Neoadjuvant Treatment in Muscle-Invasive Bladder Cancer: From the Beginning to the Latest Developments

Abstract

Urothelial carcinoma of the bladder is one of the most prevalent cancers worldwide, diagnosed as muscle invasive in 25% of cases. Although several studies have demonstrated an overall 5% absolute survival benefit at 5 years with cisplatin-based combination neoadjuvant treatment, administration of chemotherapy prior to radical cystectomy (RC) in muscle-invasive bladder cancer (MIBC) patients is still a matter of debate. This may be due to the perceived modest survival benefit, cisplatin-based chemotherapy ineligibility, or fear of delaying potentially curative surgery in non-responders. However, immunotherapy and novel targeted therapies have shown to prolong survival in advanced disease and are under investigation in the neoadjuvant and adjuvant settings to reduce systemic relapse and improve cure rates. Genomic characterization of MIBC could help select the most effective chemotherapeutic regimen for the individual patient. Large cohort studies on neoadjuvant treatments with immune checkpoint inhibitors (ICIs) and molecular therapies, alone or combined with chemotherapy, are ongoing. In this review, we trace the development of neoadjuvant therapy in MIBC and explore recent advances that may soon change clinical practice.

Lokal fortgeschrittene Stadien und perioperative Systemtherapien des Blasenkarzinoms

“…Die erfolgreiche Einführung der Immuncheckpoint-Inhibitoren (ICI) im Stadium der metastasierten und fortgeschrittenen Erkrankung führte zwangsläufig zur Anregung einer Vielzahl von Studien, in denen die Anwendung von Immuntherapie in der perioperativen Phase untersucht wurde [11,12,13]. Zum aktuellen Zeitpunkt existiert keine zugelassene neoadjuvante Immuntherapieoption [1].…”

“…In der NABUCCO-Studie erhielten 24 Patient*innen mit Urothelkarzinom im Stadium III in der neoadjuvanten Phase eine Kombination aus Ipilimumab und Nivolumab [16] Zusammenfassend liegt die Rate der pathologischen kompletten Remissionen bei Blasenkarzinompatient*innen, die eine neoadjuvante Checkpoint-Inhibitor-Therapie (Mono oder kombiniert) erhielten und anschließend einer radikalen Zystektomie unterzogen wurden, zwischen 31 und 46 %. In Subgruppenanalysen mit einem positiven PD-L1-Tumorstatus lag dieser Wert zwischen 37 und 54 % [13,14,17,18,19]. Diese Werte sind damit in etwa so hoch wie unter Chemotherapie und unterstreichen die Bedeutung dieser Substanzgruppe für die Behandlung dieser Patient*innengruppe.…”

Perioperative systemic therapy in muscle invasive bladder cancer: Current standard method, biomarkers and emerging strategies

“…Recently attempts to find biomarkers for immunotherapy have been made. PD-L1 level, TMB, immune cell infiltration and DDR gene alteration are the candidates of biomarkers for immunotherapy [ 94 ]. However, none of these has shown consistent results to be included in routine clinical practice.…”

Application of nanotechnology in bladder cancer diagnosis and therapeutic drug delivery

“…Radiotherapy, chemotherapy and immunotherapy are important ways of participating in the treatment of BC. 87,88 These therapies need to inject therapeutic drugs into the patient's body by intravenous injection or intravesical instillation, and exert anti-cancer effects through X-ray irradiation, increasing the expression of anti-cancer factors, and activating the body's immune system. [89][90][91][92][93] However, such treatment methods have side effects such as damage to normal cells, disturbance of the dynamic balance of the immune environment in the body and induction of a cytokine storm.…”