Samenvatting
Spierinvasieve blaaskanker betreft ongeveer 30 % van de blaaskankers en is typisch een ziekte van de oudere patiënt. De ziekte kent een slechte prognose na radicale cystectomie. Chemotherapie in (neo)adjuvante setting wordt gegeven om micrometastasen, welke theoretisch zouden resulteren in recidief en macrometastasen, te steriliseren. Cisplatinebevattende neoadjuvante chemotherapie dient overwogen te worden bij spierinvasieve blaaskanker ≥ cT2 en geeft een winst van ca. 6 % op de tienjaarsoverleving. Cisplatine is echter toxisch en daardoor niet altijd toepasbaar bij deze patiëntengroep met comorbiditeit. Indien er sprake is van een beperkt aantal lymfekliermetastasen is curatie mogelijk met een chemotherapieschema met een hogere dosisintensiteit. De radiologische respons correleert matig met de pathologische respons. Van adjuvante chemotherapie zijn onvoldoende data beschikbaar die een overlevingsvoordeel laten zien en studies worden beperkt door slechte inclusie.
Een nieuwe ontwikkeling bij de behandeling van blaascarcinoom betreft de immunotherapie, met name met pembrolizumab, een anti-PD-1-antilichaam, waarvan fraaie responsen zijn beschreven in een fase 1-studie.
Abstract
At the time of diagnosis of bladder cancer 30 % is found to be muscle invasive. The prognosis of muscle invasive bladder cancer is poor en recurrence after radical systectomy is common. Bladder cancer is typically a disease of the elderly patient.
Neoadjuvant chemotherapy for bladder cancer is administered to sterilize possible micrometastases at the time of diagnosis and thereby prevent recurrent disease. Neoadjuvant cisplatin-based chemotherapy is indicated for muscle invasive bladder cancer (≥ cT2) and results in a ten-year survival benefit of ±6 %. Cisplatin however is toxic and because of its toxicity it is often not suitable for the eldery patient with co-morbidity. When there is only limited lymphnode involvement, curation is possible with a dose dense chemotherapy scheme. Radiological responses are known to correlate poorly to pathologic responses after cystectomy. There are still to little robust data and adequately powered studies rendering evidence for adjuvant chemotherapy. Studies performed in the past unfortunately were terminated early due to poor accrual.
New treatment modalities include immunotherapy and pembrolizumab, a monoclonal antibody directed against PD-1. Phase 1 studies show promising results with high response rates.
Literatuur
Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917.
Chen RC, Shipley WU, Efstathiou JA, et al. Trimodality bladder preservation therapy for muscle invasive bladder cancer. J Natl Compr canc Netw. 2013;11:952–60.
Stein JP, Lieskovsky G, Cote R, et al. Radical cystectomy in the treatment of muscle invasive bladder cancer: long term results in 1,054 patients. J Clin Oncol. 2001;19:666–75.
Grossman HB, Natale RB, Tangen CM, et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. NEJM. 2003;349:859–66.
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. 2006;48:202–5. (discussion 205–6).
Advanced Bladder Cancer (ABC) Meta-analysis Collaboration. Neoadjuvant chemotherapy in invasive bladder cancer: a systematic review and meta-analysis. Lancet. 2003;361:1927–34.
International Collaboration of Trialists. 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. 2011;29: 2171–7.
Von der Maasse H, Sengelov L, Roberts JK, 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;23:4602–8.
Zargar-Shoshtari K, Zargar H, Lotan Y, et al. A multi-institutional analysis of outcomes in patients with clinically node positive urothelial bladder cancer treated with induction chemotherapy and radical cystectomy. J Urol. doi:10.1016/j.juro.2015.07.085.
Galsky MD, Pal SK, Chowdhury S, Retrospective International Study of Cancers of the Urothelial Tract (RISC) Investigators, et al. Comparative effectiveness of gemcitabine plus cisplatin versus methotrexate, vinblastine, doxorubicin, plus cisplatin as neoadjuvant therapy for muscle-invasive bladder cancer. Cancer. 2015. doi:10.1002/cncr.29387.
Sternberg CN, de Mulder PH, van Oosterom AT, et al. Escalated M-VAC chemotherapy and recombinant human granulocyte colony-stimulating factor versus classic MVAc in advanced urothelial tract tumors; EORTC protocol no. 30924. J Clin Oncol. 2001;19:2638–46.
Plimack ER, Hoffman-Censits JH, Viterbo R, et al. Accelerated methotrexate, vinblastine, doxorubicine and cisplatin is safe, effective, and efficient neoadjuvant treatment for muscle invasive bladder cancer: results of a multicenter phase II study with molecular correlates of response and toxicity. J Clin Oncol. 2014;32:1895–901.
Choueiri TK, Jacobus S, Bellmunt J, et al. Neoadjuvant dose dense Methotrexate Vinblastine, doxorubicin, and cisplatin with pegfilgastrim support in muscle-invasive urothelial cancer:pathologic, radiologic and biomarker correlates. J Clin Oncol. 2014;32:1889–94.
Sternberg CN, Apolo AB. Everything old is new again! Neoadjuvant chemotherapy in the treatment of muscle-invasive bladder cancer. J Clin Oncol. 2014;32:1868–70.
Dash A, Galsky MD, et al. Impact of renal impairment on eligibility for adjuvant cisplatin-based chemotherapy in patients with urothelial carcinoma of the bladder. Cancer. 2006;107(3):506–13.
Koie T, Ohyama C, Hashimoto Y, et al. Efficacies and safety of neoadjuvant gemcitabine plus carboplatin followed by immediate cystectomy in patients with muscle-invasive bladder cancer, including those unfit for cisplatin: a prospective single-arm study. Int J Clin Oncol. 2013;18(4):724–30.
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(1):76–86.
Leow JJ, Martin-Doyle W, Fay AP, et al. A systematic review and meta-analysis of adjuvant and neoadjuvant chemotherapy for upper tract urothelial carcinoma. Eur Urol. 2014;66(1):42–54
Galsky MD et al. ASCO GU 2015, abstract 292.
Powles T, Eder JP, Fine GD, et al. MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature. 2014;515(7528):558–62.
Witjes JA, Comperat E, Cowan NC, et al. Guidelines on muscle invasive and metastatic bladder cancer. Eur Urol. 2015. http://uroweb.org/wp-content/uploads/07-Muscle-Invasive-BC_LR.pdf.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
de Mol, P., Gerritsen, W. (Neo)adjuvante chemotherapie bij spierinvasieve blaaskanker. Tijdschr Urol 5, 215–222 (2015). https://doi.org/10.1007/s13629-015-0104-1
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13629-015-0104-1