 1, 3, 6, 9, and 12 months after the initiation of ADT and the rate of change in the eGFR (ΔeGFR) during ADT and after the discontinuation of ADT was investigated. We divided patients into two groups: Group 1 received ADT for 6 months, and group 2 received ADT for 12 months. Age; ΔeGFR; prostate-specific antigen, testosterone and hemoglobin levels; clinical stage; Gleason score; comorbidities; body mass index; heart rate; and the cardiothoracic ratio were analyzed. RESULTS: A total of 60 patients (group 1: n=23, group 2: n=37) were analyzed. The Gleason score of group 2 was higher than that of group 1 (p=0.0011). Regarding clinical stage, group 1 had more patients with stage B disease, and group 2 had more with stage C (p<0.0001). The eGFR decreased with the duration of ADT treatment. At 12 months, renal function had started to recover in group 1, while it had continued to decrease in group 2. CONCLUSION: Discontinuation of ADT tended to result in improvements in renal function. Furthermore, this study indicated that renal dysfunction caused by 6 months of ADT is transient. Normalization of the serum testosterone level seen after the discontinuation of ADT may be associated with improvements in renal function. Thus, intermittent ADT may be a useful treatment for PCa, as it would help to preserve renal function.


Assuntos
Antagonistas de Androgênios/efeitos adversos , Taxa de Filtração Glomerular/efeitos dos fármacos , Rim/fisiopatologia , Neoplasias da Próstata/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/uso terapêutico , Humanos , Japão , Rim/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Testosterona/sangue , Fatores de Tempo , Suspensão de Tratamento
2.
Medicine (Baltimore) ; 100(35): e27144, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477170

RESUMO

ABSTRACT: This study aimed to evaluate the diagnostic performance of diffusion kurtosis imaging (DKI) and prostate-specific antigen (PSA) biomarkers in differentiating prostate cancer (PCa) and benign prostatic hyperplasia (BPH).A total of 43 cases of prostate diseases verified by pathology were enrolled in the present study. These cases were assigned to the BPH group (n = 20, 68.85±10.81 years old) and PCa group (n = 23, 74.13 ±â€Š7.37 years old). All patients underwent routine prostate magnetic resonance imaging and DKI examinations, and the mean diffusivity (MD), mean kurtosis (MK), and fractional anisotropy (FA) values were calculated. Three serum indicators (PSA, free PSA [fPSA], and f/t PSA) were collected. We used univariate logistic regression to analyze the above quantitative parameters between the 2 groups, and the independent factors were further incorporated into the multivariate logistic regression model. The area under the receiver operating characteristic curve (AUC) was used to evaluate the diagnostic efficacy of the single indicator and combined model.The difference in PSA, f/t PSA, MK, and FA between PCa and BPH was statistically significant (P < .05). The AUC for the combined model (f/t PSA, MK, and FA) of 0.972 (95% confidence interval [CI]: 0.928, 1.000) was higher than the AUC of 0.902 (95% CI: 0.801, 1.000) for f/t PSA, 0.833 (95% CI: 0.707, 0.958) for MK, and 0.807 (95% CI: 0.679, 0.934) for FA.The MK and FA values for DKI and f/t PSA effectively identify PCa and BPH, compared to the PSA indicators. Combining DKI and PSA derivatives can further improve the diagnosis efficiency and might help in the clinical setting.


Assuntos
Imageamento por Ressonância Magnética/métodos , Antígeno Prostático Específico/sangue , Hiperplasia Prostática/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Hiperplasia Prostática/sangue , Neoplasias da Próstata/sangue , Estudos Retrospectivos
3.
Tumour Biol ; 43(1): 197-207, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34486998

RESUMO

BACKGROUND: The role of isoforms of prostate specific antigen (PSA) and other kallikrein-related markers in early detection of biochemical recurrence (BCR) after radical prostatectomy (RP) is not well known and serum PSA is currently used in preoperative risk nomograms. OBJECTIVE: The aim of this research was to study pre- and early postoperative levels of important PSA isoforms and human kallikrein-2 to determine their ability to predict BCR and identify disease persistence (DP). METHODS: This study included 128 consecutive patients who underwent RP for clinically localized prostate cancer. PSA, fPSA, %fPSA, [-2]proPSA, PHI and hK2 were measured preoperatively, at 1 and 3 months after RP. We determined the ability of these markers to predict BCR and identify DP. RESULTS: The DP and BCR rate were 11.7%and 20.3%respectively and the median follow up was 64 months (range 3-76 months). Preoperatively, the independent predictors of BCR were PSA (p-value 0.029), [-2]proPSA (p-value 0.002) and PHI (p-value 0.0003). Post-RP, PSA was the single marker correlating with BCR, both at one (p-value 0.0047) and 3 months (p-value 0.0004). PSA, fPSA, [-2]proPSA and PHI significantly correlated to DP at 1 and 3 months post-RP (p-value <  0.05), although PSA had the most significant existing correlation (p-value <  0.0001). CONCLUSIONS: [-2]proPSA and PHI are preoperative predictors of BCR and DP that outperform the currently used serum PSA. At the early postoperative period there is no additional benefit of the other markers tested.


