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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.
Zhonghua Yi Xue Za Zhi ; 100(34): 2658-2662, 2020 Sep 15.
Artigo em Chinês | MEDLINE | ID: mdl-32921013

RESUMO

Objective: To investigate the feasibility and safety of minimally invasive radical prostatectomy for prostate cancer patients without preoperative prostate biopsy in the new era of the continuous development of comprehensive new imaging diagnostic mode and minimally invasive surgery technology. Methods: From August 2018 to October 2019, 17 patients with prostate cancer were enrolled in this study in the Cancer Hospital, Chinese Academy of Medical Sciences. All patients were highly suspected of prostate cancer by PSMA-PET/CT-based imaging diagnostic techniques and underwent 3D laparoscopic radical prostatectomy without prostate biopsy. The perioperative data, postoperative pathology, postoperative complications and follow-up results were recorded and analyzed. Results: The average age of 17 patients with prostate cancer was (65±7) years. The body mass index (BMI) average was (24.4±3.0) kg/m(2). The American Society of Anesthesiologists (ASA) score was 1 (1-2) and the Charlson comorbidity index (CCI) score was 1 (0-4). The preoperative value of PSA was (19±11) µg/L. The PSMA PET/CT showed abnormally high expression foci and the great possibility of prostate cancer for all the 17 patients. Prostate puncture biopsy: the results of prostate biopsy were negative in 3 cases. The digital rectal examination found that the prostate volume was Ⅰ or Ⅱ degree large, 10 cases touched hard and the nodule was touched in two cases. Three patients had undergone a previous prostate biopsy, but prostate cancer was not found. All the 17 operations were successfully performed without conversion to open surgery. The surgery time was (85±21) (range from 45 to 120) min, the estimated blood loss was (25±18) (range from5 to 100) ml, the time of intake of liquid diet was (14.3±4.4) h, the intestinal recovery time was (23±10) h, the postoperative activity time was (22±7) h, the drainage duration was (3.7±0.8) d, the postoperative hospital stay was (4.9±1.2) days, and the catheter removal time was (7.4±1.5) days. In the early postoperative period (within 30 days after surgery), no obvious complications occurred. The postoperative final pathology confirmed that all the 17 specimens were prostate cancer. After a median follow-up of 6.5 months, the patient's urinary control rate reached 81.3% at postoperative 1 month, 92.3% at postoperative 3 months after surgery, and the urinary control rate reached 100% at postoperative 6 months. Postoperative PSA value was (0.08±0.08) µg/L, significantly lower than preoperative PSA level (P<0.001). There was significant difference between the preoperative and postoperative QOL (Quality of life) score (57±5 and 47±5 respectively, P<0.001) which indicated that the patients' postoperative quality of life was greatly improved. Conclusions: It is safe and feasible to perform minimally invasive radical prostatectomy without preoperative prostate biopsy for patients with highly suspected prostate cancer by comprehensive diagnostic mode based on modern new imaging technology.


Assuntos
Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Qualidade de Vida , Idoso , Biópsia , Humanos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico , Prostatectomia
7.
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
8.
Arch Esp Urol ; 73(7): 593-599, 2020 Sep.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32886074

RESUMO

OBJECTIVE: Perform a detailed anatomopathological analysis of consecutive surgical specimens in men with clinically very low risk prostate cancer according to National Comprehensive Cancer Network (NCCN) criteria.MATERIALS AND METHODS: The study included 799 prostate cancer patients who under went radical prostatectomy between January 2005 and December 2013. We identified 81 consecutive patients with clinically very low risk prostate cancer. The slides of the patients who fulfilled the inclusion criteria were re-reviewed. The parameters studied were: pathological stage, histological grade by Gleason score (GSS), margins involvement, tumor percentage (PT), and number of apparently independent tumor foci (FT). RESULTS: The patients had organ-confined tumors in almost all of them (pT2: 97.5%). Most of the cancers studied were bilateral (pT2c: 67.9%), multifocal (FT≥2:88.8%), with a low tumor percentage (PTand with a low Gleason Score (GSS≤6: 91,3%). Non-confined disease: 2.5%, all cases extra-prostatic extension (pT3a). GSS>6: 8,6%, all cases GSS7 (3+4). CONCLUSIONS: The NCCN criteria for very low risk prostate cancer help to make a good selection of non-aggressive tumors and are a useful tool for including patients in an active surveillance program.


