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[PMID]: 28453701 [Au] Autor: Sartor O; Coleman RE; Nilsson S; Heinrich D; Helle SI; O'Sullivan JM; Vogelzang NJ; Bruland Ø; Kobina S; Wilhelm S; Xu L; Shan M; Kattan MW; Parker C [Ad] Endereço: Departments of Medicine and Urology, Tulane Cancer Center, New Orleans, USA. [Ti] Título: An exploratory analysis of alkaline phosphatase, lactate dehydrogenase, and prostate-specific antigen dynamics in the phase 3 ALSYMPCA trial with radium-223. [So] Source: Ann Oncol;28(5):1090-1097, 2017 05 01. [Is] ISSN: 1569-8041 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Background: Baseline clinical variables are prognostic for overall survival (OS) in patients with castration-resistant prostate cancer (CRPC). Their prognostic and predictive value with agents targeting bone metastases, such as radium-223, is not established. Patients and methods: The radium-223 ALSYMPCA trial enrolled patients with CRPC and symptomatic bone metastases. Prognostic potential of baseline variables was assessed using Cox models. Percentage changes in biomarker levels from baseline were evaluated during the trial period; changes from baseline to week 12 were evaluated for association with OS and surrogacy. Results: Eastern Cooperative Oncology Group performance status, total alkaline phosphatase (tALP), lactate dehydrogenase (LDH), and prostate-specific antigen (PSA) at baseline were associated with OS (P ≤ 0.0003) in the intent-to-treat population (radium-223, N = 614; placebo, N = 307). tALP declined from baseline within 4 weeks after beginning radium-223, by week 12 declining in 87% of radium-223 and 23% of placebo patients (P < 0.001). LDH declined in 51% and 34% (P = 0.003), whereas PSA declined in 27% and 14% (P = 0.160). Mean tALP change from baseline was 32.2% decrease with radium-223 and 37.2% increase with placebo. Radium-223 patients with tALP decline from baseline to week 12 (confirmed ≥3 weeks from week 12) had 55% lower risk of death (hazard ratio = 0.45; 95% CI 0.34-0.61) versus those with no confirmed tALP decline. Proportional treatment effect (PTE) values for tALP, LDH, and PSA changes from baseline at week 12 as OS surrogate markers were 0.34 (95% CI: 0-0.746), 0.07 (95% CI: 0-0.211), and 0 (95% CI: 0-0.082), respectively. Conclusions: Significant tALP declines (versus placebo) occurred as early as 4 weeks after beginning radium-223 therapy. tALP or LDH declines at 12 weeks correlated with longer OS, but did not meet statistical surrogacy requirements. Dynamic changes in tALP and LDH during radium-223 treatments may be useful to monitor, but do not serve as surrogates for survival. [Mh] Termos MeSH primário: Neoplasias de Próstata Resistentes à Castração/radioterapia Compostos Radiofarmacêuticos/uso terapêutico Rádio (Elemento)/uso terapêutico [Mh] Termos MeSH secundário: Fosfatase Alcalina/metabolismo Biomarcadores Tumorais/metabolismo Seres Humanos Calicreínas/metabolismo Estimativa de Kaplan-Meier L-Lactato Desidrogenase/metabolismo Masculino Análise Multivariada Prognóstico Modelos de Riscos Proporcionais Antígeno Prostático Específico/metabolismo Neoplasias de Próstata Resistentes à Castração/enzimologia Neoplasias de Próstata Resistentes à Castração/mortalidade Resultado do Tratamento [Pt] Tipo de publicação: CLINICAL TRIAL, PHASE III; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL [Nm] Nome de substância: 0 (Biomarkers, Tumor); 0 (Radiopharmaceuticals); 0 (Radium-223); EC 1.1.1.27 (L-Lactate Dehydrogenase); EC 3.1.3.1 (Alkaline Phosphatase); EC 3.4.21.- (Kallikreins); EC 3.4.21.- (kallikrein-related peptidase 3, human); EC 3.4.21.77 (Prostate-Specific Antigen); W90AYD6R3Q (Radium) [Em] Mês de entrada: 1803 [Cu] Atualização por classe: 180308 [Lr] Data última revisão: 180308 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170429 [St] Status: MEDLINE [do] DOI: 10.1093/annonc/mdx044

