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Muscle-invasive urothelial bladder cancer: an update on systemic therapy.

ABSTRACT: Urothelial carcinoma is a common malignancy that carries a poor prognosis when the disease includes muscle invasion. Metastatic urothelial carcinoma is almost uniformly fatal. The evidence behind treatment options in the neoadjuvant, adjuvant and metastatic settings are discussed in this manuscript, with a focused review of standard and investigational cytotoxic, targeted, and immunotherapy approaches. We have focused especially on neoadjuvant cisplatin-based therapy (supported by level one evidence) and on novel immunotherapy agents such as checkpoint inhibitors, which have shown great promise in early clinical studies.

SUBMITTER: Knollman H

PROVIDER: S-EPMC4647143 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Muscle-invasive urothelial bladder cancer: an update on systemic therapy.

Knollman Hayley H Godwin J Luke JL Jain Rishi R Wong Yu-Ning YN Plimack Elizabeth R ER Geynisman Daniel M DM

Therapeutic advances in urology 20151201 6

Urothelial carcinoma is a common malignancy that carries a poor prognosis when the disease includes muscle invasion. Metastatic urothelial carcinoma is almost uniformly fatal. The evidence behind treatment options in the neoadjuvant, adjuvant and metastatic settings are discussed in this manuscript, with a focused review of standard and investigational cytotoxic, targeted, and immunotherapy approaches. We have focused especially on neoadjuvant cisplatin-based therapy (supported by level one evid ...[more]

PMID: 26622317

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Project description:Although Muscle Invasive Bladder Cancer (MIBC) is increasing in incidence, treatment has largely remained limited to radical cystectomy with or without cisplatin-based neoadjuvant and/or adjuvant chemotherapy. We reviewed the current and recent clinical trials evaluating perioperative chemotherapy, targeted therapy, and novel therapeutic regimens for MIBC patients undergoing radical cystectomy.An overview of perioperative MIBC management was conducted initially using MEDLINE. The Clinical Trials Registry and MEDLINE were further searched specifically for perioperative MIBC chemotherapy, targeted therapy, and other novel therapeutic approaches. Trials involving non-perioperative management, operative management other than radical cystectomy, multiple tumors, or purely superficial or metastatic disease were excluded from selection. These criteria were not specifically fulfilled for mTOR inhibitor and immune therapy trials. Only phase III chemotherapy and phase II targeted therapy trials found in the Clinical Trials Registry were selected. MEDLINE searches of specific treatments were limited to January 2009 to January 2014 whereas the Clinical Trials Registry search had no timeline. Systematic MEDLINE searches had no phase restrictions. Trials known by the authors to fulfill search criteria but were not found via searches were also selected.Twenty-five trials were selected from the Clinical Trials Registry including 7 phase III chemotherapy trials, 11 Phase II targeted therapy trials, 3 immune therapy trials, 1 mammalian target of rapamycin (mTOR) inhibitor trial, and 3 gene and vaccine therapy trials. Nine trials have been completed and 5 have been terminated early or withdrawn. Nine trials have data available when individually searched using MEDLINE and/or Google. Systematic searches of MEDLINE separately found 12 trials in the past 5 years. Two phase III chemotherapy trials were selected based on knowledge by the authors. No phase III trials of targeted therapy have been registered or published.New trials are currently being conducted that may revolutionize MIBC treatment preceding or following cystectomy. Head-to-head phase III trials of perioperative chemotherapy and further phase II and phase III trials of targeted therapy and other therapeutic approaches are necessary before the current cisplatin-based perioperative chemotherapy paradigm is altered.

Dataset Information

Muscle-invasive urothelial bladder cancer: an update on systemic therapy.

Publications

Muscle-invasive urothelial bladder cancer: an update on systemic therapy.

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