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Aktuelle Urol 2017; 48(04): 314-328
DOI: 10.1055/s-0043-108944
Übersicht
© Georg Thieme Verlag KG Stuttgart · New York

Konservative Therapieoptionen beim nicht-muskelinvasiven Urothelkarzinom der Harnblase nach BCG-Versagen: Systematische Übersichtsarbeit

Systematic review on conservative treatment options in non-muscle-invasive bladder cancer patients refractory to Bacillus Calmette-Guérin instillation therapy
Thomas Martini
1   Klinik für Urologie und Kinderurologie, Universitätsklinikum Ulm, Deutschland
,
Felix Wezel
1   Klinik für Urologie und Kinderurologie, Universitätsklinikum Ulm, Deutschland
,
Niklas Löbig
1   Klinik für Urologie und Kinderurologie, Universitätsklinikum Ulm, Deutschland
,
Michael J. Mitterberger
2   Universitätsklinik für Urologie und Andrologie, Paracelsus Medizinischen Universität, Salzburg, Österreich
,
Daniela Colleselli
2   Universitätsklinik für Urologie und Andrologie, Paracelsus Medizinischen Universität, Salzburg, Österreich
› Author Affiliations
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Publication History

Publication Date:
13 June 2017 (online)

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Zusammenfassung

Hintergrund Die adjuvante intravesikale Instillation von Bacillus Calmette-Guérin (BCG) stellt bei Patienten mit nicht-muskelinvasivem Harnblasenkarzinom (NMIBC) mit hohem Risiko die Therapie der ersten Wahl dar. Nichtsdestotrotz entwickeln etwa 40 – 50 % dieser Patienten trotz Therapie ein Rezidiv oder eine Progression. Die radikale Cystektomie (RC) stellt für diese sogenannten BCG-Versager die Therapie der ersten Wahl dar. Da jedoch nicht alle Patienten für eine RC geeignet sind oder diese ablehnen, gibt es einen Bedarf an konservativen Therapiealternativen. Ziel dieser Studie war die Erhebung von konservativen Therapieoptionen für Patienten mit NMIBC nach BCG-Versagen.

Material und Methoden Es erfolgte eine systematische Recherche in folgenden Literaturdatenbanken: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE und EMBASE. Dabei wurden alle randomisierten kontrollierten Studien (RCTs), quasi RCTs und single-Arm Studien von Patienten mit BCG-Versagen und einer Mindest-Patientenzahl von acht, die einer intravesikalen oder systemischen Therapie unterzogen wurden, eingeschlossen. Es wurden nur Publikationen in englischer Sprache berücksichtigt. Die Literaturrecherche und Datenanalyse erfolgte durch zwei Gutachter. Folgende Kriterien wurden erhoben: vollständiges Therapieansprechen (CR), Rezidiv, rezidivfreies Überleben (RFS), Krankheitsprogression und Rate an RC.

Ergebnisse 42 Publikationen mit einer Gesamtzahl von 3521 Patienten (davon 2371 BCG-Versager) wurden in die systematische Übersichtsarbeit eingeschlossen. Als konservative Therapieoptionen wurden Valrubicin, Taxane, Gemcitabin, Chemotherapie-Kombinationen, Thermochemotherapie, Photodynamische Therapie, Kombinationstherapie aus BCG und Interferon, zielgerichtete Therapien (targeted therapies) und Immuntherapien identifiziert. Die höchste klinische Evidenz konnte für Taxane, Gemcitabin und die Thermochemotherapie bei gleichzeitig geringer Toxizität festgestellt werden.

Schlussfolgerung Trotz teilweise guter Ansprechraten mit Taxanen, Gemcitabin und der Thermochemotherapie kann für Patienten mit BCG-Versagen keine Evidenz-basierte konservative Therapieoption empfohlen werden, die der RC überlegen ist. BCG-Versager stellen eine heterogene Patientengruppe dar. Der Begriff „BCG-Versagen“ wird in der Literatur uneinheitlich verwendet. Zur Identifikation von konservativen Therapieoptionen bei BCG-Versagern sind prospektiven Studien mit homogenem Design von großer Bedeutung.

Abstract

Background Adjuvant Bacillus Calmette-Guérin (BCG) intravesical instillation is the recommended standard treatment in patients with high-risk non-muscle-invasive bladder cancer (NMIBC). However, a significant proportion of patients fail treatment, and radical cystectomy (RC) is the subsequent gold standard. On the other hand, there is an unmet need for conservative alternatives for patients who are unfit or unwilling to undergo surgery. This study aimed to identify conservative treatment options in NMIBC patients after BCG failure.

Material and Methods We performed a systematic search in the databases Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE, including all randomised controlled trials (RCTs), quasi-RCTs and single-arm studies, in which patients with NMIBC were treated with second-line intravesical or systemic therapy after BCG failure. A minimum of eight patients were included in each treatment arm. Full papers were restricted to English language. Literature research and data analysis were assessed independently by two reviewers. Data on treatment response, recurrence, time to recurrence, progression and rate of cystectomy were collected and analysed.

Results This systematic review included 42 publications with a total of 3521 patients (2371 BCG failures). Valrubicin, taxanes, gemcitabine, combination chemotherapy, thermochemotherapy, photodynamic therapy, combination of BCG and interferon and immunotherapies or targeted therapies were identified as conservative treatment options. For taxanes, gemcitabine and thermochemotherapy there is the highest evidence for a clinical meaningful response with minor toxicities.

Conclusions Despite some promising response rates for taxanes, gemcitabine or thermochemotherapy, an evidence-based recommendation for treatment options superior to RC in patients failing BCG therapy cannot be made. The definition of BCG failure is still inconsistent and heterogeneous outcomes in patients with BCG failure have been reported. In order to identify effective conservative therapy options in patients failing BCG therapy, prospective trials with a standardised trial design are needed.

Schlüsselwörter

nicht-muskelinvasives Urothelkarzinom der Harnblase - BCG-Versager - intravesikale Instillation - konservative Therapieoptionen

Keywords

non-muscle-invasive bladder cancer - BCG failure - intravesical instillation - conservative treatment options
 

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