Kastrasyon Dirençli Prostat Kanserinde Tedavi
Özet
Prostat kanseri, erkeklerde en sık görülen ikinci malignite olup, kastrasyon dirençli prostat kanseri (KDPK) önemli bir mortalite ve morbidite nedenidir. Androjen deprivasyon tedavisi (ADT) başlangıçta etkin olsa da, çoğu hasta kısa sürede kastrasyona dirençli fenotipe dönüşmektedir. Bu süreçte androjen reseptör (AR) mutasyonları, amplifikasyonu, splice varyantları ve DNA onarım mekanizmalarındaki bozukluklar direnç gelişiminde rol oynamaktadır. Tedavi yaklaşımları, metastatik olmayan ve metastatik KDPK olarak ikiye ayrılmaktadır. Metastatik olmayan olgularda enzalutamid, apalutamid ve darolutamid etkinlik göstermiştir. Metastatik hastalıkta ise taksan bazlı kemoterapi, yeni nesil hormonal ajanlar (abirateron, enzalutamid), PARP inhibitörleri, immünoterapiler, radyofarmasötikler (Ra-223, Lu-177-PSMA) ve kemik hedefli tedaviler (bifosfonatlar, denosumab) klinik kullanıma girmiştir. Özellikle BRCA1/2 mutasyonu olan hastalarda PARP inhibitörleri belirgin yarar sağlamaktadır. Bununla birlikte tedavi seçiminde hasta özellikleri, yan etki profili ve genetik alt tipler dikkate alınmalıdır. Güncel klinik çalışmalar, kombine yaklaşımların sağkalımı uzatabileceğini göstermektedir. Sonuç olarak, KDPK yönetiminde multidisipliner yaklaşım ve kişiselleştirilmiş tedavi stratejileri, sağkalım ve yaşam kalitesi üzerine kritik öneme sahiptir.
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