Several cancers are associated with abnormal serum concentrations of tumor markers such as prostate specific antigen (PSA) in prostate tumor diseases, alfa-fetoprotein (AFP) or human chorionic gonadotrophin (hCG) in germ cell tumors or persistent gestational trophoblastic diseases (GTD). Cancer treatment should induce decline of serum tumor marker concentrations. The predictive values of many kinetic parameters supposed to characterize tumor marker declines such as nadir, time-point cutoff, half-life, time to normalization etc..., have been reported in previous studies. However very few of them have been used in routine due to the lack of outcome reproducibility. Population pharmacokinetic approach-based modeling is already used in pharmacokinetic studies. It might be helpful to characterize tumor marker decline equations dynamically and overcome limitations of previous studies. The feasibility and the relevance of this approach were assessed in 4 studies involving: PSA titers in patients with prostate adenoma or cancer treated with surgery; hCG-AFP in non-seminomatous germ cell tumor patients treated with BEP regimen (Bleomycin-Etoposide-Cisplatin) and hCG in GTD patients treated with methotrexate. Tumor marker decline modeling was feasible in all studies provided the methodology was adjusted to marker specificities. Apparent clearance of hCG and PSA might enable identification of patients with unfavorable decline profiles and thereby with high risk of relapse. Confirmatory studies with independent cohorts of patients are warranted

Background: To compare the clinical value of the measurement of complex and total PSA in the discrimination between benign prostatic hyperplasia (BPH) and prostate cancer. Methods: In serum samples collected from 166 men with histopathologically proven clinically localized prostate cancer and of 97 men with BPH, total prostate-specific antigen (PSA), complexed PSA and the free to total PSA ratio were determined. The statistical analysis was done by the comparison of the receiver operator characteristic (ROC) curves. Results: The areas under the ROC curves were 0.776 for total PSA, 0.799 for complexed PSA (total PSA vs. cPSA: p < 0.0001) and 0.812 for the free to total PSA ratio. With a cut-off of 3.0 ng/ml for complexed PSA, the sensitivity was 90%, the specificity 58%, the positive and the negative predictive values 79 and 78%, respectively. With a cut-off of 4.0 ng/ml for total PSA, the sensitivity was 87%, the specificity 59%, the positive and the negative predictive values were 78 and 72%, respectively. Conclusions: There was a statistically significant advantage for complexed PSA compared to total PSA in the discrimination between BPH and prostate cancer. The difference was, however, small and its clinical relevance is questionable. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Submitted by Vasti Diniz (vastijpa@hotmail.com) on 2017-09-08T14:06:42Z No. of bitstreams: 1 arquivototal.pdf: 2742380 bytes, checksum: cf8f43acdec2329a5d6d78a8a373b6b7 (MD5) / Made available in DSpace on 2017-09-08T14:06:42Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 2742380 bytes, checksum: cf8f43acdec2329a5d6d78a8a373b6b7 (MD5) Previous issue date: 2017-04-20 / The finding of sperm through the screening tests on samples collected from rape victims confirms the occurrence of the sexual act, but its absence usually closes biological research in the crime in question, leaving a gap about the authorship of the crime, as well as about the criminal typification. The present work aimed to analyze the need of implementation in forensic routine of Genetics Laboratories of molecular analysis of negative samples to the prostate-specific antigen (PSA) collected from sex crimes victims. Vaginal swabs were selected and proceedings collected from 200 women who have been victims of those crimes in Paraíba from January 2015 to January 2016. Such materials had been sorted and presented negative result for PSA. Proceeded to the sample quantification by Real-time PCR using the Plexor® HY kit and there was a far greater concentration of autosomal DNA in relation to the male DNA. With the use of thermal cyclers GeneAmp® PCR System 9700, 200 DNA samples extracted from the sperm fraction (SF) were amplified for Y-STR with the use of PowerPlex® Y23 Systems and AmpFlSTR® Yfiler PCR Amplification kits. Such products have been subjected to capillary electrophoresis in genetic sequencer ABI PRISM™ 3500 Genetic Analyzer and the results analyzed by GeneMapper® ID software v 3.2. The fractions analyzed, only two full profiles amplification (1%), 24 (12%) partials, while the 174 remaining