Chemo-hyperthermia using Combat HIVEC® Study

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Non–muscle–invasive bladder cancer (NMIBC) presents a significant therapeutic challenge. Nearly 70% of NMIBC cases recur, and a considerable subset progress to muscle invasion, requiring radical cystectomy – a procedure which many patients either refuse or cannot undergo due to other health conditions. Bladder-sparing approaches to treating NMIBC are therefore critically important. Chemohyperthermia using Combat HIVEC® (Hyperthermic Intravesical Chemotherapy) is proving to be a promising treatment option. A 2024 retrospective study by Kastner et al., conducted at University Hospital Cologne, offers insightful data on HIVEC’s effectiveness, safety profile, and hopefully its place as a mainstay of NMIBC treatment in the near future.

Study Overview and Patient Population

Between 2018 and 2023, Kastner and colleagues retrospectively analysed the first 60 patients treated at the University Hospital of Cologne using Combat HIVEC®, a device-assisted hyperthermic intravesical chemotherapy platform. Key patient characteristics were:

  1. 69% had recurrent NMIBC after or during BCG (Bacillus Calmette–Guérin) therapy.
  2. 55% met criteria for BCG-unresponsive disease, indicating high-risk status and limited standard treatment options.

These patients were either ineligible for or refused radical cystectomy, so HIVEC® was suggested as an alternative bladder-sparing therapy.

Treatment Protocol and Methodology

The therapeutic protocol utilised Combat HIVEC® as follows:

  1. Intravesical instillation of 80 mg mitomycin C in 80 mL of 0.9% saline.
  2. The solution was extravesically heated to 41–43 °C using the Combat BRS (Bladder Recirculation System).
  3. The heated regimen was recirculated continuously between the device and the bladder for 1 hour at a controlled pressure.

The treatment regimen included:

  1. Induction phase: 6 weekly instillations.
  2. Maintenance phase: 6 monthly instillations, totalling 12 cycles on average.

Surveillance involved:

  1. Fluorescence‑guided cystoscopy,
  2. Urine cytology, and
  3. Bladder mapping following completion of induction, then at 3- and 12-month intervals.

The median follow-up duration was 12 months, capturing completion of both induction and maintenance phases.

Findings – Recurrence and Progression-Free Survival

This study found:

  1. A 1-year recurrence-free-survival (RFS) of 67%
  2. A 2-year RFS of 40%

Progression-Free Survival (PFS)

  1. Only 1 of 60 patients progressed to muscle-invasive disease.
  2. 2-year progression-free-survival (PFS) was 98%, indicating excellent prevention of disease advancement.

Stratified Outcomes

Notably, analysis revealed no statistically significant differences in RFS when comparing:

  1. BCG-unresponsive versus BCG-naïve patients, or
  2. Patients with carcinoma in situ (CIS) versus those without CIS

Safety, Tolerability, and Bladder Preservation

Kastner et al. reported that Combat HIVEC® demonstrated better tolerability and safety compared with newer systemic and intravesical agents, such as pembrolizumab and nadofaragene firadenovec.

Although precise toxicity grading details were not provided in the summary, existing literature on HIVEC indicates that adverse events are generally low-grade, including urinary frequency, urgency, and dysuria, with serious adverse events in fewer than 10% of patients.

Overall, Kastner et al. concluded that:

  1. Combat HIVEC® confers a bladder preservation rate of nearly 80%, through sustained disease control and limited progression.
  2. Its oncological efficacy coupled with a favourable safety profile make it an attractive alternative to radical cystectomy.

Reports from Other HIVEC Studies

Other studies, including multicentre registries and international observational cohorts, report:

  1. RFS at 24 months around 54% and PFS around 92% in BCG-unresponsive populations using HIVEC (Mitomycin C, heated to ~43 °C, Combat BRS): https://combatcancer.com/wp-content/uploads/2021/08/HIV020_2.pdf
  2. In larger datasets (e.g., 502 patients in Spain), long-term experience shows that HIVEC is both effective and well tolerated in intermediate- and high-risk NMIBC: https://www.researchgate.net/publication/355851016_Long-Term_Experience_with_Hyperthermic_Chemotherapy_HIVEC_Using_Mitomycin-C_in_Patients_with_Non-Muscle_Invasive_Bladder_Cancer_in_Spain
  3. Prospective studies show complete response rates of 40–60% in CIS and 35–70% 12–24-month high-grade RFS in papillary tumours: https://journals.lww.com/co-urology/abstract/9900/hyperthermic_intravesical_chemotherapy_for.276.aspx

In Conclusion

Combat HIVEC® represents a compelling bladder-sparing intervention for NMIBC, and is well tolerated, with recurrence and progression outcomes that are favourable in comparison to other therapies.

The 2024 retrospective study by Kastner et al. provides valuable, practical data on Combat HIVEC® in a real-world NMIBC setting. With 1-year RFS of 67%, 2-year RFS of 40%, 2-year PFS of 98%, and near 80% bladder preservation, the treatment not only demonstrates efficacy and safety, but also puts the patient and their quality of life first. Combat HIVEC is therefore a great alternative for patients unsuitable for radical cystectomy and hopefully reveals the broader potential of device-assisted chemotherapy in modern bladder cancer care.

Kastner et al: “HIVEC as an alternative option in non-muscle-invasive bladder cancer: experiences from a high-volume center.” Urologic Oncology Seminars and Original Investigations, 2024: https://www.sciencedirect.com/science/article/pii/S1078143924003405

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