Assuntos
Biomarcadores Tumorais/sangue , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico , Calicreínas Teciduais/sangue , Idoso , Detecção Precoce de Câncer , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/genética , Nomogramas , Período Pós-Operatório , Próstata/patologia , Próstata/cirurgia , Prostatectomia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/genética , Neoplasias da Próstata/cirurgia , Isoformas de Proteínas/sangue , Isoformas de Proteínas/genética
4.
Adv Gerontol ; 34(3): 404-408, 2021.
Artigo em Russo | MEDLINE | ID: mdl-34409819

RESUMO

At this moment differential diagnostic of the prostate cancer (PC) needs the new, more effective ways with regard of multifactor analysis. One of this factor is patient's age. Men older than 45 years old have expressed involution changes of prostate tissues. This fact must be take into account in valuation morphologic and laboratory criteria's in PC. The goal of the investigation is to take into account age-related changes of the prostate volume and laboratory criteria of blood analysis in PC. 632 patients in age from 42 to 88 years old were exanimated by trans rectal ultrasound examination (TRUS) method (volume parameters of the prostate) and by levels of prostate-specific antigen (PSA) and (-2) pro-PSA in blood. The increase of patient's age correlated with increase of the density of transient, peripheral and central zones of prostate. It correlates with the probability of the frequency of PC verification. Levels of PSA and 2-pro-PSA in blood of PC patients increase during the transition from middle to elderly age in 1,4-2,8 times. Thus the information, which was obtained during the examination of volume prostate characteristics by TRUS method and laboratory diagnostic of PC, must take to account patient's age.


Assuntos
Fatores Etários , Antígeno Prostático Específico , Neoplasias da Próstata , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Humanos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico , Ultrassonografia
5.
Medicine (Baltimore) ; 100(31): e26833, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34397848

RESUMO

ABSTRACT: To compare the outcomes of patients with high-risk prostate cancer treated by primary radical prostatectomy (RP) and primary androgen deprivation therapy (ADT).The study included patients with high-risk or very high-risk prostate cancer. Patients treated with definitive radiation therapy and those with clinical N1 and M1 disease were excluded. The RP group was divided into sub-cohorts of patients treated with ADT and those who received ADT after biochemical recurrence post-RP. Cancer-specific survival (CSS) and overall survival (OS) were analyzed using the Kaplan-Meier method and the Cox proportional hazards model.The study analyzed 859 patients divided into the RP group (n = 654) and ADT group (n = 205). Castration-resistant prostate cancer was detected in 23 (3.5%) patients in the RP group and 43 (21.0%) patients in the ADT group. Mortality cases included 63 (9.6%) patients in the RP group and 91 (44.4%) patients in the ADT group. CSS (P = .0002) and OS (P < .0001) were significantly higher in the RP group than in the ADT group. In the sub-cohort, CSS did not differ significantly between the RP and ADT groups, whereas OS was significantly higher in the RP group than in the ADT group (P < .0001). In the multivariate analysis, primary ADT increased CSS (hazard ratio, 2.068; P = .0498) and OS (hazard ratio, 3.218; P < .0001) compared with RP.In clinically localized high-risk prostate cancer patients, primary RP was associated with better CSS and OS than primary ADT. Comprehensive counseling in this cohort of patients will help the selection of treatment.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Prostatectomia , Neoplasias da Próstata , Radioterapia , Idoso , Biomarcadores Tumorais/sangue , Terapia Combinada/métodos , Humanos , Estimativa de Kaplan-Meier , Masculino , Estadiamento de Neoplasias , Avaliação de Processos e Resultados em Cuidados de Saúde , Seleção de Pacientes , Modelos de Riscos Proporcionais , Antígeno Prostático Específico/sangue , Prostatectomia/efeitos adversos , Prostatectomia/métodos , Neoplasias da Próstata/sangue , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Neoplasias de Próstata Resistentes à Castração/diagnóstico , Neoplasias de Próstata Resistentes à Castração/epidemiologia , Radioterapia/efeitos adversos , Radioterapia/métodos , República da Coreia/epidemiologia , Medição de Risco
6.
Lancet Oncol ; 22(9): 1240-1249, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34391509