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[PMID]: 28453693 [Au] Autor: Mahal BA; Chen YW; Muralidhar V; Mahal AR; Choueiri TK; Hoffman KE; Hu JC; Sweeney CJ; Yu JB; Feng FY; Kim SP; Beard CJ; Martin NE; Trinh QD; Nguyen PL [Ad] Endereço: Harvard Radiation Oncology Program, Boston, USA. [Ti] Título: Racial disparities in prostate cancer outcome among prostate-specific antigen screening eligible populations in the United States. [So] Source: Ann Oncol;28(5):1098-1104, 2017 05 01. [Is] ISSN: 1569-8041 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Background: In 2012, the United States Preventive Services Task Force (USPSTF) recommended against prostate-specific antigen (PSA) screening, despite evidence that Black men are at a higher risk of prostate cancer-specific mortality (PCSM). We evaluated whether Black men of potentially screening-eligible age (55-69 years) are at a disproportionally high risk of poor outcomes. Patients and methods: The SEER database was used to study 390 259 men diagnosed with prostate cancer in the United States between 2004 and 2011. Multivariable logistic regression modeled the association between Black race and stage of presentation, while Fine-Gray competing risks regression modeled the association between Black race and PCSM, both as a function of screening eligibility (age 55-69 years versus not). Results: Black men were more likely to present with metastatic disease (adjusted odds ratio [AOR] 1.65; 1.58-1.72; P < 0.001) and were at a higher risk of PCSM (adjusted hazard ratio [AHR] 1.36; 1.27-1.46; P < 0.001) compared to non-Black men. There were significant interactions between race and PSA-screening eligibility such that Black patients experienced more disproportionate rates of metastatic disease (AOR 1.76; 1.65-1.87 versus 1.55; 1.47-1.65; Pinteraction < 0.001) and PCSM (AHR 1.53; 1.37-1.70 versus 1.25; 1.14-1.37; Pinteraction = 0.01) in the potentially PSA-screening eligible group than in the group not eligible for screening. Conclusions: Racial disparities in prostate cancer outcome among Black men are significantly worse in PSA-screening eligible populations. These results raise the possibility that Black men could be disproportionately impacted by recommendations to end PSA screening in the United States and suggest that Black race should be included in the updated USPSTF PSA screening guidelines. [Mh] Termos MeSH primário: Neoplasias da Próstata/diagnóstico [Mh] Termos MeSH secundário: Afroamericanos Idoso Detecção Precoce de Câncer Disparidades em Assistência à Saúde Seres Humanos Calicreínas/metabolismo Masculino Meia-Idade Modelos de Riscos Proporcionais Antígeno Prostático Específico/metabolismo Neoplasias da Próstata/metabolismo Neoplasias da Próstata/mortalidade Neoplasias da Próstata/terapia Fatores de Risco Programa de SEER Resultado do Tratamento Estados Unidos/epidemiologia [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: EC 3.4.21.- (Kallikreins); EC 3.4.21.- (kallikrein-related peptidase 3, human); EC 3.4.21.77 (Prostate-Specific Antigen) [Em] Mês de entrada: 1803 [Cu] Atualização por classe: 180308 [Lr] Data última revisão: 180308 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170429 [St] Status: MEDLINE [do] DOI: 10.1093/annonc/mdx041

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[PMID]: 29321194 [Au] Autor: Seibert TM; Fan CC; Wang Y; Zuber V; Karunamuni R; Parsons JK; Eeles RA; Easton DF; Kote-Jarai Z; Al Olama AA; Garcia SB; Muir K; Grönberg H; Wiklund F; Aly M; Schleutker J; Sipeky C; Tammela TL; Nordestgaard BG; Nielsen SF; Weischer M; Bisbjerg R; Røder MA; Iversen P; Key TJ; Travis RC; Neal DE; Donovan JL; Hamdy FC; Pharoah P; Pashayan N; Khaw KT; Maier C; Vogel W; Luedeke M; Herkommer K; Kibel AS; Cybulski C; Wokolorczyk D; Kluzniak W; Cannon-Albright L; Brenner H; Cuk K; Saum KU; Park JY; Sellers TA; Slavov C; Kaneva