samples (87%) did not present any amplification. Screening with PSA testing negative served, statistically, how to determine guiding absence of sperm in swabs of vaginal origin and anally for victims of sex crimes. However, in this study were analyzed samples from rape victims. Due to the large social call caused by this type of crime, any nonzero statistic must be acceptable to a presumptive test. The results obtained have awakened to the need to study a new way of sorting this material, as well as the repetition of some analytical steps in order to get a genetic profile informative for illicit criminal resolution. / A constatação de espermatozoides, através dos testes de triagem, em amostras coletadas de vítimas de estupro confirma a ocorrência do ato sexual, todavia a sua ausência geralmente encerra a investigação biológica no crime em questão, ficando uma lacuna quanto à autoria do delito, bem como quanto à tipificação penal. O presente trabalho objetivou analisar a necessidade de implantação na rotina dos laboratórios de genética forense da análise molecular de amostras negativas para o antígeno específico da próstata (PSA) coletadas de vítimas de crimes sexuais. Foram selecionadas swabs vaginais e anais coletados de 200 mulheres que foram vítimas desses crimes na Paraíba entre os meses de janeiro de 2015 e janeiro de 2016. Tais materiais haviam sido triados e apresentaram resultado negativo para PSA. Procedeu-se à quantificação amostral por PCR em tempo real, com uso do kit Plexor® HY e observou-se uma concentração bem maior de DNA autossômico com relação ao DNA masculino. Com uso de termocicladores GeneAmp® PCR System 9700, 200 amostras de DNA extraído das frações espermáticas (FE) foram amplificadas para Y-STR com o emprego dos sistemas PowerPlex® Y23 System e AmpFlSTR® Yfiler® PCR Amplification. Tais produtos foram submetidos à eletroforese capilar em seqüenciador genético ABI PRISM 3500™ Genetic Analyzer e os resultados analisados pelo software GeneMapper® ID v3.2. Das frações analisadas, constatou-se amplificação de apenas dois perfis completos (1%), 24 parciais (12%), enquanto as 174 amostras restantes (87%) não apresentaram amplificação alguma. O teste de triagem com PSA negativo serviu, estatisticamente, como norteador para se determinar a ausência de esperma em swabs de origem vaginal e anal das vítimas de crimes sexuais. Contudo, no presente trabalho foram analisadas amostras provenientes de vítimas de estupro. Devido ao grande apelo social provocado por esse tipo de crime, nenhuma estatística diferente de zero deve ser aceitável para um teste presuntivo. Os resultados obtidos despertaram para a necessidade de estudar uma nova forma de triagem desse material, bem como pela repetição de alguns passos analíticos no intuito de se obter um perfil genético informativo para resolução do ilícito penal.

Introdução: O câncer de próstata é a neoplasia maligna não-cutânea mais frequente nos homens brasileiros. Seu rastreamento é tema controverso na literatura, e a maioria das entidades médicas não recomenda sua realização a partir dos 70 anos. Não existem estudos sobre suas características nessa faixa etária da população brasileira, que não é submetida a rastreamento ativo sistemático. Objetivos: Avaliar a prevalência e critérios de agressividade do câncer de próstata diagnosticado por rastreamento ativo em homens com idade inferior e superior a 70 anos no Brasil. Pacientes e métodos: Estudo transversal retrospectivo incluindo 17.571 voluntários no Brasil, submetidos a rastreamento ativo através de toque retal e dosagem sérica do antígeno prostático específico (PSA), entre janeiro de 2004 e dezembro de 2007. Os critérios de indicação para a biópsia foram: PSA>4,0ng/ml, ou PSA entre 2,5 e 4,0ng/ml com relação PSA livre/total <=15%, ou toque retal suspeito. Todos os homens rastreados foram divididos em dois grupos etários: grupo A, entre 45 e 69 anos; grupo B, acima de 70 anos. Os grupos foram comparados com relação a prevalência e critérios de agressividade da doença (valor do PSA sérico, escore de Gleason da biópsia e estadiamento clínico TNM). Resultados e discussão: A prevalência do câncer de próstata na nossa amostra foi de 3,71%. O grupo dos homens com mais de 70 anos apresentou prevalência da doença 2,9 vezes maior (RP 2,90; p <0,001), o valor médio de PSA foi mais elevado nos acometidos (17,28ng/ml no grupo B versus 9,54ng/ml no grupo A), assim como ocorreu maior chance de haver portadores de câncer com PSA acima de 10,0ng/ml (OR 2,63; p=0,003). No grupo de homens com mais de 70 anos também houve uma prevalência 3,59 vezes maior do padrão histológico mais agressivo (Gleason 