Skip to main content
Erschienen in: Der Onkologe 1/2018

15.11.2017 | Harnblasenkarzinom | Leitthema

Perioperative Chemotherapie des Harnblasenkarzinoms

Neoadjuvante, induktive und adjuvante Strategien

verfasst von: Univ.-Prof. Dr. Anja Lorch, Axel S. Merseburger, Carsten-Henning Ohlmann

Erschienen in: Die Onkologie | Ausgabe 1/2018

Einloggen, um Zugang zu erhalten

Zusammenfassung

Hintergrund

Etwa 16.000 Menschen erkranken jährlich in Deutschland an einem muskelinvasiven Harnblasenkarzinom. Standardtherapie ist dabei die radikale Zystektomie mit regionaler Lymphadenektomie. Innerhalb der ersten 2 Jahre nach erfolgter Operation erleiden bis zu 50 % der Patienten mit einem initial nicht metastasiertem Tumorstadium T2–T4a Lymphknotenbefall und/oder Fernmetastasen.

Methode

Recherche und Analyse aktueller Literatur.

Ergebnisse

Zur Eliminierung möglicher Mikrometastasen wird heute der Einsatz perioperativer Therapiekonzepte in Form einer neoadjuvanten, induktiven oder adjuvanten Chemotherapie empfohlen. Obwohl der Nutzen einer perioperativen Chemotherapie mit einer Verbesserung der Überlebensrate durch klinische Studien und Metaanalysen klar belegt ist, findet das Verfahren in Europa noch immer nur eine geringe Akzeptanz. Neben der aktuellen Datenlage werden die Vor- und Nachteile der verschiedenen Modalitäten dargestellt und diskutiert.
Literatur
1.
Zurück zum Zitat Robert Koch-Institut, Gesellschaft der epidemiologischen Krebsregister in Deutschland e. V. (Hrsg) (2012) Krebs in Deutschland 2007/2008. Robert Koch-Institut, Berlin Robert Koch-Institut, Gesellschaft der epidemiologischen Krebsregister in Deutschland e. V. (Hrsg) (2012) Krebs in Deutschland 2007/2008. Robert Koch-Institut, Berlin
2.
Zurück zum Zitat Lynch CFDJ, Platz CE (2007) Cancer of the urinary bladder. In: Ries LAGYJ, Keel GE, Eisner MP, Lin YD, Horner M‑J (Hrsg) Seer survival monograph: Cancer survival among adults: Us seer program, 1988–2001, patient and tumor characteristics national cancer institute, seer program, nih pub no 07-6215. Bethesda, S 181–192 Lynch CFDJ, Platz CE (2007) Cancer of the urinary bladder. In: Ries LAGYJ, Keel GE, Eisner MP, Lin YD, Horner M‑J (Hrsg) Seer survival monograph: Cancer survival among adults: Us seer program, 1988–2001, patient and tumor characteristics national cancer institute, seer program, nih pub no 07-6215. Bethesda, S 181–192
3.
Zurück zum Zitat Bellmunt J, Orsola A, Wiegel T, Guix M, De Santis M, Kataja V (2011) Bladder cancer: Esmo clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 22(Suppl 6):vi45–49PubMed Bellmunt J, Orsola A, Wiegel T, Guix M, De Santis M, Kataja V (2011) Bladder cancer: Esmo clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 22(Suppl 6):vi45–49PubMed
4.
Zurück zum Zitat Stenzl A, Cowan NC, De Santis M, Kuczyk MA, Merseburger AS, Ribal MJ, Sherif A, Witjes JA (2011) Treatment of muscle-invasive and metastatic bladder cancer: Update of the eau guidelines. Eur Urol 59:1009–1018CrossRefPubMed Stenzl A, Cowan NC, De Santis M, Kuczyk MA, Merseburger AS, Ribal MJ, Sherif A, Witjes JA (2011) Treatment of muscle-invasive and metastatic bladder cancer: Update of the eau guidelines. Eur Urol 59:1009–1018CrossRefPubMed
5.
