Elsevier

European Urology

Volume 66, Issue 1, July 2014, Pages 120-137
European Urology

Collaborative Review – Bladder Cancer
Critical Analysis of Bladder Sparing with Trimodal Therapy in Muscle-invasive Bladder Cancer: A Systematic Review

https://doi.org/10.1016/j.eururo.2014.02.038Get rights and content

Abstract

Context

Aims of bladder preservation in muscle-invasive bladder cancer (MIBC) are to offer a quality-of-life advantage and avoid potential morbidity or mortality of radical cystectomy (RC) without compromising oncologic outcomes. Because of the lack of a completed randomised controlled trial, oncologic equivalence of bladder preservation modality treatments compared with RC remains unknown.

Objective

This systematic review sought to assess the modern bladder-preservation treatment modalities, focusing on trimodal therapy (TMT) in MIBC.

Evidence acquisition

A systematic literature search in the PubMed and Cochrane databases was performed from 1980 to July 2013.

Evidence synthesis

Optimal bladder-preservation treatment includes a safe transurethral resection of the bladder tumour as complete as possible followed by radiation therapy (RT) with concurrent radiosensitising chemotherapy. A standard radiation schedule includes external-beam RT to the bladder and limited pelvic lymph nodes to an initial dose of 40 Gy, with a boost to the whole bladder to 54 Gy and a further tumour boost to a total dose of 64–65 Gy. Radiosensitising chemotherapy with phase 3 trial evidence in support exists for cisplatin and mitomycin C plus 5-fluorouracil. A cystoscopic assessment with systematic rebiopsy should be performed at TMT completion or early after TMT induction. Thus, nonresponders are identified early to promptly offer salvage RC. The 5-yr cancer-specific survival and overall survival rates range from 50% to 82% and from 36% to 74%, respectively, with salvage cystectomy rates of 25–30%. There are no definitive data to support the benefit of using of neoadjuvant or adjuvant chemotherapy. Critical to good outcomes is proper patient selection. The best cancers eligible for bladder preservation are those with low-volume T2 disease without hydronephrosis or extensive carcinoma in situ.

Conclusions

A growing body of accumulated data suggests that bladder preservation with TMT leads to acceptable outcomes and therefore may be considered a reasonable treatment option in well-selected patients.

Patient summary

Treatment based on a combination of resection, chemotherapy, and radiotherapy as bladder-sparing strategies may be considered as a reasonable treatment option in properly selected patients.

Introduction

Radical cystectomy (RC) with pelvic lymph node dissection remains widely accepted as the gold-standard treatment for muscle-invasive bladder cancer (MIBC) supported by a substantial body of evidence [1], [2], [3] with long-term follow-up. Nevertheless, removal of the bladder may lead to significant morbidity and affect patients’ comfort and quality of life (QoL) [4], [5]. Concerns about oncologic equivalence may in part explain differences in local utilisation rates of bladder preservation in eligible patients among different countries [6], [7], [8], [9].

Several bladder-preservation options exist, including single-modality treatments such as transurethral resection (TUR) alone, partial cystectomy, radiation therapy (RT), or chemotherapy alone. Nevertheless, it is generally accepted that single-modality treatments result in inferior outcomes compared with RC. A trimodal therapy (TMT) approach, including maximal TUR followed by concurrent radiosensitising chemotherapy and RT, is the most-studied bladder-sparing strategy. The aim of this systematic review was to assess the modern bladder-preservation treatment modalities, focusing on TMT in MIBC.

Section snippets

Evidence acquisition

A systematic literature search in the PubMed and Cochrane databases was performed to identify clinical and randomised controlled trials (RCTs) published from 1980 to July 2013 [10]. Various algorithms, including the following terms, were used: bladder cancer, bladder preservation, trimodality treatment, radiotherapy, chemotherapy, chemoradiation, chemoradiotherapy, organ-sparing, bladder-sparing, and salvage cystectomy. Inclusion criteria used were published full articles, clinical trials,

Evidence analysis

Overall, five prospective TMT phase 3 trials have been published, including two phase 3 RCTs. The remaining articles included in this review were large retrospective series (with heterogeneous treatment protocols) and phase 2 trials with small cohorts. Although use of conservative management for MIBC has yielded promising results and gained wider acceptance, most studies have small cohorts or limited follow-up, providing few data on long-term oncologic safety or late toxicity.

Conclusions

A growing body of accumulated data suggests that TMT (with prompt cystectomy reserved for tumour recurrence or nonresponders) leads to acceptable outcomes and may therefore be considered a reasonable treatment option in well-selected patients. TMT can be discussed not only in patients unfit for surgery but also for those patients who have MIBC and are not willing to undergo surgery.

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