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Controversias con el Antígeno Prostático Específico

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  • National Society of History of Medicine of Venezuela
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Abstract

RESUMEN Los motivos de ésta presentación es manifestar la preocupación que existe en el medio urológico mundial acerca de la controversia entre la asociación americana de urología (AUA) y la asociación europea de urología (EAU) en relación a la practica de los Cribados o Tamizaje de Población (Screening), que para los primeros no son procedentes por los costos económicos y psicológicos que causan y para los segundos son vitales ya que disminuye la mortalidad enfermedad-especifica en los pacientes detectados con elevaciones del PSA y que son llevados a diagnostico y tratamientos definitivos. El segundo motivo es que vemos como se están haciendo biopsias prostáticas innecesarias relacionadas con los valores absolutos de PSA total, ocasionando problemas de detección de canceres indolentes o clínicamente insignificantes y problemas de angustia tanto en el paciente como en su medio familiar circundante. El punto culminante de la investigación médica actual es dilucidar que cánceres prostáticos son indolentes y que cánceres son letales. Para eso se están dedicando miles de millones de dólares al año en investigaciones para sacar a la luz marcadores tumorales prostáticos que sean más específicos. Ahora bien no hay duda que el PSA es el mejor marcador tumoral que tenemos en la actualidad y desde 1980 cambió para siempre la expectativa de vida de los pacientes con cáncer de próstata, al punto que antes 3 de cada 4 pacientes al momento de su diagnostico eran incurables, hoy en día es lo contrario 3 de cada 4 pacientes son curables y eso gracias al antígeno prostático especifico que permite diagnósticos precoces. De lo que se trata es de hacer más juiciosa las indicaciones de estudios diagnósticos en pacientes con PSA total fuera de rango, ya que ocasionan deterioro en la calidad de vida de los pacientes y muchas veces ocasionan tratamientos innecesarios. ABSTRACT The reasons of this presentation is to show the concern in the media about the global urological dispute between the American Urological Association (AUA) and European Association of Urology (EAU) in relation to the practice of screening, that the former are not coming for economic and psychological costs that cause and for the latter are vital as it reduces disease-specific mortality in patients with elevations of PSA detected and are brought to definitive diagnosis and treatment. The second reason is that we see as unnecessary prostate biopsies are doing related to the absolute values of total PSA, causing problems of detecting indolent or clinically insignificant cancers and anxiety problems in both the patient and their family environment surrounding. The highlight of current medical research is to elucidate which prostate cancers are indolent and lethal cancers. For that you are spending billions of dollars a year on research to expose prostate tumor markers that are more specific. Now there is no doubt that the PSA is the best tumor marker that we have today and since 1980 has forever changed the life expectancy of patients with prostate cancer, to the

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The search for molecular markers of benign prostatic hyperplasia in general is based on an analysis of a limited number of biopsy samples. Little is known about the homogeneity of the expression of key genes in different zones of the prostate. We studied the intraprostatic (that is within the same gland) and inter-prostatic (that is between glands) variability of 5 alpha-reductase 2 (5aR2) gene expression. Ten tissue samples removed by open prostatectomy were the source of tissue specimens. Two frozen sections were generated from each of several random biopsies taken from each adenoma immediately after enucleation, 1 of which was used for 5aR2 gene expression analysis and 1 for morphometric analysis. Results among biopsies were compared using the 5 alpha-reductase index (ratio of 5 alpha-reductase expression to an internal standard measured as electrophoretic band intensity). Morphometric composition was determined for smooth muscle, collagen, epithelium and glandular lumens. Statistical comparisons were performed with ANOVA by pairwise multiple comparison (Dunn) and Spearman's rank correlation procedure. For the 71 biopsies analyzed mean 5 alpha-reductase index was 0.23 +/- 0.16 and overall tissue distribution was smooth muscle 34%, collagen 35%, epithelium 14% and glandular lumens 17%. Inter-prostate and intraprostate variability in 5 alpha-reductase index was statistically significant (p = 0.004) as was the variability in stromal-to-epithelial ratio (p = 0.012). The 5 alpha-reductase index showed strong correlation with stroma (%) and negative correlation with epithelium (%). Benign prostatic hyperplasia is heterogeneous in terms of tissue morphometry and expression of single important genes. This finding limits the use of single biopsy based markers to predict biological behavior, and has significant impact on the ability of distinguishing longitudinal changes in tissue composition from sampling artifacts.
