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<Provider Id="sundheddkcms"> <Item Id="{A2618E4C-E629-4753-99F3-FF886440D76F}" Name="psa-forhoejet" Type="LHContentPage" ParentProviderId="sundheddkcms" ParentItemId="{488A3120-72F2-48D6-A3D5-6D54B0EC0D2E}" SortOrder="1300" PublishDate="2011-03-03T14:11:00" DeleteDate="2999-12-31T00:00:00" PotItemType=""> <Content> <HtmlField Name="PageContent"><![CDATA[<h2>Basisoplysninger</h2> <h3>Definition</h3> <ul> <li> Prostata specifikt antigen (PSA) er et organ- og ikke et tumorspecifikt glycopeptid</li> <li>Prostatas kirtelepitel producerer enzymet PSA med det formål at hindre semen i at koagulere </li> <li> I modsætning til i sædvejene er koncentrationen af PSA i blodet meget lavt </li> <li> PSA koncentrationen i blodet stiger i takt med den aldersrelaterede øgning af prostatavolumen (<a href="~/link.aspx?_id=3452EB9CC5FD415D9E38A1BE08FB318B&_z=z">benign prostatahyperplasi</a>) eller særligt i forbindelse med vævsskade som ved f.eks. prostatitis, cystitis, <a href="~/link.aspx?_id=1FB63E52817D4AEEA315EC48CA99E233&_z=z">urinretention</a>, instrumentering/bioptering eller <a href="~/link.aspx?_id=3A046BC097F0409886A99BB24469190A&_z=z">prostatakræft</a> </li> <li> De benigne tilstande bør derfor udelukkes i forbindelse med et isoleret tilfælde af lettere PSA-forhøjelse, ligesom man bør undgå at teste PSA i forbindelse med akut UVI eller urinretention</li> <li>I forbindelse med prostatakræft indgår PSA niveauet sammen med det kliniske tumorstadie og den histologiske gradering af biopsierne i risikostratificeringen og er vigtigt i monitorering af behandlingseffekt af prostatakræft<a title="Polascik TJ, Oesterling JE, Partin AW, Prostate specific antigen: a decade of discovery--what we have learned and where we are going. J Urol 1999;162: 293-306" href="%20" data-type="journal-reference" data-value="Polascik TJ, Oesterling JE, Partin AW, Prostate specific antigen: a decade of discovery--what we have learned and where we are going. J Urol 1999;162: 293-306" data-value-piped="Polascik TJ, Oesterling JE, Partin AW|Prostate specific antigen: a decade of discovery--what we have learned and where we are going.|J Urol|1999|162|293-306|10411025" data-url="reference-link" data-pubmedid="10411025">1</a></li> <li> Den positive prædiktive værdi af serum PSA niveauer (ng/ml) for samtidig prostatakræft målt hos asymptomatiske svenske mænd<a title="Hugosson J. European ranodomized study for prostate cancer: results of PSA-related screening in Göteborg. Parthenon Publishing Group, 1997: 179-184" href="%20" data-type="other-reference" data-value="Hugosson J. European ranodomized study for prostate cancer: results of PSA-related screening in Göteborg. Parthenon Publishing Group, 1997: 179-184" data-url="reference-link">2</a> (Figur 1):<img alt="Den positive prædiktive værdi af serum PSA niveauer (ng/ml) for samtidig prostatakræft målt hos asymptomatiske svenske mænd" src="A1C87539B2BA44EFA7227889B666438A-350-164" style="height: 164px; width: 350px;" title="Den positive prædiktive værdi af serum PSA niveauer (ng/ml) for samtidig prostatakræft målt hos asymptomatiske svenske mænd" height="164" width="350"> </li> <li>Anbefaling af den nedenstående aldersdifferentierede øvre PSA grænseværdi er begrundet i ønsket om, at øge PSA