Zurück zum Zitat Advanced Bladder Cancer (ABC) Meta-analysis Collaboration (2005) Neoadjuvant chemotherapy in invasive bladder cancer: update of a systematic review and meta-analysis of individual patient data advanced bladder cancer (abc) meta-analysis collaboration. Eur Urol 48(2):202–205. https://doi.org/10.1016/j.eururo.2005.04.006 (discussion 205–206)CrossRef Advanced Bladder Cancer (ABC) Meta-analysis Collaboration (2005) Neoadjuvant chemotherapy in invasive bladder cancer: update of a systematic review and meta-analysis of individual patient data advanced bladder cancer (abc) meta-analysis collaboration. Eur Urol 48(2):202–205. https://​doi.​org/​10.​1016/​j.​eururo.​2005.​04.​006 (discussion 205–206)CrossRef
6.
Zurück zum Zitat Raj GV, Karavadia S, Schlomer B, Arriaga Y, Lotan Y, Sagalowsky A, Frenkel E (2011) Contemporary use of perioperative cisplatin-based chemotherapy in patients with muscle-invasive bladder cancer. Cancer 117:276–282CrossRefPubMed Raj GV, Karavadia S, Schlomer B, Arriaga Y, Lotan Y, Sagalowsky A, Frenkel E (2011) Contemporary use of perioperative cisplatin-based chemotherapy in patients with muscle-invasive bladder cancer. Cancer 117:276–282CrossRefPubMed
7.
Zurück zum Zitat Burger M, Mulders P, Witjes W (2012) Use of neoadjuvant chemotherapy for muscle-invasive bladder cancer is low among major european centres: results of a feasibility questionnaire. Eur Urol 61:1070–1071CrossRefPubMed Burger M, Mulders P, Witjes W (2012) Use of neoadjuvant chemotherapy for muscle-invasive bladder cancer is low among major european centres: results of a feasibility questionnaire. Eur Urol 61:1070–1071CrossRefPubMed
11.
Zurück zum Zitat International collaboration of trialists (1999) Neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: a randomised controlled trial. Lancet 354:533–540CrossRef International collaboration of trialists (1999) Neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: a randomised controlled trial. Lancet 354:533–540CrossRef
12.
Zurück zum Zitat Griffiths G, Hall R, Sylvester R, Raghavan D, Parmar MK (2011) International phase iii trial assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: long-term results of the ba06 30894 trial. J Clin Oncol 29:2171–2177CrossRefPubMed Griffiths G, Hall R, Sylvester R, Raghavan D, Parmar MK (2011) International phase iii trial assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: long-term results of the ba06 30894 trial. J Clin Oncol 29:2171–2177CrossRefPubMed
13.
Zurück zum Zitat Grossman HB, Natale RB, Tangen CM, Speights VO, Vogelzang NJ, Trump DL, deVere White RW, Sarosdy MF, Wood DP Jr., Raghavan D, Crawford ED (2003) Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med 349:859–866CrossRefPubMed Grossman HB, Natale RB, Tangen CM, Speights VO, Vogelzang NJ, Trump DL, deVere White RW, Sarosdy MF, Wood DP Jr., Raghavan D, Crawford ED (2003) Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med 349:859–866CrossRefPubMed
14.
Zurück zum Zitat Sherif A, Holmberg L, Rintala E, Mestad O, Nilsson J, Nilsson S, Malmstrom PU (2004) Neoadjuvant cisplatinum based combination chemotherapy in patients with invasive bladder cancer: a combined analysis of two nordic studies. Eur Urol 45:297–303CrossRefPubMed Sherif A, Holmberg L, Rintala E, Mestad O, Nilsson J, Nilsson S, Malmstrom PU (2004) Neoadjuvant cisplatinum based combination chemotherapy in patients with invasive bladder cancer: a combined analysis of two nordic studies. Eur Urol 45:297–303CrossRefPubMed
15.
