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1.
Clin Genitourin Cancer ; 22(2): 610-617.e1, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38402089

RESUMO

OBJECTIVE: To describe the impact of a multidisciplinary tumor board (MTB) for renal cell carcinoma (RCC) patients in a locoregional renal cancer network by evaluating shared decision making (SDM) and adherence to MTB recommendations. DESIGN, SETTING AND PARTICIPANTS: This prospective cohort study included all cases from a Dutch renal cancer network with suspicion of or histologically confirmed RCC discussed in MTBs between 2017-2022. Main endpoints were distribution of cases presented, proportion of recommendations with multiple treatment options enabling shared decision making (SDM), definite treatment after SDM and adherence to MTB recommendations. Further endpoints were definite treatment per tumor stage stratified by age and inclusion in clinical trials. Outcomes were displayed as means and proportions (%). Pearson's Chi-Squared test was used to analyze the effect of age on definite treatment advice. RESULTS: Overall, 2651 cases were discussed, of which 1900 (72%) were new referrals and 751 (28%) rediscussions. Majority of cases were cT1a-b tumors (46%) and 22% were local recurrences or metachronous metastatic. Adherence to MTB recommendation was 96% and in 30% multiple treatment options were recommended, allowing for SDM. In 45% of cases with cT1a tumors multiple treatment options were recommended by the MTB, resulting in (cryo)ablation (32%) and AS (30%) as most frequent definite treatments after SDM. Among patients with cT3-4 tumors the inclusion rate in clinical trials was 47%. CONCLUSIONS: A network MTB creates opportunity to discuss multiple treatment options and clinical trials in SDM with patients at a high rate of adherence to MTB recommendation.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/terapia , Estudos Prospectivos , Tomada de Decisão Compartilhada , Neoplasias Renais/terapia , Tomada de Decisões
2.
Cancers (Basel) ; 15(11)2023 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-37296924

RESUMO

There is currently no consensus on the optimal treatment for patients with a primary diagnosis of clinically and pathologically node-positive (cN1M0 and pN1M0) hormone-sensitive prostate cancer (PCa). The treatment paradigm has shifted as research has shown that these patients could benefit from intensified treatment and are potentially curable. This scoping review provides an overview of available treatments for men with primary-diagnosed cN1M0 and pN1M0 PCa. A search was conducted on Medline for studies published between 2002 and 2022 that reported on treatment and outcomes among patients with cN1M0 and pN1M0 PCa. In total, twenty-seven eligible articles were included in this analysis: six randomised controlled trials, one systematic review, and twenty retrospective/observational studies. For cN1M0 PCa patients, the best-established treatment option is a combination of androgen deprivation therapy (ADT) and external beam radiotherapy (EBRT) applied to both the prostate and lymph nodes. Based on most recent studies, treatment intensification can be beneficial, but more randomised studies are needed. For pN1M0 PCa patients, adjuvant or early salvage treatments based on risk stratification determined by factors such as Gleason score, tumour stage, number of positive lymph nodes, and surgical margins appear to be the best-established treatment options. These treatments include close monitoring and adjuvant treatment with ADT and/or EBRT.

