Orientadores: Ubirajara Ferreira, Wagner Eduardo Matheus / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-14T02:30:40Z (GMT). No. of bitstreams: 1 Stopiglia_RafaelMamprin_M.pdf: 1039972 bytes, checksum: dbe43d140e3febb1ab34ec6ff75b33be (MD5) Previous issue date: 2009 / Resumo: A prostatite assintomática é definida através da detecção laboratorial do aumento de células inflamatórias em secreções uretrais ou urina após massagem da glândula prostática e também detectada em biópsias. Esta alteração inflamatória é reconhecidamente uma causa de elevação dos níveis do PSA. Devido esta elevação também estar associada ao câncer prostático, desenvolvemos um estudo para avaliar a correlação entre prostatite assintomática com a referida doença maligna. No período de janeiro de 2006 à dezembro de 2007 foram selecionados 200 pacientes com idade variando entre 50 e 75 anos e com PSA maior de 2,5ng/ml e menor de 10ng/ml, para pesquisa de prostatite inflamatória assintomática nessa população. Desses pacientes, 98 (49%) apresentaram diagnóstico de prostatite assintomática inflamatória ou tipo IV através de exames laboratoriais com o teste de Meares-Stamey modificado (1). Em seguida, foram randomizados em 2 grupos: Grupo 1 com 49 pacientes que foram tratados com cloridrato de ciprofloxacin 500mg (antibiótico) 2 vezes ao dia por 4 semanas e grupo 2 com 49 pacientes que usaram placebo da mesma forma. No seguimento, o PSA foi dosado após o tratamento e todos os pacientes foram submetidos à biópsia transrretal da próstata. Foram excluídos do estudo pacientes com idade menor de 50, maior de 75 anos, os que recusaram a biópsia, os que apresentaram PSA maior que 10ng/ml devido à maior incidência de tumor (2) e os pacientes que não aceitaram participar do estudo após a aplicação do termo de consentimento. Como resultados, no grupo 1, dos 49 pacientes que receberam antibiótico, 26 (53,06%) apresentaram diminuição do PSA e desses, 7 (26,9%) foram diagnosticados com câncer de próstata na biópsia. Dos 49 pacientes do grupo 2 que receberam placebo, 29 (59,18%) apresentaram diminuição do PSA, sendo que 9 (31%) tiveram câncer na biópsia. Não houve diferença estatística nos grupos estudados, tanto com relação a diminuição do PSA após o tratamento (53,06% X 59,18%) (p=0,10), quanto a presença de tumor nas biópsias nesses casos (26,9% X 31%) (p=0,06). Embora não demonstrada diferença estatística comparado com placebo, foi observado taxa de 26,9% de câncer de próstata na biópsia dos pacientes que apresentaram diminuição do PSA após uso de antibiótico, os quais provavelmente não seriam diagnosticados. Como conclusão a existência de câncer de próstata em pacientes com prostatite assintomática é aproximadamente um terço, mesmo após a diminuição do PSA com tratamento antibiótico / Abstract: Asymptomatic prostatitis is defined through the laboratorial detention of the increase of inflammatory cells in urethral secretions or piss after massage of the prostate gland and also detected in biopsies. This inflammatory alteration is admittedly a cause of rise of the levels of the PSA. Had this rise also to be associated to the prostate cancer, we develop a study to evaluate the correlation between asymptomatic prostatitis with the related malignant illness. In the period of January of 2006 to the December of 2007, 200 patients with age varying between 50 and 75 years and with PSA bigger of 2,5ng/ml and minor of 10ng/ml had been selected, for research of asymptomatic inflammatory prostatitis in this population. Of these patients, 98 (49%) had presented diagnosis of inflammatory asymptomatic prostatitis or type IV through laboratorial examinations with the test of modified Mears-Stamey (1). After that, they had been randomized in 2 groups: Group 1 with 49 patients who had been dealt with ciprofloxacin cloridrate 500mg (antibiotic) 2 times to the day per 4 weeks and group 2 with 49 patients who had used placebo in the same way. In the pursuing, the PSA was dosed the treatment after and all the patients had been submitted to the trans rectal biopsy of the prostate. They had been excluded