8-10: RP 3,59; p<0,001) e maior prevalência de doença metastática (RP 4,95; p<0,05). Conclusão: O rastreamento do câncer de próstata nos homens com idade acima de 70 anos e expectativa de vida superior a 10 anos pode ser relevante no Brasil. Neste grupo etário detectamos uma maior prevalência desta doença, quando comparado ao grupo de idade entre 45 e 69 anos. Nosso estudo também demonstrou que o grupo de homens com mais de 70 anos possui maior probabilidade de apresentar doença de alto risco ao diagnóstico (PSA sérico mais elevado e em faixas de maior risco; escore de Gleason 8 a 10 e disseminação metastática à distância mais frequentes) / Background: Prostate cancer (PC) is the leading non-cutaneous malignancy among Brazilian men. PC may present as an indolent or aggressive life-threatening disease. There is no consensus in the literature regarding PC screening, and most medical organizations do not recommend it over the age of 70 years old. There are no studies in the literature addressing this topic in the Brazilian population. Objectives: To compare the prevalence and the aggressiveness of prostate cancer diagnosed, by active screening, in men under and over 70 years. Patients and methods: We performed a retrospective cross-sectional study including 17,571 volunteers. Screening was performed by digital rectal examination and prostatespecific antigen (PSA) measurement. Individuals who met the criteria for PC suspicion (PSA>4.0ng/ml, or PSA 2.5-4.0ng/ml with free/total PSA ratio <=15%, or suspicious digital rectal examination) underwent prostate biopsy. Those diagnosed with cancer were staged. The screened men were stratified by age in two groups: group A, between 45 and 69 years old, and group B, over 70 years old. The groups were compared regarding PC prevalence and its aggressiveness criteria (seric PSA value, Gleason score from biopsy and TNM staging). Results and discussion: The prevalence of prostate cancer was 3.71% in all population. The group of men over 70 years old had disease prevalence 2.9 times higher (RP 2.90; p<0.001); higher mean PSA value in men diagnosed with prostate cancer (17.28ng/ml vs. 9.54ng/ml); and greater likelihood to present PC when PSA level was above 10.0ng/ml (OR 2.63; p=0.003), when compared with men between 45 and 69 years old. The group of men aged over 70 years also presented a prevalence of histologic aggressive disease 3.59 times higher (Gleason 8-10: RP 3.59, p<0.001) and greater prevalence of metastatic disease (RP 4,95; p<0,05). Conclusion: Our study reveals that men over 70 years old presented a higher prevalence of prostate cancer and a higher probability to present high-risk disease at diagnosis (higher PSA; Gleason score 8-10 and metastatic disease more frequent), when compared to men aged 45-69 years. Screening for prostate cancer in men aged over 70 years and life expectancy over 10 years may be relevant in Brazil

Introdução: Os micro RNA (miRNA) são formados a partir de RNA precursores de fita dupla que contém entre 60 a 110 nucleotídeos e formam estruturas do tipo hairpin. Imediatamente após sua transcrição pela RNA polimerase II a enzima Dicer promove a clivagem do RNA precursor em seqüências menores contendo 19 a 22 nucleotídeos. Após a clivagem, o miRNA integra-se ao complexo silenciador induzido pelo RNA (RISC) que o conduz ao seu RNA mensageiro (mRNA) homólogo recém transcrito. Esta associação promove a degradação do mRNA, ou interfere na tradução da proteína caracterizando um grande mecanismo de controle da expressão dos genes. Este mecanismo está relacionado ao desenvolvimento de órgãos e tecidos, e está envolvido no processo de carcinogênese. Nosso objetivo é identificar um perfil de expressão de miRNA que defina o adenocarcinoma de próstata de prognóstico favorável e desfavorável considerando os níveis de PSA e dados anatomopatológicos. Materiais e métodos: Foram selecionados 53 pacientes com tumores desfavoráveis (mediana do escore de Gleason igual a 8, 79,2% estadiados pT3, mediana de PSA 10,1 ng/mL e mediana do volume tumoral de 23%) e 45 considerados favoráveis (mediana do escore de Gleason igual a 5, 80% estadiados pT2, mediana de PSA de 7,8 ng/mL e mediana do volume tumoral de 11,5%). O controle foi representado por 7 pacientes com hiperplasia prostática benigna (HPB). Todos os pacientes foram submetidos a prostatectomia radical pelo mesmo cirurgião. Os espécimes cirúrgicos foram examinados na sua totalidade pelo mesmo patologista. A análise dos miRNA foi feita a partir de tecido congelado e tecido incluído em parafina usando a técnica da reação em cadeia da polimerase em tempo real quantitativa (qRT-PCR) utilizando