Nur die Chirurgie? Multimodalkonzepte mit kurativer Intention für das Urothelkarzinom der Harnblase

Victor Schuettfort; Shahrokh F. Shariat; Michael Rink

doi:10.1055/a-1146-2938

Aktuelle Urologie, Table of Contents

Aktuelle Urol 2020; 51(04): 353-362
DOI: 10.1055/a-1146-2938

Übersicht

Nur die Chirurgie? Multimodalkonzepte mit kurativer Intention für das Urothelkarzinom der Harnblase

Surgery only? Multimodal treatment for urothelial carcinoma of the bladder

Victor Schuettfort

¹Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Urologie, Hamburg

,

Shahrokh F. Shariat

²Allgemeines Krankenhaus der Stadt Wien-Klinikum der Medizinischen Universität Wien, Univ. Klinik für Urologie, Wien

,

Michael Rink

¹Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Urologie, Hamburg

› Author Affiliations

Abstract

Zusammenfassung

Die radikale Zystektomie ist der Goldstandard zur Behandlung des muskelinvasiven Urothelkarzinoms. Insbesondere bei Patienten mit fortgeschrittenen Tumoren spielen multimodale, neoadjuvante oder adjuvante Therapiekonzepte eine zunehmend wichtige Rolle für die optimale Patientenversorgung. Zudem sind bei älteren und komorbideren Patienten, die unfit für eine radikale Zystektomie sind, alternative Therapiekonzepte erforderlich. Dieser Artikel fasst die aktuelle Literatur multimodaler Therapien im neoadjuvanten und adjuvanten Setting zusammen und beleuchtet Alternativen zur radikalen Zystektomie mit kurativem Therapieansatz. Ebenfalls werden erste Erkenntnisse über den Einsatz neuer, vielversprechender Therapieoptionen wie der Immuncheckpoint-Blockade im multimodalen Therapieansatz zusammengefasst.

Abstract

Radical cystectomy is the gold standard in treatment of muscle invasive bladder carcinoma. Especially for patients with advanced tumours, multimodal therapies play an important role in optimising patient care. In older patients with multiple comorbidities, who are not eligible for surgery, alternative treatment modalities are needed as well. This article summarises the current literature on multimodal treatment options in a neoadjuvant and adjuvant setting and analyses alternative potentially curative treatments. The article also summarises the initial results using checkpoint inhibitors in a multimodal treatment setting.

Schlüsselwörter

Urothelkarzinom - Radikale Zystektomie - Perioperative Chemotherapie - Multimodale Therapie - Trimodale Therapie

Keywords

Urothelial carcinoma - Multimodal therapy - Perioperative chemotherapy - Radical cystectomy - Trimodal therapy