R; Mitev V; Batra J; PRACTICAL Consortium* [Ad] Endereço: Center for Multimodal Imaging and Genetics, University of California, San Diego, La Jolla, CA, USA tseibert@ucsd.edu amdale@ucsd.edu. [Ti] Título: Polygenic hazard score to guide screening for aggressive prostate cancer: development and validation in large scale cohorts. [So] Source: BMJ;360:j5757, 2018 01 10. [Is] ISSN: 1756-1833 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: OBJECTIVES: To develop and validate a genetic tool to predict age of onset of aggressive prostate cancer (PCa) and to guide decisions of who to screen and at what age. DESIGN: Analysis of genotype, PCa status, and age to select single nucleotide polymorphisms (SNPs) associated with diagnosis. These polymorphisms were incorporated into a survival analysis to estimate their effects on age at diagnosis of aggressive PCa (that is, not eligible for surveillance according to National Comprehensive Cancer Network guidelines; any of Gleason score ≥7, stage T3-T4, PSA (prostate specific antigen) concentration ≥10 ng/L, nodal metastasis, distant metastasis). The resulting polygenic hazard score is an assessment of individual genetic risk. The final model was applied to an independent dataset containing genotype and PSA screening data. The hazard score was calculated for these men to test prediction of survival free from PCa. SETTING: Multiple institutions that were members of international PRACTICAL consortium. PARTICIPANTS: All consortium participants of European ancestry with known age, PCa status, and quality assured custom (iCOGS) array genotype data. The development dataset comprised 31 747 men; the validation dataset comprised 6411 men. MAIN OUTCOME MEASURES: Prediction with hazard score of age of onset of aggressive cancer in validation set. RESULTS: In the independent validation set, the hazard score calculated from 54 single nucleotide polymorphisms was a highly significant predictor of age at diagnosis of aggressive cancer (z=11.2, P<10 ). When men in the validation set with high scores (>98th centile) were compared with those with average scores (30th-70th centile), the hazard ratio for aggressive cancer was 2.9 (95% confidence interval 2.4 to 3.4). Inclusion of family history in a combined model did not improve prediction of onset of aggressive PCa (P=0.59), and polygenic hazard score performance remained high when family history was accounted for. Additionally, the positive predictive value of PSA screening for aggressive PCa was increased with increasing polygenic hazard score. CONCLUSIONS: Polygenic hazard scores can be used for personalised genetic risk estimates that can predict for age at onset of aggressive PCa. [Mh] Termos MeSH primário: Detecção Precoce de Câncer/métodos Calicreínas/análise Polimorfismo de Nucleotídeo Único/genética Antígeno Prostático Específico/análise Neoplasias da Próstata/sangue Neoplasias da Próstata/genética [Mh] Termos MeSH secundário: Idade de Início Idoso Estudos de Coortes Intervalo Livre de Doença Grupo com Ancestrais do Continente Europeu/genética Genótipo Seres Humanos Masculino Meia-Idade Avaliação de Resultados (Cuidados de Saúde) Valor Preditivo dos Testes Neoplasias da Próstata/diagnóstico Medição de Risco Análise de Sobrevida [Pt] Tipo de publicação: COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S. [Nm] Nome de substância: EC 3.4.21.- (Kallikreins); EC 3.4.21.- (kallikrein-related peptidase 3, human); EC 3.4.21.77 (Prostate-Specific Antigen) [Em] Mês de entrada: 1803 [Cu] Atualização por classe: 180305 [Lr] Data última revisão: 180305 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 180112 [St] Status: MEDLINE [do] DOI: 10.1136/bmj.j5757

