Neo- oder adjuvante Chemotherapie beim Harnblasenkarzinom?

 

 Buy Article Permissions and Reprints

Zusammenfassung

Das fortgeschrittene Urothelkarzinom der Harnblase ist ein Tumor, der häufig metastasiert und daher meist nur eine Lebenserwartung von wenigen Monaten bis Jahren zur Folge hat. Die neoadjuvante Chemotherapie vor kurativer Operation kann in einem Downstaging des Tumors und einer Verbesserung des Gesamtüberlebens resultieren. Eine adjuvante Systemtherapie wird aufgrund der gegenwärtigen Datenlage bislang nur zurückhaltend empfohlen. Am ehesten scheinen Patienten mit einer lymphknotenpositiven Erkrankung hiervon zu profitieren. Falls es die Tumorlokalisation zulässt, kann eine Metastasenresektion die Prognose verbessern. In der metastasierten Situation wird aufgrund der geringeren Nebenwirkungen bei gleichen Ansprechraten die Kombination von Gemcitabin und Cisplatin dem MVAC Regime (Methotrexat, Vinblastin, Adriamycin, Cisplatin) vorgezogen. Vinflunin hat in der Zweitliniensituation nach Platinversagen einen festen Stellenwert.

Abstract

Advanced urothelial carcinoma of the bladder is associated with a high metastatic potential. Life expectancy for metastatic patients is poor and rarely exceeds more than one year without further therapy. Neoadjuvant chemotherapy can decrease the tumour burden while reducing the risk of death. Adjuvant chemotherapy has been discussed controversially. Patients with lymph node-positive metastases seem to benefit the most from adjuvant chemotherapy. In selected patients, metastasectomy can prolong survival. In metastastic patients, the combination of gemcitabine and cisplatin has become the new standard regimen due to a lower toxicity in comparison to the combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC). For second-line treatment, vinflunine is the only approved therapeutic agent.

