Clinical and patient-reported outcomes of SPARE - a randomised feasibility study of selective bladder preservation versus radical cystectomy.
MetadataShow full item record
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.
Version of record
muscle-invasive bladder cancer
randomised controlled trial
selective bladder preservation
Aged, 80 and over
Organ Sparing Treatments
Urinary Bladder Neoplasms
Clinical Trials & Statistics Unit
ICR-CTSU Urology and Head and Neck Trials Team
Clinical Academic Radiotherapy (Huddart)
License start date
BJU Int, 120 (5), pp. 639 - 650
Showing items related by title, author, creator and subject.
Prospective Study Delivering Simultaneous Integrated High-dose Tumor Boost (≤70 Gy) With Image Guided Adaptive Radiation Therapy for Radical Treatment of Localized Muscle-Invasive Bladder Cancer. Hafeez, S; Warren-Oseni, K; McNair, HA; Hansen, VN; Jones, K; Tan, M; Khan, A; Harris, V; McDonald, F; Lalondrelle, S; Mohammed, K; Thomas, K; Thompson, A; Kumar, P; Dearnaley, D; Horwich, A; Huddart, R (2016-04)Image guided adaptive radiation therapy offers individualized solutions to improve target coverage and reduce normal tissue irradiation, allowing the opportunity to increase the radiation tumor dose and spare normal bladder ...
An orally bioavailable Chk1 inhibitor, CCT244747, sensitizes bladder and head and neck cancer cell lines to radiation. Patel, R; Barker, HE; Kyula, J; McLaughlin, M; Dillon, MT; Schick, U; Hafsi, H; Thompson, A; Khoo, V; Harrington, K; Zaidi, SPURPOSE: Chk1 inhibition increases cell sensitivity to both chemotherapy and radiotherapy in several tumour types and is, therefore, a promising anti-cancer approach. Although several Chk1 inhibitors have been developed, ...
The Patient Deficit Model Overturned: a qualitative study of patients' perceptions of invitation to participate in a randomized controlled trial comparing selective bladder preservation against surgery in muscle invasive bladder cancer (SPARE, CRUK/07/011). Moynihan, C; Lewis, R; Hall, E; Jones, E; Birtle, A; Huddart, R (2012-01)BACKGROUND: Evidence suggests that poor recruitment into clinical trials rests on a patient 'deficit' model - an inability to comprehend trial processes. Poor communication has also been cited as a possible barrier to ...