RESUMO

BACKGROUND: Screening for prostate cancer using prostate-specific antigen (PSA) reduces prostate cancer mortality but can lead to adverse outcomes. We aimed to compare a traditional screening approach with a diagnostic strategy of blood-based risk prediction combined with MRI-targeted biopsies. METHODS: We did a prospective, population-based, randomised, open-label, non-inferiority trial (STHLM3-MRI) in Stockholm county, Sweden. Men aged 50-74 years were randomly selected by Statistics Sweden and invited by mail to participate in screening; those with an elevated risk of prostate cancer, defined as either a PSA of 3 ng/mL or higher or a Stockholm3 score of 0·11 or higher were eligible for randomisation. Men with a previous prostate cancer diagnosis, who had undergone a prostate biopsy within 60 days before the invitation to participate, with a contraindication for MRI, or with severe illness were excluded. Eligible participants were randomly assigned (2:3) using computer-generated blocks of five, stratified by clinically significant prostate cancer risk, to receive either systematic prostate biopsies (standard group) or biparametric MRI followed by MRI-targeted and systematic biopsy in MRI-positive participants (experimental group). The primary outcome was the detection of clinically significant prostate cancer at prostate biopsy, defined as a Gleason score of 3 + 4 or higher. We used a margin of 0·78 to assess non-inferiority for the primary outcome. Key secondary outcome measures included the proportion of men with clinically insignificant prostate cancer (defined as a Gleason score of 3 + 3), and the number of any prostate MRI and biopsy procedures done. We did two comparisons: Stockholm3 (using scores of 0·11 and 0·15 as cutoffs) versus PSA in the experimental group (paired analyses) and PSA plus standard biopsy versus Stockholm3 plus MRI-targeted and systematic biopsy (unpaired, randomised analyses). All analyses were intention to treat. This study is registered with ClinicalTrials.gov, NCT03377881. FINDINGS: Between Feb 5, 2018, and March 4, 2020, 49 118 men were invited to participate, of whom 12 750 were enrolled and provided blood specimens, and 2293 with elevated risk were randomly assigned to the experimental group (n=1372) or the standard group (n=921). The area under the receiver-operating characteristic curve for detection of clinically significant prostate cancer was 0·76 (95% CI 0·72-0·80) for Stockholm3 and 0·60 (0·54-0·65) for PSA. In the experimental group, a Stockholm3 of 0·11 or higher was non-inferior to a PSA of 3 ng/mL or higher for detection of clinically significant prostate cancer (227 vs 192; relative proportion [RP] 1·18 [95% CI 1·09-1·28], p<0·0001 for non-inferiority), and also detected a similar number of low-grade prostate cancers (50 vs 41; 1·22 [0·96-1·55], p=0·053 for superiority) and was associated with more MRIs and biopsies. Compared with PSA of 3 ng/mL or higher, a Stockholm3 of 0·15 or higher provided identical sensitivity to detect clinically significant cancer, and led to fewer MRI procedures (545 vs 846; 0·64 [0·55-0·82]) and fewer biopsy procedures (311 vs 338; 0·92 (0·86-1·03). Compared with screening using PSA and systematic biopsies, a Stockholm3 of 0·11 or higher combined with MRI-targeted and systematic biopsies was associated with higher detection of clinically significant cancers (227 [3·0%] men tested vs 106 [2·1%] men tested; RP 1·44 [95% CI 1·15-1·81]), lower detection of low-grade cancers (50 [0·7%] vs 73 [1·4%]; 0·46 [0·32-0·66]), and led to fewer biopsy procedures. Patients randomly assigned to the experimental group had a lower incidence of prescription of antibiotics for infection (25 [1·8%] of 1372 vs 41 [4·4%] of 921; p=0·0002) and a lower incidence of admission to hospital (16 [1·2%] vs 31 [3·4%]; p=0·0003) than those in the standard group. INTERPRETATION: The Stockholm3 test can inform risk stratification before MRI and targeted biopsies in prostate cancer screening. Combining the Stockholm3 test with an MRI-targeted biopsy approach for prostate cancer screening decreases overdetection while maintaining the ability to detect clinically significant cancer. FUNDING: The Swedish Cancer Society, the Swedish Research Council, and Stockholm City Council.