Zurück zum Zitat Von der Maase H, Sengelov L, Roberts JT, Ricci S, Dogliotti L, Oliver T, Moore MJ, Zimmermann A, Arning M (2005) Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol 23:4602–4608CrossRefPubMed Von der Maase H, Sengelov L, Roberts JT, Ricci S, Dogliotti L, Oliver T, Moore MJ, Zimmermann A, Arning M (2005) Long-term survival results of a randomized trial comparing gemcitabine plus cisplatin, with methotrexate, vinblastine, doxorubicin, plus cisplatin in patients with bladder cancer. J Clin Oncol 23:4602–4608CrossRefPubMed
17.
Zurück zum Zitat Advanced Bladder Cancer (ABC) Meta-analysis Collaboration (2003) Neoadjuvant chemotherapy in invasive bladder cancer: a systematic review and meta-analysis. Lancet 361(9373):1927–1934CrossRef Advanced Bladder Cancer (ABC) Meta-analysis Collaboration (2003) Neoadjuvant chemotherapy in invasive bladder cancer: a systematic review and meta-analysis. Lancet 361(9373):1927–1934CrossRef
18.
Zurück zum Zitat Winquist E, Kirchner TS, Segal R, Chin J, Lukka H (2004) Neoadjuvant chemotherapy for transitional cell carcinoma of the bladder: a systematic review and meta-analysis. J Urol 171:561–569CrossRefPubMed Winquist E, Kirchner TS, Segal R, Chin J, Lukka H (2004) Neoadjuvant chemotherapy for transitional cell carcinoma of the bladder: a systematic review and meta-analysis. J Urol 171:561–569CrossRefPubMed
19.
Zurück zum Zitat Lawrentschuk N, Colombo R, Hakenberg OW, Lerner SP, Mansson W, Sagalowsky A, Wirth MP (2011) Prevention and management of complications following radical cystectomy for bladder cancer. Eur Urol 57:983–1001CrossRef Lawrentschuk N, Colombo R, Hakenberg OW, Lerner SP, Mansson W, Sagalowsky A, Wirth MP (2011) Prevention and management of complications following radical cystectomy for bladder cancer. Eur Urol 57:983–1001CrossRef
20.
Zurück zum Zitat European Organization for Research on Treatment of Cancer–Genitourinary Group, Splinter TA, Scher HI, Denis L, Bukowski R, Simon S, Klimberg I, Soloway M, Vogelzang NJ, van Tinteren H, Herr H (1992) The prognostic value of the pathological response to combination chemotherapy before cystectomy in patients with invasive bladder cancer. J Urol 147(3):606–608CrossRef European Organization for Research on Treatment of Cancer–Genitourinary Group, Splinter TA, Scher HI, Denis L, Bukowski R, Simon S, Klimberg I, Soloway M, Vogelzang NJ, van Tinteren H, Herr H (1992) The prognostic value of the pathological response to combination chemotherapy before cystectomy in patients with invasive bladder cancer. J Urol 147(3):606–608CrossRef
21.
Zurück zum Zitat Canter D, Viterbo R, Kutikov A, Wong YN, Plimack E, Zhu F, Oblaczynski M, Berberian R, Chen DY, Greenberg RE, Uzzo RG, Boorjian SA (2011) Baseline renal function status limits patient eligibility to receive perioperative chemotherapy for invasive bladder cancer and is minimally affected by radical cystectomy. Urology 77:160–165CrossRefPubMed Canter D, Viterbo R, Kutikov A, Wong YN, Plimack E, Zhu F, Oblaczynski M, Berberian R, Chen DY, Greenberg RE, Uzzo RG, Boorjian SA (2011) Baseline renal function status limits patient eligibility to receive perioperative chemotherapy for invasive bladder cancer and is minimally affected by radical cystectomy. Urology 77:160–165CrossRefPubMed
23.
Zurück zum Zitat Hoffmann AC, Wild P, Leicht C, Bertz S, Danenberg KD, Danenberg PV, Stohr R, Stockle M, Lehmann J, Schuler M, Hartmann A (2010) Mdr1 and ercc1 expression predict outcome of patients with locally advanced bladder cancer receiving adjuvant chemotherapy. Neoplasia 12:628–636CrossRefPubMedPubMedCentral Hoffmann AC, Wild P, Leicht C, Bertz S, Danenberg KD, Danenberg PV, Stohr R, Stockle M, Lehmann J, Schuler M, Hartmann A (2010) Mdr1 and ercc1 expression predict outcome of patients with locally advanced bladder cancer receiving adjuvant chemotherapy. Neoplasia 12:628–636CrossRefPubMedPubMedCentral
