Neoadjuvantno liječenje urotelnog raka mokraćnog mjehura

master's thesis

• Title (english): Neoadjuvant therapy of urothelial bladder cancer
• Author: Dora Antunović
• Mentor: Marija Gamulin (mentor)
• Committee member: Nikola Đaković (predsjednik povjerenstva)
• Committee member: Jasmina Marić Brozić (član povjerenstva)
• Committee member: Marija Gamulin (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Clinical Oncology); Zagreb
• Defense date and country: 2022-07-15, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Oncology

Abstract

Urotelni karcinom mokraćnog mjehura zloćudna je novotvorina povezana s visokim morbiditetom i mortalitetom. Površinski oblik raka mokraćnog mjehura liječi se transuretralnom endoskopskom resekcijom, a mišićno invazivni radikalnom cistektomijom uz prethodnu neoadjuvantnu kemoterapiju (NAC) temeljenu na cisplatini. Prednosti neoadjuvantne sistemske terapije su uklanjanje mikrometastaza, postizanje boljeg patohistološkog odgovora, negativnih resekcijskih rubova i boljeg preživljenja. Dva neoadjuvantna protokola koja se najčešće primjenjuju su GC (gemcitabin, cisplatina) i ddMVAC (metotreksat, vinblastin, doksorubicin, cisplatina). Više puta su provođene usporedbe njihove učinkovitosti i oba protokola su pokazala kao rezultat liječenja potpuni patohistološki odgovor kod približno 30% bolesnika i poboljšala su petogodišnje preživljenje za 5 do 8%. Nova ispitivanja su ipak pokazala veću učinkovitost ddMVAC protokola koji se stoga preporuča po najnovijim smjernicama. Najveći problem neoadjuvantne kemoterapije je njena toksičnost. Zbog toga postoje brojni pokušaji da se unaprijed odredi koji će bolesnik imati dobar odgovor na NAC, a koji ne, ali zasad nijedan kriterij nije dovoljno precizan. Imunoterapija trenutno se primjenjuje samo u slučaju metastatskog ili lokalno uznapredovalog karcinoma kod bolesnika koji ne mogu primiti cisplatinu. Neoadjuvantna imunoterapija kao se za sada uglavnom koristi samo u kliničkim ispitivanjima. Istražuje se efikasnost inhibitora kontrolnih točaka s obećavajućim rezultatima. Za probrane bolesnike koji žele izbjeći cistektomiju postoji opcija trimodalnog liječenja koja obuhvaća TURBT, kemoterapiju i radioterapiju. Potrebno je napraviti više kliničkih ispitivanja trimodalne terapije i usporediti je s neoadjuvantnom sistemskom terapijom i radiklanom cistektomijom kako bi se odredio optimalan protokol za bolesnike s lokalnim urotelnim rakom.

Abstract (english)

Urothelial bladder cancer is a malignant neoplasm linked to high morbidity and mortality. Superficial bladder cancer is treated with endoscopic treatment with transurethral resection (TURBT), and muscle‐invasive bladder cancer with radical cystectomy with prior cisplatin-based neoadjuvant chemotherapy (NAC). The advantages of neoadjuvant systemic treatment are removal of micro metastases and achievement of better pathohistological response, negative resection margins and better survival chances. Two most commonly applied NAC protocols are GC (gemcitabine, cisplatin) and ddMVAC (methotrexate, vinblastine, doxorubicin, cisplatin).
Multiple comparisons between their efficiency and both protocols have shown a complete pathohistological response in approximately 30% of patients and have increased 5-year OS by 5 – 8%. However, new trials have shown better efficacy of ddMVAC regimen which is therefore now recommended according to the latest guidelines. The biggest issue of neoadjuvant chemotherapy is its toxicity. There are multiple attempts at determining in advance which patient will or will not respond positively to NAC, but unfortunately so far none of these factors have shown as precise enough. Immunotherapy is currently used only in patients with metastatic or locally advanced cancer unsuitable for cisplatin. Neoadjuvant immunotherapy is used only in clinical trials for the time being. Checkpoint inhibitor efficiency is being investigated with promising results. For selected patients who wish to avoid cystectomy there is an option of trimodal treatment which consists of TURBT, chemotherapy and radiotherapy. To determine optimal protocol for patients with local urothelial cancer, more clinical trials for trimodal treatment need to be conducted and to compare it with neoadjuvant systemic treatment and radical cystectomy.

• Keywords: kemoterapija; imunoterapija; patohistološki odgovor; ukupno preživljenje
• Keywords (english): chemotherapy; immunotherapy; pathohistological response; overall survival
• Language: croatian
• URN:NBN: urn:nbn:hr:105:967905
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-01-02 10:38:48