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[PMID]: 28464446 [Au] Autor: Zumsteg ZS; Zelefsky MJ; Woo KM; Spratt DE; Kollmeier MA; McBride S; Pei X; Sandler HM; Zhang Z [Ad] Endereço: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. [Ti] Título: Unification of favourable intermediate-, unfavourable intermediate-, and very high-risk stratification criteria for prostate cancer. [So] Source: BJU Int;120(5B):E87-E95, 2017 11. [Is] ISSN: 1464-410X [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: OBJECTIVE: To improve on the existing risk-stratification systems for prostate cancer. PATIENTS AND METHODS: This was a retrospective investigation including 2 248 patients undergoing dose-escalated external beam radiotherapy (EBRT) at a single institution. We separated National Comprehensive Cancer Network (NCCN) intermediate-risk prostate cancer into 'favourable' and 'unfavourable' groups based on primary Gleason pattern, percentage of positive biopsy cores (PPBC), and number of NCCN intermediate-risk factors. Similarly, NCCN high-risk prostate cancer was stratified into 'standard' and 'very high-risk' groups based on primary Gleason pattern, PPBC, number of NCCN high-risk factors, and stage T3b-T4 disease. Patients with unfavourable-intermediate-risk (UIR) prostate cancer had significantly inferior prostate-specific antigen relapse-free survival (PSA-RFS, P < 0.001), distant metastasis-free survival (DMFS, P < 0.001), prostate cancer-specific mortality (PCSM, P < 0.001), and overall survival (OS, P < 0.001) compared with patients with favourable-intermediate-risk (FIR) prostate cancer. Similarly, patients with very high-risk (VHR) prostate cancer had significantly worse PSA-RFS (P < 0.001), DMFS (P < 0.001), and PCSM (P = 0.001) compared with patients with standard high-risk (SHR) prostate cancer. Moreover, patients with FIR and low-risk prostate cancer had similar outcomes, as did patients with UIR and SHR prostate cancer. RESULTS: Consequently, we propose the following risk-stratification system: Group 1, low risk and FIR; Group 2, UIR and SHR; and Group 3, VHR. These groups have markedly different outcomes, with 8-year distant metastasis rates of 3%, 9%, and 29% (P < 0.001) for Groups 1, 2, and 3, respectively, and 8-year PCSM of 1%, 4%, and 13% (P < 0.001) after EBRT. This modified stratification system was significantly more accurate than the three-tiered NCCN system currently in clinical use for all outcomes. CONCLUSION: Modifying the NCCN risk-stratification system to group FIR with low-risk patients and UIR with SHR patients, results in modestly improved prediction of outcomes, potentially allowing better personalisation of therapeutic recommendations. [Mh] Termos MeSH primário: Gradação de Tumores Neoplasias da Próstata/patologia [Mh] Termos MeSH secundário: Idoso Seres Humanos Masculino Meia-Idade Recidiva Local de Neoplasia/mortalidade Recidiva Local de Neoplasia/patologia Estadiamento de Neoplasias Guias de Prática Clínica como Assunto Prognóstico Próstata/patologia Antígeno Prostático Específico/sangue Prostatectomia Neoplasias da Próstata/sangue Neoplasias da Próstata/mortalidade Estudos Retrospectivos Medição de Risco [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: EC 3.4.21.77 (Prostate-Specific Antigen) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180305 [Lr] Data última revisão: 180305 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170503 [St] Status: MEDLINE [do] DOI: 10.1111/bju.13903

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[PMID]: 29206373 [Au] Autor: Matheus WE; Ferreira U [Ad] Endereço: Departamento de Cirurgia, Departamento de Uro-oncologia, Faculdade de Ciências Médicas, Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brasil. [Ti] Título: Focal therapy will be the next step on prostate cancer management? | Opinion: No. [So] Source: Int Braz J Urol;43(6):1017-1020, 2017 Nov-Dec. [Is] ISSN: 1677-6119 [Cp] País de publicação: Brazil [La] Idioma: eng [Mh] Termos MeSH primário: Neoplasias da Próstata/cirurgia [Mh] Termos MeSH secundário: Medicina