Clinical and patient reported outcomes of SPARE - a randomised feasibility study of selective bladder preservation versus radical cystectomy

Objectives:

To test the feasibility of a randomised trial in muscle invasive bladder cancer (MIBC) and compare outcomes in patients who receive neoadjuvant chemotherapy followed by radical cystectomy or selective bladder preservation, where definitive treatment (cystectomy or radiotherapy) is determined by response to chemotherapy.

Patients and methods:

SPARE is a multi-centre randomised controlled trial comparing radical cystectomy and selective bladder preservation in patients with MIBC staged T2-3 N0 M0, fit for both treatment strategies and receiving three cycles of neoadjuvant chemotherapy. Patients were randomised between radical cystectomy and selective bladder preservation prior to a cystoscopy after cycle three of neoadjuvant chemotherapy. Patients with ≤T1 residual tumour received a fourth cycle of neoadjuvant chemotherapy in both groups, followed by radical radiotherapy in the selective bladder preservation group and radical cystectomy in in the radical cystectomy group; non-responders in both groups proceeded immediately to radical cystectomy following cycle three. Feasibility study primary endpoints were accrual rate and compliance with assigned treatment strategy. The phase III trial was designed to demonstrate non-inferiority of selective bladder preservation in terms of overall survival in patients whose tumours responded to neoadjuvant chemotherapy. Secondary endpoints included patient reported quality of life, clinician assessed toxicity, loco-regional recurrence free survival and rate of salvage cystectomy after bladder preservation.

Results:

Trial recruitment was challenging and below the predefined target with 45 patients recruited in 30 months (25 radical cystectomy; 20 selective bladder preservation). Non-compliance with assigned treatment strategy was frequent, 6/25 patients (24%) randomised to radical cystectomy received radiotherapy.

Long term bladder preservation rate was 11/15 (73%) in those who received radiotherapy per protocol. Overall survival was not significantly different between groups.

Conclusions:

Randomising MIBC patients between radical cystectomy and selective bladder
preservation based on response to neoadjuvant chemotherapy was not feasible in the UK health system. Strong clinician and patient preferences for treatments impacted willingness to undergo randomisation and acceptance of treatment allocation. Due to the small number of participants, firm conclusions about disease and toxicity outcomes cannot be drawn.