Article
To provide the first update of the EAU guidelines on assessment, therapy and follow-up of men with lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO). A systematic literature review was conducted based on the results of a MEDLINE search concentrating on the years 1999-2003. In combination with expert opinions recommendations were made on the usefulness of diagnostic tests, therapeutic options and follow-up. During initial assessment the following tests are recommended: medical history, physical examination including digital-rectal examination, International Prostate Symptom Score, urinalysis, serum creatinine and prostate specific antigen measurement, uroflowmetry and post-void residual volume. All other tests are optional or not recommended. Aim of treatment is to improve LUTS and quality of life and to prevent severe BPE-related complications. Development of a 5alpha-reductase type I and II inhibitor and the data of the MTOPS trial providing scientific evidence for a combination therapy were the most significant innovations since the first version. Finally a more detailed knowledge on the natural history with identification of several risk factors for progression is the basis for a risk-profile orientated (preventive) therapy. Updated recommendations for assessment, treatment, and follow-up of patients with LUTS due to BPO are presented.
Article
To determine the prevalence and importance of pain/discomfort on ejaculation (prostatitis-like symptom) in men with lower urinary tract symptoms (LUTS) diagnosed with clinical benign prostatic hyperplasia (BPH). Baseline data from 5096 men reporting LUTS suggestive of BPH, and enrolled in the ALF-ONE study by general practitioners and urologists in Europe, Asia, Latin America, the Middle East and Canada, were analysed to determine the prevalence and significance of pain/discomfort on ejaculation. All the men were asked to complete the International Prostate Symptom Score (IPSS) questionnaire, the bother score (IPSS question 8), and the Danish Prostate Symptom Score sexual-function questionnaire (DAN-PSSsex) which assesses three symptoms (rigidity of erection, amount of ejaculate and pain/discomfort on ejaculation) and their bothersomeness. There were 3700 sexually active men who had an evaluable answer to the DAN-PSSsex question related to pain/discomfort on ejaculation. Of these, 688 (18.6%) reported pain/discomfort on ejaculation and 609 (88%) considered it was a problem. Patients with painful ejaculation had more severe LUTS and reported greater bother (P < 0.001). Of men with painful ejaculation, 72% reported erectile dysfunction, of whom 91% considered it a problem, and 75% reported reduced ejaculation, of whom 81% considered it a problem. By contrast, of men with no ejaculatory discomfort, 57% reported erectile dysfunction, of whom 79% considered it a problem, and 56% reported reduced ejaculation, of whom 57% considered it a problem. A history of urinary tract infection was reported by 12% of men in the ejaculatory pain group, compared with 7% in the LUTS-only group, while 5% of men in the ejaculatory pain group reported macroscopic haematuria, compared to 3% in the LUTS-only group. Men with ejaculatory pain were slightly younger, but there were no significant differences in duration of LUTS, history of acute urinary retention, prostate-specific antigen concentrations or maximum urinary flow rate compared to the LUTS-only group. Of sexually active men with LUTS suggestive of BPH, approximately 20% complain of specific prostatitis-like symptoms of pain/discomfort on ejaculation, and these men clearly differ from those who present with LUTS only. For most the symptom is a significant bother. Men with BPH and painful ejaculation have more severe LUTS and reported greater bother, and had a higher prevalence of erectile dysfunction and reduced ejaculation, than men with LUTS only. Evaluation and treatment strategies should address this population of men with symptoms suggestive of both prostatitis and BPH.