Baseada em Evidências Seguimentos Seres Humanos Biópsia Guiada por Imagem/métodos Masculino Antígeno Prostático Específico Prostatectomia/métodos Neoplasias da Próstata/diagnóstico por imagem Neoplasias da Próstata/radioterapia Medição de Risco Carga Tumoral Ultrassom Focalizado Transretal de Alta Intensidade/métodos [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: EC 3.4.21.77 (Prostate-Specific Antigen) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180228 [Lr] Data última revisão: 180228 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 171206 [St] Status: MEDLINE [do] DOI: 10.1590/S1677-5538.IBJU.2017.06.03

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[PMID]: 29206372 [Au] Autor: Zequi SC [Ad] Endereço: Editor Associado do International Braz J Urol. [Ti] Título: Focal therapy will be the next step on prostate cancer management? | Opinion: Yes. [So] Source: Int Braz J Urol;43(6):1013-1016, 2017 Nov-Dec. [Is] ISSN: 1677-6119 [Cp] País de publicação: Brazil [La] Idioma: eng [Mh] Termos MeSH primário: Neoplasias da Próstata/cirurgia [Mh] Termos MeSH secundário: Braquiterapia Seres Humanos Masculino Recidiva Local de Neoplasia Antígeno Prostático Específico Prostatectomia/métodos Neoplasias da Próstata/patologia Neoplasias da Próstata/radioterapia Medição de Risco [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: EC 3.4.21.77 (Prostate-Specific Antigen) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180228 [Lr] Data última revisão: 180228 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 171206 [St] Status: MEDLINE [do] DOI: 10.1590/S1677-5538.IBJU.2017.06.02

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[PMID]: 28463150 [Au] Autor: Gay HA; Sanda MG; Liu J; Wu N; Hamstra DA; Wei JT; Dunn RL; Klein EA; Sandler HM; Saigal CS; Litwin MS; Kuban DA; Hembroff L; Regan MM; Chang P; Michalski JM; Prostate Cancer Outcomes and Satisfaction with Treatment Quality Assessment Consortium [Ad] Endereço: Department of Radiation Oncology, Washington University School of Medicine, St. Louis, Missouri. Electronic address: hiramgay@wustl.edu. [Ti] Título: External Beam Radiation Therapy or Brachytherapy With or Without Short-course Neoadjuvant Androgen Deprivation Therapy: Results of a Multicenter, Prospective Study of Quality of Life. [So] Source: Int J Radiat Oncol Biol Phys;98(2):304-317, 2017 06 01. [Is] ISSN: 1879-355X [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: PURPOSE: The long-term effects of neoadjuvant androgen deprivation therapy (NADT) with radiation therapy on participant-reported health-related quality of life (HRQOL) have not been characterized in prospective multicenter studies. We evaluated HRQOL for 2 years among participants undergoing radiation therapy (RT) with or without NADT for newly diagnosed, early-stage prostate cancer. METHODS AND MATERIALS: We analyzed longitudinal cohort data from the Prostate Cancer Outcomes and Satisfaction with Treatment Quality Assessment Consortium to ascertain the HRQOL trajectory of men receiving NADT with external beam RT (EBRT) or brachytherapy. HRQOL was measured using the expanded prostate cancer index composite 26-item questionnaire at 2, 6, 12, and 24 months after the initiation of NADT. We used the χ or Fisher exact test to compare the shift in percentages between groups that did or did not receive NADT. Analyses were conducted at the 2-sided 5% significance level. RESULTS: For subjects receiving EBRT, questions regarding the ability to have an erection, ability to reach an orgasm, quality of erections, frequency of erections, ability to function sexually, and lack of energy were in a significantly worse dichotomized category for the patients receiving NADT. Comparing the baseline versus 24-month outcomes, 24%, 23%, and 30% of participants receiving EBRT plus NADT shifted to the worse dichotomized category for the ability to reach