3.
Eur Urol Open Sci ; 28: 52-61, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34337526

RESUMO

BACKGROUND: Androgen deprivation therapy (ADT) for prostate cancer with luteinizing hormone-releasing hormone (LHRH) agonists can be improved. OBJECTIVE: To assess safety, the frequency and severity of hot flushes (HFs), bone health, and antitumor effects of high-dose estetrol (HDE4) when combined with ADT. DESIGN SETTING AND PARTICIPANTS: A phase II, double-blind, randomized, placebo-controlled study was conducted in advanced prostate cancer patients requiring ADT (the PCombi study). INTERVENTION: Patients receiving LHRH agonist treatment were randomized 2:1 to 40 mg HDE4 (n = 41) or placebo (n = 21) cotreatment for 24 wk. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Coprimary endpoints were frequency/severity of HFs and levels of total and free testosterone (T). Secondary endpoints included assessments of bone metabolism (osteocalcin and type I collagen telopeptide [CTX1]), prostate-specific antigen (PSA), and follicle-stimulating hormone (FSH). Efficacy analysis was based on the selected per-protocol (PP) population. RESULTS AND LIMITATIONS: Of 62 patients included in the study, 57 were suitable for a PP analysis (37 HDE4; 20 placebo). No E4-related serious cardiovascular adverse events occurred at 24 wk. Weekly HFs were reported by 13.5% of patients with HDE4 and 60.0% with placebo (p < 0.001). Daily HFs occurred in 5.9% versus 55%. Bone turnover parameters decreased significantly with HDE4 (p < 0.0001). Total and free T decreased earlier (p < 0.05), and free T was suppressed further (p < 0.05). PSA suppression was more profound and earlier (p < 0.005). FSH levels were suppressed by 98% versus 57% (p < 0.0001). Estrogenic side effects were nipple sensitivity (34%) and gynecomastia (17%). CONCLUSIONS: HDE4 cotreatment of ADT patients with advanced prostate cancer was well tolerated, and no treatment-related cardiovascular adverse events were observed at 24 wk. HFs and bone turnover were substantially reduced. Suppression of free T, PSA, and FSH was more rapid and profound, suggesting enhanced disease control by HDE4 cotreatment. Larger and longer-lasting studies are needed to confirm the results of the study reported here. PATIENT SUMMARY: Cotreatment of androgen deprivation therapy with high-dose estetrol in advanced prostate cancer patients results in fewer occurrences of hot flushes, bone protection, and other antitumor benefits. Nipple sensitivity and gynecomastia may occur as side effects.

4.
J Palliat Med ; 24(12): 1789-1797, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34415798

RESUMO

Background: Intensive end-of-life care (i.e., the overuse of treatments and hospital resources in the last months of life), is undesirable since it has a minimal clinical benefit with a substantial financial burden. The aim was to investigate the care in the last three months of life (end-of-life [EOL]) in castration-resistant prostate cancer (CRPC). Methods: Castration-resistant prostate cancer registry (CAPRI) is an investigator-initiated, observational multicenter cohort study in 20 hospitals retrospectively including patients diagnosed with CRPC between 2010 and 2016. High-intensity care was defined as the initiation of life-prolonging drugs (LPDs) in the last month, continuation of LPD in last 14 days, >1 admission, admission duration ≥14 days, and/or intensive care admission in last three months of life. Descriptive and binary logistic regression analyses were performed. Results: High-intensity care was experienced by 41% of 2429 patients in the EOL period. Multivariable analysis showed that age (odds ratio [OR] 0.98, 95% confidence interval [CI] 0.97-0.99), performance status (OR 0.57, 95% CI 0.33-0.97), time from CRPC to EOL (OR 0.98, 95% CI 0.97-0.98), referral to a medical oncologist (OR 1.99, 95% CI 1.55-2.55), prior LPD treatment (>1 line OR 1.72, 95% CI 1.31-2.28), and opioid use (OR 1.45, 95% CI 1.08-1.95) were significantly associated with high-intensity care. Conclusions: High-intensity care in EOL is not easily justifiable due to high economic cost and little effect on life span, but further research is awaited to give insight in the effect on patients' and their caregivers' quality of life.


Assuntos
Uso Excessivo dos Serviços de Saúde , Neoplasias de Próstata Resistentes à Castração , Assistência Terminal , Humanos , Masculino , Países Baixos , Neoplasias de Próstata Resistentes à Castração/terapia , Sistema de Registros , Estudos Retrospectivos , Assistência Terminal/métodos
5.
Eur Urol Oncol ; 3(2): 231-238, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31401014