from the study patient with lesser age of 50, greater of 75 years, the ones that had refused the biopsy, the ones that had presented bigger PSA that 10ng/ml due to bigger incidence of tumor (2) e the patients whom they had not accepted to after participate of the study the application of the assent term. As results, in group 1, of the 49 patients who had received antibiotic, 26 (53.06%) had presented reduction of the PSA and of these, 7 (26.9%) had been diagnosed with cancer of prostate in the biopsy. Of the 49 patients of group 2 that they had received placebo, 29 (59.18%) had presented reduction of the PSA, being that 9 (31%) had had cancer in the biopsy. It did not have difference statistics in the studied groups, as much with regard to reduction of the PSA after the treatment (53.06% X 59.18%) (p=0,10), how much the presence of tumor in the biopsies in these cases (26.9% X 31%) (p=0,06). Although not demonstrated to difference statistics compared with placebo, tax of 26,9% of cancer of prostate in the biopsy of the patients was observed who had presented reduction of the PSA after antibiotic use, which they would probably not be diagnosed. As conclusion the existence of cancer of prostate in patients with asymptomatic prostatitis is approximately one third, exactly after the reduction of the PSA with antibiotic treatment / Mestrado / Cirurgia / Mestre em Cirurgia

Orientador: Wagner José Fávaro, Ubirajara Ferreira / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-25T23:53:11Z (GMT). No. of bitstreams: 1 SilvaJunior_MauricioMoreira_M.pdf: 2314249 bytes, checksum: be24263c754c5e69f527d328e09d006b (MD5) Previous issue date: 2014 / Resumo: Caracterização do Estroma Reativo na Progressão do Câncer de Próstata: Envolvimento dos Fatores de Crescimento, Metaloproteinases da Matriz, Receptores de Hormônios Sexuais e Células-Tronco Prostáticas RESUMO A contribuição do estroma para a progressão do câncer de próstata (CaP) ainda é pouco conhecida. As células neoplásicas podem alterar seu componente estromal adjacente para formar um ambiente que possibilita e suporta a progressão tumoral. A modificação desse estroma é denominado de estroma reativo (EstR), o qual ocorre em muitos tipos de cânceres humanos relacionando-se à progressão e recidiva tumorais. Os fatores de crescimento e as metaloproteinases da matriz (MMP) são altamente expressos no CaP e podem atuar como fatores de crescimento parácrinos e/ ou autócrinos. As relações entre os hormônios sexuais esteróides e seus receptores com os fatores de crescimento e MMPs são cruciais reguladores da homeostase prostática, sendo fundamental o entendimento dessas relações com o desenvolvimento do EstR e progressão do CaP. Além disso, a ocorrência das células-tronco prostáticas cancerosas representam um passo importante na patogênese glandular. Assim, os objetivos principais do presente estudo foram caracterizar morfológica e molecularmente o microambiente do EstR em amostras com CaP, bem como encontrar alguma associação dos fatores de crescimento, MMPs, receptores de hormônios sexuais esteróides e células-tronco cancerosas na sua patogênese. Além disso, verificou-se a relevância da reatividade estromal e de seus marcadores moleculares na progressão do CaP.O presente trabalho baseou-se em estudo retrospectivo, o qual utilizou 40 amostras prostáticas de pacientes, na faixa etária de 60 a 80 anos, com diagnóstico de CaP. Tais amostras foram divididas em 2 grupos (20 amostras por grupo): Grupo 1: amostras de CaP sem estroma reativo; Grupo 2: amostras de CaP com intensa reatividade estromal; e posteriormente submetidas à análises histopatológicas e imunohistoquímicas. Os resultados demonstraram que o EstR foi caracterizado morfologicamente pela significativa diminuição das fibras musculares lisas e pela abundante quantidade de fibras colágenas no estroma adjacente aos ácinos neoplásicos. Intensa reatividade estromal foi verificada nos tumores de graus intermediário (Gleason 7, 3+4) e alto (Gleason 7, 4+3). Com relação à caracterização molecular do EstR, os presentes resultados demonstraram