Assuntos
Detecção Precoce de Câncer/métodos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Idoso , Biomarcadores Tumorais/sangue , Humanos , Biópsia Guiada por Imagem , Análise de Intenção de Tratamento , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Prospectivos , Próstata/diagnóstico por imagem , Próstata/patologia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Curva ROC , Distribuição Aleatória , Medição de Risco , Suécia/epidemiologia
7.
N Engl J Med ; 385(10): 908-920, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34237810

RESUMO

BACKGROUND: High rates of overdiagnosis are a critical barrier to organized prostate cancer screening. Magnetic resonance imaging (MRI) with targeted biopsy has shown the potential to address this challenge, but the implications of its use in the context of organized prostate cancer screening are unknown. METHODS: We conducted a population-based noninferiority trial of prostate cancer screening in which men 50 to 74 years of age from the general population were invited by mail to participate; participants with prostate-specific antigen (PSA) levels of 3 ng per milliliter or higher were randomly assigned, in a 2:3 ratio, to undergo a standard biopsy (standard biopsy group) or to undergo MRI, with targeted and standard biopsy if the MRI results suggested prostate cancer (experimental biopsy group). The primary outcome was the proportion of men in the intention-to-treat population in whom clinically significant cancer (Gleason score ≥7) was diagnosed. A key secondary outcome was the detection of clinically insignificant cancers (Gleason score 6). RESULTS: Of 12,750 men enrolled, 1532 had PSA levels of 3 ng per milliliter or higher and were randomly assigned to undergo biopsy: 603 were assigned to the standard biopsy group and 929 to the experimental biopsy group. In the intention-to-treat analysis, clinically significant cancer was diagnosed in 192 men (21%) in the experimental biopsy group, as compared with 106 men (18%) in the standard biopsy group (difference, 3 percentage points; 95% confidence interval [CI], -1 to 7; P<0.001 for noninferiority). The percentage of clinically insignificant cancers was lower in the experimental biopsy group than in the standard biopsy group (4% [41 participants] vs. 12% [73 participants]; difference, -8 percentage points; 95% CI, -11 to -5). CONCLUSIONS: MRI with targeted and standard biopsy in men with MRI results suggestive of prostate cancer was noninferior to standard biopsy for detecting clinically significant prostate cancer in a population-based screening-by-invitation trial and resulted in less detection of clinically insignificant cancer. (Funded by the Swedish Research Council and others; STHLM3-MRI ClinicalTrials.gov number, NCT03377881.).


Assuntos
Biópsia/métodos , Imageamento por Ressonância Magnética , Próstata/patologia , Neoplasias da Próstata/patologia , Idoso , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Próstata/diagnóstico por imagem , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico por imagem
8.
Aging Male ; 24(1): 92-94, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34319201

RESUMO

Digital rectal examination (DRE) is routinely performed as part of a urology clinical assessment in patients with a clinical suspicion of prostate cancer. An abnormal DRE or a raised prostate specific antigen (PSA) level are part of the criteria for primary care referral to secondary care due to a suspicion of prostate cancer. The current Coronavirus-19 (COVID-19) pandemic has resulted in the rapid adoption of virtual consultations in the form of telephone or video consultations making clinical examination difficult. In the case of prostate cancer diagnostic pathways, often clinicians now rely on PSA measurements and MRI, where radiological services are available, without the requirement for a DRE. We discuss the limited role DRE has in the modern prostate cancer diagnostic pathway due to the widespread adoption of MRI particularly in the COVID-19 era.


Assuntos
Exame Retal Digital , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico , COVID-19 , Humanos , Imageamento por Ressonância Magnética , Masculino , Neoplasias da Próstata/diagnóstico por imagem , SARS-CoV-2
9.
Urol Clin North Am ; 48(3): 339-347, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34210489

RESUMO

Androgen receptor function, tumor cell plasticity, loss of tumor suppressors, and defects in DNA repair genes affect aggressive features of prostate cancer. Prostate cancer development, progression, and aggressive behavior are often attributable to function of the androgen receptor. Tumor cell plasticity, neuroendocrine features, and loss of tumor suppressors lend aggressive behavior to prostate cancer cells. DNA repair defects have ramifications for prostate cancer cell behavior.


Assuntos
Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Receptores Androgênicos/genética , Antagonistas de Androgênios/uso terapêutico , Biomarcadores Tumorais/genética , Plasticidade Celular , Reparo do DNA , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Testes Genéticos , Mutação em Linhagem Germinativa , Humanos , Masculino , Medicina de Precisão , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/patologia
10.
Urol Clin North Am ; 48(3): 373-386, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34210492

RESUMO

Prostate cancer represents a significant health care burden in the United States due to its incidence, treatment-related morbidity, and cancer-specific mortality. The burden begins with prostate-specific antigen screening, which has been subject to controversy due to concerns of overdiagnosis and overtreatment. Advancements in molecular oncology have provided evidence for the inherited predisposition to prostate cancer, which could improve individualized, risk-adapted approaches to screening and mitigate the harms of routine screening. This review presents the current evidence for the genetic basis of prostate cancer and novel genetically informed, risk-adapted screening strategies for prostate cancer.


