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1.
Urol Clin North Am ; 47(4): 457-467, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33008496

RESUMO

Biochemically recurrent prostate cancer represents a stage of prostate cancer where conventional (continued on next page) computed tomography and technetium Tc 99m bone scan imaging are unable to detect disease after curative intervention despite rising prostate-specific antigen. There is no clear standard of care and no systemic therapy has been shown to improve survival. Immunotherapy-based treatments potentially are attractive options relative to androgen deprivation therapy due to the generally more favorable side-effect profile. Biochemically recurrent prostate cancer patients have a low tumor burden and likely lymph node-based disease, which may make them more likely to respond to immunotherapy.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Imunoterapia/métodos , Recidiva Local de Neoplasia/terapia , Neoplasias da Próstata/patologia , Idoso , Terapia Combinada , Intervalo Livre de Doença , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Seleção de Pacientes , Prognóstico , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/terapia , Medição de Risco , Papel (figurativo) , Análise de Sobrevida , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
2.
Lancet Oncol ; 21(10): 1331-1340, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33002437

RESUMO

BACKGROUND: Adjuvant radiotherapy has been shown to halve the risk of biochemical progression for patients with high-risk disease after radical prostatectomy. Early salvage radiotherapy could result in similar biochemical control with lower treatment toxicity. We aimed to compare biochemical progression between patients given adjuvant radiotherapy and those given salvage radiotherapy. METHODS: We did a phase 3, randomised, controlled, non-inferiority trial across 32 oncology centres in Australia and New Zealand. Eligible patients were aged at least 18 years and had undergone a radical prostatectomy for adenocarcinoma of the prostate with pathological staging showing high-risk features defined as positive surgical margins, extraprostatic extension, or seminal vesicle invasion; had an Eastern Cooperative Oncology Group performance status of 0-1, and had a postoperative prostate-specific antigen (PSA) concentration of 0·10 ng/mL or less. Patients were randomly assigned (1:1) using a minimisation technique via an internet-based, independently generated allocation to either adjuvant radiotherapy within 6 months of radical prostatectomy or early salvage radiotherapy triggered by a PSA of 0·20 ng/mL or more. Allocation sequence was concealed from investigators and patients, but treatment assignment for individual randomisations was not masked. Patients were stratified by radiotherapy centre, preoperative PSA, Gleason score, surgical margin status, and seminal vesicle invasion status. Radiotherapy in both groups was 64 Gy in 32 fractions to the prostate bed without androgen deprivation therapy with real-time review of plan quality on all cases before treatment. The primary endpoint was freedom from biochemical progression. Salvage radiotherapy would be deemed non-inferior to adjuvant radiotherapy if freedom from biochemical progression at 5 years was within 10% of that for adjuvant radiotherapy with a hazard ratio (HR) for salvage radiotherapy versus adjuvant radiotherapy of 1·48. The primary analysis was done on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, NCT00860652. FINDINGS: Between March 27, 2009, and Dec 31, 2015, 333 patients were randomly assigned (166 to adjuvant radiotherapy; 167 to salvage radiotherapy). Median follow-up was 6·1 years (IQR 4·3-7·5). An independent data monitoring committee recommended premature closure of enrolment because of unexpectedly low event rates. 84 (50%) patients in the salvage radiotherapy group had radiotherapy triggered by a PSA of 0·20 ng/mL or more. 5-year freedom from biochemical progression was 86% (95% CI 81-92) in the adjuvant radiotherapy group versus 87% (82-93) in the salvage radiotherapy group (stratified HR 1·12, 95% CI 0·65-1·90; pnon-inferiority=0·15). The grade 2 or worse genitourinary toxicity rate was lower in the salvage radiotherapy group (90 [54%] of 167) than in the adjuvant radiotherapy group (116 [70%] of 166). The grade 2 or worse gastrointestinal toxicity rate was similar between the salvage radiotherapy group (16 [10%]) and the adjuvant radiotherapy group (24 [14%]). INTERPRETATION: Salvage radiotherapy did not meet trial specified criteria for non-inferiority. However, these data support the use of salvage radiotherapy as it results in similar biochemical control to adjuvant radiotherapy, spares around half of men from pelvic radiation, and is associated with significantly lower genitourinary toxicity. FUNDING: New Zealand Health Research Council, Australian National Health Medical Research Council, Cancer Council Victoria, Cancer Council NSW, Auckland Hospital Charitable Trust, Trans-Tasman Radiation Oncology Group Seed Funding, Cancer Research Trust New Zealand, Royal Australian and New Zealand College of Radiologists, Cancer Institute NSW, Prostate Cancer Foundation Australia, and Cancer Australia.


