HIVECNot holding the promise?

Hyperthermic Intravesical Chemotherapy (HIVEC) is an innovative approach for treating non-

muscle invasive bladder cancer (NMIBC), particularly in patients with intermediate to high-risk

disease or those unresponsive to Bacillus Calmette-Guérin (BCG) therapy. HIVEC therapy

presented a new alternative for management in a clinical situation of NMIBC which is desperately looking for alternatives because of limited efficacy and non-ignorable adverse effects of available options. HIVEC involves the intravesical administration of chemotherapeutic agents, such as mitomycin-C (MMC) or epirubicin, heated to approximately 43°C using devices like Combat BRS system. The rationale is that hyperthermia enhances drug penetration and efficacy, potentially improving recurrence-free survival (RFS) and progression-free survival (PFS) compared to standard chemotherapy.

Initial studies with HIVEC suggested that it could be a viable alternative to BCG, especially during BCG shortages or for patients unfit for radical cystectomy. Sousa et al reported 2-year cumulative recurrence rate of 12.5% in adjuvant HIVEC settings, with minimal adverse effects. A retrospective single-centre study from Germany by Kastner et al on 51 patients receiving HIVEC in BCG naïve and BCG failure revealed 1 and 2-year RFS as 67% and 40% respectively. GuerreroRamos et al in his RCT found RFS to be 95.0% for HIVEC and 75.1% for BCG (p=0.064). In a study by Pignot et alone BCG failure NMIBC, HIVEC achieved a RFS rate of 62.9% at 1 year and enabled a bladder preservation rate of 87.1%. However, the risk of progression to muscle-invasive disease was not negligible, particularly for patients with very high-risk tumors. As more and better-quality evidence is building up, HIVEC does not seem to be living up to its

promise. Multicentre prospective study (HIVEC -E) showed that HIVEC using the Combat BRS is effective in the medium term but later RCT (HIVEC-II study) by Tan et al reported that 2-yr DFS (61% vs 60%, HR 0.98; p = 0.8), PFS (HR 2.87; p = 0.06), and OS (HR 2.55; p = 0.09) were similar between the HIVEC and conventional MMC. Also, progression was more common among patients treated with HIVEC in comparison to patients with conventional MMC. Another 3-arm RCT from AIIMS New Delhi by Sachan et al, found no significant difference in recurrence rate between MMC, HIVEC and BCG in intermediate-risk group patients. Nonetheless, HIVEC’s tolerability is notable in comparison to BCG, with most side effects being low-grade and not disrupting treatment schedules.

Based on current evidence HIVEC cannot be projected as an alternative to regular intravesical

usage of mitomycin C in intermediate risk group NMIBC because of much higher cost. Even though in high-risk groups, HIVEC therapy continues to be used and offers a safe, bladder-sparing option, but disappointing results from RCTs in intermediate risk setting bring into question its role even in high-risk groups. HIVEC’s inconsistent efficacy and non-superiority over existing therapies

highlight the need for further research and well conducted randomized trials to define its role even in high-risk NMIBC management.

by Dr Ankit Sachan, UP university of Medical Sciences, Saifai, Etawah