Introducing "HEDGE": sequential intravesical gemcitabine-based thermochemotherapy (HIVEC) plus docetaxel as a potential novel bladder-sparing strategy for BCG-unresponsive non-muscle-invasive bladder cancer.

INTRODUCTION: BCG-unresponsive non-muscleinvasive bladder cancer (NMIBC) remains a major clinical challenge, with radical cystectomy recommended yet frequently declined or deferred. We introduce a regimen that combines hyperthermic intravesical chemotherapy (HIVEC) with gemcitabine immediately followed by intravesical docetaxel, which we named as "HEDGE" (HE = HIVEC, D = Docetaxel, GE = Gemcitabine). The rationale integrates: (i) the Guidelines of the European Association of Urology (GEAU) construct of BCG-unresponsive disease as unlikely to benefit from further BCG; (ii) clinical experience supporting HIVEC-based chemotherapy; (iii) the growing evidence base for sequential gemcitabine/docetaxel; and (iv) experimental confirmation that gemcitabine remains stable at elevated temperatures, supporting its use within HIVEC circuits. MATERIALS AND METHODS: BCG-unresponsive patients, according to the definition of the GEAU on NMIBC, were prospectively selected to receive "HEDGE". "HEDGE" consists of sequential intravesical gemcitabine-based thermochemotherapy (HIVEC) and intravesical docetaxel. It includes induction and maintenance scheme. Primary endpoints are recurrence and progression at 3, 6, 9, and 12 months. Secondary endpoints are feasibility and safety through documentation of adverse events (AE) based on The Common Terminology Criteria for Adverse Events (CTCAE) v6.0 (MedDRA) (National Cancer Institute/NCI, 2025). We applied this treatment to 7 patients (5 men, 2 women). RESULTS: The included patients showed neither recurrence nor progression at 3 and 6 months. Finally, we documented Grade 2 AE in only 3 patients. CONCLUSIONS: "HEDGE" looks feasible, safe, and showed no three- and six month recurrences in our first 7 BCG unresponsive NMIBC patients, supporting further clinical implementation and evaluation. This could be a therapeutic option for these patients.