Assuntos
Neoplasias da Próstata , Humanos , Masculino , Gradação de Tumores , Estadiamento de Neoplasias , Antígeno Prostático Específico , Prostatectomia
9.
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
10.
Medicine (Baltimore) ; 99(36): e20755, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32898989

RESUMO

Ga-PSMA-11 positron emission computed tomography /computed tomography (PET/CT) is more sensitive than magnetic resonance imaging (MRI) in detecting prostate cancer (PCa). We evaluated the value of Ga-PSMA-11 PET/CT with MRI in treatment-naive PCa.This retrospective study was approved by the hospital ethics committee. The MRI and Ga-PSMA-11 PET/CT imaging data of 63 cases of highly suspected PCa were enrolled in this study. The SUVmax and apparent diffusion coefficient (ADC), and their ratio, were assessed as diagnostic markers to distinguish PCa from benign disease.There were 107 prostate lesions detected in 63 cases. Forty cases with 64 malignant primary lesions were confirmed PCa, whereas 23 cases had 43 benign lesions. PSMA-avid lesions correlated with hypointense signal on ADC maps and hyperintense signal on diffusion-weighted imaging. The ADC of PCa was lower than that of benign lesions, and SUVmax and SUVmax/ADC of PCa was higher than that of benign lesions (P < .01). ADC had significant negative correlation with Gleason score (GS) and SUVmax, SUVmax, and SUVmax/ADC positively correlated with GS. From ROC analysis, we established cutoff values of ADC, SUVmax, and SUVmax/ADC at 1.02 × 10mm/s, 11.72, and 12.35, respectively, to differentiate PCa from benign lesions. The sensitivity, specificity, and AUC were 90.6%, 58.1%, and 0.816 for ADC, 67.2%, 97.7%, and 0.905 for SUVmax, and 81.2%, 88.4%, and 0.929 for SUVmax/ADC, respectively.Ga-PSMA-11 PET/CT combined with MRI offers higher diagnostic efficacy in the detection of PCa than either modality alone.


Assuntos
Espectroscopia de Ressonância Magnética/métodos , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Antígeno Prostático Específico/análise , Neoplasias da Próstata/patologia , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/diagnóstico por imagem , Estudos Retrospectivos
13.
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
14.
Yonsei Med J ; 61(8): 652-659, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32734728

RESUMO

PURPOSE: The benefits of early administration of androgen-deprivation therapy (ADT) in patients with prostate-specific antigen (PSA)-only recurrent prostate cancer (PCa) following radical prostatectomy (RP) are controversial. We investigated the impact of early versus delayed ADT on survival outcomes in patients with non-metastatic, localized or locally advanced PCa who received radiation therapy (RT) following RP and later developed distant metastasis. MATERIALS AND METHODS: A retrospective analysis was performed on 69 patients with non-metastatic, localized or locally advanced PCa who received RT following RP and later developed distant metastasis between January 2006 and December 2012. Patients were stratified according to the level of PSA at which ADT was administered (<2 ng/mL vs. ≥2 ng/mL). Study endpoints were progression to castration-resistant prostate cancer (CRPC)-free survival and cancer-specific survival (CSS). RESULTS: Patients were stratified according to the criteria of 2 ng/mL of PSA at which ADT was administered, based on the Youden sensitivity analysis. Delayed ADT at PSA ≥2 ng/mL was an independent prognosticator of cancer-specific mortality (p=0.047), and a marginally significant prognosticator of progression to CRPC (p=0.051). During the median follow-up of 81.0 (interquartile range 54.2-115.7) months, patients who received early ADT at PSA <2 ng/mL had significantly higher CSS rates compared to patients who received delayed ADT at PSA ≥2 ng/mL (p=0.002). Progression to CRPC-free survival was comparable between the two groups (p=0.331). CONCLUSION: Early ADT at the PSA level of less than 2 ng/mL confers CSS benefits in patients with localized or locally advanced PCa who were previously treated with RP.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Antígeno Prostático Específico/metabolismo , Prostatectomia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/cirurgia , Idoso , Progressão da Doença , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias da Próstata/patologia , Neoplasias da Próstata/radioterapia , Radioterapia Adjuvante , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
15.
Beijing Da Xue Xue Bao Yi Xue Ban ; 52(4): 625-631, 2020 Aug 18.
Artigo em Chinês | MEDLINE | ID: mdl-32773790