RESUMO

BACKGROUND: Oligometastatic prostate cancer (OMPC) is a heterogeneous disease state that is imperfectly understood, and its clinical implications are unclear. OBJECTIVE: To determine the consensus of a Dutch multidisciplinary expert panel on biological aspects, treatment goals, and management of OMPC in daily clinical practice. DESIGN, SETTING, AND PARTICIPANTS: The study comprised a modified Delphi method including an explorative survey with various statements and questions, followed by a consensus meeting to discuss and determine the agreement with revised statements and related items. The panel consisted of 34 Dutch representatives from urology, medical and radiation oncology, radiology, nuclear medicine, and basic research. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Agreement was determined with statements (five-point scale). Consensus was defined as ≥75% panel agreement with a statement. RESULTS AND LIMITATIONS: Consensus existed for 56% of statements. The panel agreed that OMPC comprises a limited metastatic spread in the hormone-sensitive setting, in both the synchronous and the metachronous presentation. Limited metastatic spread was believed to involve three to five metastases and a maximum of two organs. Prostate-specific membrane antigen positron emission tomography/computed tomography scan was currently perceived as the most accurate diagnostic imaging modality. Although there was a consensus that targeted treatment of all metastases in OMPC will delay further dissemination of the disease, opinions on specific treatment regimens were divided. Panel outcomes were limited by the lack of scientific evidence on OMPC. CONCLUSIONS: A multidisciplinary panel reached a consensus that OMPC is a specific disease state requiring a tailored treatment approach. OMPC registries and clinical studies should focus on both the biology and the clinical parameters in relation to optimal treatment strategies in synchronous and metachronous OMPC. PATIENT SUMMARY: A group of Dutch medical specialists agreed that prostate cancer patients having few metastases may benefit from a new therapeutic approach. Clinical studies need to determine which treatment is best for each specific situation.


Assuntos
Neoplasias da Próstata/complicações , Técnica Delphi , Humanos , Masculino , Metástase Neoplásica , Suécia
6.
Future Oncol ; 15(19): 2203-2209, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31023100

RESUMO

Surgery is the standard treatment for nonmetastatic renal cell carcinoma. Despite curative intent, patients with a high risk of relapse have a 5-year metastasis-free survival rate of only 30% and prevention of recurrence is an unmet need. In a Phase III trial (JAVELIN Renal 101), progression-free survival of axitinib + avelumab was superior to sunitinib with a favorable objective response rate and no added toxicity profiles as known for axitinib or avelumab single agent. NEOAVAX is designed as open label, single arm, Phase II trial with a Simon's two-stage design evaluating neoadjuvant axitinib + avelumab followed by complete surgical resection in 40 patients with high-risk nonmetastatic clear-cell renal cell carcinoma. Primary end point is remission of the primary tumor (RECIST 1.1; Response Evaluation Criteria In Solid Tumors) following neoadjuvant therapy. Secondary end points include disease-free survival, overall survival, rate of metastasis and local recurrence, safety, and tolerability. Exploratory end points include investigation of effects on neoangiogenesis, immune infiltrates and myeloid-derived suppressor cell components to support a rationale for the combined use of axitinib and avelumab (NCT03341845).


Assuntos
Anticorpos Monoclonais/administração & dosagem , Axitinibe/administração & dosagem , Carcinoma de Células Renais/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Axitinibe/efeitos adversos , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Recidiva Local de Neoplasia/patologia , Nefrectomia/efeitos adversos , Prevenção Secundária
7.
PLoS One ; 14(3): e0212952, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30845233

RESUMO

Birt-Hogg-Dubé syndrome is associated with an increased risk for renal cell carcinoma. Surveillance is recommended, but the optimal imaging method and screening interval remain to be defined. The main aim of our study was to evaluate the outcomes of RCC surveillance to get insight in the safety of annual US in these patients. Surveillance data and medical records of 199 patients with Birt-Hogg-Dubé syndrome were collected retrospectively using medical files and a questionnaire. These patients were diagnosed in two Dutch hospitals and data were collected until June 2014. A first screening for renal cell carcinoma was performed in 172/199 patients (86%). Follow-up data were available from 121 patients. The mean follow-up period per patient was 4.2 years. Of the patients known to be under surveillance, 83% was screened at least annually and 94% at least every two years. Thirty-eight renal cell carcinomas had occurred in 23 patients. The mean age at diagnosis of the first tumour was 51. Eighteen tumours were visualized by ultrasound. Nine small tumours (7-27 mm) were visible on MRI or CT and not detected using ultrasound. Our data indicate that compliance to renal screening is relatively high. Furthermore, ultrasound might be a sensitive, cheap and widely available alternative for MRI or part of the MRIs for detecting clinically relevant renal tumours in BHD patients,but the limitations should be considered carefully. Data from larger cohorts are necessary to confirm these observations.