testens sensitivitet og derved opnå tidligere diagnostik af klinisk signifikant sygdom hos yngre mænd, samtidig med at øge PSA testens specificitet og derved nedsætte risikoen for overdiagnostik og deraf følgende risiko for overbehandling af latent sygdom hos ældre mænd</li> <li> <table> <tbody> <tr> <td><strong>Alder</strong></td> <td><strong>Øvre grænseværdi</strong></td> </tr> <tr> <td>Under 60 år</td> <td>>3,0 ng/ml</td> </tr> <tr> <td>60-70 år</td> <td>>4,0 ng/ml </td> </tr> <tr> <td>Over 70 år</td> <td>>5,0 ng/ml</td> </tr> </tbody> </table> </li> </ul> <h3>PSA testning/screening</h3> <ul> <li>I det tidlige klinisk lokaliserede tilfælde af prostatakræft vil forhøjet PSA typisk være eneste abnorme fund</li> <li>Skønt systematisk PSA-screening i store studier har vist at reducere den sygdomsspecifikke mortalitet, har det været på bekostning af en uacceptabel overdiagnostik og overbehandling<a title="Schröder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V, Kwiatkowski M, Lujan M, Lilja H, Zappa M, Denis LJ, Recker F, Berenguer A, Määttänen L, Bangma CH, Aus G, Villers A, Rebillard X, van der Kwast T, Blijenberg BG, Moss SM, de Koning HJ, Auvinen A, ERSPC Investigators., Screening and prostate-cancer mortality in a randomized European study. N Engl J Med 2009;360: 1320-8" href="/%20" data-type="journal-reference" data-value="Schröder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V, Kwiatkowski M, Lujan M, Lilja H, Zappa M, Denis LJ, Recker F, Berenguer A, Määttänen L, Bangma CH, Aus G, Villers A, Rebillard X, van der Kwast T, Blijenberg BG, Moss SM, de Koning HJ, Auvinen A, ERSPC Investigators., Screening and prostate-cancer mortality in a randomized European study. N Engl J Med 2009;360: 1320-8" data-value-piped="Schröder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V, Kwiatkowski M, Lujan M, Lilja H, Zappa M, Denis LJ, Recker F, Berenguer A, Määttänen L, Bangma CH, Aus G, Villers A, Rebillard X, van der Kwast T, Blijenberg BG, Moss SM, de Koning HJ, Auvinen A, ERSPC Investigators.|Screening and prostate-cancer mortality in a randomized European study.|N Engl J Med|2009|360|1320-8|19297566" data-url="reference-link" data-pubmedid="19297566">3</a></li> <li>PSA bør generelt kun testes hos mænd, som er grundigt orienteret om mulige konsekvenser af en forhøjet værdi</li> <li>I henhold til de landsdækkende <a href="https://www.dmcg.dk/Kliniske-retningslinjer/kliniske-retningslinjer-opdelt-paa-dmcg/daproca/opsporing-og-diagnostisk-udredning-af-prostatacancer/">DAPROCA retningslinjer</a> anbefales derfor følgende: <ul> <li><strong>1)</strong> PSA-testen bør tilbydes mænd med palpatorisk malignitetssuspekt hård, uregelmæssig eller asymmetrisk prostata, samt hos mænd > 45 år med symptomer, der rejser mistanke om prostatakræft, eksempelvis: <ul> <li><strong>a)</strong> Perineale smerter</li> <li><strong>b)</strong> Lymfødem svarende til genitalier og/eller underekstremiteter</li> <li><strong>c)</strong> Knoglesmerter</li> <li><strong>d)</strong> Gentagne tilfælde af hæmospermi </li> </ul> </li> <li><strong>2)</strong> <span>PSA-test kan tilbydes den velinformerede, familiært disponerede* mand > 45 år med en forventet restlevetid >10-15 år</span></li> <li><span><strong>* Familiær disposition</strong> gælder for mænd, hvis familie opfylder