Assuntos
Adenocarcinoma/radioterapia , Prostatectomia , Neoplasias da Próstata/radioterapia , Terapia de Salvação , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Idoso , Austrália , Progressão da Doença , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Humanos , Masculino , Doenças Urogenitais Masculinas/epidemiologia , Doenças Urogenitais Masculinas/etiologia , Pessoa de Meia-Idade , Nova Zelândia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Radioterapia Adjuvante/efeitos adversos , Terapia de Salvação/efeitos adversos , Resultado do Tratamento
4.
N Z Med J ; 133(1523): 87-95, 2020 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-33032306

RESUMO

Prostate cancer represents a significant health burden worldwide. The cancer incidence had substantially increased since the introduction of prostate specific antigen (PSA) in cancer screening. This had led to considerable debates among health professionals and epidemiologists, since PSA as a screening tool seemed to be far from perfect. In New Zealand, the controversy was quite prominent in the last three decades, with some advocating the benefits of screening, while others concerned regarding the risk of harms. With the absence of an organised screening programme and the appropriate monitoring and quality assurance procedures, the effects of the PSA testing debate had undoubtedly caused a variability in the opportunistic prostate cancer screening practices in the community. This, in addition to the recent rapid advancements in prostate cancer imaging, and updated results from randomised trials, have made it mandatory to question the validity of continuing with the current approach to prostate cancer screening. However, high-quality local data on these aspects had been lacking, which represents an ongoing challenge to developing robust and sound health policies.


Assuntos
Detecção Precoce de Câncer , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia , Adulto , Idoso , Grupo com Ancestrais do Continente Europeu , Humanos , Masculino , Pessoa de Meia-Idade , Nova Zelândia/epidemiologia , Grupo com Ancestrais Oceânicos , Antígeno Prostático Específico/sangue
5.
Urologiia ; (4): 79-83, 2020 Sep.
Artigo em Russo | MEDLINE | ID: mdl-32897659

RESUMO

OBJECTIVE: To study the survival rate of patients without biochemical recurrence according to the Stuttgart and Phoenix criteria in terms of their correlation with four different PSA nadir values as predictors of clinical recurrence in patients with localized prostate cancer who underwent total HIFU prostate ablation. MATERIAL AND METHODS: The object of the study was patients with morphologically proven localized RP by biopsy results, who were treated with prostate cancer by HIFU ablation on the Ablatherm Integrated Imaging apparatus (EDAP TMS, France). The study included 658 patients in whom HIFU ablation was used as primary treatment of localized prostate cancer (stages T1 - T2) without previous use of other methods (hormonal, radiation therapy) For the analysis, a continuous sample of patients was selected, which were divided into four groups depending on the PSA nadir level: less or equal 0.2 ng / ml (1 group), 0.21-0.5 ng / ml (group 2), 0.51-1 ng / ml (group 3) and> 1 ng / ml (group 4). sensitivity, specificity, predictive value, and 5-year biochemical relapse-free survival according to the Stuttgart definition and the Phoenix definition in the PSA nadir groups. RESULTS: The median (range) of the observation period for the patients was 5.3 (3-7) years, the mean time to reaching PSA nadir was 14.5+/-2.6 weeks. PSA nadirs less or equal 0.2, 0.21-0.5, 0.51-1.0 and > 1 ng/ml were achieved in 231 (35.1%), 132 (20.0%), 105 (15, 9%) and 190 (28.8%) patients, respectively. Survival without biochemical relapse in accordance with the Stuttgart definition in the four groups allocated for the PSA nadir was 82, 65, 43 and 32%, respectively (p<0.001), according to the Phoenix definition - 94, 74, 66 and 47% (p<0.001) respectively. According to the results of the control biopsy, 601 (91.3%) patients in the 1st and 2nd groups had a negative oncological status (approximately 85%). CONCLUSION: This study confirms that PSA nadir after HIFU ablation predicts biochemical recurrence-free survival and is a reliable marker that is easy to integrate into routine clinical practice.


Assuntos
Antígeno Prostático Específico/sangue , Neoplasias da Próstata/terapia , Ultrassom Focalizado Transretal de Alta Intensidade , Intervalo Livre de Doença , Seguimentos , Humanos , Masculino , Recidiva Local de Neoplasia , Neoplasias da Próstata/patologia , Resultado do Tratamento
6.
N Engl J Med ; 383(11): 1040-1049, 2020 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-32905676

RESUMO

BACKGROUND: Darolutamide is a structurally distinct androgen-receptor inhibitor that is approved for the treatment of nonmetastatic, castration-resistant prostate cancer. In the planned primary analysis of a phase 3 trial, the median metastasis-free survival was significantly longer with darolutamide (40.4 months) than with placebo (18.4 months). The data for the analysis of overall survival were immature at the time of the primary analysis. METHODS: In this double-blind, placebo-controlled trial, we randomly assigned 1509 men, in a 2:1 ratio, to receive darolutamide (955 patients) or placebo (554 patients) while they continued to receive androgen-deprivation therapy. After the results of the primary end-point analysis were found to be positive, unblinding of the treatment assignments occurred, and patients in the placebo group were permitted to cross over to receive open-label darolutamide treatment. At the time of this prespecified final analysis, which had been planned to be performed after approximately 240 deaths had occurred, overall survival and all other secondary end points were evaluated. RESULTS: The median follow-up time was 29.0 months. At the time of unblinding of the data, all 170 patients who were still receiving placebo crossed over to receive darolutamide; 137 patients who had discontinued placebo before unblinding had occurred received at least one other life-prolonging therapy. Overall survival at 3 years was 83% (95% confidence interval [CI], 80 to 86) in the darolutamide group and 77% (95% CI, 72 to 81) in the placebo group. The risk of death was significantly lower, by 31%, in the darolutamide group than in the placebo group (hazard ratio for death, 0.69; 95% CI, 0.53 to 0.88; P = 0.003). Darolutamide was also associated with a significant benefit with respect to all other secondary end points, including the time to first symptomatic skeletal event and the time to first use of cytotoxic chemotherapy. The incidence of adverse events after the start of treatment was similar in the two groups; no new safety signals were observed. CONCLUSIONS: Among men with nonmetastatic, castration-resistant prostate cancer, the percentage of patients who were alive at 3 years was significantly higher among those who received darolutamide than among those who received placebo. The incidence of adverse events was similar in the two groups. (Funded by Bayer HealthCare and Orion Pharma; ARAMIS ClinicalTrials.gov number, NCT02200614.).


