Adjuvant intravesical chemotherapy following tumour resection is recommended for intermediate-risk non-muscle-invasive bladder cancer (NMIBC).
To assess the efficacy and safety of adjuvant intravesical chemohyperthermia (CHT) for intermediate-risk NMIBC.
HIVEC-II is an open-label, phase 2 randomised controlled trial of CHT versus chemotherapy alone in patients with intermediate-risk NMIBC recruited at 15 centres between May 2014 and December 2017 (ISRCTN 23639415). Randomisation was stratified by treating hospital.
Patients were randomly assigned (1:1) to adjuvant CHT with mitomycin C at 43°C or to room-temperature mitomycin C (control). Both treatment arms received six weekly instillations of 40 mg of mitomycin C lasting for 60 min.
The primary endpoint was 24-mo disease-free survival as determined via cystoscopy and urinary cytology. Analysis was by intention to treat.
A total of 259 patients (131 CHT vs 128 control) were randomised. At 24 mo, 42 patients (32%) in the CHT group and 49 (38%) in the control group had experienced recurrence. Disease-free survival at 24 mo was 61% (95% confidence interval [CI] 51-69%) in the CHT arm and 60% (95% CI 50-68%) in the control arm (hazard ratio [HR] 0.92, 95% CI 0.62-1.37; log-rank p = 0.8). Progression-free survival was higher in the control arm (HR 3.44, 95% CI 1.09-10.82; log-rank p = 0.02) on intention-to-treat analysis but was not significantly higher on per-protocol analysis (HR 2.87, 95% CI 0.83-9.98; log-rank p = 0.06). Overall survival was similar (HR 2.55, 95% CI 0.77-8.40; log-rank p = 0.09). Patients undergoing CHT were less likely to complete their treatment (n =75, 59% vs n = 111, 89%). Adverse events were reported by 164 patients (87 CHT vs 77 control). Major (grade III) adverse events were rare (13 CHT vs 7 control).
CHT cannot be recommended over chemotherapy alone for intermediate-risk NMIBC. Adverse events following CHT were of low grade and short-lived, although patients were less likely to complete their treatment.
The HIVEC-II trial investigated the role of heated chemotherapy instillations in the bladder for treatment of intermediate-risk non-muscle-invasive bladder cancer. We found no cancer control benefit from heated chemotherapy instillations over room-temperature chemotherapy. Adverse events following heated chemotherapy were low grade and short-lived, although these patients were less likely to complete their treatment.
European urology. 2022 Aug 20 [Epub ahead of print]
Wei Shen Tan, Aaron Prendergast, Charlotte Ackerman, Yathushan Yogeswaran, Joanne Cresswell, Paramananthan Mariappan, Jaspal Phull, Paul Hunter-Campbell, Henry Lazarowicz, Vibhash Mishra, Abhay Rane, Melissa Davies, Hazel Warburton, Peter Cooke, Hugh Mostafid, Daniel Wilby, Robert Mills, Rami Issa, John D Kelly
Division of Surgery & Interventional Science, University College London, London, UK; Department of Urology, University College London Hospital, London, UK. Electronic address: ., Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London, London, UK., Department of Urology, The James Cook University Hospital, Middlesbrough, UK., Department of Urology, Edinburgh Bladder Cancer Surgery, Western General Hospital, Edinburgh, UK., Department of Urology, Royal United Hospital, Bath, UK., Department of Urology, University Hospital Plymouth, Plymouth, UK., Department of Urology, The Royal Liverpool University Hospital, Liverpool, UK., Department of Urology, Royal Free Hospital, London, UK., Department of Urology, East Surry Hospital, Redhill, UK., Department of Urology, Salisbury District Hospital, Salisbury, UK., Department of Urology, University Hospital of South Manchester, Manchester, UK., Department of Urology, New Cross Hospital, Wolverhampton, UK., Department of Urology, The Royal Surrey County Hospital, Guildford, UK., Department of Urology, Queen Alexandra Hospital, Portsmouth, UK., Department of Urology, Norfolk and Norwich University Hospital, Norwich, UK., Department of Urology, St George's Hospital, London, UK., Division of Surgery & Interventional Science, University College London, London, UK; Department of Urology, University College London Hospital, London, UK.
PubMed http://www.ncbi.nlm.nih.gov/pubmed/35999119