primers e sondas Taqman® específicas. O RNU43 foi usado como controle interno. Resultados: Com exceção dos miRNA 199a, 21, 15a, 16 e 25 que se mostraram subexpressos tanto nos casos desfavoráveis como nos favoráveis, houve uma diminuição global na expressão dos miRNA com redução estatisticamente significativa na expressão dos miRNA 143, 145 e 146a, 191, 218 e Let7c em tumores desfavoráveis em relação aos tumores favoráveis. Conclusão: Demonstramos que no processo de transição entre os carcinomas favoráveis e desfavoráveis de próstata existe uma perda global na expressão de miRNA que podem ser importantes controladores de expressão de uma série de genes relacionados a progressão desta neoplasia. Dados experimentais avaliando o papel desses miRNA devem ser conduzidos para que possamos definir seu papel na evolução do câncer de próstata / Introduction: micro RNA (miRNA) are formed from double-stranded RNA precursors that contain between 60-110 nucleotides and form structures such as hairpin. Immediately after their transcription by RNA polymerase II, the enzyme Dicer promotes the cleavage of precursor RNA sequences containing minor 19-22 nucleotides. After cleavage, the miRNA is part of the RNA-induced silencing complex (RISC) that leads to its messenger RNA (mRNA) newly transcribed counterpart. This association promotes the degradation of mRNA, or interferes with the protein translation characterizing a great mechanism for controlling gene expression. This mechanism is related to the development of organs and tissues, and may be involved in the process of carcinogenesis. Our goal is to identify a miRNA expression profile that distinguishes prostate adenocarcinoma of favorable and unfavorable prognosis considering the PSA and pathological findings. Material and Methods: We studied 53 patients with tumors considered unfavorable (Median of Gleason score 8, 79.2% staged pT3, median of PSA 10.1 ng/mL and median of tumor volume of 23%) and 45 considered favorable (Median of Gleason score 5, 80% staged pT2, median of PSA 7.8 ng/mL and median of tumor volume of 11.5%). The control group was represented by seven patients with benign prostatic hyperplasia (BPH). All patients underwent radical prostatectomy by the same surgeon. The surgical specimen was examined entirely by the same pathologist. The analysis of miRNA was made from frozen and paraffin embedded tissue by quantitative real-time polymerase chain reaction (qRT-PCR) using the Taqman® specific primers and probes. The RNU43 was used as a internal control. Results: Except for miRNAs 199a, 21, 15a, 16 e 25 that were underexpressed by both favorable and unfavorable prostate cancer, there was a global decrease of all miRNAs studied, and some differences were statistically significant as miRNAs 143, 145 e 146a, 191, 218 e Let7c that were underexpressed in unfavorable carcinomas compared favorable tumor. Conclusion: We have demonstrated that in the process of transition between favorable and unfavorable prostate cancer there is a global loss of expression of miRNAs. These molecules can be important controllers of a series of genes related to cancer progression. Experimental studies are needed in order to comprehend the role of these genes in prostate carcinogenesis

INTRODUÇÃO: O câncer de próstata é a segunda causa de morte relacionada ao câncer nos Estados Unidos e no Brasil. Sua incidência tem aumentado significativamente após a década de 90 devido a implantação de programas de rastreamento pelo PSA, que embora seja considerado um método sensível para identificar os pacientes com risco para o câncer de próstata, sua especificidade é considerada baixa. O objetivo foi desenvolver e validar nomogramas para estimar a probabilidade de câncer de próstata e câncer de próstata indolente em pacientes submetidos a um rastreamento oportunístico. MÉTODOS: Trata-se de um estudo observacional transversal baseado em uma coorte de pacientes atendidos pela Unidade Móvel de Prevenção e biopsiados no Departamento de Radiologia do Hospital de Câncer de Barretos entre janeiro de 2004 e dezembro de 2007. Os dados clínicos e patológicos foram coletados dos prontuários dos pacientes, seguindo uma ficha de coleta padronizada previamente elaborada e digitada em banco de dados no Software IBM® SPSS® Statistics 20.0.1 for Windows para posterior análise. Análises de regressão logística binária foram realizadas para avaliar o modo como cada um dos fatores em combinação permitiria supor a presença de câncer de próstata. RESULTADOS: Dos 1.639 pacientes que foram encaminhados para o Hospital de Câncer de Barretos para a realização da biópsia prostática, 553 (42,1%) tiveram