imunorreatividades aumentadas para vimentina, IGF-1, MMP-2, FGF-2 e C-Myc nas amostras com intensa reatividade estromal quando comparadas às amostras sem reatividade estromal. As imunorreatividades para AR e ER'alfa' foram aumentadas nas amostras prostáticas com intensa reatividade estromal Em contraste, a imunorreatividade para o ER'beta' foi aumentada nas amostras sem reatividade estromal. Com relação à ocorrência das células-tronco prostáticas cancerosas, estas ocorreram com maior frequência no estroma com intensa reatividade estromal. Considerando os dados em conjunto, pode-se concluir que o EstR pode ser considerado um marcador preditivo o da progressão do CaP, uma vez que este foi mais frequente nos tumores de intermediário e alto graus. As imunorreatividades aumentadas para vimentina, IGF-1, MMP-2, FGF-2 e C-Myc foram fundamentais para a ativação do EstR e tornaram o microambiente prostático favorável à progressão do câncer, devido a potencialização do desequilíbrio da interação epitélio-estroma. As imunorreatividades aumentadas para AR e ER? demonstraram o envolvimento desses receptores tanto na sinalização para o aumento dos fatores de crescimento e metaloproteinases da matriz quanto nos mecanismos de ativação do EstR. Em contraste, a sinalização do ER? indicou papel inibitório desse receptor nos mecanismos de ativação do EstR e na progressão tumoral. Finalmente, a ocorrência de células-tronco prostáticas cancerosas indicou um possível envolvimento dessas células na sinalização para o desenvolvimento do EstR e progressão do CaP / Abstract: haracterization of Reactive Stroma in the Progression of Prostate Cancer: Involvement of Growth Factors, Matrix Metalloproteinases, Receptors, Sex Hormones and Prostatic Stem Cells ABSTRACT The contribution of the stroma to the progression of prostate cancer (CaP) cancer is still unknown. The cancer cells can alter their adjacent stromal component to form an environment that enables and supports tumor progression. A modification of this is called the stroma reactive stroma (EstR), which occurs in many types of human cancers relating to the progression and tumor recurrence. Growth factors and matrix metalloproteinasys (MMP) are highly expressed in CaP and can act as a paracrine and / or autocrine growth factors. The relationship between sex steroid hormones and their receptors with growth factors and MMPs are crucial regulators of prostatic homeostasis, a fundamental understanding of these relationships with the development and progression of Estr of CaP. Moreover, addition, the occurrence of prostate stem cells cancer represent an important step in the pathogenesis glandular. Thus, the main objectives of this study were to characterize the morphological and molecular microenvironment EstR in samples with CaP as well as find some association of growth factors, MMPs, sex steroid hormone receptors and cancer stem cells in its pathogenesis. Furthermore, we verified the relevance of stromal reactivity and its molecular markers in the progression of CaP. The present work was based on a retrospective study, which used 40 prostate samples from patients, aged 60-80 years, diagnosis of CaP. These samples were divided into 2 groups (20 samples per group): Group 1: CaP samples without reactive stroma; Group 2: CaP samples with intense stromal reactivity; and subsequently subjected to histopathological and immunohistochemical analyzes. The resulted showed that EstR was morphologically characterized by the significant reduction of smooth muscle fibers and the abundant amount of collagen fibers in the stroma adjacent to the neoplastic acini. Intense reactivity was observed in stromal tumors of intermediate grades (Gleason 7, 3 +4) and high (Gleason 7, 4 +3). With respect to the molecular characterization of EstR, our results showed increased vimentin immunoreactivity, IGF-1, MMP-2, FGF-2 and C-Myc in samples with intense stromal reactivity when compared to samples without stromal reactivity. The immunoreactivity for AR and ER'alfa' were elevated in prostatic stromal samples with intense reactivity In contrast, immunostaining