Assuntos
Antagonistas de Receptores de Andrógenos/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Pirazóis/uso terapêutico , Idoso , Antagonistas de Receptores de Andrógenos/efeitos adversos , Estudos Cross-Over , Método Duplo-Cego , Fadiga/induzido quimicamente , Fraturas Ósseas/induzido quimicamente , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Antígeno Prostático Específico/sangue , Neoplasias de Próstata Resistentes à Castração/mortalidade , Neoplasias de Próstata Resistentes à Castração/patologia , Pirazóis/efeitos adversos
7.
Medicine (Baltimore) ; 99(39): e22336, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991446

RESUMO

Over the past decades, the incidence of prostate cancer in Taiwan kept rising. Many possible factors including the utility of prostate specific antigen tests, lifestyle remodeling, and patient's comorbidities may contribute to the increasing of incidence or prostate cancer. We aim to use the nationwide Health and Welfare Database (HWD) to investigate possible associated factors.We used HWD, a nationwide database of medical information, to assess the incidence of prostate cancer, utilization of prostate-specific antigen (PSA) test, and underlying diseases of patients and to evaluate whether there was a common trend among these factors.In total, 32,508 patients with newly diagnosed prostate cancer from 2006 to 2013 were identified. The incidence rate of prostate cancer per 100,000 men increased from 35.47 in 2006 to 52.87 in 2012. The number of patients with prostate cancer and underlying diseases related to metabolic syndrome increased every year. The number of total PSA tests and patients undergoing PSA testing, as well as average times of PSA testing per person in the whole population, increased every year. The average PSA test times of patients with newly diagnosed prostate cancer within 3 years before the diagnosis of prostate cancer also increased every year. There was a high correlation between the average PSA test times and the number of patients with newly diagnosed prostate cancer (r = 0.9734).The trends of incidence of prostate cancer, utilization of PSA testing, and underlying diseases related to metabolic syndrome at the diagnoses of cancer were similar, increasing every year in the study period. The results suggested that increasing use of PSA tests may increase the diagnosis of prostate cancers. Underlying diseases related to metabolic syndrome might also affect the incidence of prostate cancer.


Assuntos
Programas de Rastreamento/métodos , Síndrome Metabólica/epidemiologia , Antígeno Prostático Específico/normas , Neoplasias da Próstata/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade/tendências , Bases de Dados Factuais , Humanos , Incidência , Estilo de Vida , Masculino , Síndrome Metabólica/complicações , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Taiwan/epidemiologia
8.
Am J Clin Oncol ; 43(9): 628-635, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32889832

RESUMO

OBJECTIVES: Stereotactic body radiation treatment represents an intriguing therapeutic option for patients with early-stage prostate cancer. In this phase II study, stereotactic body radiation treatment was delivered by volumetric modulated arc therapy with flattening filter free beams and was gated using real-time electromagnetic transponder system to maximize precision of radiotherapy and, potentially, to reduce toxicities. MATERIALS AND METHODS: Patients affected by histologically proven prostate adenocarcinoma and National Comprehensive Cancer Network (NCCN) intermediate class of risk were enrolled in this phase II study. Beacon transponders were positioned transrectally within the prostate parenchyma 7 to 10 days before simulation computed tomography scan. The radiotherapy schedule was 38 Gy in 4 fractions delivered every other day. Toxicity assessment was performed according to Common Terminology Criteria for Adverse Events (CTCAE), v4.0. RESULTS: Thirty-six patients were enrolled in this study. Median initial prostate-specific antigen was 7.0 ng/mL (range: 2.3 to 14.0 ng/mL). Median nadir-prostate-specific antigen after treatment was 0.2 ng/mL (range: 0.006 to 4.8 ng/mL). A genitourinary acute toxicity was observed in 21 patients (dysuria grade [G] 1: 41.7%, G2: 16.7%). Gastrointestinal acute toxicity was found in 9 patients (proctitis G1: 19.4%, G2: 5.6%). Late toxicity was mild (genitourinary toxicity G1: 30.6%; G2: 8.3%; gastrointestinal toxicity G1: 13.9%; G2: 19.4%). At a median follow-up time of 41 months, 3 biochemical recurrences were observed (2 local recurrences, 1 distant metastasis). Three-year biochemical recurrence-free survival was 89.8% (International Society of Urologic Pathology Grade Group 2: 100%, Grade Group 3: 77.1%, P=0.042). CONCLUSION: Ultrahypofractionated radiotherapy, delivered with flattening filter free-volumetric modulated arc therapy and gated by electromagnetic transponders, is a valid option for intermediate-risk prostate cancer.