Article
The lack of cure with medical therapy implies life-long treatment emphasising the need for a thorough understanding of the long-term outcome. We review the natural history, markers for progression, placebo effect, efficacy, pharmacoeconomic aspects, and preventive measures. Literature review with particular reference to long-term controlled studies using plant extracts, alpha1-blockers, 5alpha-reductase inhibitors (5-ARIs), and combination therapy. There is a long-lasting (>or=12 mo) placebo response of symptoms (20% decrease) and maximum flow rate (10% rise). The five long-term controlled trials of plant extracts are inconclusive and therefore their role in contemporary medical management is still controversial. The alpha1-blockers provide fast amelioration of symptoms yet have no relevant impact on the risk of acute urinary retention or surgery. Combination therapy should be reserved for moderately or severely symptomatic patients with a high risk of progression; in the majority of patients the alpha1-blocker can be safely stopped after 6-12 mo. The preventive use of 5-ARIs in men with no or mild symptoms at risk of progression is scientifically sound yet not generally accepted mainly for economic reasons. A sharp contrast exists between the duration of the longest controlled trial (4.5 yr) and the situation in real life with treatment periods up to one or two decades of life. Real-life and registry data will be the only source of this important information in the future.
Article
Learning Objectives After completing this course, the reader will be able to: Take advantage of the use of total PSA thresholds for predicting prostate cancer risk and determining the need for prostate biopsy.Distinguish prostate cancer from benign conditions based on the relative proportions of complexed and free forms.Use PSA density as a means to correct for the effect of prostate volume on the PSA level.Explain the evolving role of PSA kinetics in the prediction of aggressive prostate cancer.Perform the calculations for PSA velocity and PSA doubling time. CME Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com For more than a decade, prostate-specific antigen (PSA) has been used for prostate cancer screening. Over the years, this screening has been continually refined, including investigation into the use of lower total PSA thresholds, PSA isoforms, and PSA kinetics. This review describes the evolution of prostate cancer screening and provides clinical insights into the informed use of PSA and its adjunctive measurements.
Article
Many patients diagnosed with low grade and early stage prostate cancer have indolent disease and may not benefit from immediate therapy. In patients referred for biopsy following community screening we validated the Kattan and Steyerberg nomograms for predicting indolent disease in a contemporary urological practice. A total of 296 patients who underwent prostate biopsy and radical prostatectomy at a single institution were identified for nomogram validation. All patients had clinically localized, stage T1c or T2a and biopsy Gleason score 6 prostate cancer. Clinical and biopsy pathological information was compared to surgery pathology results for nomogram validation with indolent disease defined as surgical Gleason score 6 or less, tumor volume less than 0.5 cc and organ confined disease. Nomogram performance was assessed by the ROC curve. Of the patients 27.4% had pathologically indolent disease at prostatectomy. Based on pretreatment variables the Kattan and Steyerberg nomograms were able to predict indolent disease with similar discrimination levels (AUC 0.777 and 0.772, respectively). Two previously described nomograms performed equally well for predicting indolent disease. These data further establish the role of validated nomograms for clinical decision making for managing screening detected prostate cancer.
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Vis AN, Schöder FH, Van der Kwast TH. Characteristics of prostate cancer in different prostate-specific antigen ranges. In: Kurth KH, Mickisch GH, Schröder FH, Editores. Renal, bladder, prostate and testicular cancer, an update. New York: The Parthenon Publishing Group Inc; 97-111, 2000
PSA Testing Continues to Polarize Medical Community' Medscape Medical News Oncology Cancer
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Roxanne Nelson. 'PSA Testing Continues to Polarize Medical Community' Medscape Medical News Oncology Cancer Epidemiol Biomarkers Prev. 2012;21:391-394, 395-397, 2012
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The role of inflammation in the pathogenesis of prostate cancer
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AUA Practice Guidelines Committee
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American Urological Association
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