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

Robert A Huddart, Alison Birtle, Lauren Maynard, Mark Beresford, Jane Blazeby, Jenny Donovan, John D Kelly, Tony Kirkbank, Duncan B McLaren, Graham Mead, Clare Moynihan, Raj Persad, Christopher Scrase, Rebecca Lewis, Emma Hall, Robert A Huddart, Alison Birtle, Lauren Maynard, Mark Beresford, Jane Blazeby, Jenny Donovan, John D Kelly, Tony Kirkbank, Duncan B McLaren, Graham Mead, Clare Moynihan, Raj Persad, Christopher Scrase, Rebecca Lewis, Emma Hall

Abstract

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 (RC) or selective bladder preservation (SBP), where definitive treatment [RC or radiotherapy (RT)] is determined by response to chemotherapy.

Patients and methods: SPARE is a multicentre randomised controlled trial comparing RC and SBP 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 RC and SBP before 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 RT in the SBP group and RC in in the RC group; non-responders in both groups proceeded immediately to RC 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 SBP in terms of overall survival (OS) 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 RC after SBP.

Results: Trial recruitment was challenging and below the predefined target with 45 patients recruited in 30 months (25 RC; 20 SBP). Non-compliance with assigned treatment strategy was frequent, six of the 25 patients (24%) randomised to RC received RT. Long-term bladder preservation rate was 11/15 (73%) in those who received RT per protocol. OS survival was not significantly different between groups.

Conclusions: Randomising patients with MIBC between RC and SBP 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 few participants, firm conclusions about disease and toxicity outcomes cannot be drawn.

Keywords: #BladderCancer; #blcsm; muscle-invasive bladder cancer; radical cystectomy; radiotherapy; randomised controlled trial; selective bladder preservation.

© 2017 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.

Figures

Figure 1
Figure 1
Trial schema.
Figure 2
Figure 2
Patient flow through trial.
Figure 3
Figure 3
(a) Time to first CTCAE grade 3–4 toxicity by definitive treatment received and (b) when excluding erectile dysfunction.
Figure 4
Figure 4
Time‐to‐event endpoints. Presented by allocated treatment for the population of patients who responded to chemotherapy. In all cases, patients with a second primary without a prior event were censored at the date of second primary and patients without an event were censored at the date last seen. Comparisons between groups were made using the log‐rank test.
Figure 5
Figure 5
Mean change from baseline in EORTC QLQ‐C30 subscales.
Figure 6
Figure 6
Mean change from baseline in EORTC QLQ‐BLM30 subscales.

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