an orgasm, quality of erections, and ability to function sexually compared with 14%, 13%, and 16% in the EBRT group, respectively. CONCLUSIONS: Compared with baseline, at 2 years, participants receiving NADT plus EBRT compared with EBRT alone had worse HRQOL, as measured by the ability to reach orgasm, quality of erections, and ability to function sexually. However, no difference was found in the ability to have an erection, frequency of erections, overall sexual function, hot flashes, breast tenderness/enlargement, depression, lack of energy, or change in body weight. The improved survival in intermediate- and high-risk patients receiving NADT and EBRT necessitates pretreatment counseling of the HRQOL effect of NADT and EBRT. [Mh] Termos MeSH primário: Antagonistas de Androgênios/efeitos adversos Braquiterapia/efeitos adversos Terapia Neoadjuvante/efeitos adversos Orgasmo Ereção Peniana Neoplasias da Próstata/terapia Qualidade de Vida [Mh] Termos MeSH secundário: Idoso Idoso de 80 Anos ou mais Antagonistas de Androgênios/uso terapêutico Peso Corporal/efeitos dos fármacos Peso Corporal/efeitos da radiação Braquiterapia/métodos Braquiterapia/estatística & dados numéricos Mama/efeitos dos fármacos Mama/efeitos da radiação Distribuição de Qui-Quadrado Terapia Combinada/efeitos adversos Terapia Combinada/métodos Terapia Combinada/estatística & dados numéricos Depressão/etiologia Disfunção Erétil/etiologia Fadiga/etiologia Fogachos/etiologia Seres Humanos Masculino Meia-Idade Terapia Neoadjuvante/métodos Terapia Neoadjuvante/estatística & dados numéricos Orgasmo/efeitos dos fármacos Orgasmo/efeitos da radiação Ereção Peniana/efeitos dos fármacos Ereção Peniana/efeitos da radiação Estudos Prospectivos Antígeno Prostático Específico/sangue Neoplasias da Próstata/sangue Neoplasias da Próstata/patologia Inquéritos e Questionários Fatores de Tempo [Pt] Tipo de publicação: JOURNAL ARTICLE; MULTICENTER STUDY; RESEARCH SUPPORT, N.I.H., EXTRAMURAL [Nm] Nome de substância: 0 (Androgen Antagonists); EC 3.4.21.77 (Prostate-Specific Antigen) [Em] Mês de entrada: 1707 [Cu] Atualização por classe: 180228 [Lr] Data última revisão: 180228 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170503 [St] Status: MEDLINE

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[PMID]: 28463149 [Au] Autor: Lawton CAF; Lin X; Hanks GE; Lepor H; Grignon DJ; Brereton HD; Bedi M; Rosenthal SA; Zeitzer KL; Venkatesan VM; Horwitz EM; Pisansky TM; Kim H; Parliament MB; Rabinovitch R; Roach M; Kwok Y; Dignam JJ; Sandler HM [Ad] Endereço: Medical College of Wisconsin, Milwaukee, Wisconsin. Electronic address: clawton@mcw.edu. [Ti] Título: Duration of Androgen Deprivation in Locally Advanced Prostate Cancer: Long-Term Update of NRG Oncology RTOG 9202. [So] Source: Int J Radiat Oncol Biol Phys;98(2):296-303, 2017 06 01. [Is] ISSN: 1879-355X [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: PURPOSE: Trial RTOG 9202 was a phase 3 randomized trial designed to determine the optimal duration of androgen deprivation therapy (ADT) when combined with definitive radiation therapy (RT) in the treatment of locally advanced nonmetastatic adenocarcinoma of the prostate. Long-term follow-up results of this study now available are relevant to the management of this disease. METHODS AND MATERIALS: Men (N=1554) with adenocarcinoma of the prostate (cT2c-T4, N0-Nx) with a prostate-specific antigen (PSA) <150 ng/mL and no evidence of distant metastasis were randomized (June 1992 to April 1995) to short-term ADT (STAD: 4 months of flutamide 250 mg 3 times per day and goserelin 3.6 mg per month) and definitive RT versus long-term ADT (LTAD: STAD with definitive RT plus an additional 24 months of monthly goserelin). RESULTS: Among 1520 protocol-eligible and evaluable patients, the median follow-up time for this analysis was 19.6 years. In analysis adjusted for prognostic covariates, LTAD