Full Text

References

References
1 Bray F, Ferlay J, Soerjomataram I. et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68: 394-424
2 Burger M, Catto JW, Dalbagni G. et al. Epidemiology and risk factors of urothelial bladder cancer. Eur Urol 2013; 63: 234-241
3 Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft DK, AWMF). S3-Leitlinie Früherkennung, Diagnose, Therapie und Nachsorge des Harnblasenkarzinoms, Langversion 1.1, AWMF-Registrierungsnummer 032/038OL. 2016 (Stand: 13.02.2020) http://leitlinienprogramm-onkologie.de/Harnblasenkarzinom.92.0.html
4 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: 466-465; discussion 475-467
5 Gontero P, Sylvester R, Pisano F. et al. Prognostic factors and risk groups in T1G3 non-muscle-invasive bladder cancer patients initially treated with Bacillus Calmette-Guerin: results of a retrospective multicenter study of 2451 patients. Eur Urol 2015; 67: 74-82
6 Xylinas E, Kent M, Kluth L. et al. Accuracy of the EORTC risk tables and of the CUETO scoring model to predict outcomes in non-muscle-invasive urothelial carcinoma of the bladder. Br J Cancer 2013; 109: 1460-1466
7 Witjes J, Bruins M, Cathomas R. et al. EAU Guidelines on Muscle-invasive and Metastatic Bladder Cancer. EAU Guidelines; 2019
8 Gore JL, Litwin MS, Lai J. et al. Use of radical cystectomy for patients with invasive bladder cancer. J Natl Cancer Inst 2010; 102: 802-811
9 Shariat SF, Milowsky M, Droller MJ. Bladder cancer in the elderly. Urol Oncol 2009; 27: 653-667
10 Isbarn H, Jeldres C, Zini L. et al. A population based assessment of perioperative mortality after cystectomy for bladder cancer. J Urol 2009; 182: 70-77
11 Shariat SF, Karakiewicz PI, Palapattu GS. et al. Outcomes of radical cystectomy for transitional cell carcinoma of the bladder: a contemporary series from the Bladder Cancer Research Consortium. J Urol 2006; 176: 2414-2422; discussion 2422
12 Rink M, Lee DJ, Kent M. et al. Predictors of cancer-specific mortality after disease recurrence following radical cystectomy. BJU Int 2013; 111: E30-36
13 Advanced Bladder Cancer Meta-analysis C. 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
14 Dogan S, Hennig M, Frank T. et al. Acceptance of Adjuvant and Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer in Germany: A Survey of Current Practice. Urol Int 2018; 101: 25-30
15 van de Putte EE, Mertens LS, Meijer RP. et al. Neoadjuvant induction dose-dense MVAC for muscle invasive bladder cancer: efficacy and safety compared with classic MVAC and gemcitabine/cisplatin. World J Urol 2016; 34: 157-162
16 Peyton CC, Tang D, Reich RR. et al. Downstaging and Survival Outcomes Associated With Neoadjuvant Chemotherapy Regimens Among Patients Treated With Cystectomy for Muscle-Invasive Bladder Cancer. JAMA Oncol 2018; 4: 1535-1542
17 Motterle G, Andrews JR, Morlacco A. et al. Predicting Response to Neoadjuvant Chemotherapy in Bladder Cancer. Eur Urol Focus 2019;
18 Robertson AG, Kim J, Al-Ahmadie H. et al. Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer. Cell 2017; 171: 540-556 e525
19 Lawrence MS, Stojanov P, Polak P. et al. Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature 2013; 499: 214-218
20 Cancer Genome Atlas Research N. Comprehensive molecular characterization of urothelial bladder carcinoma. Nature 2014; 507: 315-322
21 Seiler R, Ashab HAD, Erho N. et al. Impact of Molecular Subtypes in Muscle-invasive Bladder Cancer on Predicting Response and Survival after Neoadjuvant Chemotherapy. Eur Urol 2017; 72: 544-554
22 Rink M. The landscape of genetics and biomarkers in bladder cancer. Transl Androl Urol 2017; 6: 1027-1030
23 Soria F, Krabbe LM, Todenhofer T. et al. Molecular markers in bladder cancer. World J Urol 2019; 37: 31-40
24 Gore JL, Lai J, Setodji CM. et al. Mortality increases when radical cystectomy is delayed more than 12 weeks: results from a Surveillance, Epidemiology, and End Results-Medicare analysis. Cancer 2009; 115: 988-996
25 Boeri L, Soligo M, Frank I. et al. Delaying Radical Cystectomy After Neoadjuvant Chemotherapy for Muscle-invasive Bladder Cancer is Associated with Adverse Survival Outcomes. Eur Urol Oncol 2019; 2: 390-396
26 Aldhaam NA, Elsayed AS, Jing Z. et al. Neoadjuvant Chemotherapy is Not Associated with Adverse Perioperative Outcomes after Robot-Assisted Radical Cystectomy: A Case for Increased Use from the IRCC. J Urol 2020; 203: 57-61
