HORMONSKA TERAPIJA RAKA PROSTATE: IMA LI JOŠ DILEMA?

Lana Jajac Bručić, Antonio Juretić, Mladen Solarić, Vesna Bišof, Martina Bašić-Koretić, Zoran Rakušić, Fedor Šantek

Strategija liječenja bolesnika s adenokarcinomom prostate ovisi o procjeni proširenosti bolesti, procjeni rizika od povratka bolesti, dobi, očekivanom trajanju života, komorbiditetima, afinitetima i načinu života. Jedan od standardnih terapijskih modaliteta jest i hormonska terapija. Hormonska terapija raka prostate zapravo je terapija koja suprimira androgen (AST) ili koja terapija deprivira androgen (ADT). Njezinom primjenom dolazi do sniženja razine androgena u krvi, a kako su stanice adenokarcinoma najvećim dijelom (³80%) hormonski ovisne o androgenima, prestanak stimulacije stanica raka androgenima dovodi do njihove apoptoze, usporava se rast tumora i smanjuje se njegova veličina. Stoga se ta vrsta terapije rabi u liječenju karcinoma prostate. Hormonska terapija indicirana je kao prvi terapijski modalitet kod nalaza metastatske bolesti. U slučaju primjene radioterapije na prostatu zahvaćenu rakom s kurativnom namjerom (kod nemetastatske bolesti) preporučuje se primjena terapije koja deprivira androgen u bolesnika sa srednjim i visokim rizikom od povratka bolesti prije, za vrijeme i poslije radioterapije u trajanju od 6 mjeseci ili 2–3 godine ovisno o procijenjenom riziku od povratka bolesti. U vezi s primjenom terapije koja deprivira androgen, a koja se može primijeniti na više načina i u više kombinacija, za određene kliničke situacije ne postoje konačne preporuke. Razloga je više: premalen broj odgovarajućih kliničkih studija, heterogenost bolesnika u studijama što otežava interpretaciju podataka te nekonzistentni rezultati. Također, kako novije dijagnostičke metode i postupci omogućavaju ranije otkrivanje raka prostate, a ranije i sve uspješnije liječenje produžava život bolesnika s metastatskom bolešću, rezultati »ranijih« kliničkih studija mogu gubiti na aktualnosti. Isto tako, sa sve dužim preživljenjem bolesnika sve važnija postaje kvaliteta života, odnosno nuspojave liječenja, kao i procjena koristi u odnosu prema štetnosti same terapije. Cilj je prikaza da upozori na novije spoznaje, kao i na moguće dileme o mjestu i primjeni terapije koja deprivira androgen.

The strategy for treating prostate cancer patients depends on the assessment of disease extent, assessment of the risk of disease relapse, assessment of life expectancy, comorbidities, affinities and life-style. Since the activity and survival of prostate cancer cells is at least initially dependent on androgen stimulation, hormonal therapy is one of the several standard treatment modalities. Hormonal therapy is aimed at decreasing this androgen stimulation either by lowering androgen production or by blocking receptor binding. Hormonal therapy is in fact androgen-suppressive therapy (AST) or androgen-deprivation therapy (ADT). If effective, it results in the lack of cancer cell stimulation, thus causing their apoptosis and consequently decline in tumor growth and size. Hormonal therapy is used as a first-line treatment modality for metastatic disease. In addition to this indication, hormonal therapy is also used as an adjunct to radiotherapy with curative intent for patients with non-metastic disease but having an intermediate and high risk of disease relapse. In combination with radiotherapy, hormonal therapy can be applied before, concomitantly and after radiotherapy for the duration of 6 months or 2 to 3 years depending on the risk estimation. Regarding hormonal therapy, it can be applied in combination with other treatments, in several ways, and sometimes there might be several options available. This possible lack of a specific recommendation is a consequence of the fact that there is a limited number of adequate clinical studies which, moreover, may have yielded inconsistent results sometimes simply due to the patients’ heterogeneity. Moreover, thanks to the newer and better diagnostic methods enabling the discovery of prostate cancer in earlier disease stages, as well as to the more effective treatments, there is also a prolongation of relapse-free survival and possibly of overall survival in patients having metastic disease. Consequently, the results of earlier clinical studies might no longer be applicable to the new »generations« of upcoming patients. As regards this improved survival, issues of patient’s quality of life and possible side-effects of hormonal therapy are also becoming increasingly relevant because hormonal adverse events are time-dependant and tend to increase in severity with prolongation of hormonal manipulation. Therefore, this paper aims to give an overview of the more recent findings, indications and observations regarding hormonal therapy.