Hyperthermic Intravesical Chemotherapy as a Bladder-Sparing Alternative to BCG in the Management of Non-Muscle-Invasive Bladder Cancer: A Systematic Review of Oncological Outcomes in the Era of BCG Shortage
In brief
Hyperthermic intravesical chemotherapy yields 12-month recurrence-free survival up to 98% in BCG-naive bladder cancer
A systematic review of 24 studies (over 3,600 patients) found that HIVEC achieved 12-month recurrence-free survival ranging from 78% to 98% and 24-month rates of 57% to 88% in BCG-naive or mixed-risk NMIBC, with progression rare and severe side effects in about 2% of cases. Comparative data do not yet prove HIVEC equivalent to BCG, especially after BCG failure, highlighting the need for larger randomized trials.
- Journal
- Journal of clinical medicine (Q1)
- Published
- 17 August 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Alexei Croitor, Victor Cadariu-Brailoiu, Andrei-Dan Zbircea, Razvan Bardan, Vlad Dema, Sorin Dema, et al.
- PMID
- 42652756
- DOI
- 10.3390/jcm15166352
Why clinicians should know about it
- Picked for Urology (top studies of the week, 30 August 2026): Systematic review of hyperthermic intravesical chemo for NMIBC
Abstract
Background/Objectives: The ongoing Bacillus Calmette-Guérin (BCG) shortage, treatment intolerance, and BCG-unresponsive disease necessitate bladder-sparing alternatives for non-muscle-invasive bladder cancer (NMIBC). We reviewed the clinical evidence for hyperthermic intravesical chemotherapy (HIVEC). Methods: PubMed and PubMed Central were searched from inception to 15 March 2026 (updated 10 July 2026) for primary studies of device-assisted HIVEC in NMIBC. Studies reporting recurrence-free survival (RFS), progression, response, or safety were eligible. Records were screened and data extracted independently in duplicate, and risk of bias was assessed with RoB 2 (randomised trials), ROBINS-I (non-randomised comparative studies), and the Newcastle-Ottawa Scale (single-arm and registry cohorts). Outcomes were synthesised narratively within pre-specified clinical strata, with carcinoma in situ (CIS) analysed separately from papillary-only disease. Results: Twenty-four studies (>3600 patients), including seven randomised trials and a large multinational registry, were included. In BCG-naive or mixed-risk populations, 12-month RFS generally ranged from 78% to 98% and 24-month RFS from 57% to 88%; progression was uncommon. In BCG-unresponsive or BCG-failure disease, 24-month RFS was typically 40-60%, with poorer control in carcinoma in situ. Comparative studies mostly reported no statistically significant difference in RFS or progression versus BCG, but these analyses were predominantly retrospective or underpowered, and the single randomised signal favouring HIVEC over BCG was confined to a per-protocol analysis. Two randomised trials against non-heated mitomycin C (HIVEC-1 and HIVEC-II) found no recurrence benefit from hyperthermia, whereas an earlier randomised trial of radiofrequency thermochemotherapy reported a large long-term advantage over mitomycin C alone. Severe adverse events were infrequent, including approximately 2% in the largest series. Conclusions: HIVEC appears to be a tolerable bladder-sparing option in selected intermediate- and high-risk NMIBC. The available evidence is compatible with, but does not establish, equivalence or non-inferiority to BCG, because most comparative data are non-randomised, underpowered, and at moderate-to-serious risk of bias. Disease control after BCG failure is clinically meaningful but less durable, particularly in CIS. Adequately powered randomised trials reporting intention-to-treat outcomes are needed.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.