Assuntos
Síndrome de Birt-Hogg-Dubé/complicações , Carcinoma de Células Renais/diagnóstico por imagem , Neoplasias Renais/diagnóstico por imagem , Programas de Rastreamento/estatística & dados numéricos , Cooperação do Paciente/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Síndrome de Birt-Hogg-Dubé/genética , Carcinoma de Células Renais/genética , Feminino , Seguimentos , Predisposição Genética para Doença , Humanos , Rim/diagnóstico por imagem , Neoplasias Renais/genética , Imageamento por Ressonância Magnética , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Países Baixos , Proteínas Proto-Oncogênicas/genética , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Proteínas Supressoras de Tumor/genética , Ultrassonografia , Adulto Jovem
8.
J Biomed Opt ; 23(8): 1-11, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30094972

RESUMO

Diagnostic accuracy of needle-based optical coherence tomography (OCT) for prostate cancer detection by visual and quantitative analysis is defined. 106 three-dimensional (3-D)-OCT data sets were acquired in 20 prostates after radical prostatectomy and precisely matched with pathology. OCT images were grouped per histological category. Two reviewers performed blind assessments of the OCT images. Sensitivity and specificity for malignancy detection were calculated. Quantitative analyses by automated optical attenuation coefficient calculation were performed. OCT can reliably differentiate between fat, cystic, and regular atrophy and benign glands. The overall sensitivity and specificity for malignancy detection was 79% and 88% for reviewer 1 and 88% and 81% for reviewer 2. Quantitative analysis for differentiation between stroma and malignancy showed a significant difference (4.6 mm - 1 versus 5.0 mm - 1 Mann-Whitney U-test p < 0.0001). A Kruskal-Wallis test showed a significant difference in median attenuation coefficient between stroma, inflammation, Gleason 3, and Gleason 4 (4.6, 4.1, 5.9, and 5.0 mm - 1, respectively). However, attenuation coefficient varied per patient and a related-samples Wilcoxon signed-rank test showed no significant difference per patient (p = 0.17). This study confirmed the one to one correlation of histopathology and OCT. Precise matching showed that most histological tissues categories in the prostate could be distinguished by their unique pattern in OCT images. In addition, the optical attenuation coefficient can play a role in the differentiation between stroma and malignancy; however, a per patient analysis of the optical attenuation coefficient did not show a significant difference.


Assuntos
Interpretação de Imagem Assistida por Computador/métodos , Próstata/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico por imagem , Tomografia de Coerência Óptica/métodos , Adulto , Humanos , Masculino , Agulhas , Estudos Prospectivos , Próstata/patologia , Neoplasias da Próstata/patologia , Sensibilidade e Especificidade
9.
Int J Radiat Oncol Biol Phys ; 101(2): 406-410, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29559285

RESUMO

PURPOSE: To investigate the predictive value of [18F]-fluoromethylcholine positron emission tomography/computed tomography (PET/CT)-derived parameters on progression-free survival (PFS) in oligometastatic prostate cancer patients treated with stereotactic body radiation therapy (SBRT). METHODS AND MATERIALS: In [18F]-fluoromethylcholine PET/CT scans of 40 consecutive patients with ≤4 metachronous metastases treated with SBRT we retrospectively measured the number of metastases, standardized uptake values (SUVmean, SUVmax, SUVpeak), metabolically active tumor volume (MATV), and total lesion choline uptake. Partial-volume correction was applied using the iterative deconvolution Lucy-Richardson algorithm. RESULTS: Thirty-seven lymph node and 13 bone metastases were treated with SBRT. Thirty-three patients (82.5%) had 1 lesion, 4 (10%) had 2 lesions, and 3 (7.5%) had 3 lesions. After a median follow-up of 32.6 months (interquartile range, 35.5 months), the median PFS was 11.5 months (95% confidence interval 8.4-14.6 months). Having more than a single metastasis was a significant prognostic factor (hazard ratio 2.74; P = .03), and there was a trend in risk of progression for large MATV (hazard ratio 1.86; P = .10). No SUV or total lesion choline uptake was significantly predictive for PFS, regardless of partial-volume correction. All PET semiquantitative parameters were significantly correlated with each other (P ≤ .013). CONCLUSIONS: The number of choline-avid metastases was a significant prognostic factor for progression after [18F]-fluormethylcholine PET/CT-guided SBRT for recurrent oligometastatic prostate cancer, and there seemed to be a trend in risk of progression for patients with large MATVs. The lesional level of [18F]-fluoromethylcholine uptake was not prognostic for progression.


