Elsevier

European Urology

Volume 71, Issue 6, June 2017, Pages 952-960
European Urology

Bladder Cancer
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

https://doi.org/10.1016/j.eururo.2016.12.020Get rights and content

Abstract

Background

Tri-modality therapy (TMT) is a recognized treatment strategy for selected patients with muscle-invasive bladder cancer (MIBC).

Objective

Report long-term outcomes of patients with MIBC treated by TMT.

Design, setting, and participants

Four hundred and seventy-five patients with cT2–T4a MIBC were enrolled on protocols or treated as per protocol at the Massachusetts General Hospital between 1986 and 2013.

Intervention

Patients underwent transurethral resection of bladder tumor followed by concurrent radiation and chemotherapy. Patients with less than a complete response (CR) to chemoradiation or with an invasive recurrence were recommended to undergo salvage radical cystectomy.

Outcome measurements and statistical analysis

Disease-specific survival (DSS) and overall survival (OS) were calculated using the Kaplan-Meier method.

Results and limitations

Median follow-up for surviving patients was 7.21 yr. Five- and 10-yr DSS rates were 66% and 59%, respectively. Five- and 10-yr OS rates were 57% and 39%, respectively. The risk of salvage cystectomy at 5 yr was 29%. In multivariate analyses, T2 disease (OS hazard ratio [HR]: 0.57, 95% confidence interval [CI]: 0.44–0.75, DSS HR: 0.51, 95% CI: 0.36–0.73), CR to chemoradiation (OS HR: 0.61, 95% CI: 0.46–0.81, DSS HR: 0.49, 95% CI: 0.34–0.71), and presence of tumor-associated carcinoma in situ (OS HR: 1.56, 95% CI: 1.17–2.08, DSS HR: 1.50, 95% CI: 1.03–2.17) were significant predictors for OS and DSS. When evaluating our cohort over treatment eras, rates of CR improved from 66% to 88% and 5-yr DSS improved from 60% to 84% during the eras of 1986–1995 to 2005–2013, while the 5-yr risk of salvage radical cystectomy rate decreased from 42% to 16%.

Conclusions

These data demonstrate high rates of CR and bladder preservation in patients receiving TMT, and confirm DSS rates similar to modern cystectomy series. Contemporary results are particularly encouraging, and therefore TMT should be discussed and offered as a treatment option for selected patients.

Patient summary

Tri-modality therapy is an alternative to radical cystectomy for patients with muscle-invasive bladder cancer, and is associated with comparable long-term survival and high rates of bladder preservation.

Introduction

Radical cystectomy (RC) has long been the standard of care for the management of muscle-invasive bladder cancer (MIBC). Modern RC series have demonstrated 5-yr overall survival (OS) rates of 56–66% [1], [2], [3], [4]. The morbidity and mortality of RC are well documented [5]. There has been an increasing trend of utilizing organ-preserving therapies in the management of multiple cancers over the past several decades. In bladder cancer, a multidisciplinary approach has led to the development of bladder-sparing approaches using maximal transurethral resection (TURBT) followed by radiotherapy with concomitant radio-sensitizing chemotherapy for MIBC. There are no completed randomized studies comparing RC and TMT, but multiple series have suggested that TMT can yield favorable results in well-selected patients [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17]. Herein we report the long-term results of an updated analysis from a single institutional experience. To our knowledge, this represents the largest experience of TMT for MIBC.

Section snippets

Material and methods

This is a retrospective analysis of 475 patients with MIBC treated at the Massachusetts General Hospital (MGH) and enrolled on prospective institutional or Radiation Therapy Oncology Group (RTOG) protocols, or patients that were treated as per protocol. Further details regarding the protocol design and treatment specifics for each protocol were detailed previously [9], [10], [11], [12], [15], [18], [19], [20], [21].

Patient characteristics

Between 1986 and 2013, 475 patients with MIBC underwent TMT. Median follow-up was 4.55 yr for all patients (interquartile range [IQR]: 1.9–9.4), and 7.21 yr for surviving patients (IQR: 3.5–12.3). Full patient and tumor characteristics are listed in Table 2.

Response to induction therapy

Seventy-five percent of patients achieved a CR to chemoradiation. Patients with a visibly complete TURBT had a CR rate of 84% versus 58% in patients with a visibly incomplete TURBT (p < 0.001). When evaluated by clinical T stage, patients with

Discussion

In this large cohort of patients treated with TMT, we demonstrate favorable long-term DSS and OS, with bladder preservation possible in over 70%. Furthermore, our analyses show marked improvements in DSS when evaluated over time, with 5-yr DSS approaching 85% in the modern treatment era. Our results compare favorably with other large experiences, including the RTOG pooled analysis and a large institutional experience from the University of Erlangen [15], [23]. To our knowledge, this represents

Conclusions

In conclusion, these data demonstrate long-term outcomes for TMT similar to RC, and continue to support and establish the role for bladder-preserving TMT as an appropriate alternative to RC for well-selected patients with MIBC who are motivated to preserve their native bladder. Engaging patients in shared decision-making through multidisciplinary clinics is key to more widespread utilization of this treatment strategy, and it would be reasonable to offer it routinely, as an alternative to RC,

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