Neoadjuvant treatment for muscle-invasive bladder cancer: The past, the present, and the future.

Hermans, Tom J N; Voskuilen, Charlotte S; van der Heijden, Michiel S; Schmitz-Dräger, Bernd J; Kassouf, Wassim; Seiler, Roland; Kamat, Ashish M; Grivas, Petros; Kiltie, Anne E; Black, Peter C; van Rhijn, Bas W G (2018). Neoadjuvant treatment for muscle-invasive bladder cancer: The past, the present, and the future. Urologic oncology - seminars and original investigations, 36(9), pp. 413-422. Elsevier 10.1016/j.urolonc.2017.10.014

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BACKGROUND Approximately half of patients who undergo radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) will succumb to metastatic disease. We summarize the evidence for neoadjuvant radiation (NAR), chemo (NAC), and immunotherapy (checkpoint inhibition) prior to RC for MIBC. MATERIALS AND METHODS Data were obtained by a search of PubMed, ClinicalTrials.gov, and Cochrane databases for English language articles published from 1925 up to 2017. RESULTS NAC usage has increased over the last decade, while NAR is rarely administered. Although NAR results in downstaging, its impact on survival is inconclusive. Based on level I evidence, cisplatin-based NAC (CB-NAC) is considered standard of care in cT2-4aN0M0 MIBC. NAC results in a 6% absolute 10-year overall survival (OS) benefit. In-depth analyses of key randomized controlled trials showed that failure to correct for uniform staging, surgical variation, and patient selection compromises the ability to identify factors predictive of response to NAC. The benefit appears to be restricted to patients downstaged to ypT1N0 or less. In these patients, 5-year OS is 80% to 90%. Regarding a number needed to treat of 17, most patients with cT2-4aN0M0 MIBC will be exposed to toxicity without benefit. Possible approaches to reduce overtreatment are suggested in this article and include patient selection, the chosen NAC regimen, and emerging molecular data to predict responsiveness to NAC. Neoadjuvant immunotherapy with checkpoint inhibitors is a promising future perspective currently under investigation. CONCLUSIONS Past studies on NAR show inconclusive results and NAR is rarely administered. Instead, CB-NAC is advised in eligible patients with cT2-4aN0M0 MIBC prior to RC. In the near future, predictive biomarkers will be the key to tailor the use of CB-NAC and reduce harm to nonresponders.

Item Type:

Journal Article (Review Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Urology

UniBE Contributor:

Seiler, Roland

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1078-1439

Publisher:

Elsevier

Language:

English

Submitter:

Laetitia Hayoz

Date Deposited:

30 Jan 2018 14:14

Last Modified:

25 Oct 2019 00:16

Publisher DOI:

10.1016/j.urolonc.2017.10.014

PubMed ID:

29128420

Uncontrolled Keywords:

Bladder cancer Chemotherapy Cystectomy Immunotherapy Neoadjuvant Radiation

BORIS DOI:

10.7892/boris.108758

URI:

https://boris.unibe.ch/id/eprint/108758

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