for ER"beta' was increased in samples with no stromal reactivity. With regard to the occurrence of prostate cancer stem cells, they occurred more frequently in the stroma with intense stromal reactivity. Considering the data together, we can conclude that the EstR can be considered a predictive marker of the progression of CaP, since this was more common in tumors intermediate, and high grades. The immunoreactivity increased vimentin, IGF-1, MMP-2, FGF-2 and C-Myc were essential for the activation of rd and made a favorable microenvironment for prostate cancer progression due to the potentiating imbalance of epithelial-stromal interaction. The immunoreactivity increased to AR and ER? demonstrated the involvement of these receptors in signaling both to the increase of growth factors and matrix metalloproteinasys as the engine that activation EstR. In contrast, ER? showed inhibitory signaling role of this receptor in the mechanism of activation of the rd and in tumor progression. Finally, the occurrence of prostate cancer stem cells indicated a possible involvement of these cells in signaling for EstR development and progression of CaP / Mestrado / Fisiopatologia Cirúrgica / Mestre em Ciências

Abstract Prostate cancer is the most common solid tumor among men in Western industrialized countries. A major problem in prostate cancer treatment is the development of androgen-independence, as androgen-deprivation therapy is the basic therapy for the disease. Molecular mechanisms behind prostate cancer and androgen-independent growth development are poorly known. In this study, subtractive hybridization was used for the generation of a cDNA library specific for prostate cancer. Analysis of the cDNA library revealed over-expression of several ribosomal proteins namely L4, L5, L7a, L23a, L30, L37, S14 and S18, in prostate cancer cell lines. Over-expression of L7a and L37 was also confirmed in prostate cancer tissue samples. Further, cDNA array was used in order to examine differentially expressed genes in androgen-dependent and androgen-independent prostate cancer cell line LNCaP. Monoamine oxidase A, an Expressed Sequence Tag (EST) similar to rat P044, and EST AA412049 were highly over-expressed in androgen-dependent LNCaP cells. Tissue-type plasminogen activator, interferon-inducible protein p78 (MxB), an EST similar to galectin-1, follistatin, fatty acid-binding protein 5, EST AA609749, annexin I, the interferon-inducible gene 1-8U and phospholipase D1 were highly over-expressed in androgen-independent LNCaP cells. The EST similar to rat P044, the EST similar to galectin-1, follistatin, annexin I and the interferon-inducible gene 1-8U were also expressed in benign prostatic hyperplasia tissue. The Y-linked ribosomal protein S4, Mat-8, and EST AA307912 were highly expressed in benign prostatic hyperplasia tissue. In situ hybridization of mouse embryos and adult mouse tissues revealed the expression of TMPRSS2 in the epithelium throughout the gastrointestinal, urogenital and respiratory tracts during development. In human multiple tissue RNA dot blot, the highest level of expression was detected in prostate, and lower levels in colon, stomach and salivary gland. TMPRSS2 transcript levels were significantly higher in prostate cancer tissue between benign and malignant epithelium of prostate cancer patients with untreated disease. Similarly, in poorly differentiated adenocarcinomas, expression in malignant tissue was significantly higher. Enzymatic mutation detection and direct sequencing of TMPRSS2 coding region revealed only one deletion in aggressive disease among 9 non-aggressive and 9 aggressive prostate cancer samples. No other mutations were found. Detected 7-base pair deletion leads to premature stop codon and disruption of serine protease substrate binding and catalytic active site. We cloned several potential genes whose expression is changed during prostate cancer initiation or progression. These genes may serve as prostate cancer markers, and further studies are needed to clarify the expression of these proteins during the disease.

