Clinical recommendations for diagnosis, treatment and monitoring of patients with bladder cancer

Rak mokraćnog mjehura (RMM) jest, u skladu s podatcima hrvatskog Registra za rak iz 2015. godine, drugi prema učestalosti tumor urinarnog sustava, odmah nakon raka prostate. U 90% slučajeva radi se o urotelnom karcinomu, a razlika u preživljenju kod bolesnika s mišićnoinvazivnim RMM-om (MIRMM) i nemišićnoinvazivnim RMM-om (NMIRMM) znatna je. Liječenje NMIRMM-a usmjereno je na smanjenje recidiva i sprječavanje napredovanja bolesti, a sastoji se od transuretralne resekcije (TUR) tumora i primjene intravezikalne terapije ovisno o procjeni rizika od povrata bolesti. Temelj liječenja bolesnika s MIRMM-om jest radikalno kirurško liječenje, tj. cistektomija kojoj u bolesnika koji su sposobni primiti cisplatinu prethodi neoadjuvantna kemoterapija (NKT). U trenutku postavljanja dijagnoze bolest je kod 4 – 6% bolesnika proširena, dok će se u 50% bolesnika razviti povrat bolesti nakon cistektomije. Metode liječenja proširenje bolesti uključuju: kemoterapiju temeljenu na cisplatini, imunoterapiju, palijativnu radioterapiju te simptomatsko i potporno liječenje. Važno obilježje RMM-a jest prisutnost visoke stope somatskih mutacija koje su omogućile promjenu paradigme u liječenju proširenog RMM-a i dovele do odobravanja niza novih lijekova koji pripadaju inhibitorima PD-1 i PD-L1, tj. inhibitorima nadzornih točaka imunosnog odgovora posredovanog T-stanicama .Bladder cancer is the second most common malignancy of urinary system according to data from the Croatian National Cancer Registry for 2015. In 90% of cases the underlying histology is urothelial carcinoma. Difference in survival in patients with muscle-invasive disease (MIBC) compared to the survival of patients with non-muscle invasive disease (NMIBC) is enormous. Management of NMIBC, traditionally, has been focused on the reduction of subsequent bladder recurrence and prevention of disease progression and is primarily based on transurethral resection (TUR) of the tumor, followed by intravesical therapy based on estimated individual risk of recurrence. Conversely, in patients with MIBC radical cystectomy remains the corne stone of the treatment, optimally in conjunction with neoadjuvant platinum-based chemotherapy in cisplatin-eligible patients. At the moment of diagnosis, 4–6% of patients already have distant metastases, and post cystectomy recurrence could be expected in 50% of patients. Treatment options in metastatic disease range from cisplatin-based chemotherapy, immunotherapy, palliative radiotherapy and finally supportive care. Landmark feature of bladder cancer is the high prevalence of somatic mutations which enabled profound change for decades held treatment paradigm for advanced bladder cancer leading to regulatory approval of whole array of novel immunotherapy agents. These emerging therapeutics (programmed death ligand-1 (PD-L1) and programmed cell death protein-1 (PD-1)) belong to the class of inhibitors of checkpoint proteins, which are key targets that regulate T-cell mediated immune response