Niveaux-de-preuves-pour-lutilisation-du-PSA-et-des-autres-biomarqueurs-dans-la-dtection-prcoce-du-cancer-de-la-prostate-2014

CNBH Association Franỗaise dUrologie Collốge National de Biochimie des Hụpitaux Sociộtộ Franỗaise de biologie Clinique Sociộtộ franỗaise de mộdecine Nuclộaire – Groupe de Biologie Spécialisée GROUPE DE BIOLOGIE DE LA PROSTATE Niveaux de preuves pour l’utilisation du PSA et des autres biomarqueurs dans la détection précoce du cancer de la prostate Review of evidence for the use of PSA and other biomarkers in the early detection of prostate cancer Coordonnateur du groupe de travail: Pierre-Jean Lamy1 pierre-jean.lamy@icm.unicancer.fr Et Anne-Sophie Gauchez2 asgauchez@chu-grenoble.fr Laurent Salomon laurent.salomon@hmn.aphp.fr Margaret Haugh4 mhaugh@medicom-consult.com Jocelyn Ceraline5 jocelyn.ceraline@chru-strasbourg.fr Yvonne Fulla6 yvonne.fulla@gmail.com Agnès Georges7 agnes.georges@chu-bordeaux.fr Stéphane Larré8 stephanelarre@yahoo.fr Sylvain Loric9 sylvain.loric@hmn.ap-hop-paris.fr Elisabeth Luporsi10 e.luporsi@nancy.unicancer.fr Pierre-Marie Martin11 pierre-marie.martin@mail.ap-hm.fr Catherine Mazerolles12 mazerolles.c@chu-toulouse.fr Vincent Molinié13 vincent.molinie@chu-fortdefrance.fr Pierre Mongiat-Artus14 pierre.mongiat-artus@sls.aphp.fr Jacques Piffret15 jacques.piffret@orange.fr Franỗois Thuillier16 thuillierfrancois@sfr.fr Paul Perrin17 paul.perrin@chu-lyon.fr Xavier Rebillard18 xavier.rebillard@wanadoo.fr, et le groupe de relecture du biologie de la prostate : Drs, David Azria, Maguy Bernard, Karim Chick, Cyril Clavel, Stéphane Culine, Olivier Cussenot, Alexandre de la Taille, Aurélien Descazeaud, David Guenet, Franỗois Iborra, Jacques Irani, Igor Latorzeff, Marie-Pierre Moineau, Didier Peiffert, Pierre Richaud, Jean Marc Riedinger, Pascal Rischmann, Franỗois Rozet, Corinne Sault, Virginie Vlaeminck-Guillem Biologie Spộcialisộe et Oncogénétique, CRLC Val d’Aurelle, Montpellier France UMR-S INSERM 1039, Institut de Biologie et de Pathologie CHU Grenoble, France Service d'Urologie, APHP CHU Henri Mondor, Créteil, France MediCom Consult, Villeurbanne, France UMR_S 1113, FMTS, Université de Strasbourg, Strasbourg, France Sociộtộ Franỗaise de Mộdecine Nuclộaire, Paris, France Médecine Nucléaire, CHU Bordeaux, France Service d'urologie, CHU de Reims, Reims, France Biochimie clinique et génétique, APHP CHU Henri Mondor Créteil, France 10 Service d’Oncologie, Centre Alexis Vautrin, Nancy, France 11 Laboratoire de Transfert d’Oncologie Biologie, APHM, Marseille, France 12 Laboratoire d'Anatomie et Cytologie Pathologiques, IUCT Oncopole 1, Toulouse, France 13 Laboratoire d'Anatomie et Cytologie Pathologiques CHU La Meynard Fort de France, France 14 Service d'urologie, APH, CHU Saint-Louis, Paris, France 15 Association Franỗaise dUrologie, Paris, France 16 Sociộtộ Franỗaise de Biologie Clinique, Collốge National de Biochimie des Hôpitaux Paris, France 17 Service d'urologie, Hôpital Lyon-Sud, Hospices Civils de Lyon, Lyon 18 Clinique Beausoleil, Montpellier, France RESUME Contexte: Malgré des preuves contradictoires sur le bénéfice de l'utilisation de l'antigène prostatique spécifique (PSA) pour la détection précoce du cancer de la prostate celui-ci est actuellement largement utilisé De nouveaux biomarqueurs visant améliorer la valeur prédictive du PSA sont également utilisés Objectif: Examiner systématiquement les données scientifiques sur l'utilisation du PSA et d'autres biomarqueurs pour la détection précoce du cancer de la prostate Acquisition des données: nous avons cherché dans PubMed les essais cliniques et des études publiés entre 2000 et mai 2013, évaluant le PSA et d'autres biomarqueurs pour la détection précoce du cancer de la prostate, étude qui comprenait plus de 200 sujets Le niveau de preuve de l’utilité clinique a été évalué en utilisant un système d’évaluation spécifique aux marqueurs tumoraux Un total de 84 publications, correspondant 70 essais et études ont été sélectionnés pour cette revue Synthèse: Six essais cliniques randomisés évaluant le PSA ont été identifiés, mais quatre présentaient des faiblesses méthodologiques Bien que ces essais aient inclus un grand nombre de sujets avec un long suivi, leurs résultats présentent des limites qui sont dues la contamination (par des dosages antérieurs du PSA) dans le groupe de contrôle, la qualité du suivi de ce groupe et de la variabilité dans les méthodes Malgré ces limites, nous avons attribué un niveau de preuve IA (le plus élevé) pour l’utilisation du PSA pour la détection précoce, mais nous ne recommandons pas son utilisation dans le dépistage de masse Les biomarqueurs émergents ont été évalués dans les études cas-témoins et de cohorte prospectives: PCA3 (n = 3); kallicréines (n = 3); [-2] ProPSA n = 5); oncogènes de fusion (n = 2) Ces études ont utilisé les résultats des biopsies pour le