Abstract Prostate cancer is the most frequently diagnosed cancer in men in industrialized countries. Despite the substantial clinical importance of the disease, the mechanisms underlying the development and progression of prostate cancer are poorly understood. In the present study, fragment analysis of chromosome arm 16q was carried out with the aim of searching for sites of consistent chromosomal deletion, possibly uncovering the location of target genes that become inactivated in prostate carcinogenesis. The highest percentage of loss of heterozygosity (LOH) was found at chromosomal region 16q24.1-q24.2, including the gene for 17β-hydroxysteroid dehydrogenase/17-ketosteroid reductase (17HSD/KSR) type 2, HSD17B2. The data further indicated an association between loss of the most commonly deleted region and clinically aggressive features of the disease. A fragment analysis performed using sequential primary and locally recurrent prostate cancer specimens suggested the location of the genes related to prostate cancer progression to be at 16q24.3 and, further, gave rise to a hypothesis of the potential role of locus HSD17B2 as a prognostic marker for prostate cancer progression. Quantitative real-time polymerase chain reaction (PCR) revealed a decreased HSD17B2 gene copy number in prostate cancer specimens compared to their normal counterparts. A diminished HSD17B2 gene copy number was significantly associated with poor differentiation of the tumor. The progression of prostate cancer during androgen deprivation is a serious clinical problem, the molecular mechanisms of which largely remain to be clarified. The present data of enzyme activity measurements performed using high-performance liquid chromatography (HPLC) provided evidence of a substantial decrease in oxidative and an increase in reductive 17HSD/KSR activity during the transition of prostate cancer LNCaP cells into an androgen-independent state. Further, the changes detected in the activities largely coincided with the changes in the relative expression levels of genes for the potential 17HSD/KSR isoenzymes; 17HSD/KSR types 2, 5, and 7, as evidenced by relative quantitative reverse transcription PCR (RT-PCR). The data on the expression analysis of mRNA for 17HSD/KSR types 5 and 7 in prostate tissue specimens performed using in situ hybridization showed a moderately low but constitutive level for 17HSD/KSR7 mRNA in tissues of cancerous as well as hyperplastic origin. The expression of mRNA for 17HSD/KSR type 5, instead, varied considerably between different specimens, the highest expressions being strongly associated with aggressive and metastatic prostate cancer. Interestingly, furthermore, the intense expression of 17HSD/KSR5 was significantly associated with the androgen deprivation achieved either surgically or medically. Since 17HSD/KSRs critically contribute to the control of the bioavailability of active sex steroid hormones locally in the prostate, the variation in intraprostatic 17HSD/KSR activity might be crucially involved in the regulation of the growth and function of the organ.

Objetivos: La calidad de vida de pacientes en estadios III y IV de cáncer de próstata disminuye significativamente debido a varios factores como: efectos secundarios al tratamiento, pronóstico de la enfermedad, entre otros. Este estudio busca describir qué áreas de la calidad de vida son más afectadas y en qué medida, en pacientes con tratamiento antineoplásico. Material y métodos: El estudio es descriptivo transversal. Se calculó un tamaño muestral de 81 pacientes. Se incluyeron a aquellos entre 50 y 80 años, con diagnóstico histopatológico de cáncer de próstata en estadios clínicos III y IV y que recibieron tratamiento entre 3 meses y 2 años en el INEN. Para evaluar calidad de vida se empleó el UCLA-PCI-SF y el SF-12 v2. Para evaluar riesgo de episodio depresivo mayor se empleó el test de Zung abreviado. Resultados: Se incluyeron 82 pacientes. La edad media fue 68,2, el 51.2% tenía estadio III y el 48.8% estadio IV. El 7,3% recibió radioterapia, 56% terapia hormonal y 36.7% tratamiento combinado. Las áreas más afectadas fueron la función sexual y urinaria con una mediana de puntaje de 2.5 y 43.75, respectivamente. El 57.3% de los pacientes presentó riesgo de desarrollar un episodio depresivo mayor. Conclusión: La calidad de vida está afectada significativamente en pacientes con cáncer de próstata avanzado, siendo la función sexual la más comprometida. Un alto porcentaje tuvo riesgo de depresión mayor. Se recomienda introducir intervenciones de salud mental e intervenciones para abordar la disfunción sexual en este grupo de pacientes.