improved disease-free survival (29% relative reduction in failure rate, P<.0001), local progression (46% relative reduction, P=.02), distant metastases (36% relative reduction, P<.0001), disease-specific survival (30% relative reduction, P=.003), and overall survival (12% relative reduction, P=.03). Other-cause mortality (non-prostate cancer) did not differ (5% relative reduction, P=.48). CONCLUSIONS: LTAD and RT is superior to STAD and RT for the treatment of locally advanced nonmetastatic adenocarcinoma of the prostate and should be considered the standard of care. [Mh] Termos MeSH primário: Adenocarcinoma/terapia Antagonistas de Androgênios/uso terapêutico Neoplasias da Próstata/terapia [Mh] Termos MeSH secundário: Adenocarcinoma/sangue Adenocarcinoma/mortalidade Adenocarcinoma/patologia Adulto Idoso Idoso de 80 Anos ou mais Antagonistas de Androgênios/administração & dosagem Antagonistas de Androgênios/efeitos adversos Terapia Combinada/efeitos adversos Terapia Combinada/métodos Terapia Combinada/estatística & dados numéricos Intervalo Livre de Doença Flutamida/administração & dosagem Flutamida/efeitos adversos Flutamida/uso terapêutico Seguimentos Gosserrelina/administração & dosagem Gosserrelina/efeitos adversos Gosserrelina/uso terapêutico Seres Humanos Masculino Meia-Idade Antígeno Prostático Específico/sangue Neoplasias da Próstata/sangue Neoplasias da Próstata/mortalidade Neoplasias da Próstata/patologia Fatores de Tempo Resultado do Tratamento [Pt] Tipo de publicação: CLINICAL TRIAL, PHASE III; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL; RESEARCH SUPPORT, N.I.H., EXTRAMURAL [Nm] Nome de substância: 0 (Androgen Antagonists); 0F65R8P09N (Goserelin); 76W6J0943E (Flutamide); EC 3.4.21.77 (Prostate-Specific Antigen) [Em] Mês de entrada: 1707 [Cu] Atualização por classe: 180228 [Lr] Data última revisão: 180228 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170503 [St] Status: MEDLINE

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[PMID]: 28459059 [Au] Autor: Hsieh PC; Lin HT; Chen WY; Tsai JJP; Hu WP [Ad] Endereço: Department of Bioinformatics and Medical Engineering, Asia University, Taichung City 41354, Taiwan. [Ti] Título: The Combination of Computational and Biosensing Technologies for Selecting Aptamer against Prostate Specific Antigen. [So] Source: Biomed Res Int;2017:5041683, 2017. [Is] ISSN: 2314-6141 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Herein, we report a method of combining bioinformatics and biosensing technologies to select aptamers against prostate specific antigen (PSA). The main objective of this study is to select DNA aptamers with higher binding affinity for PSA by using the proposed method. Based on the five known sequences of PSA-binding aptamers, we adopted the functions of reproduction and crossover in the genetic algorithm to produce next-generation sequences for the computational and experimental analysis. RNAfold web server was utilized to analyze the secondary structures, and the 3-dimensional molecular models of aptamer sequences were generated by using RNAComposer web server. ZRANK scoring function was used to rerank the docking predictions from ZDOCK. The biosensors, the quartz crystal microbalance (QCM) and a surface plasmon resonance (SPR) instrument, were used to verify the binding ability of selected aptamer for PSA. By carrying out the simulations and experiments after two generations, we obtain one aptamer that can have the highest binding affinity with PSA, which generates almost 2-fold and 3-fold greater measured signals than the responses produced by the best known DNA sequence in the QCM and SPR experiments, respectively. [Mh] Termos MeSH primário: Aptâmeros de Nucleotídeos/química Técnicas Biossensoriais/métodos Biologia Computacional/métodos Antígeno Prostático Específico/sangue [Mh] Termos MeSH secundário: Algoritmos Seres Humanos Masculino Técnicas de Microbalança de Cristal de Quartzo [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Aptamers, Nucleotide); EC 3.4.21.77 (Prostate-Specific Antigen) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180227 [Lr] Data última revisão: 180227 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170502 [St] Status: MEDLINE [do] DOI: 10.1155/2017/5041683