Assuntos
Adenocarcinoma/radioterapia , Recidiva Local de Neoplasia/sangue , Neoplasias da Próstata/radioterapia , Radiocirurgia/métodos , Radioterapia de Intensidade Modulada , Adenocarcinoma/secundário , Idoso , Diarreia/etiologia , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Disuria/etiologia , Fenômenos Eletromagnéticos , Humanos , Masculino , Pessoa de Meia-Idade , Noctúria/etiologia , Proctite/etiologia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/patologia , Lesões por Radiação/etiologia , Radiocirurgia/efeitos adversos , Radioterapia de Intensidade Modulada/efeitos adversos
9.
Gene ; 763: 145067, 2020 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-32827681

RESUMO

BACKGROUND: rs2274911 (Pro91Ser, G > A) is a missense mutation located on the second exon of the GPRC6A gene. Increasing evidence revealed a significant association between the A allele of rs2274911 and male diseases, such as oligospermia, cryptorchidism, and prostate tumor. However, the function of rs2274911 in healthy males is unclear. SUBJECTS AND METHODS: A total of 1742 healthy men were selected from the Fangchenggang Area Male Health and Examination Survey (FAMHES). The association between rs2274911 and phenotype was evaluated. The cell characteristics of rs2274911 mutation (mu), wild-type GPRC6A (WT), and RFP control in human embryonic kidney (293T) and human prostate cancer (PC3) cells were analyzed. RNA sequencing was performed on PC3 cells. RESULTS: E2 and PSA serum levels increased with the accumulation of the A allele (E2: G vs. A, -0.029 [-0.050, -0.008], P < 0.01, P trend = 0.027; PSA: G vs. A, -0.040 [-0.079, 0.000], P < 0.05, P trend = 0.048). rs2274911 enhanced the proliferation and invasion ability of PC3 or 293T cells and activated the ERK pathway. The genes were identified as rs2274911 mu-affected genes through RNA sequential analysis of rs2274911 mu, GPRC6A WT, and RFP control of PC3 cells. Most of these genes were related to cancer development processes, cAMP, and the ERK cell signaling pathway. CONCLUSION: This project represents that rs2274911 is associated with E2 and PSA serum levels in Southern Chinese men. Rs2274991 mutation promotes 293T and PC3 cell proliferation in vitro. These results suggest that rs2274911 is a functional variant of GPRC6A.


Assuntos
Antígeno 12E7/sangue , Polimorfismo de Nucleotídeo Único , Antígeno Prostático Específico/sangue , Receptores Acoplados a Proteínas-G/genética , Adulto , Proliferação de Células , Células HEK293 , Humanos , Sistema de Sinalização das MAP Quinases , Masculino , Pessoa de Meia-Idade , Células PC-3 , Receptores Acoplados a Proteínas-G/metabolismo
10.
Cochrane Database Syst Rev ; 8: CD013641, 2020 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-32813279