Assuntos
Predisposição Genética para Doença , Programas de Rastreamento/métodos , Neoplasias da Próstata/genética , Adulto , Biomarcadores Tumorais/genética , Detecção Precoce de Câncer , Mutação em Linhagem Germinativa , Humanos , Imageamento por Ressonância Magnética , Masculino , Polimorfismo de Nucleotídeo Único , Antígeno Prostático Específico/sangue
11.
Urol Clin North Am ; 48(3): 387-399, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34210493

RESUMO

More than 40% of the risk of developing prostate cancer (PCa) is from genetic factors. Genome-wide association studies have led to the discovery of more than 140 variants associated with PCa risk. Polygenic risk scores (PRS) generated using these variants show promise in identifying individuals at much higher (and lower) lifetime risk than the average man. PCa PRS also improve the predictive value of prostate-specific antigen screening, may inform the age for starting PCa screening, and are informative for development of more aggressive tumors. Despite the promise, few clinical trials have evaluated the benefit of PCa PRS for clinical care.


Assuntos
Predisposição Genética para Doença , Programas de Rastreamento/métodos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Detecção Precoce de Câncer , Estudo de Associação Genômica Ampla , Humanos , Masculino , Antígeno Prostático Específico/sangue , Medição de Risco , Fatores de Risco
12.
J Proteome Res ; 20(7): 3590-3599, 2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34106707

RESUMO

Recently, we have found that two urinary glycoproteins, prostatic acid phosphatase (ACPP) and clusterin (CLU), combined with serum prostate-specific antigen (PSA) can serve as a three-signature panel for detecting aggressive prostate cancer (PCa) based on a quantitative glycoproteomic study. To facilitate the translation of candidates into clinically applicable tests, robust and accurate targeted parallel reaction monitoring (PRM) assays that can be widely adopted in multiple labs were developed in this study. The developed PRM assays for the urinary glycopeptides, FLN*ESYK from ACPP and EDALN*ETR from CLU, demonstrated good repeatability and a sufficient working range covering three to four orders of magnitude, and their performance in differentiating aggressive PCa was assessed by the quantitative analysis of urine specimens collected from 69 nonaggressive (Gleason score = 6) and 73 aggressive (Gleason ≥ 8) PCa patients. When ACPP combined with CLU, the discrimination power was improved from an area under a curve (AUC) of 0.66 to 0.78. By combining ACPP, CLU, and serum PSA to form a three-signature panel, the AUC was further improved to 0.83 (sensitivity: 84.9%, specificity: 66.7%). Since the serum PSA test alone had an AUC of 0.68, our results demonstrated that the new urinary glycopeptide PRM assays can serve as an adjunct to the serum PSA test to achieve better predictive power toward aggressive PCa. In summary, our developed PRM assays for urinary glycopeptides were successfully applied to clinical PCa urine samples with a promising performance in aggressive PCa detection.


Assuntos
Fosfatase Ácida/urina , Clusterina/urina , Antígeno Prostático Específico , Neoplasias da Próstata , Biomarcadores Tumorais , Glicoproteínas/urina , Humanos , Masculino , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico
13.
J Urol ; 206(3): 623-629, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34003011

RESUMO

PURPOSE: There were 3 recent U.S. Food and Drug Administration approvals for drugs to be used in nonmetastatic castration resistant prostate cancer, a state that arises from the unproven start of continuous androgen deprivation therapy (ADT) for biochemical recurrent prostate cancer (BCR), before metastatic disease is evident. This report examines the outcome of men with BCR who defer ADT until time of metastasis. MATERIALS AND METHODS: Retrospective review of men diagnosed with clinically localized prostate cancer who underwent radical prostatectomy at Johns Hopkins Hospital and Walter Reed National Military Medical Center and developed BCR with a prostate specific antigen doubling time of not more than 10 months (806 patients). The primary end points were metastasis-free survival and overall survival from time of local treatment among men who delayed ADT until time of metastasis. RESULTS: The median metastasis-free survival of men with BCR and a prostate specific antigen doubling time <6 months and 10 months who delay ADT until metastasis is 144 months (95% CI 48-not reached) and 192 months (95% CI 72-not reached), respectively, with a median overall survival of 168 months (95% CI 96-276 months) and 204 months (95% CI 120-276), respectively. CONCLUSIONS: Metastasis-free survival and overall survival of men with BCR who delay hormone therapy is long. This underscores the need to reevaluate when to start primary ADT in this patient population.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Calicreínas/sangue , Recidiva Local de Neoplasia/tratamento farmacológico , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/terapia , Tempo para o Tratamento/estatística & dados numéricos , Idoso , Quimioterapia Adjuvante/métodos , Tomada de Decisão Clínica , Progressão da Doença , Intervalo Livre de Doença , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/epidemiologia , Guias de Prática Clínica como Assunto , Próstata/patologia , Próstata/cirurgia , Prostatectomia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/mortalidade , Estudos Retrospectivos , Fatores de Tempo , Tempo para o Tratamento/normas
14.
Theranostics ; 11(13): 6214-6224, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33995654

