Review article
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

https://doi.org/10.1016/j.urolonc.2017.10.002Get rights and content

Highlights

  • This is a comprehensive comparison of oncological outcomes of both modalities.

  • The survival outcomes of patients after TMT and RC for MIBC were comparable.

  • Downstaging after NAC and RC exhibited improved survival compared to RC only.

  • Best survival outcomes after TMT are associated with complete response.

Abstract

Objective

This study aimed to comprehensively analyze the oncological long-term outcomes of trimodal therapy (TMT) and radical cystectomy (RC) for the treatment of muscle-invasive bladder cancer (BC) with or without neoadjuvant chemotherapy (NAC).

Patients and methods

A systematic search was conducted according to the PRISMA guidelines for studies reporting on outcomes after TMT and RC. A total of 57 studies including 30,293 patients were included. The 10-year overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) rates for TMT and RC were assessed.

Results

The mean 10-year OS was 30.9% for TMT and 35.1% for RC (P = 0.32). The mean 10-year DSS was 50.9% for TMT and 57.8% for RC (P = 0.26). NAC was administered before therapy to 453 (13.3%) of 3,402 patients treated with TMT and 812 (3.0%) of 27,867 patients treated with RC (P<0.001). Complete response (CR) was achieved in 1,545 (75.3%) of 2,051 evaluable patients treated with TMT. A 5-year OS, DSS, and RFS after CR were 66.9%, 78.3%, and 52.5%, respectively. Downstaging after transurethral bladder tumor resection or NAC to stage ≤pT1 at RC was reported in 2,416 (29.1%) of 8,311 patients. NAC significantly increased the rate of pT0 from 20.2% to 34.3% (P = 0.007) in cT2 and from 3.8% to 23.9% (P<0.001) in cT3–4. A 5-year OS, DSS, and RFS in downstaged patients (≤pT1) at RC were 75.7%, 88.3%, and 75.8%, respectively.

Conclusion

In this analysis, the survival outcomes of patients after TMT and RC for MIBC were comparable. Patients who experienced downstaging after NAC and RC exhibited improved survival compared to patients treated with RC only. Best survival outcomes after TMT are associated with CR to this approach.

Introduction

Bladder cancer (BC) is one of the most common malignant diseases worldwide [1]. Up to 25% of the patients present with muscle-invasive BC (MIBC) at the time of primary diagnosis. In addition, among patients with nonmuscle invasive disease, progression to MIBC occurs in 20%–30% in the long term [2]. Although radical cystectomy (RC) has been considered as the mainstay of treatment for MIBC for many years [3], the oncological outcomes are still not satisfying. The reported 5-year overall survival (OS) rate after RC is approximately 50% [4]. Cisplatin-based neoadjuvant chemotherapy (NAC) has been adopted into clinical practice to improve outcomes after RC. Although the curative potential of NAC is supported by level one evidence, its use is limited by the eligibility and tolerability of some patients to receive perioperative systemic treatment [3]. In addition, patients with severe comorbidities are sometimes considered unfit to undergo major surgery [5]. Furthermore, due to possible drawbacks on quality of life (QOL) [6], a portion of patients refuse to undergo surgery regardless of their performance status [7], [8], [9].

For patients who refuse RC after confirmation of MIBC at transurethral bladder tumor resection (TURBT), either external beam radiotherapy (RT) or chemotherapy have been investigated as alternatives to RC. Yet, the reported survival benefits were considerably lower than RC alone [3]. The concept of trimodal therapy (TMT), in which external beam RT and radiosensitizing chemotherapy are delivered after maximal TURBT is nowadays the most commonly used bladder-preserving modality for MIBC [3]. Many trials on TMT have reported oncological outcomes comparable to RC [10], [11], [12]. However, until now, no randomized trials have been published on the oncological outcomes of patients treated with TMT compared to RC.

We aimed to systematically compare the outcomes of patients treated with TMT and RC with or without NAC regarding the oncological long-term efficacy of both modalities.

Section snippets

Search strategy

A systematic search was conducted on the PubMed online database according to the PRISMA statement [13] for studies published between 1990 and 2017. The following keywords were used for this search to detect all full-text publications written in English: bladder sparing, bladder preservation, chemotherapy, chemoradiation, combined, downstaging, invasive BC, multimodal, outcomes, pT0, RC, RT, radiochemotherapy, survival, trimodal, triple.

Inclusion and exclusion criteria

We included all studies on patients treated for clinical

Search results, patient criteria and risk of bias assessment

A CONSORT diagram is provided in Fig. 1, which outlines the selection process of the included studies. The initial online search displayed 4,534 results. After application of the inclusion and exclusion criteria, 57 studies were finally included in this study: 32 studies reporting on TMT [7], [8], [9], [10], [11], [12], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], 2 studies comparing

Discussion

MIBC is an aggressive malignancy with an unfavorable prognosis if not treated promptly and adequately. TMT has been introduced as a bladder-preserving approach with the aim to overcome the limitations of surgical morbidity and impaired QOL after RC without compromising oncological outcomes. To the best of our knowledge, the present meta-analysis is the most comprehensive comparison between TMT and RC available so far. We found that more men were treated with TMT than women. The reasons for this

Conclusion

In this analysis, the survival outcomes of patients after TMT and RC for MIBC were comparable. We found that patients who experienced downstaging after NAC and RC exhibited improved survival compared to patients treated with RC only. Best survival outcomes after TMT are associated with CR to this approach.

Acknowledgments

We would like to thank Michael Hanna, PhD, for proof-reading the article.

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