• References

• 1 Merseburger AS, Shariat SF. Urothelial carcinoma. World J Urol 2011; 29: 405-407
  CrossrefPubMedGoogle Scholar
• 2 Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin 2013; 63: 11-30
  CrossrefPubMedGoogle Scholar
• 3 Shariat SF, Sfakianos JP, Droller MJ et al. The effect of age and gender on bladder cancer: a critical review of the literature. BJU Int 2010; 105: 300-308
  CrossrefPubMedGoogle Scholar
• 4 Rink M, Chun FK, Chromecki TF et al. Advanced bladder cancer in elderly patients. Prognostic outcomes and therapeutic strategies. Urologe A 2012; 51: 820-828
  CrossrefPubMedGoogle Scholar
• 5 Fajkovic H, Halpern JA, Cha EK et al. Impact of gender on bladder cancer incidence, staging, and prognosis. World J Urol 2011; 29: 457-463
  CrossrefPubMedGoogle Scholar
• 6 Sylvester RJ, van der Meijden AP, Oosterlinck W et al. Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials. Eur Urol 2006; 49: 466-475 discussion 475-477
  CrossrefPubMedGoogle Scholar
• 7 Hautmann RE, de Petriconi RC, Pfeiffer C et al. Radical cystectomy for urothelial carcinoma of the bladder without neoadjuvant or adjuvant therapy: long-term results in 1100 patients. Eur Urol 2012; 61: 1039-1047
  CrossrefPubMedGoogle Scholar
• 8 Goebell PJ, vom Dorp F, Rubben H. Value of systemic chemotherapy in bladder cancer. Urologe A 2006; 45 586, 588-590 592-593
  PubMedGoogle Scholar
• 9 European Association of Urology. Guidelines on muscle-invasive and metastatic bladder cancer. http://uroweb.org/guideline/bladder-cancer-muscle-invasive-and-metastatic/ Accessed March 27, 2015
  PubMedGoogle Scholar
• 10 Advanced Bladder Cancer Meta-analysis Collaboration . Neoadjuvant chemotherapy in invasive bladder cancer: a systematic review and meta-analysis. Lancet 2003; 361: 1927-1934
  CrossrefPubMedGoogle Scholar
• 11 Advanced Bladder Cancer (ABC) Meta-analysis Collaboration . 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 2005; 48: 202-205 discussion 205-206
  CrossrefPubMedGoogle Scholar
• 12 Winquist E, Kirchner TS, Segal R et al. Neoadjuvant chemotherapy for transitional cell carcinoma of the bladder: a systematic review and meta-analysis. J Urol 2004; 171: 561-569
  CrossrefPubMedGoogle Scholar
• 13 Sternberg CN, Bellmunt J, Sonpavde G et al. ICUD-EAU International Consultation on Bladder Cancer 2012: Chemotherapy for urothelial carcinoma-neoadjuvant and adjuvant settings. Eur Urol 2013; 63: 58-66
  CrossrefPubMedGoogle Scholar
• 14 Witjes JA, Comperat E, Cowan NC et al. EAU guidelines on muscle-invasive and metastatic bladder cancer: summary of the 2013 guidelines. Eur Urol 2014; 65: 778-792
  CrossrefPubMedGoogle Scholar
• 15 von der Maase H, Hansen SW, Roberts JT et al. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol 2000; 18: 3068-3077
  CrossrefPubMedGoogle Scholar
• 16 von der Maase H, Sengelov L, Roberts JT et al. 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 2005; 23: 4602-4608
  CrossrefPubMedGoogle Scholar
• 17 Advanced Bladder Cancer (ABC) Meta-analysis Collaboration . 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 2005; 48: 189-199 discussion 199-201
  Google Scholar
• 18 Leow JJ, Martin-Doyle W, Rajagopal PS et al. Adjuvant chemotherapy for invasive bladder cancer: a 2013 updated systematic review and meta-analysis of randomized trials. Eur Urol 2014; 66: 42-54
  CrossrefPubMedGoogle Scholar
• 19 Paz-Ares LG, Solsona E, Esteban E et al. 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 2010; 28: 18s (suppl; abstr LBA4518)
  PubMedGoogle Scholar
• 20 Lehmann J, Kuehn M, Fischer C et al. Randomized phase III study of adjuvant versus progression-triggered treatment with gemcitabine (G) after radical cystectomy (RC) for locally advanced bladder cancer (LABC) in patients not suitable for cisplatin-based chemotherapy (CBC) (AUO-trial AB22/00). J Clin Oncol 2013; 31 (suppl 6; abstr 250)
  PubMedGoogle Scholar
• 21 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
  CrossrefPubMedGoogle Scholar
• 22 Stadler WM, Lerner SP, Groshen S et al. Phase III study of molecularly targeted adjuvant therapy in locally advanced urothelial cancer of the bladder based on p53 status. J Clin Oncol 2011; 29: 3443-3449
  CrossrefPubMedGoogle Scholar