min. ét af følgende kriterier og som er 1. gradsslægtning** til en mand med prostatacancer</span> <ul> <li><span><strong>a)</strong> To 1. - eller 2. gradsslægtninge*** fra samme gren af familien diagnosticerede med klinisk betydende prostatacancer < 60 år</span></li> <li><span></span><strong>b)</strong> Tre indbyrdes 1. gradsslægtninge fra samme gren af familien, heraf minimum én diagnosticeret med klinisk signifikant prostatacancer < 60 år</li> </ul> </li> <li><span><strong>**1. gradsslægtninge</strong> omfatter far, brødre og sønner </span></li> <li><span><strong>***2. gradsslægtninge</strong> omfatter farfar og farbrødre samt morfar og morbrødre</span><span></span></li> <li><strong>3)</strong> <span>PSA-test kan tilbydes mænd > 40 år med en forventet restlevetid >10-15 år og påvist patogen BRCA2-variant. Opfølgende forløb forestås af urinvejskirurgisk afdeling </span></li> </ul> </li> <li><span></span>Mænd som opsøger læge for at få en generelt helbredskontrol eller undersøgelse for monosymptomatiske vandladningsgener (LUTS) med normal DRE (digital rektaleksploration), <strong>bør ikke</strong> automatisk have foretaget en PSA test og vil under alle omstændigheder først skulle informeres om den manglende evidens for værdi heraf samt evt. konsekvenser herved inden en diagnostisk test og undersøgelse påbegyndes.<a href="/EditorPage.aspx?da=core&id=%7BA2618E4C-E629-4753-99F3-FF886440D76F%7D&ed=FIELD7539693175&vs&la=da&fld=%7B850D32D3-55A1-49E4-9CDF-F0C88D91563C%7D&so=%2Fsitecore%2Fsystem%2FSettings%2FHtml%20Editor%20Profiles%2FRich%20Text%20LHPH&di=0&hdl=H7539693234&us=sitecore%5Cmibo&mo&pe=0&fbd=1" data-type="journal-reference" data-value="Østerø Í Jákupsstovu J, Brodersen J, Do men with lower urinary tract symptoms have an increased risk of advanced prostate cancer?. BMJ 2018;361: k1202" data-value-piped="Østerø Í Jákupsstovu J, Brodersen J|Do men with lower urinary tract symptoms have an increased risk of advanced prostate cancer?|BMJ|2018|361|k1202|29724877" data-url="reference-link" data-pubmedid="29724877" title="Østerø Í Jákupsstovu J, Brodersen J, Do men with lower urinary tract symptoms have an increased risk of advanced prostate cancer?. BMJ 2018;361: k1202">4</a> Se i øvrigt patientinformation om <a href="~/link.aspx?_id=37CA01C16D8D4384A4CBF040C39B7732&_z=z">PSA - prostata specifikt antigen</a></li> <li>Et Cochrane review <span>baseret på 339 artikler identificeret ved den systematiske gennemgang </span>bekræfter, at der mangler dokumentation for at anbefale systematisk PSA screening, og at risikoen for skadelige effekter forbundet med screening er uacceptabelt store<a title="Ilic D, Neuberger MM, Djulbegovic M, Dahm P. Screening for prostate cancer. Cochrane Database of Systematic Reviews 2013, Issue 1" href="http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004720.pub3/full" data-type="other-reference" data-value="Ilic D, Neuberger MM, Djulbegovic M, Dahm P. Screening for prostate cancer. Cochrane Database of Systematic Reviews 2013, Issue 1" data-url="http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD004720.pub3/full">5</a><sup>,</sup><a href="https://uroweb.org/guidelines/prostate-cancer" data-type="other-reference" data-value="European Association of Urology Guidelines on Prostate Cancer, N. Mottet (chair), P.J. Bastian, J. Bellmunt, R.C.N. van den Bergh, M. Bolla, N.J. van Casteren, P. Cornford, S. Joniau, M.D. Mason, V. Matveev, T.H. van der Kwast, H. van der Poel, O. Rouvière, T. Wiegel" data-url="https://uroweb.org/guidelines/prostate-cancer" title="European Association of Urology Guidelines on Prostate Cancer, N. Mottet (chair), P.J. Bastian, J. Bellmunt, R.C.N. van den Bergh, M. Bolla, N.J. van Casteren, P. Cornford, S. Joniau, M.D. Mason, V. Matveev, T.H. van der Kwast, H. van der Poel, O. Rouvière, T. Wiegel">6</a></li> <li>De lavt differentierede meget aggressive kræfttyper mister evnen til at producere PSA, som derfor typisk testes lav. Ved undladt rektaleksploration er der dermed risiko for alvorlig fejlvurdering af tilstanden</li> <li>PSA-velocity refererer til hastigheden, hvormed PSA-værdien tiltager over tid. En PSA-fordoblingstid på under 10 måneder skønnes forbundet med betydelig øget risiko for aggressiv sygdom</li> </ul> <h3>Prostatacancer</h3> <ul> <li>Prostatacancer diagnosticeres sjældent før 50-årsalderen, hvorefter incidensen stiger stejlt</li> <li>Prostatakræft udvikler sig generelt langsomt og meget forskelligt</li> <li>Mens hver 6. mand (17 %) får stillet diagnosen prostatakræft, dør ”kun” 1 af 30 mænd (3 %) af prostatakræft<a title="Jemal A, Thomas A, Murray T, Thun M, Cancer statistics, 2002. CA Cancer J Clin 2002;52: 23-47" href="%20" data-type="journal-reference" data-value="Jemal A, Thomas A, Murray T, Thun M, Cancer statistics, 2002. CA Cancer J Clin 2002;52: 23-47" data-value-piped="Jemal A, Thomas A, Murray T, Thun M|Cancer statistics, 2002.|CA Cancer J Clin|2002|52|23-47|11814064" data-url="reference-link" data-pubmedid="11814064">7</a></li> <li>Diagnosen kunne ved intensiv opsporing reelt stilles hos mange flere, dvs. hos op imod ca. hver anden 60-årige mand og hos tre ud af fire 75-årige</li> <li>Hos de fleste vil forandringerne aldrig udvikle sig til klinisk kræftsygdom<a title="Sakr WA, Grignon DJ, Crissman JD, Heilbrun LK, Cassin BJ, Pontes JJ, Haas GP, High grade prostatic intraepithelial neoplasia (HGPIN) and prostatic adenocarcinoma between the ages of 20-69: an autopsy study of 249 cases. In Vivo 1994;8: 439-43" href="%20" data-type="journal-reference" data-value="Sakr WA, Grignon DJ, Crissman JD, Heilbrun LK, Cassin BJ, Pontes JJ, Haas GP, High grade prostatic intraepithelial neoplasia (HGPIN) and prostatic adenocarcinoma between the ages of 20-69: an autopsy study of 249 cases. In Vivo 1994;8: 439-43" data-value-piped="Sakr WA, Grignon DJ, Crissman JD, Heilbrun LK, Cassin BJ, Pontes JJ, Haas GP|High grade prostatic intraepithelial neoplasia (HGPIN) and prostatic adenocarcinoma between the ages of 20-69: an autopsy study of 249 cases.|In Vivo|1994|8|439-43|7803731" data-url="reference-link" data-pubmedid="7803731">8</a></li> <li>Det store flertal af mænd med (erkendt og ikke erkendt) prostatakræft dør fortsat <strong>med </strong>og ikke<em> </em><strong>af </strong>sygdommen</li> </ul> <h3>ICPC-2</h3> <p>[ICPC]</p> <h3>ICD-10/SKS-koder</h3> <p>[ICD10]</p> <h2>Prostatapalpation ved rektaleksploration</h2> <ul> <li>Prostatakræft - hård, uregelmæssig, knudret, udvisket midtfure</li> <li>Benign prostatahyperplasi - fast, glat elastisk konsistens</li> <li>Prostatitis - smertefuld palpation</li> </ul> <h2>Supplerende