confirmação histopatológica de adenocarcinoma prostático. Os tumores indolentes foram encontrados em 66 (5,0%) dos casos positivos. As análises de regressão logística forneceram uma área sob a curva ROC de 0,737 (IC 95% = 0,678 a 0,796) para predição do câncer de próstata e de 0,696 (IC 95% = 0,591 a 0,802) para predição de câncer de próstata indolente. CONCLUSÃO: Os modelos construídos apresentaram poder de predição razoável considerando-se os eventos estudados / BACKGROUND: Prostate cancer is the second leading cause of cancerrelated death in the United States and in Brazil. Its incidence has increased significantly after the 90\'s due to the implementation of PSA screening programs, despite being considered a sensitive method to identify patients at risk of prostate cancer, its specificity is considered low. The aim was to develop and validate nomograms to estimate the probability of prostate cancer and indolent prostate cancer in patients undergoing opportunistic screening. METHODS: This was a cross sectional observational study based on a cohort of patients seen at the Prevention Mobile Unit and biopsied in the Radiology Department of the Barretos Cancer Hospital between January 2004 and December 2007. The clinical and pathological data were collected from patient charts, following a standardized collection form previously completed and entered into the database in IBM® SPSS® Software Statistics 20.0.1 for Windows for further analysis. Binary logistic regression analyses were performed in order to assess how each factor in combination would predict the presence of prostate cancer. RESULTS: Out of the 1,639 patients who were referred to the Barretos Cancer Hospital for prostate biopsy, 553 (42.1%) had histopathological confirmation of prostatic adenocarcinoma. Indolent tumors were found in 66 (5.0%) of the positive cases. The logistic regression analyses provided an area under the ROC curve of 0.737 (95% CI = 0.678 to 0.796) for prediction of prostate cancer and 0.696 (95% CI = 0.591 to 0.802) for the prediction of indolent prostate cancer. CONCLUSION: The constructed models showed a reasonable predictive power, considering the events studied

Background: To compare the clinical value of the measurement of complex and total PSA in the discrimination between benign prostatic hyperplasia (BPH) and prostate cancer. Methods: In serum samples collected from 166 men with histopathologically proven clinically localized prostate cancer and of 97 men with BPH, total prostate-specific antigen (PSA), complexed PSA and the free to total PSA ratio were determined. The statistical analysis was done by the comparison of the receiver operator characteristic (ROC) curves. Results: The areas under the ROC curves were 0.776 for total PSA, 0.799 for complexed PSA (total PSA vs. cPSA: p < 0.0001) and 0.812 for the free to total PSA ratio. With a cut-off of 3.0 ng/ml for complexed PSA, the sensitivity was 90%, the specificity 58%, the positive and the negative predictive values 79 and 78%, respectively. With a cut-off of 4.0 ng/ml for total PSA, the sensitivity was 87%, the specificity 59%, the positive and the negative predictive values were 78 and 72%, respectively. Conclusions: There was a statistically significant advantage for complexed PSA compared to total PSA in the discrimination between BPH and prostate cancer. The difference was, however, small and its clinical relevance is questionable. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

This project is aimed toward finding DNA aptamers against prostate cancer peptide antigens. DNA aptamers can function to find and indicate the presence of certain molecules in a specimen. These aptamers will be obtained through the process of evolutionary selection, a specific process called SELEX which stands for Systemic Evolution of Ligands by Experimental Enrichment. By conducting several rounds of SELEX, a DNA aptamer will be selected to bind to a known peptide antigen. A biotinylated column will be utilized to stabilize a random library of DNA aptamers, and those peptides that bind to certain aptamers will cause a conformational change leading to the elution of those specific DNA aptamers. This SELEX process will be conducted again on the eluted aptamers to further select for strong binding DNA aptamers. The DNA aptamers that are obtained can further on be sequenced or used for prostate cancer research studies. Another possible usage of aptamers is to diagnose and determine the stage of various different cancer types. Our prediction is that this research will produce a DNA aptamer that will bind to a specific prostate cancer peptide antigen.