Assuntos
Adenocarcinoma/diagnóstico por imagem , Colina/análogos & derivados , Radioisótopos de Flúor/farmacocinética , Recidiva Local de Neoplasia/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias da Próstata/diagnóstico por imagem , Radiocirurgia , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma/radioterapia , Idoso , Antagonistas de Androgênios/uso terapêutico , Colina/farmacocinética , Humanos , Estimativa de Kaplan-Meier , Masculino , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/radioterapia , Prognóstico , Intervalo Livre de Progressão , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Neoplasias da Próstata/radioterapia , Radioterapia Guiada por Imagem/métodos
10.
BMJ Open ; 7(9): e015154, 2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28918408

RESUMO

INTRODUCTION: Patient decision aids (PDAs) have been developed to help patients make an informed choice for a treatment option. Despite proven benefits, structural implementation falls short of expectations. The present study aims to assess the effectiveness and cost-utility of the PDA among newly diagnosed patients with localised prostate cancer and their partners, alongside implementation of the PDA in routine care. METHODS/ANALYSIS: A stepped-wedge cluster randomised trial will be conducted. The PDA will be sequentially implemented in 18 hospitals in the Netherlands, over a period of 24 months. Every 3 or 6 months, a new cluster of hospitals will switch from usual care to care including a PDA.The primary outcome measure is decisional conflict experienced by the patient. Secondary outcomes comprise the patient's quality of life, treatment preferences, role in the decision making, expectations of treatment, knowledge, need for supportive care and decision regret. Furthermore, societal cost-utility will be valued. Other outcome measures considered are the partner's treatment preferences, experienced participation to decision making, quality of life, communication between patient, partner and health care professional, and the effect of prostate cancer on the relationship, social contacts and their role as caregiver. Patients and partners receiving the PDA will also be asked about their satisfaction with the PDA.Baseline assessment takes place after the treatment choice and before the start of a treatment, with follow-up assessments at 3, 6 and 12 months following the end of treatment or the day after deciding on active surveillance. Outcome measures on implementation include the implementation rate (defined as the proportion of all eligible patients who will receive a PDA) and a questionnaire for health care professionals on determinants of implementing an innovation. ETHICS AND DISSEMINATION: This study will be conducted in accordance with local laws and regulations of the Medical Ethics Committee of VU University Medical Center, Amsterdam, The Netherlands. The results from this stepped-wedge trial will be presented at scientific meetings and published in peer-reviewed journals. TRIAL REGISTRATION: Nederlands Trial Register NTR TC5177, registration date: May 28th 2015.Pre-results.


Assuntos
Cuidadores/psicologia , Técnicas de Apoio para a Decisão , Participação do Paciente , Neoplasias da Próstata/psicologia , Projetos de Pesquisa , Atitude do Pessoal de Saúde , Custos e Análise de Custo , Tomada de Decisões , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Países Baixos , Neoplasias da Próstata/terapia , Qualidade de Vida
11.
Oncotarget ; 7(16): 22566-78, 2016 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-26992225