RESUMO

Background: Current PSA-based tests used to detect prostate cancer (PCa) lack sufficient specificity, leading to significant overdetection and overtreatment. Our previous studies showed that serum fucosylated PSA (Fuc-PSA) and soluble TEK receptor tyrosine kinase (Tie-2) had the ability to predict aggressive (AG) PCa. Additional biomarkers are needed to address this significant clinical problem. Methods: A comprehensive Pubmed search followed by multiplex immunoassays identified candidate biomarkers associated with AG PCa. Subsequently, multiplex and lectin-based immunoassays were applied to a case-control set of sera from subjects with AG PCa, low risk PCa, and non-PCa (biopsy negative). These candidate biomarkers were further evaluated for their ability as panels to complement the prostate health index (phi) in detecting AG PCa. Results: When combined through logistic regression, two panel of biomarkers achieved the best performance: 1) phi, Fuc-PSA, SDC1, and GDF-15 for the detection of AG from low risk PCa and 2) phi, Fuc-PSA, SDC1, and Tie-2 for the detection of AG from low risk PCa and non-PCa, with noticeable improvements in ROC analysis over phi alone (AUCs: 0.942 vs 0.872, and 0.934 vs 0.898, respectively). At a fixed sensitivity of 95%, the panels improved specificity with statistical significance in detecting AG from low risk PCa (76.0% vs 56%, p=0.029), and from low risk PCa and non-PCa (78.2% vs 65.5%, p=0.010). Conclusions: Multivariate panels of serum biomarkers identified in this study demonstrated clinically meaningful improvement over the performance of phi, and warrant further clinical validation, which may contribute to the management of PCa.


Assuntos
Adenocarcinoma/sangue , Biomarcadores Tumorais/sangue , Proteínas de Neoplasias/sangue , Neoplasias da Próstata/sangue , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Idoso , Área Sob a Curva , Estudos de Casos e Controles , Fucose/metabolismo , Glicosilação , Humanos , Imunoensaio , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Antígeno Prostático Específico/sangue , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Processamento de Proteína Pós-Traducional , Curva ROC , Receptor TIE-2/sangue , Risco , Sensibilidade e Especificidade
15.
Pan Afr Med J ; 38: 56, 2021.
Artigo em Francês | MEDLINE | ID: mdl-33854685

RESUMO

The purpose of this study was to assess outcomes of radical prostatectomy in patients with prostate cancer. We conducted a retrospective single-center study in the Department of Urology and Andrology at the Aristide Le Dantec Hospital in Dakar from June 1, 2010 to May 31, 2016. We collected data of 60 patients undergoing radical retropubic prostatectomy associated with dissection of the iliac and obturator nodes. After radical prostatectomy, prostate specific antigen (PSA) levels were undetectable (<0.1 ng/mL) in 20 patients (33.3%). Eleven patients (18.3%), who had biochemical relapse, received complementary hormone therapy. Patients achieved a response after initiation of treatment, and total PSA became undetectable again after an 8-month follow-up period. Mean overall survival was 17.5 months, with a median of 9.49. Cumulative overall survival rates at 1 year, 3 years and 4 years were 42.4, 13.6 and 6.8%, respectively. Mean relapse-free survival was 17.3 months, with a median biochemical relapse-free survival of eleven (11) months. The mean duration of specific survival was 8.1 months, with a median of 3 months. Seven patients had positive resection margins (11.6%). Four patients had lymph node involvement. Radical prostatectomy, suggested in some patients with prostate cancer in our practice, has been shown to be an effective therapeutic method leading to good outcomes.