RESUMO

OBJECTIVE: To analyze the clinicopathological characteristics of prostate cancer patients undertaking radical prostatectomy with single positive core biopsy, and to optimize the rational choice of therapeutic strategy. METHODS: In the study, 53 patients with single positive core prostate biopsy and treated by radical prostatectomy from January 2010 to December 2018, were analyzed retrospectively. The mean age was (69.7±6.9) years (54-81 years), the mean prostate specific antigen (PSA) level was (9.70±5.24) µg/L (1.69-25.69 µg/L), and the mean prostate volume was (50.70±28.39) mL (12.41-171.92 mL). Thirty-nine out of 54 (73.6%) patients presented Gleason score with 6, 11 patients (20.8%) had Gleason score of 7 and 3 patients (5.7%) showed Gleason score ≥8. For clinical stages, 6 out of the 53 patients (11.3%) had prostate cancer in cT1, 44 cases (83.0%) had prostate cancer in cT2, and 3 cases (5.7%) in cT3.The patients were divided into subgroups according to age, preoperative PSA level, Gleason score, percentage of tumor in single needle tissue and clinical stage, and the differences of their clinicopathological characteristics were compared. RESULTS: Postoperative Gleason score of 6, 7 and ≥8 were found in 20 cases (37.7%), 21 cases (39.6%) and 10 cases (18.9%) respectively, another 2 cases (3.8%) were pT0 prostate cancer; pathological stages of T0, T2a, T2b, T2c and T3 were found in 2 cases (3.8%), 9 cases (17.0%), 2 cases (3.8%), 29 cases (54.7%) and 11 cases (20.8%) respectively; 11 cases (20.8%) had positive surgical margin, 10 cases (18.9%) had extracapsular invasion of prostate, and 1 case (1.9%) showed seminal vesicle invasion. Forty-two cases (79.2%) had multifocal lesions and 37 cases (69.8%) presented bilateral lesion. Compared with the biopsy Gleason score, the postoperative Gleason score was downgrated in 3 cases (5.7%), unchanged in 28 cases (52.8%), and upgraded in 20 cases (37.7%), of which 2 cases (3.8%) were pT0. Compared with the clinical stage, the postoperative pathological stage decreased in 2 cases (3.8%), unchanged in 10 cases (18.9%), and upgraded in 41 cases (77.4%). According to the postoperative pathology, the patients were divided into two groups: microfocus cancer group (n=8) and non-microfocus cancer group (n=45). The difference between the two groups in the percentage of tumor in the single-needle tissue ≤5% was statistically significant (P=0.014). Other parameter diffe-rences including age, prostate volume, and preoperative prostate special antigen density (PSAD) and Gleason scores were not statistically significant (P>0.05). The method to determine the location of cancer at the apex of prostate according to biopsy results showed 41.4% (12/29) false negative rate and 50.0% (12/24) false positive rate. There was statistically significant difference between the actual cases of lymph node dissection and reserved nerve and the cases of scheme selection in theory according to the postoperative pathology (P < 0.05). CONCLUSION: The proportion of single needle cancer tissue less than or equal to 5% is a predictor of prostate microfocal cancer. 37.7% cases had pathological upgrading and 77.4% cases had pathological staging upgrading. When choosing the operation scheme, such as sexual nerve reserved, lymph node dissection and apex operation skill, it is necessary to comprehensively analyze multiple factors, such as tumor risk classification, prediction factors of nomogram, multi-parameter MRI and intraoperative situation and so on.


Assuntos
Neoplasias da Próstata , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Antígeno Prostático Específico , Prostatectomia , Estudos Retrospectivos
16.
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
17.
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
19.
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
20.
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
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