RESUMO

In many cancer types, the expression and function of ~22 nucleotide-long microRNAs (miRNA) is deregulated. Mature miRNAs can be stably detected in extracellular vesicles (EVs) in biofluids, therefore they are considered to have great potential as biomarkers. In the present study, we investigated whether miRNAs have a distinct expression pattern in urine-EVs of prostate cancer (PCa) patients compared to control males. By next generation sequencing, we determined the miRNA expression in a discovery cohort of 4 control men and 9 PCa patients. miRNAs were validated by using a stemloop RT-PCR in an independent cohort of 74 patients (26 control and 48 PCa-patients). Whereas standard mapping protocols identified > 10 PCa associated miRNAs in urinary EVs, miR-21, miR-375 and miR-204 failed to robustly discriminate for disease in a validation study with RT-PCR-detection of mature miRNA sequences. In contrast, we observed that miRNA isoforms (isomiRs) with 3' end modifications were highly discriminatory between samples from control men and PCa patients. Highly differentially expressed isomiRs of miR-21, miR-204 and miR-375 were subsequently validated in an independent group of 74 patients. Receiver-operating characteristic analysis was performed to evaluate the diagnostic performance of three isomiRs, resulting in a 72.9% sensitivity with a high (88%) specificity and an area under the curve (AUC) of 0.866. In comparison, prostate specific antigen had an AUC of 0.707 and measuring the mature form of these miRNAs yielded a lower 70.8% sensitivity and 72% specificity (AUC 0.766). We propose that isomiRs may carry discriminatory information which is useful to generate stronger biomarkers.


Assuntos
Biomarcadores Tumorais/urina , Vesículas Extracelulares/genética , MicroRNAs/urina , Neoplasias da Próstata/urina , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Biomarcadores Tumorais/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Isoformas de Proteínas/genética , Curva ROC , Sensibilidade e Especificidade
12.
Oncotarget ; 7(13): 16676-87, 2016 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-26918338

RESUMO

The centrosome plays a key role in cancer invasion and metastasis. However, it is unclear how abnormal centrosome numbers are regulated when prostate cancer (PCa) cells become metastatic. CP110 was previously described for its contribution of centrosome amplification (CA) and early development of aggressive cell behaviour. However its regulation in metastatic cells remains unclear. Here we identified miR-129-3p as a novel metastatic microRNA. CP110 was identified as its target protein. In PCa cells that have metastatic capacity, CP110 expression was repressed by miR-129-3p. High miR-129-3p expression levels increased cell invasion, while increasing CP110 levels decreased cell invasion. Overexpression of CP110 in metastatic PCa cells resulted in a decrease in the number of metastasis. In tissues of PCa patients, low CP110 and high miR-129-3p expression levels correlated with metastasis, but not with the expression of genes related to EMT. Furthermore, overexpression of CP110 in metastatic PCa cells resulted in excessive-CA (E-CA), and a change in F-actin distribution which is in agreement with their reduced metastatic capacity. Our data demonstrate that miR-129-3p functions as a CA gatekeeper in metastatic PCa cells by maintaining pro-metastatic centrosome amplification (CA) and preventing anti-metastatic E-CA.


Assuntos
Proteínas de Ciclo Celular/biossíntese , Centrossomo/patologia , Regulação Neoplásica da Expressão Gênica/fisiologia , MicroRNAs/metabolismo , Proteínas Associadas aos Microtúbulos/biossíntese , Fosfoproteínas/biossíntese , Neoplasias da Próstata/patologia , Animais , Linhagem Celular Tumoral , Humanos , Masculino , MicroRNAs/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Ratos
13.
Ned Tijdschr Geneeskd ; 160: D385, 2015.
Artigo em Holandês | MEDLINE | ID: mdl-27142505

RESUMO

(68)Gallium (Ga)-PSMA PET/CT scans have been introduced in clinical practice in the Netherlands too. Although there are some indications that this new imaging modality for prostate cancer might be superior to other techniques, evidence is lacking both for primary diagnosis and in the case of recurrent disease. The exact role of the (68)Ga-PSMA PET/CT scan needs to be defined on the basis of well-designed studies that also evaluate the impact of earlier diagnosis on the outcome for the individual patient.