27 Salminen AP, Koskinen I, Perez IM. et al. Neoadjuvant Chemotherapy Does Not Increase the Morbidity of Radical Cystectomy: A 10-year Retrospective Nationwide Study. Eur Urol Oncol 2018; 1: 525-530
28 Kapadia AA, Martinez Acevedo A, Liu JJ. et al. Unconventional Bladder Preservation: Factors Predicting Failure to Receive Definitive Surgery following Chemotherapy for Nonmetastatic Muscle Invasive Bladder Cancer in the National Cancer Database. J Urol 2018; 200: 535-540
29 Klinga G, Sherif A. A retrospective evaluation of preoperative anemia in patients undergoing radical cystectomy for muscle-invasive urothelial urinary bladder cancer, with or without neoadjuvant chemotherapy. Springerplus 2016; 5: 1167
30 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
31 Lehmann J, Franzaring L, Thuroff J. et al. Complete long-term survival data from a trial of adjuvant chemotherapy vs control after radical cystectomy for locally advanced bladder cancer. BJU Int 2006; 97: 42-47
32 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
33 Galsky MD, Stensland KD, Moshier E. et al. Effectiveness of Adjuvant Chemotherapy for Locally Advanced Bladder Cancer. J Clin Oncol 2016; 34: 825-832
34 Svatek RS, Shariat SF, Lasky RE. et al. The effectiveness of off-protocol adjuvant chemotherapy for patients with urothelial carcinoma of the urinary bladder. Clin Cancer Res 2010; 16: 4461-4467
35 Lucca I, Roupret M, Kluth L. et al. Adjuvant cisplatin-based combined chemotherapy for lymph node (LN)-positive urothelial carcinoma of the bladder (UCB) after radical cystectomy (RC): a retrospective international study of >1500 patients. BJU Int 2015; 115: 722-727
36 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
37 Millikan R, Dinney C, Swanson D. et al. Integrated therapy for locally advanced bladder cancer: final report of a randomized trial of cystectomy plus adjuvant M-VAC versus cystectomy with both preoperative and postoperative M-VAC. J Clin Oncol 2001; 19: 4005-4013
38 Del Bene G, Calabro F, Giannarelli D. et al. Neoadjuvant vs. Adjuvant Chemotherapy in Muscle Invasive Bladder Cancer (MIBC): Analysis From the RISC Database. Front Oncol 2018; 8: 463
39 Macleod LC, Fam MM, Yabes JG. et al. Comparison of Neoadjuvant and Adjuvant Chemotherapy in Muscle-invasive Bladder Cancer. Clin Genitourin Cancer 2019;
40 Martinez Chanza N, Werner L, Plimack E. et al. Incidence, Patterns, and Outcomes with Adjuvant Chemotherapy for Residual Disease After Neoadjuvant Chemotherapy in Muscle-invasive Urinary Tract Cancers. Eur Urol Oncol 2019;
41 Cahn DB, Handorf EA, Ghiraldi EM. et al. Contemporary use trends and survival outcomes in patients undergoing radical cystectomy or bladder-preservation therapy for muscle-invasive bladder cancer. Cancer 2017; 123: 4337-4345
42 Fischer-Valuck BW, Rao YJ, Rudra S. et al. Treatment Patterns and Overall Survival Outcomes of Octogenarians with Muscle Invasive Cancer of the Bladder: An Analysis of the National Cancer Database. J Urol 2018; 199: 416-423
43 Moonen L, vd Voet H, de Nijs R. et al. Muscle-invasive bladder cancer treated with external beam radiotherapy: pretreatment prognostic factors and the predictive value of cystoscopic re-evaluation during treatment. Radiother Oncol 1998; 49: 149-155
44 Hall E, Hussain S, Porta N. et al. BC2001 long-term outcomes: A phase III randomized trial of chemoradiotherapy versus radiotherapy (RT) alone and standard RT versus reduced high-dose volume RT in muscle-invasive bladder cancer. Journal of Clinical Oncology 2017; 35: 280-280
45 James ND, Hussain SA, Hall E. et al. Radiotherapy with or without chemotherapy in muscle-invasive bladder cancer. N Engl J Med 2012; 366: 1477-1488
46 Lutkenhaus LJ, van Os RM, Bel A. et al. Clinical results of conformal versus intensity-modulated radiotherapy using a focal simultaneous boost for muscle-invasive bladder cancer in elderly or medically unfit patients. Radiat Oncol 2016; 11: 45
47 Ali A, Song YP, Mehta S. et al. Palliative Radiation Therapy in Bladder Cancer-Importance of Patient Selection: A Retrospective Multicenter Study. Int J Radiat Oncol Biol Phys 2019; 105: 389-393
48 Granfors T, Tomic R, Ljungberg B. Downstaging and survival benefits of neoadjuvant radiotherapy before cystectomy for patients with invasive bladder carcinoma. Scand J Urol Nephrol 2009; 43: 293-299