Assuntos
Antígeno Prostático Específico/sangue , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Intervalo Livre de Doença , Seguimentos , Hospitais Universitários , Humanos , Excisão de Linfonodo , Metástase Linfática , Masculino , Margens de Excisão , Neoplasias da Próstata/patologia , Estudos Retrospectivos , Senegal , Taxa de Sobrevida , Resultado do Tratamento
16.
Medicine (Baltimore) ; 100(17): e25602, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33907111

RESUMO

ABSTRACT: To explore the influencing factors of prostate cancer occurrence, set up risk prediction model, require reference for the preliminary diagnosis of clinical doctors, this model searched database through the data of prostate cancer patients and prostate hyperplasia patients National Clinical Medical Science Data Center.With the help of Stata SE 12.0 and SPSS 25.0 software, the biases between groups were balanced by propensity score matching. Based on the matched data, the relevant factors were further screened by stepwise logistic regression analysis, the key variable and artificial neural network model are established. The prediction accuracy of the model is evaluated by combining the probability of test set with the area under receiver operating characteristic curve (ROC).After 1:2 PSM, 339 pairs were matched successfully. There are 159 cases in testing groups and 407 cases in training groups. And the regression model was P = 1 / (1 + e (0.122 ∗ age + 0.083 ∗ Apo lipoprotein C3 + 0.371 ∗ total prostate specific antigen (tPSA) -0.227 ∗ Apo lipoprotein C2-6.093 ∗ free calcium (iCa) + 0.428 ∗ Apo lipoprotein E-1.246 ∗ triglyceride-1.919 ∗ HDL cholesterol + 0.083 ∗ creatine kinase isoenzyme [CKMB])). The logistic regression model performed very well (ROC, 0.963; 95% confidence interval, 0.951 to 0.978) and artificial neural network model (ROC, 0.983; 95% confidence interval, 0.964 to 0.997). High degree of Apo lipoprotein E (Apo E) (Odds Ratio, [OR], 1.535) in blood test is a risk factor and high triglyceride (TG) (OR, 0.288) is a protective factor.It takes the biochemical examination of the case as variables to establish a risk prediction model, which can initially reflect the risk of prostate cancer and bring some references for diagnosis and treatment.


Assuntos
Modelos Biológicos , Neoplasias da Próstata/etiologia , Medição de Risco/métodos , Adulto , Idoso , Apolipoproteínas/sangue , Biomarcadores/sangue , Cálcio/sangue , HDL-Colesterol/sangue , Creatina Quinase/sangue , Humanos , Calicreínas/sangue , Masculino , Pessoa de Meia-Idade , Redes Neurais de Computação , Valor Preditivo dos Testes , Pontuação de Propensão , Antígeno Prostático Específico/sangue , Curva ROC , Análise de Regressão , Triglicerídeos/sangue
18.
J Urol ; 206(3): 638-645, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33890485

RESUMO

PURPOSE: We assessed whether prostate cancer (PCa) location might affect oncologic outcomes after focal therapy (FT) for PCa. MATERIALS AND METHODS: We identified 274 men receiving FT for PCa using either high intensity focused ultrasound (HIFU) or cryotherapy at a high volume center between 2009 and 2018. Survival analyses using Kaplan-Meier method were used to assess any additional treatment and radical treatment rates according to PCa location. Propensity-score match analysis was used to compare oncologic outcomes of HIFU vs cryotherapy according to PCa location. Covariates were prostate specific antigen, clinical stage, prostate volume, Gleason score, maximum cancer core length, percentage of positive cores and treatment modality. RESULTS: A total of 166 and 108 men received FT with HIFU and cryotherapy, respectively. Overall, 39% (106) and 31% (85) received at least an additional treatment and a radical treatment after FT, respectively, with a median followup of 51 months. At 36 months' followup, the rates of any additional treatment-free survival were 71%, 75%, and 69% for patients with basal, mid-prostate and apical disease, respectively (p=0.7). At multivariable logistic regression analysis, PCa location was not significantly associated with higher risk of either any additional treatment or radical treatment (all p >0.4). After matching, there was no difference between HIFU vs cryotherapy in terms of any additional treatment rates according to PCa location. CONCLUSIONS: The PCa location does not significantly affect the rate of failure after FT. The presence of an apical lesion should not be considered an exclusion criteria for FT. Both HIFU and cryotherapy likely achieve similar medium-term oncologic results regardless of PCa location.