undersøgelser</h2> <h3>I almen praksis</h3> <ul> <li>Anamnestisk familiær disposition</li> <li>Urinundersøgelse</li> <li>Blodprøver</li> <li>Prostatapalpation ved rektaleksploration (hård, uøm og uregelmæssig knude?) - de fleste tilfælde af tidlig lokaliseret prostatakræft kan ikke erkendes ved palpation eller transrektal ultralydsskanning</li> <li>MR-skanning har øget muligheden for at identificere og lokalisere klinisk betydende kræftforandringer i prostata</li> <li>Bemærk at omkring halvdelen af alle unormale PSA resultater normaliseres ved 1-4 års opfølgning uden medicinsk eller kirurgisk intervention<a title="Eastham JA, Riedel E, Scardino PT, Shike M, Fleisher M, Schatzkin A, Lanza E, Latkany L, Begg CB, Polyp Prevention Trial Study Group., Variation of serum prostate-specific antigen levels: an evaluation of year-to-year fluctuations. JAMA 2003;289: 2695-700" href="%20" data-type="journal-reference" data-value="Eastham JA, Riedel E, Scardino PT, Shike M, Fleisher M, Schatzkin A, Lanza E, Latkany L, Begg CB, Polyp Prevention Trial Study Group., Variation of serum prostate-specific antigen levels: an evaluation of year-to-year fluctuations. JAMA 2003;289: 2695-700" data-value-piped="Eastham JA, Riedel E, Scardino PT, Shike M, Fleisher M, Schatzkin A, Lanza E, Latkany L, Begg CB, Polyp Prevention Trial Study Group.|Variation of serum prostate-specific antigen levels: an evaluation of year-to-year fluctuations.|JAMA|2003|289|2695-700|12771116" data-url="reference-link" data-pubmedid="12771116">9</a></li> </ul> <h4>Vurdering af prøvesvar</h4> <p>Se figur 1</p> <ul> <li>Værdier 3-5 - Normal øvre aldersdifferentierede grænseværdier, men udelukker ikke kræft. Specielt anaplastiske højmaligne Gleason score 10-tumorer har mistet evnen til at producere PSA</li> <li>Værdier 4-10 - Gråzone, hvor hver tredje patient vil kunne diagnosticeres med prostatacancer </li> <li>Værdier 10-30 - Risikoen for cancer stiger med PSA niveauet. Ved cancer vil sygdommen typisk være lokal/lokal avanceret med mulighed for helbredelse</li> <li>Værdier >30 - den prædiktive værdi nærmer sig 50 %. Risikoen for lokalavanceret og ikke helbredelig sygdom stiger</li> <li>Værdier over 100 - typisk ensbetydende med dissemineret uhelbredelig prostatacancer. Svær cystit kan i sjældne tilfælde resultere i trecifret PSA værdi </li> </ul> <h4>Hurtigt stigende PSA</h4> <ul> <li>Er forbundet med klart dårligere prognose end hvor stigningen sker langsomt <a href=" " data-type="journal-reference" data-value="D'Amico AV, Chen MH, Roehl KA, Catalona WJ, Preoperative PSA velocity and the risk of death from prostate cancer after radical prostatectomy.. N Engl J Med 2004;351: 125-35" data-value-piped="D'Amico AV, Chen MH, Roehl KA, Catalona WJ|Preoperative PSA velocity and the risk of death from prostate cancer after radical prostatectomy.