cancer de la prostate pour déterminer la spécificité et la sensibilité des tests, mais elles n’ont pas évalué l'effet sur la mortalité Le niveau de preuve attribué était III-C, insuffisant pour une utilisation en clinique Conclusions: Le PSA peut être utilisé pour la détection précoce du cancer de la prostate, mais le dépistage de masse n’est pas recommandé Les études sur d'autres biomarqueurs suggèrent qu'ils pourraient être utilisés, individuellement ou en combinaison, pour améliorer la sélection des patients avec des niveaux élevés de PSA en vue de la réalisation d’une biopsie, mais des essais cliniques évaluant leur impact sur la gestion du cancer de la prostate et sur la mortalité sont nécessaires ABSTRACT Context: Despite conflicting evidence for the benefit of using of prostate specific antigen (PSA) screening in the early detection of prostate cancer (PCa), is currently widely used New biomarkers aiming to improve the predictive value of PSA are also used Objective: To systematically review the evidence for the use of PSA and other biomarkers in the early detection of prostate cancer Evidence acquisition: We searched PubMed for clinical trials and studies assessing PSA and other biomarkers in the early detection of prostate cancer, published between 2000 and May 2013 that included >200 subjects The level of evidence (LOE) for clinical utility was evaluated using the tumor marker utility grading system A total of 84 publications, corresponding to 70 trials and studies were selected for inclusion in this review Evidence synthesis: Six randomised controlled trials (RCTs) assessing PSA were identified but four were found to have methodological weaknesses Although these trials included large numbers of subjects and long-term follow-up, their limitations include contamination in the control group, lower quality follow-up in this group and variability in methods Despite these limitations, we attributed a level of evidence (LoE) of IA to PSA for early PCa detection, but we not recommend its use in mass screening Emerging biomarkers were assessed in prospective case-control and cohort studies: PCA3 (n=3); kallikreins (n=3); [-2]proPSA n=5); fusion oncogenes (n=2) These studies used biopsy results for prostate cancer to determine specificity and sensitivity, but they did not assess the effect on PCa mortality The LoE attributed was III-C Conclusions: PSA can be used for early prostate cancer detection but mass screening is not recommended Studies on other biomarkers suggest that they could be used, individually or in combination, to improve the selection of patients with elevated PSA levels for biopsy, but RCTs assessing their impact on prostate cancer management and mortality are needed Message pour les patients: Dans cette étude nous avons recherché quelles sont les preuves scientifiques pour l’utilisation du PSA et des autres biomarqueurs pour détecter précocement un cancer de la prostate Le PSA reste le marqueur diagnostique standard du cancer de la prostate Plus le PSA est élevé plus le risque du cancer est grand A des niveaux élevés (> 10ng/mL), il y a un intérêt non discutable de rechercher un cancer par biopsie Nous n’avons pas de preuves permettant de valider un dépistage de masse utilisant le PSA Pour les autres biomarqueurs, les données suggèrent un intérêt de leur utilisation dans la sélection des patients avec un PSA élevé qui auraient besoin d’une biopsie Néanmoins cela doit être confirmé dans des essais cliniques dédiés Patient summary: In this study, we reviewed evidence for the use of PSA and other biomarkers for the early detection of prostate cancer PSA remains the standard diagnostic biomarker in prostate cancer PSA level is a continuous risk factor of prostate cancer At high levels (>10ng/mL) the need for further investigation, e.g biopsy is generally accepted We did not find any evidence to support mass PSA screening Data for other biomarkers suggest that these may have a role to play in selecting subjects with elevated PSA levels for biopsy but well-designed RCTs assessing their impact on prostate cancer management are needed Introduction Prostate cancer is the second most frequently diagnosed cancer in men worldwide (899 000 new cases, 13.6% of the total) and the fifth most common cancer overall More than 70% of the cases occur in developed countries (644 000 cases) The incidence of prostate cancer varies worldwide, with the highest rates observed in Australia/New Zealand (104.2 per 100,000), and the lowest in South-Central Asia (4.1 per 100 000) Incidence rates are relatively high in some developing regions such as the Caribbean islands, South America and sub-Saharan Africa This variation can be partly explained by differences in prostate specific antigen (PSA) testing and subsequent biopsies that are more frequently performed in countries with the highest incidence