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MEDLINE

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[PMID]: 29189042 [Au] Autor: Brizmohun Appayya M; Sidhu HS; Dikaios N; Johnston EW; Simmons LA; Freeman A; Kirkham AP; Ahmed HU; Punwani S [Ad] Endereço: 1 Centre for Medical Imaging, University College London, Wolfson House , London , UK. [Ti] Título: Characterizing indeterminate (Likert-score 3/5) peripheral zone prostate lesions with PSA density, PI-RADS scoring and qualitative descriptors on multiparametric MRI. [So] Source: Br J Radiol;91(1083):20170645, 2018 Feb. [Is] ISSN: 1748-880X [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: OBJECTIVE: To determine whether indeterminate (Likert-score 3/5) peripheral zone (PZ) multiparametric MRI (mpMRI) studies are classifiable by prostate-specific antigen (PSA), PSA density (PSAD), Prostate Imaging Reporting And Data System version 2 (PI-RADS_v2) rescoring and morphological MRI features. METHODS: Men with maximum Likert-score 3/5 within their PZ were retrospectively selected from 330 patients who prospectively underwent prostate mpMRI (3 T) without an endorectal coil, followed by 20-zone transperineal template prostate mapping biopsies ＋/- focal lesion-targeted biopsy. PSAD was calculated using pre-biopsy PSA and MRI-derived volume. Two readers A and B independently assessed included men with both Likert-assessment and PI-RADS_v2. Both readers then classified mpMRI morphological features in consensus. Men were divided into two groups: significant cancer (≥ Gleason 3 ＋ 4) or insignificant cancer (≤ Gleason 3 ＋ 3)/no cancer. Comparisons between groups were made separately for PSA & PSAD using Mann-Whitney test and morphological descriptors with Fisher's exact test. PI-RADS_v2 and Likert-assessment were descriptively compared and percentage inter-reader agreement calculated. RESULTS: 76 males were eligible for PSA & PSAD analyses, 71 for PI-RADS scoring, and 67 for morphological assessment (excluding significant image artefacts). Unlike PSA (p = 0.915), PSAD was statistically different (p = 0.004) between the significant [median: 0.19 ng ml (interquartile range: 0.13-0.29)] and non-significant/no cancer [median: 0.13 ng ml (interquartile range: 0.10-0.17)] groups. Presence of mpMRI morphological features was not significantly different between groups. Subjective Likert-assessment discriminated patients with significant cancer better than PI-RADS_v2. Inter-reader percentage agreement was 83% for subjective Likert-assessment and 56% for PI-RADS_v2. CONCLUSION: PSAD may categorize presence of significant cancer in patients with Likert-scored 3/5 PZ mpMRI findings. Advances in knowledge: PSAD may be used in indeterminate PZ mpMRI to guide decisions between biopsy vs monitoring. [Mh] Termos MeSH primário: Imagem por Ressonância Magnética/métodos Antígeno Prostático Específico/sangue Neoplasias da Próstata/sangue Neoplasias da Próstata/diagnóstico por imagem [Mh] Termos MeSH secundário: Adulto Idoso Idoso de 80 Anos ou mais Biomarcadores Tumorais/sangue Seres Humanos Biópsia Guiada por Imagem Masculino Meia-Idade Estudos Retrospectivos [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Biomarkers, Tumor); EC 3.4.21.77 (Prostate-Specific Antigen) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180226 [Lr] Data última revisão: 180226 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 171201 [St] Status: MEDLINE [do] DOI: 10.1259/bjr.20170645

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