Assuntos
Criocirurgia , Neoplasias da Próstata/cirurgia , Ultrassom Focalizado Transretal de Alta Intensidade , Idoso , Biópsia com Agulha de Grande Calibre , Seguimentos , Humanos , Calicreínas/sangue , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética Multiparamétrica , Gradação de Tumores , Estadiamento de Neoplasias , Próstata/diagnóstico por imagem , Próstata/patologia , Próstata/efeitos da radiação , Próstata/cirurgia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/mortalidade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
19.
J Urol ; 206(3): 630-637, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33904759

RESUMO

PURPOSE: We aimed to explore the association between genomic status and clinical outcome of platinum-based chemotherapy among patients with metastatic castration-resistant prostate cancer (mCRPC). MATERIALS AND METHODS: We conducted a retrospective study of 55 patients with mCRPC who received platinum-based chemotherapy after the progression to docetaxel chemotherapy and underwent genomic profiling of 14 homologous recombination (HR) pathway genes. Progression-free survival (PFS) was analyzed using the Kaplan-Meier method. RESULTS: Of 55 patients, 23 harbored genomic defects in HR pathway genes. Median prostate specific antigen (PSA)-PFS for the HR defect group was 6.7 months compared with 2.6 months for the no HR defect group (p=0.001). The patients harboring somatic HR defect displayed shorter PSA-PFS than those harboring germline HR defect (4.5 months vs not available; p=0.066). The PSA50 (patients who survived for 12 weeks and had a PSA decline over 50% from baseline) response rate displayed higher in patients harboring BRCA2 or ATM defect (6/8, 75.0%) than in those harboring CDK12 defect (2/9, 22.2%; p=0.06). Patients harboring BRCA2 or ATM defect displayed prolonged PSA-PFS, compared with those harboring CDK12 defect and those harboring other HR defect (p=0.038). In multivariate Cox regression analysis, HR defect and BRCA2 or ATM defect were independent significant factors associated with superior PAS-PFS to platinum-based chemotherapy. CONCLUSIONS: The patients with mCRPC harboring alterations in different HR genes displayed distinct response to platinum-based chemotherapy. Patients with mCRPC harboring genomic defects in crucial HR genes either in the germline or somatic, especially BRCA2 and ATM, might experience superior outcomes to platinum-based chemotherapy, compared with those harboring CDK12 defect.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Carboplatina/uso terapêutico , Cisplatino/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteína BRCA2/genética , Biópsia , Carboplatina/farmacologia , Cisplatino/farmacologia , Quinases Ciclina-Dependentes/genética , Análise Mutacional de DNA , Docetaxel/farmacologia , Docetaxel/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Recombinação Homóloga/genética , Humanos , Calicreínas/sangue , Masculino , Pessoa de Meia-Idade , Mutação , Intervalo Livre de Progressão , Próstata/patologia , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/mortalidade , Neoplasias de Próstata Resistentes à Castração/secundário , Estudos Retrospectivos
20.
J Urol ; 206(3): 507-516, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33904755

RESUMO

PURPOSE: Although the Prostate Imaging-Reporting and Data System™ version 2 (PI-RADS™ v2) is a reliable diagnostic tool for significant prostate cancer, less is known about the prognostic significance of the structured reporting scheme for estimating oncologic outcomes after treatment. We aimed to synthesize the available evidence regarding the association of PI-RADS v2 score and risk of biochemical recurrence (BCR) among patients undergoing primary definitive treatment for prostate cancer. MATERIALS AND METHODS: We systematically queried the PubMed® and Web of Science™ databases to identify studies addressing the association between the PI-RADS v2 and treatment outcomes. We included studies through November 2020 that assessed the independent prognostic significance of PI-RADS v2. After assessing risk of bias and quality, we conducted a formal meta-analysis to estimate the pooled effects of prostate magnetic resonance imaging (MRI) classification on the risk of BCR. RESULTS: We identified 9 and 7 eligible studies including 2,274 and 1,215 patients for the systematic review and meta-analysis, respectively. Eight were conducted in the context of radical prostatectomy and 1 post-radiation. Among patients treated with radical prostatectomy, higher PI-RADS v2 scores were significantly associated with risk of BCR (pooled HR 3.06, 95% CI 2.16-4.33; p <0.01). There was no significant heterogeneity among studies. For all studies, PI-RADS v2 score remained significantly associated with BCR (pooled HR 3.19, 95% CI 2.28-4.45; p <0.01). CONCLUSIONS: Prostate MRI findings assessed with the PI-RADS v2 classification were independently associated with risk of BCR after definitive local therapy, primarily based on data from radical prostatectomy. These findings support the prognostic significance of MRI, in addition to its role in prostate cancer diagnosis.


Assuntos
Calicreínas/sangue , Imageamento por Ressonância Magnética , Recidiva Local de Neoplasia/epidemiologia , Antígeno Prostático Específico/sangue , Próstata/diagnóstico por imagem , Neoplasias da Próstata/terapia , Braquiterapia , Humanos , Masculino , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/prevenção & controle , Prognóstico , Próstata/efeitos da radiação , Próstata/cirurgia , Prostatectomia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia , Medição de Risco/métodos
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