14.
Eur Urol ; 66(1): 87-97, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24560818

RESUMO

CONTEXT: Live surgery is an important part of surgical education, with an increase in the number of live surgery events (LSEs) at meetings despite controversy about their real educational value, risks to patient safety, and conflicts of interest. OBJECTIVE: To provide a European Association of Urology (EAU) policy on LSEs to regulate their organisation during urologic meetings. EVIDENCE ACQUISITION: The project was carried out in phases: a systematic literature review generating key questions, surveys sent to Live Surgery Panel members, and Internet- and panel-based consensus finding using the Delphi process to agree on and formulate a policy. EVIDENCE SYNTHESIS: The EAU will endorse LSEs, provided that the EAU Code of Conduct for live surgery and all organisational requirements are followed. Outcome data must be submitted to an EAU Web-based registry and complications reported using the revised Martin criteria. Regular audits will take place to evaluate compliance as well as the educational role of live surgery. CONCLUSIONS: This policy represents the consensus view of an expert panel established to advise the EAU. The EAU recognises the educational role of live surgery and endorses live case demonstration at urologic meetings that are conducted within a clearly defined regulatory framework. The overriding principle is that patient safety must take priority over all other considerations in the conduct of live surgery. PATIENT SUMMARY: Controversy exists regarding the true educational value of live surgical demonstrations on patients at surgical meetings. An EAU committee of experts developed a policy on how best to conduct live surgery at urologic meetings. The key principle is to ensure safety for every patient, including a code of conduct and checklist for live surgery, specific rules for how the surgery is organised and performed, and how each patient's results are reported to the EAU. For detailed information, please visit www.uroweb.org.


Assuntos
Equipe de Assistência ao Paciente/organização & administração , Políticas , Sociedades Médicas , Procedimentos Cirúrgicos Urológicos/educação , Urologia/educação , Europa (Continente) , Humanos , Equipe de Assistência ao Paciente/normas , Segurança do Paciente/normas , Seleção de Pacientes , Procedimentos Cirúrgicos Urológicos/normas , Urologia/organização & administração , Urologia/normas
17.
Crit Rev Oncol Hematol ; 68 Suppl 1: S9-S22, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18723368

RESUMO

A multidisciplinary panel of 20 international experts, including urologists, radiation oncologists, and medical oncologists, convened during the Advanced Prostate Cancer Multidisciplinary Team meeting in Rome, Italy, in January 2007, to discuss the multidisciplinary team approach and current patterns of care for patients with hormone-refractory prostate cancer (HRPC). During the meeting, the experts discussed several definitions currently used in prostate cancer management, including those for senior adult patients. In addition, the panel reviewed a series of patient case studies in order to provide feedback on current treatment practices and to identify possible strategies for best practice. It was stressed that treatment decisions for senior adult patients should not be based solely on patient age. Additionally, although historically treatment decisions for advanced prostate cancer have focused on palliative care, given the survival benefit associated with docetaxel-based chemotherapy across patient subgroups, more men are likely to be offered chemotherapy for advanced-stage disease in the future.


Assuntos
Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Estudos de Casos e Controles , Progressão da Doença , Humanos , Masculino , Antígeno Prostático Específico/análise , Neoplasias da Próstata/diagnóstico
18.
BJU Int ; 101(8): 944-7, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18070170

RESUMO

For the delivery of good-quality external beam radiotherapy (EBRT) in localized prostate cancer, under-dosage to the peripheral zone (tumour) is one likely cause of poor results. The quality is improved by daily verification of the position of the prostate, and the use of magnetic resonance imaging (MRI) in delineation. Currently these are demands on quality that should be incorporated in each radiotherapy department. The use of MRI in staging is also expected to improve patient selection for EBRT. Furthermore, an adequate radiation dose should be delivered. In this overview we describe what the urologist should expect from radiation oncologists to obtain the optimum results for the patients.


Assuntos
Neoplasias da Próstata/radioterapia , Previsões , Humanos , Imageamento por Ressonância Magnética , Masculino , Estadiamento de Neoplasias , Neoplasias da Próstata/patologia , Radioterapia/normas , Radioterapia/tendências , Dosagem Radioterapêutica , Resultado do Tratamento
19.
Int J Radiat Oncol Biol Phys ; 69(3): 656-61, 2007 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-17512127