RESUMO

BACKGROUND: Robotic-assisted laparoscopic prostatectomy (RALP) is widely used to surgically treat clinically localized prostate cancer. It is typically performed using an approach (standard RALP) that mimics open retropubic prostatectomy by dissecting the so-called space of Retzius anterior to the bladder. An alternative, Retzius-sparing (or posterior approach) RALP (RS-RALP) has been described, which is reported to have better continence outcomes but may be associated with a higher risk of incomplete resection and positive surgical margins (PSM). OBJECTIVES: To assess the effects of RS-RALP compared to standard RALP for the treatment of clinically localized prostate cancer. SEARCH METHODS: We performed a comprehensive search of the Cochrane Library, MEDLINE, Embase, three other databases, trials registries, other sources of the grey literature, and conference proceedings, up to June 2020. We applied no restrictions on publication language or status. SELECTION CRITERIA: We included trials where participants were randomized to RS-RALP or standard RALP for clinically localized prostate cancer. DATA COLLECTION AND ANALYSIS: Two review authors independently classified and abstracted data from the included studies. Primary outcomes were: urinary continence recovery within one week after catheter removal, at three months after surgery, and serious adverse events. Secondary outcomes were: urinary continence recovery six and 12 months after surgery, potency recovery 12 months after surgery, positive surgical margins (PSM), biochemical recurrence-free survival (BCRFS), and urinary and sexual function quality of life. We performed statistical analyses using a random-effects model. We rated the certainty of evidence using the GRADE approach. MAIN RESULTS: Our search identified six records of five unique randomized controlled trials, of which two were published studies, one was in press, and two were abstract proceedings. There were 571 randomized participants, of whom 502 completed the trials. Mean age of participants was 64.6 years and mean prostate-specific antigen was 6.9 ng/mL. About 54.2% of participants had cT1c disease, 38.6% had cT2a-b disease, and 7.1 % had cT2c disease. Primary outcomes RS-RALP probably improves continence within one week after catheter removal (risk ratio (RR) 1.74, 95% confidence interval (CI) 1.41 to 2.14; I2 = 0%; studies = 4; participants = 410; moderate-certainty evidence). Assuming 335 per 1000 men undergoing standard RALP are continent at this time point, this corresponds to 248 more men per 1000 (137 more to 382 more) reporting continence recovery. RS-RALP may increase continence at three months after surgery compared to standard RALP (RR 1.33, 95% CI 1.06 to 1.68; I2 = 86%; studies = 5; participants = 526; low-certainty evidence). Assuming 750 per 1000 men undergoing standard RALP are continent at this time point, this corresponds to 224 more men per 1000 (41 more to 462 more) reporting continence recovery. We are very uncertain about the effects of RS-RALP on serious adverse events compared to standard RALP (RR 1.40, 95% CI 0.47 to 4.17; studies = 2; participants = 230; very low-certainty evidence). Secondary outcomes There is probably little to no difference in continence recovery at 12 months after surgery (RR 1.01, 95% CI 0.97 to 1.04; I2 = 0%; studies = 2; participants = 222; moderate-certainty evidence). Assuming 982 per 1000 men undergoing standard RALP are continent at this time point, this corresponds to 10 more men per 1000 (29 fewer to 39 more) reporting continence recovery.  We are very uncertain about the effect of RS-RALP on potency recovery 12 months after surgery (RR 0.98, 95% CI 0.54 to 1.80; studies = 1; participants = 55; very low-certainty evidence).  RS-RALP may increase PSMs (RR 1.95, 95% CI 1.19 to 3.20; I2 = 0%; studies = 3; participants = 308; low-certainty evidence) indicating a higher risk for prostate cancer recurrence. Assuming 129 per 1000 men undergoing standard RALP have positive margins, this corresponds to 123 more men per 1000 (25 more to 284 more) with PSMs. We are very uncertain about the effect of RS-RALP on BCRFS compared to standard RALP (hazard ratio (HR) 0.45, 95% CI 0.13 to 1.60; I2 = 32%; studies = 2; participants = 218; very low-certainty evidence). AUTHORS' CONCLUSIONS: Findings of this review indicate that RS-RALP may result in better continence outcomes than standard RALP up to six months after surgery. Continence outcomes at 12 months may be similar. Downsides of RS-RALP may be higher positive margin rates. We are very uncertain about the effect on BCRFS and potency outcomes. Longer-term oncologic and functional outcomes are lacking, and no preplanned subgroup analyses could be performed to explore the observed heterogeneity. Surgeons should discuss these trade-offs and the limitations of the evidence with their patients when considering this approach.


Assuntos
Tratamentos com Preservação do Órgão/métodos , Complicações Pós-Operatórias/prevenção & controle , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Incontinência Urinária/prevenção & controle , Idoso , Humanos , Calicreínas/sangue , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Tratamentos com Preservação do Órgão/efeitos adversos , Ereção Peniana , Complicações Pós-Operatórias/epidemiologia , Antígeno Prostático Específico/sangue , Prostatectomia/efeitos adversos , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Incontinência Urinária/epidemiologia
11.
PLoS One ; 15(8): e0236553, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32756597

RESUMO

OBJECTIVES: The importance of clinical outcome prediction models using artificial intelligence (AI) is being emphasized owing to the increasing necessity of developing a clinical decision support system (CDSS) employing AI. Therefore, in this study, we proposed a "Dr. Answer" AI software based on the clinical outcome prediction model for prostate cancer treated with radical prostatectomy. METHODS: The Dr. Answer AI was developed based on a clinical outcome prediction model, with a user-friendly interface. We used 7,128 clinical data of prostate cancer treated with radical prostatectomy from three hospitals. An outcome prediction model was developed to calculate the probability of occurrence of 1) tumor, node, and metastasis (TNM) staging, 2) extracapsular extension, 3) seminal vesicle invasion, and 4) lymph node metastasis. Random forest and k-nearest neighbors algorithms were used, and the proposed system was compared with previous algorithms. RESULTS: Random forest exhibited good performance for TNM staging (recall value: 76.98%), while k-nearest neighbors exhibited good performance for extracapsular extension, seminal vesicle invasion, and lymph node metastasis (80.24%, 98.67%, and 95.45%, respectively). The Dr. Answer AI software consisted of three primary service structures: 1) patient information, 2) clinical outcome prediction, and outcomes according to the National Comprehensive Cancer Network guideline. CONCLUSION: The proposed clinical outcome prediction model could function as an effective CDSS, supporting the decisions of the physicians, while enabling the patients to understand their treatment outcomes. The Dr. Answer AI software for prostate cancer helps the doctors to explain the treatment outcomes to the patients, allowing the patients to be more confident about their treatment plans.