With an estimated 258 000 deaths in 2008, prostate cancer is the sixth cause of cancer death in men (6.1% of the total) Because PSA testing has a much greater effect on the incidence of prostate cancer than on its mortality rate, there is less variation in mortality rates worldwide (10-fold) than observed for incidence (25-fold) Prostate cancers, which occur mainly in older men, are often slow growing The worldwide weighted mean of the age-specific rates (ASR (W)) for prostate cancer mortality in developed regions is only twice that in developing regions (10.5 vs 5.6, respectively) These rates are generally higher in predominantly black populations (Caribbean, 26.3 per 100,000 and sub-Saharan Africa, 18-19 per 100 000), and very low in Asia (e.g 2.5 per 100 000 in Eastern Asia) and intermediate in Europe, North America and Oceania In Europe the incidence of prostate cancer is 59.3 per 100 000, with a mortality rate of 12.0 per 100 000 In France and the UK the mortality rates are similar, 12.7 and 13.8 per 100 000, respectively but the incidence is almost twice as high (118.3 and 64.0 per 100 000, respectively) This difference in the apparent incidence of prostate cancer may be explained by the fact that in France 50% of men ≥50 years have undergone PSA testing, compared with 10% in the UK The impact of PSA testing on the incidence of prostate cancer detection was demonstrated through the surveillance of the incidence of prostate cancer in the US [1] The introduction of PSA testing in the US resulted in an increase in the incidence of prostate cancer from 140/100 000 in 1987 to 240/100 000 in 1993 After this peak, there was a reduction in the incidence of detected prostate cancer to 170/100 000, because there were no more ‘undetected’ cancers, just new cancers developing This incidence remains, nevertheless, higher than that prior to the introduction of PSA testing in 1987 PSA is a glycoprotein that is produced mainly in the prostate epithelial cells In healthy men, PSA is generally concentrated in prostatic tissue and serum PSA levels are very low PSA is an organ-specific marker rather than tumour specific and serum levels can be elevated in the event of various non-malignant (e.g benign prostatic hyperplasia (BPH), prostatitis, trauma) and malignant prostatic diseases Increasing levels of serum PSA have been shown to be associated with a higher risk of prostate cancer [2] However, there is no clear-cut point that can differentiate insignificant cancers, which are not likely to be life-threatening, from those that are significant and likely to be life-threatening [2] Screening can help to detect chronic diseases and cancers in people before they develop symptoms with the aim of being able to offer treatment before it is too late In 1968 the World Health Organisation (WHO) commissioned a report on screening which, at that time, was becoming an important but controversial topic [3] The report listed criteria for screening Over the years, other criteria have been proposed but they are mainly based on the WHO criteria [4] One of these recent criteria is that there should be strong scientific evidence that the screening program is effective From a public health point-of-view, the aim of prostate cancer screening is to improve overall survival and from an individual point-of-view, the aim is to increase prostate cancer disease-free survival and decrease the prostate cancer-specific mortality rate In the USA prostate cancer screening began in the eighties when the majority of patients were diagnosed with advanced prostate cancer and a poor survival rate Screening resulted in prostate cancer being detected at earlier stages and therefore the patients had higher disease-free survival rates In addition, the lower PSA threshold introduced and the increased number of biopsy cores resulted in the detection and treatment of a large number of patients with low-volume and low-grade tumours [5] Prostate cancer screening is now widely used in the developed world, although the scientific evidence supporting its benefits is controversial One of the controversies concerns the choice between mass screening, i.e offering screening to all men after a certain age, or targeted or individual screening, i.e proposing screening to men ‘at risk’, also known as ‘early detection' Another controversy concerns the PSA cut-point since many studies have shown that there is a continuum of prostate cancer risk at all values of PSA and no cut-point with a simultaneously high specificity and high sensitivity [6, 7] Even at low PSA levels, e.g 2.1 ng/mL, the results from Prostate Cancer Prevention Trial (PCPT) showed a sensitivity of 52.6% and a specificity of 72.5% It is possible that some of the emerging biomarkers could improve the specificity of PSA and other prognostic factors and thus help in the management decision 10