A Study of the Morbidity, Mortality and Long-Term Survival Following Radical Cystectomy and Radical Radiotherapy in the Treatment of Invasive Bladder Cancer in Yorkshire

Abstract

Objectives: To study the morbidity of radical cystectomy and radical radiotherapy in the treatment of patients with invasive carcinoma of the bladder and to report the long-term survival following these treatments.

Patient and Methods: 398 patients with invasive carcinoma of the bladder treated between 1993 and 1996 in the Yorkshire region were studied. Of 398 patients studied, 302 patients received radical radiotherapy and 96 underwent radical cystectomy. A retrospective review of patients’ case notes was performed to construct a highly detailed database. Crude estimates of survival differences were derived using Kaplan–Meier methods. Log-rank tests (or, where appropriate, Wilcoxon tests) were used to test for the equality of these survivor functions. These functions were produced as all-cause survival. The proportional hazards regression modelling was used to assess the impact of definitive treatment on survival. A backwards-stepwise approach was used to derive a final predictive model of survival, with likelihood ratio tests to assess the statistical significance of variables to be included in the model.

Results: The patients undergoing radiotherapy were significantly older (mean age: 71 years versus 66 years), but no difference was identified in the distribution of American Society of Anaesthesiologists (ASA) grades in the two treatment groups. The stage distribution of cases in the treatment groups was not significantly different. Significant treatment delays were observed in both treatment groups. The median time from being seen in the clinic to transurethral resection of bladder tumour (TURBT) and subsequent radical treatment (cystectomy or radiotherapy) was 4.3 and 9 weeks, respectively. Age was the most significant independent factor accounting for treatment delays (p<0.001).

The 30-day and 3-month treatment-associated mortality for radical cystectomy and radiotherapy was 3.1% and 8.3% and 0.3% and 1.65%. Of the patients who received radiotherapy, 57 (18.8%) were subsequently subjected to a salvage cystectomy. For these 57 patients, 30-day and 3-month mortality after the salvage cystectomy were 8.8% and 15.7%. Gastrointestinal complications were the major source of early morbidity after primary and salvage cystectomy. Bowel leakage occurred in 3% following radical and 8.7% after salvage cystectomy. Bowel complications (leakage and obstruction) were the major cause of death following salvage cystectomy. No specific cause was predominant in those undergoing radical cystectomy with intestinal anastomotic leakage and urinary leakage accounting for one death each. Exacerbation of co-morbid conditions accounted for the remaining causes of mortality. Urinary leakage occurred in 4% following both forms of cystectomy. Recurrent pyelonephritis and intestinal obstruction were responsible for the majority of complications in the follow-up period.

Bladder and gastrointestinal complications accounted for the majority of complications following radical radiotherapy. Some degree of irritative bladder and rectal were noted commonly. Severe bladder problems, which rendered the bladder non-functional or required surgical correction, occurred in 6.3% of patients. 2.3% of patients underwent surgery for bowel obstruction related to radiotherapy induced bowel strictures.

Following radiotherapy, 43.6% of patients had a recurrence in the bladder at varying intervals post-treatment. Of these, 40% had ≥T2 disease. The 5-year survival following radiotherapy (with or without salvage cystectomy) was 37.4% while 36.5% of patients were alive 5 years after radical cystectomy. There was no statistically significant difference in the overall 5-year survival figures between the two primary treatments. Tumour stage, ASA grade and sex were the only independent predictors of 5-year survival on multivariate analysis.

Conclusions: This retrospective regional study shows that there is no significant difference in the 5-year survival of patients with invasive bladder cancer treated with either radical radiotherapy or radical cystectomy. All forms of radical treatment for bladder cancer are associated with a significant treatment-associated morbidity and mortality. Gastrointestinal complications were responsible for the majority of complications. The treatment-associated mortality at 3 months was two- or three-fold higher than the 30-day mortality; emphasising its importance as an indicator of the true risks of cystectomy. The clinical T stage, the sex and the ASA grade of the patient were the only independent predictors of survival. The data in this series suggests that radical radiotherapy and radical cystectomy should be both considered as valid primary treatment options for the management of invasive bladder cancer.

Introduction

Bladder cancer is a common urological malignancy with an incidence of 32.5 per 100,000 in England and Wales [1]. Bladder cancer accounts for 4% of all cancers in the Yorkshire region [2]. It is estimated that about 30% of cancers are muscle invasive. Primary radical options for treatment include external beam radiotherapy and radical cystectomy.

Over the last 20 years, several centres have demonstrated impressive 5-year survival results following radical cystectomy [3], [4]. Such results have influenced contemporary United Kingdom practice so that the use of radical cystectomy is seen to be increasing although radical radiotherapy continues to be widely used [5].

Despite a clear need for large prospective studies, there is no current major trial being performed which could provide comparative data for the two treatments, so that, clinician preference will remain an important determinant of the choice of therapy for invasive bladder cancer. In a recent Cochrane database review Shelley et al. concluded that there is no overall statistically significant benefit to radiotherapy or surgery (with pre-operative radiotherapy) in muscle invasive bladder cancer in terms of survival, but the trends consistently favour surgery [6]. The role of these primary treatments remains the subject of ongoing debate.

While the paramount issue in the choice of treatment should be oncological cure, in the absence of clear cut superiority (on the basis of prospective randomised controlled trials), morbidity and mortality of treatment and subsequent quality of life will be important factors in deciding how patients may best be treated. Thomas and Riddle [7] reported a 7% peri-operative mortality following radical cystectomy although recent series report a figure closer to <2% [1]. Radical radiotherapy can be associated with serious side effects although Bell et al. [8] reported minimal morbidity and no treatment-related mortality following radiotherapy [9]. Changes in clinical practice in both the surgical and radiotherapeutic fields have led to improvements in treatment delivery which have had an impact on morbidity and mortality with consequent difficulties in comparing data from different eras [8], [10].

With the recent implementation of clinical governance and the increasing emphasis on clinical effectiveness and evidence-based practice, clear demonstration of outcomes will become increasingly important. It is therefore important to have access to appropriate data so that patients can be counselled appropriately and informed choices about different therapies made. It is against this background that the current study was undertaken.

The study reports the outcomes, in terms of morbidity and survival, following radical cystectomy and radical radiotherapy for all patients with invasive bladder cancer treated in the Yorkshire region between the years 1993 and 1996. Classical prognostic indicators and several patient-related, tumour-related and external factors were also investigated as predictors of survival.