24.
Zurück zum Zitat Goldie JH (1987) Scientific basis for adjuvant and primary (neoadjuvant) chemotherapy. Semin Oncol 14:1–7PubMed Goldie JH (1987) Scientific basis for adjuvant and primary (neoadjuvant) chemotherapy. Semin Oncol 14:1–7PubMed
26.
Zurück zum Zitat Wiesner C, Salzer A, Thomas C, Gellermann-Schultes C, Gillitzer R, Hampel C, Thuroff JW (2009) Cancer-specific survival after radical cystectomy and standardized extended lymphadenectomy for node-positive bladder cancer: prediction by lymph node positivity and density. BJU Int 104:331–335CrossRefPubMed Wiesner C, Salzer A, Thomas C, Gellermann-Schultes C, Gillitzer R, Hampel C, Thuroff JW (2009) Cancer-specific survival after radical cystectomy and standardized extended lymphadenectomy for node-positive bladder cancer: prediction by lymph node positivity and density. BJU Int 104:331–335CrossRefPubMed
27.
Zurück zum Zitat Bruins HM, Huang GJ, Cai J, Skinner DG, Stein JP, Penson DF (2009) Clinical outcomes and recurrence predictors of lymph node positive urothelial cancer after cystectomy. J Urol 182:2182–2187CrossRefPubMed Bruins HM, Huang GJ, Cai J, Skinner DG, Stein JP, Penson DF (2009) Clinical outcomes and recurrence predictors of lymph node positive urothelial cancer after cystectomy. J Urol 182:2182–2187CrossRefPubMed
28.
Zurück zum Zitat Osawa T, Abe T, Shinohara N, Harabayashi T, Sazawa A, Kubota K, Matsuno Y, Shibata T, Shinno Y, Kamota S, Minami K, Sakashita S, Kumagai A, Mori T, Nonomura K (2009) Role of lymph node density in predicting survival of patients with lymph node metastases after radical cystectomy: a multi-institutional study. Int J Urol 16:274–278 (discussion 278)CrossRefPubMed Osawa T, Abe T, Shinohara N, Harabayashi T, Sazawa A, Kubota K, Matsuno Y, Shibata T, Shinno Y, Kamota S, Minami K, Sakashita S, Kumagai A, Mori T, Nonomura K (2009) Role of lymph node density in predicting survival of patients with lymph node metastases after radical cystectomy: a multi-institutional study. Int J Urol 16:274–278 (discussion 278)CrossRefPubMed
31.
Zurück zum Zitat Pas-Arez LGS, Solsona E, Esteban E, Saez A, Gonzalez-Larriba J, Anton A, Hevia M, De la Guillem Bellmunt RFFJ (2010) Randomized phase iii trial comparing adjuvant paclitaxel/gemcitabine/cisplatin (pgc) to observation in patients with resected invasive bladder cancer: Results of the spanish oncology genitourinary group (sogug) 99/01 study. J Clin Oncol. https://doi.org/10.1200/jco.2010.28.18_suppl.lba4518 Pas-Arez LGS, Solsona E, Esteban E, Saez A, Gonzalez-Larriba J, Anton A, Hevia M, De la Guillem Bellmunt RFFJ (2010) Randomized phase iii trial comparing adjuvant paclitaxel/gemcitabine/cisplatin (pgc) to observation in patients with resected invasive bladder cancer: Results of the spanish oncology genitourinary group (sogug) 99/01 study. J Clin Oncol. https://​doi.​org/​10.​1200/​jco.​2010.​28.​18_​suppl.​lba4518
32.
Zurück zum Zitat Cognetti F, Ruggeri EM, Felici A, Gallucci M, Muto G, Pollera CF, Massidda B, Rubagotti A, Giannarelli D, Boccardo F (2012) Adjuvant chemotherapy with cisplatin and gemcitabine versus chemotherapy at relapse in patients with muscle-invasive bladder cancer submitted to radical cystectomy: an italian, multicenter, randomized phase iii trial. Ann Oncol 23:695–700CrossRefPubMed Cognetti F, Ruggeri EM, Felici A, Gallucci M, Muto G, Pollera CF, Massidda B, Rubagotti A, Giannarelli D, Boccardo F (2012) Adjuvant chemotherapy with cisplatin and gemcitabine versus chemotherapy at relapse in patients with muscle-invasive bladder cancer submitted to radical cystectomy: an italian, multicenter, randomized phase iii trial. Ann Oncol 23:695–700CrossRefPubMed