• 23 Gakis G, Stenzl A. Gender-specific differences in muscle-invasive bladder cancer: the concept of sex steroid sensitivity. World J Urol 2013; 31: 1059-1064
  CrossrefPubMedGoogle Scholar
• 24 Bajorin DF, Dodd PM, Mazumdar M et al. Long-term survival in metastatic transitional-cell carcinoma and prognostic factors predicting outcome of therapy. J Clin Oncol 1999; 17: 3173-3181
  PubMedGoogle Scholar
• 25 Galsky MD, Hahn NM, Rosenberg J et al. A consensus definition of patients with metastatic urothelial carcinoma who are unfit for cisplatin-based chemotherapy. Lancet Oncol 2011; 12: 211-214
  CrossrefPubMedGoogle Scholar
• 26 De Santis M, Bellmunt J, Mead G et al. Randomized phase II/III trial assessing gemcitabine/ carboplatin and methotrexate/carboplatin/vinblastine in patients with advanced urothelial cancer “unfit” for cisplatin-based chemotherapy: phase II–results of EORTC study 30986. J Clin Oncol 2009; 27: 5634-5639
  CrossrefPubMedGoogle Scholar
• 27 De Santis M, Wiechno PJ, Lucas C et al. Feasibility and activity of two vinflunine (VFL)-based combinations as first-line chemotherapy (CT) in CDDP-unfit patients (pts) with advanced urothelial carcinoma (UC): VFL-gemcitabine (GEM) or VFL-CBDCA in a randomized international phase II trial (JASINT). J Clin Oncol 2014; 32: 5s (suppl; abstr 4534)
  CrossrefPubMedGoogle Scholar
• 28 Heck MM, Gschwend JE, Retz M et al. Chemotherapy for bladder cancer: 2012 Update. From AUO („Arbeitsgemeinschaft Urologische Onkologie“) and IABC („Interdisziplinare Arbeitsgruppe BlasenCarcinom“). Urologe A 2012; 51: 829-836
  CrossrefPubMedGoogle Scholar
• 29 Hahn NM, Stadler WM, Zon RT et al. Phase II trial of cisplatin, gemcitabine, and bevacizumab as first-line therapy for metastatic urothelial carcinoma: Hoosier Oncology Group GU 04-75. J Clin Oncol 2011; 29: 1525-1530
  CrossrefPubMedGoogle Scholar
• 30 Bellmunt J, Theodore C, Demkov T et al. Phase III trial of vinflunine plus best supportive care compared with best supportive care alone after a platinum-containing regimen in patients with advanced transitional cell carcinoma of the urothelial tract. J Clin Oncol 2009; 27: 4454-4461
  CrossrefPubMedGoogle Scholar
• 31 Bellmunt J, Fougeray R, Rosenberg JE et al. Long-term survival results of a randomized phase III trial of vinflunine plus best supportive care versus best supportive care alone in advanced urothelial carcinoma patients after failure of platinum-based chemotherapy. Ann Oncol 2013; 24: 1466-1472
  CrossrefPubMedGoogle Scholar
• 32 Kramer MW, Krege S, Peters I et al. Targeted therapy of urological tumours. Experimental field or established therapeutic approach?. Urologe A 2010; 49: 1260-1265
  CrossrefPubMedGoogle Scholar
• 33 Dominguez-Escrig JL, Kelly JD, Neal DE et al. Evaluation of the therapeutic potential of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib in preclinical models of bladder cancer. Clin Cancer Res 2004; 10: 4874-4884
  CrossrefPubMedGoogle Scholar
• 34 Krege S, Rexer H, vom Dorp F et al. Gemcitabine and cisplatin with or without sorafenib in urothelial carcinoma (AUO-AB 31/05). J Clin Oncol 2010; 28: 15s (suppl; abstr 4574)
  PubMedGoogle Scholar
• 35 Powles T, Eder JP, Fine GD et al. MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature 2014; 515: 558-562
  CrossrefPubMedGoogle Scholar
• 36 Kim JW, Bellmunt J, Powles T et al. Clinical activity, safety, and biomarkers of MPDL3280A in metastatic urothelial bladder cancer: Additional analysis from phase IA study. J Clin Oncol 2015; 33 (suppl 7; abstr 297)
  PubMedGoogle Scholar
• 37 O’Donnell PH, Plimack ER, Bellmunt J et al. Pembrolizumab (Pembro; MK-3475) for advanced urothelial cancer: Results of a phase IB study. J Clin Oncol 2015; 33 (suppl 7; abstr 296)
  PubMedGoogle Scholar
• 38 Abe T, Shinohara N, Harabayashi T et al. Impact of multimodal treatment on survival in patients with metastatic urothelial cancer. Eur Urol 2007; 52: 1106-1113
  CrossrefPubMedGoogle Scholar
• 39 Lehmann J, Suttmann H, Albers P et al. Complete resection of urothelial cancer metastases with curative intent. Urologe A 2009; 48: 143-150
  CrossrefPubMedGoogle Scholar
• 40 Abe T, Kitamura H, Obara W et al. Outcome of metastasectomy for urothelial carcinoma: a multi-institutional reotrospective study in Japan. J Urol 2014; 191: 932-936
  CrossrefPubMedGoogle Scholar