49 Widmark A, Flodgren P, Damber JE. et al. A systematic overview of radiation therapy effects in urinary bladder cancer. Acta Oncol 2003; 42: 567-581
50 Gontero P, Pisano F, Palou J. et al. Complication rate after cystectomy following pelvic radiotherapy: an international, multicenter, retrospective series of 682 cases. World J Urol 2019;
51 McAlpine K, Fergusson DA, Breau RH. et al. Radiotherapy with radical cystectomy for bladder cancer: A systematic review and meta-analysis. Can Urol Assoc J 2018; 12: 351-360
52 Christodouleas JP, Baumann BC, He J. et al. Optimizing bladder cancer locoregional failure risk stratification after radical cystectomy using SWOG 8710. Cancer 2014; 120: 1272-1280
53 Herr HW, Faulkner JR, Grossman HB. et al. Surgical factors influence bladder cancer outcomes: a cooperative group report. J Clin Oncol 2004; 22: 2781-2789
54 Zaghloul MS, Christodouleas JP, Smith A. et al. Adjuvant Sandwich Chemotherapy Plus Radiotherapy vs Adjuvant Chemotherapy Alone for Locally Advanced Bladder Cancer After Radical Cystectomy: A Randomized Phase 2 Trial. JAMA Surg 2018; 153: e174591
55 Lewis GD, Haque W, Verma V. et al. The Role of Adjuvant Radiation Therapy in Locally Advanced Bladder Cancer. Bladder Cancer 2018; 4: 205-213
56 Tran E, Souhami L, Tanguay S. et al. Bladder conservation treatment in the elderly population: results and prognostic factors of muscle-invasive bladder cancer. Am J Clin Oncol 2009; 32: 333-337
57 Turgeon GA, Souhami L, Cury FL. et al. Hypofractionated intensity modulated radiation therapy in combined modality treatment for bladder preservation in elderly patients with invasive bladder cancer. Int J Radiat Oncol Biol Phys 2014; 88: 326-331
58 Giacalone NJ, Shipley WU, Clayman RH. et al. Long-term Outcomes After Bladder-preserving Tri-modality Therapy for Patients with Muscle-invasive Bladder Cancer: An Updated Analysis of the Massachusetts General Hospital Experience. Eur Urol 2017; 71: 952-960
59 Mathes J, Rausch S, Todenhofer T. et al. Trimodal therapy for muscle-invasive bladder cancer. Expert Rev Anticancer Ther 2018; 18: 1219-1229
60 El-Achkar A, Souhami L, Kassouf W. Bladder Preservation Therapy: Review of Literature and Future Directions of Trimodal Therapy. Curr Urol Rep 2018; 19: 108
61 Ploussard G, Daneshmand S, Efstathiou JA. et al. Critical analysis of bladder sparing with trimodal therapy in muscle-invasive bladder cancer: a systematic review. Eur Urol 2014; 66: 120-137
62 Caffo O, Thompson C, De Santis M. et al. Concurrent gemcitabine and radiotherapy for the treatment of muscle-invasive bladder cancer: A pooled individual data analysis of eight phase I-II trials. Radiother Oncol 2016; 121: 193-198
63 Thompson C, Joseph N, Sanderson B. et al. Tolerability of Concurrent Chemoradiation Therapy With Gemcitabine (GemX), With and Without Prior Neoadjuvant Chemotherapy, in Muscle Invasive Bladder Cancer. Int J Radiat Oncol Biol Phys 2017; 97: 732-739
64 Kang JJ, Steinberg ML, Kupelian P. et al. Whole Versus Partial Bladder Radiation: Use of an Image-guided Hypofractionated IMRT Bladder-preservation Protocol. Am J Clin Oncol 2018; 41: 107-114
65 Cowan RA, McBain CA, Ryder WD. et al. Radiotherapy for muscle-invasive carcinoma of the bladder: results of a randomized trial comparing conventional whole bladder with dose-escalated partial bladder radiotherapy. Int J Radiat Oncol Biol Phys 2004; 59: 197-207
66 Tunio MA, Hashmi A, Qayyum A. et al. Whole-pelvis or bladder-only chemoradiation for lymph node-negative invasive bladder cancer: single-institution experience. Int J Radiat Oncol Biol Phys 2012; 82: e457-462
67 Goldsmith B, Baumann BC, He J. et al. Occult pelvic lymph node involvement in bladder cancer: implications for definitive radiation. Int J Radiat Oncol Biol Phys 2014; 88: 603-610
68 Efstathiou JA, Bae K, Shipley WU. et al. Late pelvic toxicity after bladder-sparing therapy in patients with invasive bladder cancer: RTOG 89-03, 95-06, 97-06, 99-06. J Clin Oncol 2009; 27: 4055-4061
69 Mak RH, Hunt D, Shipley WU. et al. Long-term outcomes in patients with muscle-invasive bladder cancer after selective bladder-preserving combined-modality therapy: a pooled analysis of Radiation Therapy Oncology Group protocols 8802, 8903, 9506, 9706, 9906, and 0233. J Clin Oncol 2014; 32: 3801-3809
70 Fahmy O, Khairul-Asri MG, Schubert T. et al. A systematic review and meta-analysis on the oncological long-term outcomes after trimodality therapy and radical cystectomy with or without neoadjuvant chemotherapy for muscle-invasive bladder cancer. Urol Oncol 2018; 36: 43-53
