Značaj serumske izoforme prostata specifičnog antigena i njegovih derivata u ranom otkrivanju karcinoma prostate

Abstract

Karcinom prostate (CaP) je najčešći malignitet kod muškaraca preko 70 godina u zemljama Severne i Zapadne Evrope, kao i SAD. U Srbiji, CaP je na trećem mestu po učestalosti i na trećem mestu po mortalitetu. Na globalnom nivou, CaP je drugi po učestalosti od svih karcinoma i šesti uzrok smrti od karcinoma. Svi ovi epidemioški podaci pokazuju koliko je CaP veliki zdravstveni i ekonomski problem, kako u celom svetu, tako i u Srbiji. Povećanje incidence CaP posledica je široke primene prostata specifičnog antigena (PSA) testiranja koje je kasnih osamdesetih godina dovelo do revolucionarnih promena u dijagnostici CaP. MeĎutim, kako je PSA organ specifičan, ali ne i karcinom specifičan marker, on se ne može smatrati idealnim markerom. Kako bi se poboljšala specifičnost PSA za detekciju CaP, vremenom su uvoĎeni novi derivati PSA, kao što su dinamika rasta PSA u funkciji vremena (eng. PSA velocity, PSAV), odnos ukupnog PSA i zapremine prostate (eng. PSA densitiy, PSAD), udvostručenje bazične vrednosti PSA tokom vremena (eng. PSA doubling time), procentualni odnos slobodnog prema ukupnom PSA (%fPSA). Pokazano je da jedino %fPSA donekle poboljšava specifičnost PSA za rano otkrivanje CaP. Brzo se javila potreba za pronalaženjem boljih i osetljivijih biomarkera koji bi sa većom sigurnošću mogli da ukažu na CaP. Pokazalo se da su serumska izoforma prostata specifičnog antigena p2PSA i njegovi derivati %p2PSA, PHI (eng. prostate health index), najbolji novi biomarkeri koji značajno povećavaju specifičnost PSA za detekciju karcinoma prostate. Što je važnije, ovi biomarkeri mogu da naprave razliku izmeĎu klinički nesignifikantnog, nisko-rizičnog tumora i njegove agresivne forme. Njihovom primenom značajno se smanjuje broj pacijenata koji podležu suvišnim dijagnostičkim i terapijskim procedurama (eng. overdiagnosis & overtreatment) kao i svim komplikacijama koje ih prate. MeĎusobni matematički odnosi p2PSA, fPSA i ukupnog PSA dat je formulom čiji rezultat označava PHI (PHI = [p2PSA / fPSA] × PSA1/2), a meĎusobni odnos p2PSA i fPSA, odnosno %p2PSA formulom (p2PSA/fPSA x 100)...

Prostate cancer (PC) is the most common malignancy in men aged >70 in Western and Eastern European Countries, as well as in the US. In Serbia, PC is the third most common incidence rate and has the third most common mortality rate. On a global scale, PC takes second place of most common incidence in all malignancies, and sixth place for most common reason of mortality on all Carcinomas. All these epidemiological data indicate that PC is a significant health and economic issue, not only globally, but also in Serbia. The increase of PC is a consequence from high use of prostate specific antigen (PSA) assessment, which led to revolutionary changes in the diagnostics of PC in the late eighties. However, as the PSA is organ specific, but not also carcinoma specific marker, it cannot be considered as an ideal marker. Overtime, in order to improve the specificity of PSA for PC detection, new derivates of PSA were introduced, such as PSA velocity (PSAV), PSA densitiy (PSAD), PSA duobling time, the percentage of free versus total PSA (%fPSA). Only %fPSA has been proved to in some extent increase the specificity of PSA in regards to early discovery of PC. In a short time, the search for a better and more sensitive marker appeared, which would be able to indicate PC with a higher determination. It was shown that the serum isoform of the prostate specific antigen p2PSA and its derivates %p2PSA, PHI (Prostate health index), are the best of newer biomarkers that significantly increase the specificity of PSA in detecting PC. More importantly, these biomarkers can make the difference between the indolent, clinically non significant tumor and it's aggressive form which needs to be treated. Including these in diagnostic procedures significantly decreases number of patients that are undergoing unnecessary diagnostic and therapeutic procedure (overdiagnosis and overtreatment) as well as complications due to the same. The mathematic algorithm incorporating p2PSA, fPSA and total PSA is given by the formula which results in PHI (PHI = [p2PSA / fPSA] × PSA1/2), whereas the correlation between p2PSA and fPSA, e.g. %p2PSA formula (p2PSA/fPSA x 100)...