Assuntos
Inteligência Artificial , Sistemas de Apoio a Decisões Clínicas , Prognóstico , Neoplasias da Próstata/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Probabilidade , Próstata/patologia , Próstata/cirurgia , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/fisiopatologia , Neoplasias da Próstata/terapia , Glândulas Seminais/patologia , Glândulas Seminais/cirurgia , Resultado do Tratamento
12.
PLoS One ; 15(8): e0236879, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790676

RESUMO

Benign prostatic hyperplasia (BPH) is a progressive pathological condition associated with proliferation of prostatic tissues, prostate enlargement, and lower-urinary tract symptoms. However, the mechanism underlying the pathogenesis of BPH is unclear. The aim of this study was to investigate the protective effects of a combination of Stauntonia hexaphylla and Cornus officinalis (SC extract) on a testosterone propionate (TP)-induced BPH model. The effect of SC extract was examined in a TP-induced human prostate adenocarcinoma cell line. Male Sprague-Dawley rats were randomly divided into 5 groups (n = 6) for in vivo experiments. To induce BPH, all rats, except those in the control group, were administered daily with subcutaneous injections of TP (5 mg/kg) and orally treated with appropriate phosphate buffered saline/drugs (finasteride/saw palmetto/SC extract) for 4 consecutive weeks. SC extract significantly downregulated the androgen receptor (AR), prostate specific antigen (PSA), and 5α-reductase type 2 in TP-induced BPH in vitro. In in vivo experiments, SC extract significantly reduced prostate weight, size, serum testosterone, and dihydrotestosterone (DHT) levels. Histologically, SC extract markedly recovered TP-induced abnormalities and reduced prostatic hyperplasia, thereby improving the histo-architecture of TP-induced BPH rats. SC extract also significantly downregulated AR and PSA expression, as assayed using immunoblotting. Immunostaining revealed that SC extract markedly reduced the 5α-reductase type 2 and significantly downregulated the expression of proliferating cell nuclear antigen. In addition, immunoblotting of B-cell lymphoma 2 (Bcl-2) family proteins indicated that SC extract significantly downregulated anti-apoptotic Bcl-2 and markedly upregulated pro-apoptotic B cell lymphoma-associated X (Bax) expression. Furthermore, SC treatment significantly decreased the Bcl-2/Bax ratio, indicating induced prostate cell apoptosis in TP-induced BPH rats. Thus, our findings demonstrated that SC extract protects against BPH by inhibiting 5α-reductase type 2 and inducing prostate cell apoptosis. Therefore, SC extract might be useful in the clinical treatment of BPH.


Assuntos
Apoptose/efeitos dos fármacos , Colestenona 5 alfa-Redutase/química , Extratos Vegetais/farmacologia , Hiperplasia Prostática/prevenção & controle , Substâncias Protetoras/uso terapêutico , Inibidores de 5-alfa Redutase/química , Inibidores de 5-alfa Redutase/farmacologia , Inibidores de 5-alfa Redutase/uso terapêutico , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Colestenona 5 alfa-Redutase/metabolismo , Cornus/química , Cornus/metabolismo , Regulação para Baixo/efeitos dos fármacos , Humanos , Masculino , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Folhas de Planta/química , Folhas de Planta/metabolismo , Antígeno Prostático Específico/sangue , Hiperplasia Prostática/etiologia , Substâncias Protetoras/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ranunculales/química , Ranunculales/metabolismo , Ratos , Ratos Sprague-Dawley , Propionato de Testosterona/efeitos adversos
13.
Gene ; 758: 144963, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-32683077

RESUMO

Abnormal expression of enzymes involved in epigenetic mechanisms, such as DNA methyl transferases, can trigger large chaos in cellular gene expression networks and eventually lead to cancer progression. In our study, which is a pioneer in the literature that clinicopathologically evaluates the expression of 30 epi-miRNAs in prostate cancer (PCa), we investigated which of the new miRNA class epi-miRNAs could be an effective biomarker in the diagnosis and progression of PCa. In this study, the expression levels of 30 epi-miRNAs in whole blood samples from 25 control, 25 PCa and 40 metastatic PCa patients were investigated by the Quantitative Real-Time PCR method. Then, promoter methylation levels of 11 epi-miRNAs, whose expression levels were found to be significantly higher, were examined by methylation-specific qPCR method. The correlations between miRNA expression levels and clinicopathological parameters (Gleason Score (GS), PSA levels, TNM Staging) in different stages of PCa groups as well as disease-specific expression levels were examined. We found a hypomethylation in the promoter regions of miRNAs that showed a direct proportional increase with PSA levels (miR-34b/c, miR-148a, miR-152), GS's (miR-34a-5p, miR-34b/c, miR-101-2, miR-126, miR-148a, miR- 152, miR-185-5p) and T staging (miR-34a-5p, miR-34b/c, miR-101-2, miR-126, miR-140, miR-148a, miR-152, miR-185-5p) (p < 0.05). When miR-200a/b was evaluated according to clinicopathological parameters, it acted as an onco-miR in local/local advanced PCa and as a tumor-suppressor-miR in metastatic stage. This study is novel in the sense that our findings draw attention to the important role of miRNAs as diagnostic and prognostic biomarkers in PCa.