RESUMO

PURPOSE: To compare quality of life (QoL) after 70 Gy conformal radiotherapy with QoL after 76 Gy intensity-modulated radiotherapy (IMRT) in patients with locally advanced prostate carcinoma. METHODS AND MATERIALS: Seventy-eight patients with locally advanced prostate cancer were treated with 70 Gy three-field conformal radiotherapy, and 92 patients received 76 Gy IMRT with fiducial markers for position verification. Quality of life was measured by RAND-36, the European Organization for Research and Treatment of Cancer core questionnaire (EORTC QLQ-C30(+3)), and the prostate-specific EORTC QLQ-PR25, before radiotherapy (baseline) and 1 month and 6 months after treatment. Quality of life changes in time (baseline vs. 1 month and baseline vs. 6 months) of > or =10 points were considered clinically relevant. RESULTS: Differences between the treatment groups for QoL changes over time occurred in several QoL domains. The 76-Gy group revealed no significant deterioration in QoL compared with the 70-Gy group. The IMRT 76-Gy group even demonstrated a significantly better change in QoL from baseline to 1 month in several domains. The conformal 70-Gy group revealed temporary deterioration in pain, role functioning, and urinary symptoms; for the IMRT 76-Gy group a better QoL in terms of change in health existed after 1 month, which persisted after 6 months. For both treatment groups temporary deterioration in physical role restriction occurred after 1 month, and an improvement in emotional role restriction occurred after 6 months. Sexual activity was reduced after treatment for both groups and remained decreased after 6 months. CONCLUSIONS: Intensity-modulated radiotherapy and accurate position verification seem to provide a possibility to increase the radiation dose for prostate cancer without deterioration in QoL.


Assuntos
Nível de Saúde , Neoplasias da Próstata/radioterapia , Qualidade de Vida , Radioterapia Conformacional/métodos , Radioterapia de Intensidade Modulada/métodos , Idoso , Humanos , Hipertermia Induzida , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias da Próstata/patologia , Próteses e Implantes , Dosagem Radioterapêutica , Radioterapia Conformacional/efeitos adversos , Radioterapia de Intensidade Modulada/efeitos adversos
20.
Urology ; 66(2): 316-22, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16098361

RESUMO

OBJECTIVES: To assess the predictors of acute urinary retention (AUR) and/or surgery related to benign prostatic hyperplasia (BPH) in 3514 men complaining of lower urinary tract symptoms and treated for 6 months with the selective alpha1-blocker alfuzosin at 10 mg once daily. METHODS: The impact of baseline (age, prior AUR, prostate-specific antigen tertiles, lower urinary tract symptoms severity, and bother score) and dynamic (International Prostate Symptom Score [IPSS] worsening of 4 points or greater and bother greater than 3 during treatment) variables on the risk of AUR/BPH-related surgery was assessed using Kaplan-Meier curves and log-rank tests. Associated hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazard models. RESULTS: Of the 3514 men analyzed, 140 (4%) experienced a first episode of conservatively managed AUR before inclusion. Of those 140 men, 5 (3.6%) had AUR relapse during alfuzosin treatment and 6 (4.3%) underwent BPH-related surgery. Of those 3374 men without prior AUR, 19 (0.6%) experienced AUR during treatment and 41 (1.2%) underwent BPH-related surgery. During treatment, the most important predictors of AUR were prior AUR (HR 6.35, 95% CI 2.31 to 17.40; P < 0.01), IPSS worsening of 4 or greater (HR 3.34, 95% CI 1.11 to 9.99; P = 0.03), and bother score greater than 3 (HR 3.32, 95% CI 1.29 to 8.53; P < 0.01) at endpoint. Other variables (age, PSA, baseline IPSS, and bother) had much less predictive value. Similar results were observed regarding the risk of AUR and/or BPH-related surgery. CONCLUSIONS: The results of this 6-month real life practice study suggest that prior AUR and symptom deterioration during treatment with alfuzosin 10 mg once-daily (IPSS worsening of 4 or more points, bother score greater than 3) were the strongest predictors of AUR and AUR/BPH-related surgery in men with lower urinary tract symptoms.


Assuntos
Antagonistas Adrenérgicos alfa/administração & dosagem , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/cirurgia , Quinazolinas/administração & dosagem , Retenção Urinária/cirurgia , Transtornos Urinários/tratamento farmacológico , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Esquema de Medicação , Humanos , Masculino , Pessoa de Meia-Idade , Hiperplasia Prostática/complicações , Retenção Urinária/etiologia , Transtornos Urinários/etiologia
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