The goal of this research work was to understand the clinical-pharmacology based treatment approaches for sorafenib. Treatment with sorafenib is associated with high inter-patient variability in pharmacokinetic exposures, efficacy and toxicity. We explored the demographic, laboratory, clinical and pharmacogenetic factors to elucidate the sources of variability. In addition, we examined the impact of pharmacogenetic variation in VEGFR2, an important mediator of the VEGF pathway, on risk of prostate cancer. To support these investigations, (mainly single-dose) pharmacokinetic, pharmacogenetic, efficacy and toxicity information were collected from patients with solid tumors, enrolled in five phase I / II clinical trials at National Cancer Institute. Non-compartmental analysis-general linear modeling (NCA-GLM), population pharmacokinetic analysis and several correlative studies were performed to characterize the sources of variability in pharmacokinetics and response. The role of prostate specific antigen (PSA) and ex-vivo anti-angiogenic activity as efficacy markers was evaluated, respectively, for patients with prostate cancer treated with sorafenib and patients with solid tumors treated with combination of sorafenib and bevacizumab. Sweat concentrations of sorafenib were measured to study its association with development of hand-foot skin reaction (HFSR). Only body weight was a significant covariate for volume of distribution by population pharmacokinetic analysis, while BSA, albumin and UGT1A9*3 appeared to be significant by NCA-GLM. However, the contribution of these covariates in overall exposure variability was very small; hence, these were considered clinically irrelevant. The association of sorafenib exposure with efficacy in patients with prostate cancer, colorectal cancer and combined solid tumors were not significant; exposure-efficacy relationship for lung cancer patients requires further evaluation. Sorafenib exposures appeared to be associated with incidences of rash in single agent trials and with HFSR in trials involving treatment with sorafenib and bevacizumab combination. In-vitro cell-line experiments determined that prostate specific antigen (PSA) is not a suitable marker of efficacy in patients with prostate cancer treated with sorafenib. The ex-vivo anti-angiogenic activity, measured by rat-aortic ring assay using patient serum samples, appeared to be not associated with clinical response. Sorafenib concentration in sweat, upto ≥5 ng/mL, apparently was not associated with HFSR. The VEGFR2 H472Q polymorphism was associated with progression-free survival (PFS) (with an apparent heterozygous advantage for survival) and toxicities in patients treated with drugs against the VEGF pathway. Patients who developed hypertension and HFSR on bevacizumab and sorafenib therapy, respectively, appeared to have longer PFS. Therefore, these side effects should be effectively managed to avoid/delay the treatment discontinuation. The VEGFR2 H472Q and V297I genotype were not predictive of risk of prostate cancer in Caucasian subjects.

Lorsqu'un biomarqueur est mesuré de façon répétée au cours du suivi de patients, il est d'abord nécessaire d'établir un critère, issu du profil d'évolution longitudinal du marqueur, afin de détecter la survenue d'un événement, ou d'en prédire la gravité. Nous avons développé une méthode de modélisation robuste de données longitudinales, afin de calculer les différents critères pour les patients, et d'en comparer les performances diagnostiques ou pronostiques. Dans un second temps, il faut déterminer un seuil de ce critère quantitatif au dessus ou en dessous duquel le test diagnostique est considéré comme positif. Une méthode Bayésienne d'estimation de ce seuil et de son intervalle de crédibilité a été développée. Ce travail a été appliqué au diagnostic de persistance locale de cellules cancéreuses après traitement par ultrasons d'un cancer de la prostate. Ce diagnostic est effectué à partir des mesures répétées d'antigène spécifique de la prostate (PSA), dont le nadir a été retenu, avec différents seuils, comme meilleur critère diagnostique. Ceci permet de n'effectuer des biopsies que lorsqu'il y a de fortes chances qu'elles soient positives. / For the early diagnosis or prognosis of an event in presence of repeated measurements of a biomarker over time, it is necessary to define a criterion, stemming from the longitudinal profiles of that marker. A method was developed for a robust modelling of marker measurements, to calculate the various criteria for the patients, and compare their diagnostic or prognostic accuracies. Using the continuous criterion as a diagnostic test requires the specification of a threshold. A Bayesian method was developed to estimate this threshold and its credible interval. This method was applied to the diagnosis of local prostate cancer persistence after an ultrasound treatment. The diagnosis relies on serial measurements of prostate specific antigen (PSA), whose nadir (along with several thresholds) was found to be the best diagnostic criterion. This allows to trigger biopsy only when this biopsy is likely to be positive.