Assuntos
Metilação de DNA/genética , Regulação Neoplásica da Expressão Gênica/genética , MicroRNAs/genética , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Biomarcadores Tumorais/genética , Epigênese Genética/genética , Humanos , Masculino , Gradação de Tumores , Prognóstico , Regiões Promotoras Genéticas/genética , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/patologia
14.
Br J Radiol ; 93(1114): 20200484, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32706988

RESUMO

With increasing evidence to support prostate artery embolization (PAE) in the treatment of benign prostatic hyperplasia (BPH)-induced lower urinary tract symptoms (LUTS), Interventional Radiologists have begun to play an important role in the management of these patients. One area of knowledge needed when developing a PAE practice is knowledge of prostate-specific antigen (PSA) and other biomarkers utilized to detect prostate cancer in this population and what role they should play in the work up and follow-up of patients presenting with presumed BPH-induced LUTS. Furthermore, understanding how to evaluate presumed BPH-induced LUTS and stratify the risk of prostate cancer is an important skill to develop. The goal of this review is to provide Interventional Radiologists who have begun or aim to begin a PAE practice with the information they need to know regarding PSA levels and prostate cancer risk stratification for this patient population.


Assuntos
Biomarcadores Tumorais/sangue , Sintomas do Trato Urinário Inferior/terapia , Hiperplasia Prostática/terapia , Radiografia Intervencionista , Humanos , Masculino , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico por imagem
15.
AJR Am J Roentgenol ; 215(2): 267-276, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32551903

RESUMO

OBJECTIVE. The purpose of this article is to review the utility of 18F-fluciclovine PET/CT in the evaluation of recurrent prostate cancer. CONCLUSION. Fluorine-18-labeled fluciclovine PET/CT has shown promise in the evaluation of recurrent prostate cancer. Its performance has been superior to that of other imaging modalities. It has had good diagnostic accuracy, especially in the detection of extra-prostatic disease recurrence, and the findings have an impact on treatment planning. Gallium-68-labeled prostate-specific membrane antigen PET/CT has also had excellent performance in the detection of biochemically recurrent prostate cancer with detection rates superior to those of fluciclovine PET/CT.


Assuntos
Ácidos Carboxílicos , Ciclobutanos , Recidiva Local de Neoplasia/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Neoplasias da Próstata/diagnóstico por imagem , Humanos , Masculino , Recidiva Local de Neoplasia/sangue , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue
17.
PLoS One ; 15(6): e0234391, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32525914

RESUMO

BACKGROUND: Pathological and clinical stage are associated with prostate cancer-specific survival after prostatectomy. With PSA screening, the post-surgery prognostic utility of clinical stage is debatable in studies seeking to identify new biomarkers. Few studies have investigated clinical stage and lethal prostate cancer association after accounting for pathological stage. We hypothesize that clinical stage provides prognostic information beyond pathological stage in the PSA era. METHODS: Cox regression models tested associations between clinical and pathological stage and lethal prostate cancer among 3,064 participants from the Health Professionals Follow-Up Study and Physicians' Health Study (HPFS/PHS) who underwent prostatectomy. Likelihood ratio tests and c-statistics were used to assess the models' prognostic utility. Equivalent analyses were performed in 16,134 men who underwent prostatectomy at Johns Hopkins. RESULTS: Independently, clinical and pathological stage were associated (p<0.0001 for both) with rate of lethal prostate cancer in HPFS/PHS. The model with clinical and pathological stage fit significantly better than the model with only pathological stage in all men (p = 0.01) and in men diagnosed during the PSA era (p = 0.04). The mutually adjusted model also improved discriminatory ability. In the Johns Hopkins cohort, the model with clinical and pathological stage improved discriminatory ability and fit significantly better overall (p<0.0001) and in the PSA era (p<0.0001). CONCLUSIONS: Despite stage migration resulting from widespread PSA screening, clinical stage remains associated with progression to lethal prostate cancer independent of pathological stage. Future studies evaluating associations between new factors and poor outcome following prostatectomy should consider including both clinical and pathological stages since the data is already available.


Assuntos
Calicreínas/sangue , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/patologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Prostatectomia , Neoplasias da Próstata/cirurgia , Estados Unidos
18.
West Afr J Med ; 37(3): 248-252, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32476118