71 Shipley W, Winter K, Kaufman D. et al. Phase III trial of neoadjuvant chemotherapy in patients with invasive bladder cancer treated with selective bladder preservation by combined radiation therapy and chemotherapy: initial results of radiation therapy oncology group 89-03. J Urol 1999; 162: 623-624
72 Sanchez A, Wszolek MF, Niemierko A. et al. Incidence, Clinicopathological Risk Factors, Management and Outcomes of Nonmuscle Invasive Recurrence after Complete Response to Trimodality Therapy for Muscle Invasive Bladder Cancer. J Urol 2018; 199: 407-415
73 Hautmann RE, Gschwend JE, de Petriconi RC. et al. Cystectomy for transitional cell carcinoma of the bladder: results of a surgery only series in the neobladder era. J Urol 2006; 176: 486-492; discussion 491-482
74 Zietman AL, Grocela J, Zehr E. et al. Selective bladder conservation using transurethral resection, chemotherapy, and radiation: management and consequences of Ta, T1, and Tis recurrence within the retained bladder. Urology 2001; 58: 380-385
75 Krasnow RE, Drumm M, Roberts HJ. et al. Clinical Outcomes of Patients with Histologic Variants of Urothelial Cancer Treated with Trimodality Bladder-sparing Therapy. Eur Urol 2017; 72: 54-60
76 Miyamoto DT, Mouw KW, Feng FY. et al. Molecular biomarkers in bladder preservation therapy for muscle-invasive bladder cancer. Lancet Oncol 2018; 19: e683-e695
77 Vashistha V, Wang H, Mazzone A. et al. Radical Cystectomy Compared to Combined Modality Treatment for Muscle-Invasive Bladder Cancer: A Systematic Review and Meta-Analysis. Int J Radiat Oncol Biol Phys 2017; 97: 1002-1020
78 Arcangeli G, Strigari L, Arcangeli S. Radical cystectomy versus organ-sparing trimodality treatment in muscle-invasive bladder cancer: A systematic review of clinical trials. Crit Rev Oncol Hematol 2015; 95: 387-396
79 Kulkarni GS, Hermanns T, Wei Y. et al. Propensity Score Analysis of Radical Cystectomy Versus Bladder-Sparing Trimodal Therapy in the Setting of a Multidisciplinary Bladder Cancer Clinic. J Clin Oncol 2017; 35: 2299-2305
80 Mak KS, Smith AB, Eidelman A. et al. Quality of Life in Long-term Survivors of Muscle-Invasive Bladder Cancer. Int J Radiat Oncol Biol Phys 2016; 96: 1028-1036
81 ietman AL, Sacco D, Skowronski U. et al. Organ conservation in invasive bladder cancer by transurethral resection, chemotherapy and radiation: results of a urodynamic and quality of life study on long-term survivors. J Urol 2003; 170: 1772-1776
82 Kijima T, Tanaka H, Koga F. et al. Selective tetramodal bladder-preservation therapy, incorporating induction chemoradiotherapy and consolidative partial cystectomy with pelvic lymph node dissection for muscle-invasive bladder cancer: oncological and functional outcomes of 107 patients. BJU Int 2019; 124: 242-250
83 Miyata H, Osawa T, Abe T. et al. The updated outcomes of bladder-preserving trimodal therapy using a real-time tumor-tracking radiotherapy system for patients with muscle-invasive bladder cancer. Jpn J Clin Oncol 2020;
84 Necchi A, Rink M, Giannatempo P. et al. Immunotherapy for metastatic urothelial carcinoma: status quo and the future. Curr Opin Urol 2018; 28: 1-7
85 Necchi A, Anichini A, Raggi D. et al. Pembrolizumab as Neoadjuvant Therapy Before Radical Cystectomy in Patients With Muscle-Invasive Urothelial Bladder Carcinoma (PURE-01): An Open-Label, Single-Arm, Phase II Study. J Clin Oncol 2018;
86 Necchi A, Raggi D, Gallina A. et al. Updated Results of PURE-01 with Preliminary Activity of Neoadjuvant Pembrolizumab in Patients with Muscle-invasive Bladder Carcinoma with Variant Histologies. Eur Urol 2019;
87 Powles T, Rodriguez-Vida A, Duran I. et al. A phase II study investigating the safety and efficacy of neoadjuvant atezolizumab in muscle invasive bladder cancer (ABACUS). Journal of Clinical Oncology 2018; 36: 4506-4506
88 Joshi M, Tuanquin L, Kaag M. et al. Phase Ib study of concurrent durvalumab and radiation therapy (DUART) followed by adjuvant durvalumab in patients with urothelial cancer of the bladder: BTCRC-GU15-023 study. Journal of Clinical Oncology 2018; 36: 455-455
89 Rompre-Brodeur A, Shinde-Jadhav S, Ayoub M. et al. PD-1/PD-L1 Immune Checkpoint Inhibition with Radiation in Bladder Cancer: In Situ and Abscopal Effects. Mol Cancer Ther 2020; 19: 211-220