Prostate cancer is the third most common cancer in men globally, and the most common cancer among men in the United States. Dietary choices may play an important role in developing prostate cancer; in particular, a higher dairy product intake has been associated with an increased risk of developing prostate cancer. The overall positive association between milk consumption and the risk of prostate cancer development and prostate cancer mortality has been well documented in multiple epidemiological studies. However, there is limited literature on the association between types of milk, as classified by fat content (skim, low fat, and whole), and the risk of developing prostate cancer. When further examining current state of the literature on this topic, there is a number of epidemiologic studies assessing the relationship between prostate cancer and milk consumption. On the contrary, very few experimental studies explore this topic. Further experimental research may be necessary to examine the relationship between dairy and dairy products consumption and the increased risk of development of prostate cancer. At this time, there are no formal clinical recommendations regarding dairy products consumption for patients who are at risk of prostate cancer development or who have a history of prostate cancer. In this manuscript, we sought to systematically review the existing literature on the association between milk consumption classified by fat content, and the risk of developing prostate cancer. These findings may be useful for the clinicians who provide recommendations for the patients at risk of developing prostate cancer.

Prostate cancer is the most common newly diagnosed non-skin cancer and the second leading cause of cancer death in men. It is a unique neoplasm because of the large discrepancy between its clinical incidence and the much higher incidence of latent cancer. Predicting the prognosis of prostate cancer, especially the cancers detected incidentally or by screening, remains a clinically important problem. Immunoreactivity for Onco-antigen 519 (OA- 519), a recently described fatty acid synthase (FAS), has been associated with poor prognosis in breast cancers. The authors have previously shown that its detection in prostate cancer correlated with high-grade, large volume, and advanced stage tumors. This study examines the association between OA- 519 immunoreactivity in primary prostate cancer and disease progression. The authors used immunohistochemistry with an affinity-purified anti-OA-519 antibody and examined primary prostate cancers (stages A1 to D1) from 99 men with a mean follow-up of 4 years (range= 2 to 9.3). Survival analysis was used to evaluate differences in progression-free survival. OA-519 immunoreactivity was seen in 56 (57%) of the 99 primary prostate cancers examined. OA-519-positive cancers were more likely to progress than the OA- 519-negative cancers (P < .04). Univariate survival analysis showed that OA- 519 (FAS), histological grade (Gleason score), and clinical stage were significant predictors of disease progression. Multivariate analyses of all cases showed that only histological grade was significant. However, multivariate analysis of the 85 cancers with Gleason scores 2-7 (ie, low to intermediate grade) showed OA-519 (FAS) immunoreactivity to be the only statistically significant predictor of cancer progression (P<.02). Expression of the fatty acid synthase OA-519 by prostate cancers is potentially a clinically useful predictor of disease progression. It appears to be independent of histological grade (Gleason score), at least in cancers with low to intermediate grades. Further studies are needed to evaluate the role of fatty acid synthase in malignancy and the potential therapeutic implications of enzyme blockers.