RESUMO

OBJECTIVE: Within a multicentre prospective study of prostate cancer genetics, we analysed some parameters of cases seen in our centre over a 2-year period to see if there are any changes in histological grades and age compared to previous studies in this environment. METHODS: Histological grading and scoring had been done using the revised International Society of urologic pathology (ISUP) system and cases were classified into Grade groups. Gleason grades less than 3 were not assigned and Scores less than 6 not assigned. The Prostatic Specific Antigen (PSA) levels as well as the average tumour percentage in the biopsy specimens were determined. RESULTS: A hundred and forty-five (145) patients were seen. The majority of patients seen were in Grade group 5 (30.3%), followed by grade group 4 (26.2%) and then groups 1, 3 and 2 in that order. Patients' ages ranged from 47 years to 86 years, with peak age incidence in the 7th decade. PSA values ranged from 3.6 to 22,130ng/ml and tumour volumes ranged from 5% of biopsy tissue to 95%. The lowest PSA value was seen in a patient in grade group 1 but the highest PSA value was recorded in a patient in Grade group 3. The lowest and highest tumour volumes were seen in patients in grade group 4. The PSA and tumour volumes did not vary in linear fashion with Gleason grade. CONCLUSION: The results show that the majority of patients in Ibadan present with high grade prostatic carcinoma even using the new ISUP grading system but the proportion of highgrade tumours seems higher than in the previous study, likely because more diagnostic tissue has become available per case. Examining a minimum of 12 cores have definitely created an opportunity for proper grading. Peak incidence is in the 7th decade followed by the 8th decade. Very high PSA values recorded in our patients with prostatic carcinoma do not show linear relationship with prostatic carcinoma volume or grade.


Assuntos
Carcinoma/patologia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/patologia , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Carcinoma/epidemiologia , Hospitais de Ensino , Hospitais Universitários , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Nigéria/epidemiologia , Estudos Prospectivos , Neoplasias da Próstata/epidemiologia
19.
Prostate ; 80(11): 824-830, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32433780

RESUMO

BACKGROUND: Studies of prostate-specific antigen (PSA)-based population screening have been conducted in western countries, but there is little data in Asian populations. The objective of this study was to determine the efficacy of PSA screening in Asian men using real-world data over a period of 15 years after introducing population screening in Yokosuka City, Japan. METHODS: We investigated patients with pathologically diagnosed prostate cancer at four hospitals and two clinics across the Yokosuka area (Miura peninsula) between April 2001 and March 2015. Patients were divided into two groups; the S group consisted of those diagnosed by PSA-based population screening in Yokosuka City and the NS group consisted of those diagnosed by methods other than screening. Cancer-specific survival (CSS) and overall survival (OS) rates were calculated using the Kaplan-Meier method with the log-rank test to compare survival between the two groups. Clinical and pathological factors for cancer-specific mortality were assessed with Cox regression analyses to calculate the hazard ratio (HR) and 95% confidence interval (CI). RESULTS: A total of 3094 patients had been diagnosed with prostate cancer over the 15-year period. The median follow-up period was 77 months. The S group and the NS group consisted of 977 and 2117 patients, respectively. Patients in the S group were younger (age: 71 years vs 73 years, P < .001) and had a lower Charlson comorbidity index (CCI) with favorable oncological factors, such as lower initial PSA, Gleason score (GS), and risk category. Kaplan-Meier curves for OS and CSS revealed significant differences between the two groups (OS: P < .001, CSS: P < .001). Analysis with Cox proportional hazards model indicated the NS group (HR: 1.584, 95% CI, 1.065-2.356, P = .023), a CCI > 4 (HR: 1.552, 95% CI, 1.136-2.120, P = .006), a GS ≥ 8 (HR: 4.869, 95% CI, 2.631-9.001, P < .001), and nonlocalized cancer (locally advanced; HR: 2.632, 95% CI, 1.676-4.133, P < .001, advanced; HR: 9.468, 95% CI, 6.279-14.278, P < .001) as independent risk factors for cancer-specific mortality. CONCLUSIONS: PSA-based population screening of prostate cancer might be useful in the Japanese population.


Assuntos
Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Detecção Precoce de Câncer , Humanos , Japão/epidemiologia , Calicreínas/sangue , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue
20.
Nucleic Acids Res ; 48(13): e73, 2020 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-32469060

RESUMO

Digital PCR provides high sensitivity and unprecedented accuracy in DNA quantification, but current approaches require dedicated instrumentation and have limited opportunities for multiplexing. Here, we present an isothermal platform for digital enumeration of DNA reaction products in multiplex via standard fluorescence microscopy. Circular DNA strands, which may result from a wide range of molecular detection reactions, are captured on streptavidin-coated surfaces via hybridized biotinylated primers, followed by rolling circle amplification (RCA). The addition of 15% polyethylene glycol 4000 during RCA resulted in uniform, easily recorded reaction products. Immobilized DNA circles were visualized as RCA products with 100% efficiency, as determined by droplet digital PCR. We confirmed previous reports about the influence on RCA by sequence composition and size of RCA templates, and we developed an efficient one-step restaining procedure for sequential multiplexing using toehold-triggered DNA strand displacement. Finally, we exemplify applications of this digital readout platform by demonstrating more than three orders of magnitude improved sensitivity by digital measurement of prostate specific antigen (PSA) (detection threshold ∼100 pg/l), compared to a commercial enzyme-linked immunosorbent assay (ELISA) with analogue readout (detection threshold ∼500 ng/l), using the same antibody pair.


Assuntos
DNA Circular/análise , Ensaio de Imunoadsorção Enzimática/métodos , Calicreínas/sangue , Técnicas de Amplificação de Ácido Nucleico/métodos , Antígeno Prostático Específico/sangue , Feminino , Humanos , Masculino , Hibridização de Ácido Nucleico/métodos , Estreptavidina/química
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