33.
Zurück zum Zitat Sternberg CN, Skoneczna I, Kerst JM et al (2015) Immediate versus deferred chemotherapy after radical cystectomy in patients with pT3–pT4 or N+ M0 urothelial carcinoma of the bladder (EORTC 30994): an intergroup, open-label, randomised phase 3 trial. Lancet Oncol 16:76–86CrossRefPubMed Sternberg CN, Skoneczna I, Kerst JM et al (2015) Immediate versus deferred chemotherapy after radical cystectomy in patients with pT3–pT4 or N+ M0 urothelial carcinoma of the bladder (EORTC 30994): an intergroup, open-label, randomised phase 3 trial. Lancet Oncol 16:76–86CrossRefPubMed
34.
Zurück zum Zitat Ohlmann CH, Stöckle M (2015) Comment re: Sternberg CN, Skoneczna I, Kerst JM, et al. Immediate versus deferred chemotherapy after radical cystectomy in patients with pT3–pT4 or N+ M0 Urothelial carcinoma of the bladder (EORTC 30994): an intergroup, open-label, randomised phase 3 trial. Lancet Oncol 2015;16:76–86. Eur Urol 68(6):1104–1105. https://doi.org/10.1016/j.eururo.2015.08.013 CrossRefPubMed Ohlmann CH, Stöckle M (2015) Comment re: Sternberg CN, Skoneczna I, Kerst JM, et al. Immediate versus deferred chemotherapy after radical cystectomy in patients with pT3–pT4 or N+ M0 Urothelial carcinoma of the bladder (EORTC 30994): an intergroup, open-label, randomised phase 3 trial. Lancet Oncol 2015;16:76–86. Eur Urol 68(6):1104–1105. https://​doi.​org/​10.​1016/​j.​eururo.​2015.​08.​013 CrossRefPubMed
35.
Zurück zum Zitat Advanced Bladder Cancer (ABC) Meta-analysis Collaboration (2005) Adjuvant chemotherapy in invasive bladder cancer: a systematic review and meta-analysis of individual patient data advanced bladder cancer (abc) meta-analysis collaboration. Eur Urol 48:189–199 (discussion 199–201)CrossRef Advanced Bladder Cancer (ABC) Meta-analysis Collaboration (2005) Adjuvant chemotherapy in invasive bladder cancer: a systematic review and meta-analysis of individual patient data advanced bladder cancer (abc) meta-analysis collaboration. Eur Urol 48:189–199 (discussion 199–201)CrossRef
38.
Zurück zum Zitat Rosenblatt R, Sherif A, Rintala E, Wahlqvist R, Ullen A, Nilsson S, Malmstrom PU (2012) Pathologic downstaging is a surrogate marker for efficacy and increased survival following neoadjuvant chemotherapy and radical cystectomy for muscle-invasive urothelial bladder cancer. Eur Urol 61:1229–1238CrossRefPubMed Rosenblatt R, Sherif A, Rintala E, Wahlqvist R, Ullen A, Nilsson S, Malmstrom PU (2012) Pathologic downstaging is a surrogate marker for efficacy and increased survival following neoadjuvant chemotherapy and radical cystectomy for muscle-invasive urothelial bladder cancer. Eur Urol 61:1229–1238CrossRefPubMed
Metadaten
Titel
Perioperative Chemotherapie des Harnblasenkarzinoms
Neoadjuvante, induktive und adjuvante Strategien
verfasst von
Univ.-Prof. Dr. Anja Lorch
Axel S. Merseburger
Carsten-Henning Ohlmann
Publikationsdatum
15.11.2017
Verlag
Springer Medizin
Erschienen in
Die Onkologie / Ausgabe 1/2018
Print ISSN: 2731-7226
Elektronische ISSN: 2731-7234
DOI
https://doi.org/10.1007/s00761-017-0303-x

Weitere Artikel der Ausgabe 1/2018

Der Onkologe 1/2018 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.