|N Engl J Med|2004|351|125-35|15247353" data-url="reference-link" data-pubmedid="15247353" title="D'Amico AV, Chen MH, Roehl KA, Catalona WJ, Preoperative PSA velocity and the risk of death from prostate cancer after radical prostatectomy.. N Engl J Med 2004;351: 125-35">10</a> </li> </ul> <h4>Kontrol af prostatakræft</h4> <ul> <li>Ved behandlingskontrol anvendes PSA til at sikre effekt, recidiv og evt. progression af sygdommen - herunder udvikling af kastrationsresistens og metastaser</li> </ul> <h3>Andre undersøgelser</h3> <ul> <li>Multiparametrisk MR-skanning vil i dag typisk udgøre 1. billeddiagnostiske undersøgelse og være udslagsgivende i forhold til evt. diagnostiske biopsier</li> <li>Transrektal ultralydsskanning (TRUS)+/- transperineale biopsier, CT-skanning af thorax og abdomen, knoglescintigrafi samt PSMA-PET-CT</li> </ul> <h2>Tiltag og råd</h2> <h3>Henvisninger</h3> <ul> <li>Henvis til urolog ved forhøjet PSA, symptomer eller suspekt rektal eksploration</li> </ul> <h3>Råd</h3> <ul> <li>Hurtigt stigende PSA er forbund et med dårligere prognose, end hvor øgningen sker langsomt<a href=" " data-type="journal-reference" data-value="D'Amico AV, Chen MH, Roehl KA, Catalona WJ, Preoperative PSA velocity and the risk of death from prostate cancer after radical prostatectomy.. N Engl J Med 2004;351: 125-35" data-value-piped="D'Amico AV, Chen MH, Roehl KA, Catalona WJ|Preoperative PSA velocity and the risk of death from prostate cancer after radical prostatectomy.|N Engl J Med|2004|351|125-35|15247353" data-url="reference-link" data-pubmedid="15247353" title="D'Amico AV, Chen MH, Roehl KA, Catalona WJ, Preoperative PSA velocity and the risk of death from prostate cancer after radical prostatectomy.. N Engl J Med 2004;351: 125-35">10</a> </li> <li>Ved kontrol efter eller under behandling bruges PSA for at opspore recidiv, følge sygdomsaktivitet samt opdage udvikling af metastaser og kastrationsresistens</li> <li><a href="http://pro.medicin.dk/Laegemiddelgrupper/Grupper/291069">Antiandrogen behandling</a> virker antineoplastisk og reducerer ligesom finastrid PSA-niveauet </li> </ul> <h2>Patientinformation</h2> <h3>Hvad findes af patientinformation</h3> <ul> <li><a href="~/link.aspx?_id=D4F43474C7B8491CB8ED042F8A83D97C&_z=z">PSA - skal du lade dig teste?</a></li> </ul> <h3>Animationer og video</h3> <ul> <li><a href="~/link.aspx?_id=EB2969F475724939B898F458CE61EA07&_z=z">Prostata nålebiopsi</a></li> <li><a href="~/link.aspx?_id=FB4DB004289F4BA18111E42A0A759F4C&_z=z">Godartet forstørret prostata</a></li> <li><a rel="noopener noreferrer" href="https://www.cancer.dk/prostatakraeft/undersogelser-prostatakraeft/hvem-boer-fa-malt-psa-p3/" target="_blank">Hvem bør få målt PSA i blodet?</a> Information fra Kræftens Bekæmpelse </li> </ul>]]></HtmlField> <LinkListField Name="Spot2"> <LinkField linktype="internal">{99A85AFD-2F7A-4B5D-A1C9-C2701D5E7D30}</LinkField> </LinkListField> <TextField Name="DoctorsHandbookID">34023</TextField> <TextField Name="PageTitle">Prostata specifikt antigen (PSA)</TextField> <TextField Name="NavigationTitle">Prostata specifikt antigen (PSA)</TextField> <CheckBoxField Name="ShowInMenu">true</CheckBoxField> <CheckBoxField Name="ShowInContentField">true</CheckBoxField> <DateTimeField Name="RevisedDate">2024-01-12T09:19:00</DateTimeField> <LinkListField Name="Authors"> <LinkField linktype="internal">{F45E0930-717B-4509-A99F-CE9546ACB8F6}</LinkField> <LinkField linktype="internal">{9240F87A-FE81-40E5-A079-F715F683A0B5}</LinkField> </LinkListField> <LinkListField Name="Organization"> <LinkField linktype="internal">{CF77E8B9-9937-42B2-85DF-76B0F4E401F0}</LinkField> </LinkListField> <TextField Name="ICD10">R76, R76.0, R76.8</TextField> <TextField 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