Apesar de existir novas técnicas e múltiplas alternativas terapêuticas para o câncer de próstata localmente avançado, esta enfermidade se constitui em um grande problema de saúde pública mundial, resultando em índices significativos de morbidade e mortalidade, gerando desta forma um desafio para urologistas e oncologistas. Existem múltiplas e bem sucedidas estratégias de tratamento da doença localizada, tais como: a prostatectomia radical, a radioterapia externa conformacional, a braquiterapia e a crioablação. Em contraste, o tratamento da doença metastática e localmente avançada, freqüentemente necessita da alguma forma de bloqueio hormonal. Não existe consenso em vários aspectos da terapia hormonal para tumores localmente avançados tais como: o tipo de bloqueio androgênico a ser usado, terapia hormonal precoce ou tardia, associação com outras modalidades terapêuticas e o uso de bloqueio intermitente. Foi realizada uma revisão crítica deste tipo de tratamento, bem como as indicações atuais de bloqueio hormonal nos tumores de próstata localmente avançado. Não existem estudos prospectivos e randomizados que comparem as diversas formas de tratamento cirúrgico versus radioterápico do câncer de próstata localmente avançado. A hormonioterapia adjuvante à prostatectomia radical, na doença localmente avançada, parece reduzir a progressão tumoral bioquímica, porém, não há estudo que evidencie melhora na sobrevida livre de metástase ou na sobrevida global. O bloqueio androgênico neoadjuvante à prostatectomia radical aumenta a proporção dos pacientes com doença órgão-confinada e margens cirúrgicas negativas, porém sem efeito nas taxas de falha bioquímica do tratamento. A terapia hormonal adjuvante à radioterapia em pacientes portadores de câncer de próstata localmente avançado oferece vantagens na sobrevida global. A terapia hormonal neoadjuvante à radioterapia, em estudos multicêntricos e randomizados, resulta em melhor controle local do tumor bem como prolonga a sobrevida doença-específica. Não há, porém evidência de melhora na sobrevida global. O tratamento por tempo prolongado com bloqueadores hormonais adjuvante à radioterapia mostrou-se superior em relação à sobrevida global e sobrevida livre de doença quando comparado a um período curto de bloqueio, principalmente em pacientes com tumores indiferenciados (Gleason 8-10). Os análogos LHRH, orquiectomia ou o dietilestilbestrol se mostraram como opções de monoterapia, igualmente eficazes, para os pacientes que iniciam terapia hormonal de primeira linha, no tratamento da doença localmente avançada. Não existe evidência que justifique o bloqueio androgênico máximo como terapia hormonal de primeira linha ao invés de monoterapia. Existem vantagens potenciais na qualidade de vida e nos custos do tratamento quando realizada a ablação intermitente, mas a sua eficácia a longo prazo necessita ser confirmada / Despite new techniques and multiple therapeutic alternatives, locally advanced prostate cancer is a serious public health problem, resulting in significant morbidity and mortality rates, that remains a great challenge for urologists and oncologists. Several therapeutic strategies to treat localized prostate cancer have been successful such as conformational external beam radiation therapy, brachytherapy and cryoablation. In contrast, treatment of metastatic and locally advanced tumors may often involve androgenic suppression. However, there are no consensus on several aspects of hormonal therapy for locally advanced tumors such as the type of antiandrogenic drug to be used, early versus delayed hormonal therapy, association with other therapeutic modalities and the use of intermittent blockade. We set out to critically review important aspects and current indications of hormonal blockade in the locally advanced prostate tumors. There are no prospective and randomized study that compares current forms of surgical treatment versus radiation therapy of locally advanced prostate cancer. After radical prostatectomy, adjuvant hormonal therapy in the locally advanced disease reduces biochemical failure rates, although no benefit has been shown regarding metastatic free survival or overall suvival. Neoadjuvant androgen blockade enhances the proportion of patients with organ-confined disease and negative surgical margins but no benefit is seen regarding biochemical free recurrence. Neoadjuvant hormonal therapy to the radiotherapy improves local tumor control as well as it prolongs the diseasespecific survival, although there are no survival advantage. Adjuvant hormonal therapy offers overall survival advantage in patients with locally advanced prostate cancer treated with radiotherapy Long term adjuvant hormonal blockade offers survival benefit for patients with high Gleason score (8-10). LHRH analogues, bilateral orquiectomy and dietilestilbestrol were shown are equally effective as adjuvant therapy for patients with locally disease advanced. There are evidences that maximum androgenic blockade are not more efficient than monotherapy. Potential quality of life and costs advantages of intermittent ablation could be considered an alternative treatment for this group of patient

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2007. / Härtill 4 uppsatser.

Thesis (Ph. D.)--University of Washington, 2004. / Vita. Includes bibliographical references (leaves 164-179).