RECURRENT-GB Trial: Repeat ExCision Upon Recurrence: REthinking Neurosurgical Treatment of GlioBlastoma

QUESTION: In patients with recurrent glioblastoma (GB), is repeat surgery before 2nd-line medical therapy clinically and cost-effective in improving health-related quality of life (HRQoL) and survival compared to treatment with 2nd-line medical therapy alone? BACKGROUND: GB is the most frequent and aggressive brain cancer in adults. Despite surgery, chemotherapy, and radiotherapy, prognosis remains poor and disease recurrence is inevitable. There is no consensus on the best treatment approach for recurrent GB and no clear recommendation in UK NICE guidance, though further surgery can be considered. Clinical practice varies widely, particularly regarding the use of repeat surgery. Establishing repeat surgery's clinical effectiveness and cost-effectiveness could improve decision-making and standardise NHS practice. AIMS AND OBJECTIVES: This study aims to evaluate the clinical and cost-effectiveness of repeat surgery for recurrent GB. The objectives are to assess the impact of repeat surgery on HRQoL, daily function, neurological symptoms, adverse effects, adjuvant therapy completion, overall survival (OS) and cost-effectiveness. METHODS: RECURRENT-GB is a multi-centre open, 2-arm superiority, parallel-group Bayesian RCT with a health economic analysis component. It will aim to recruit 150 adults with 1st recurrence of GB following previous surgery across at least 20 NHS sites. Participants will be randomised 1:1 to receive repeat surgery followed by 2nd-line medical therapy or 2nd-line medical therapy alone. The primary outcome will be deterioration-free survival (DFS) modelled as time-to-event, defined as the time from randomisation to a 10-point deterioration in the global health status component of the EORTC QLQ-C30 HRQoL questionnaire compared with baseline or death. Secondary outcomes will include DFS using physical/social function domains from QLQ-C30 and motor/communication domains from QLQ-BN20, OS, adjuvant therapy completion, surgical complications/adverse events, seizures, neurocognitive function, physical function/mobility, activities of daily living and performance status. Health economic analysis will collect costs based on resource use data from case report forms and QALYs derived from EQ-5D-5L. Cost-effectiveness will be based on a partitioned survival model, and results will be reported as incremental cost per QALY gained from a UK NHS/PSS perspective over a lifetime horizon. Patients will be recruited with a carer as a proxy to assist with questionnaires. Participants will complete QLQ-C30 Q29/30 weekly and other HRQoL questionnaires 6 weekly. They will also be supplied with a smartwatch to collect passive outcome data (e.g. step count, homestay duration). TIMELINES FOR DELIVERY: The study will last 60 months, starting in Oct 2025. Recruitment will start in month 7 and last 36 months. Each participant will be followed for the duration of their condition or until the study ends. 6 months are allowed for analysis and reporting. ANTICIPATED IMPACT AND DISSEMINATION: This study aims to inform about the impact of repeat surgery on DFS. Increased survival without functional compromise would be expected to benefit patients with GB and their relatives. If cost-effective, repeat surgery would be anticipated to benefit society through health gains and efficient use of scarce NHS resources. The dissemination of findings could have a worldwide impact by widening access to repeat surgery for patients with recurrent GB.