Volume 33, Issue 1, January 2023, Pages 82-90Author links open overlay panel

For decades, the antineoplastic potential of hyperthermia alone or in combination with radiotherapy and/or chemotherapy has been subject of intensive preclinical and clinical research in various tumor entities. The clinical evidence on the beneficial effects of additional hyperthermia in combination with intravesical Mitomycin C for superficial non-muscle-invasive bladder cancer as well as for deep regional microwave hyperthermia techniques applied during an external beam radiotherapy or chemoradiation treatment for more advanced tumors are summarized. In some series, deep regional hyperthermia in combination with an initial transurethral resection and Cisplatin-based chemoradiation increased the 5-year overall survival rates up to 20%. The presented data justifies a fresh irrespective chance for mild regional hyperthermia in the context of new progressive prospective trials on multimodality treatment for bladder preservation.

Section snippetsHyperthermia Modes of Action

In today’ s evidence-based medicine additional hyperthermia with target temperatures of 40-44°C have been proved as a clinically relevant sensitizer combined with standard radio- and chemotherapies. Randomized trials or cohort studies on soft tissue sarcomas,9, 10, 11 breast cancer,12,13 anal cancer,14 cervical cancer,15,16 rectal cancer,17,18 melanoma,19 and bladder cancer6,7 reported significant clinical improvements. In contrary and in the absence of supporting data, the use of hyperthermia

Hyperthermia in Bladder Preservation

The urinary bladder is one of the best locations for hyperthermia treatment within the entire body. Without invasive procedures, it is easily accessible for hyperthermic instillation techniques, as well as for external microwave-based heat treatments. Because of the fact, that the bladder is an ion-rich fluid filled hollow organ, it is perfectly suited for microwave-induces deep regional hyperthermia (RHT).

There is some clinical evidence on the beneficial use of additional hyperthermia in

Hyperthermic Intravesical Chemotherapy (HIVEC)

The first randomized trial on hyperthermic intravesical chemotherapy (HIVEC) was published in 2003.6 After a complete transurethral resection (TURBT) of a primary or recurrent superficial transitional cell carcinoma of the bladder, 83 patients were randomly assigned to receive either intravesical instillations of Mitomycin C alone (n=41), or in combination with intravesical microwave-induced hyperthermia (n = 42) applied with an endoluminal 915 MHz Synergo101-1 applicator (Medical Enterprises

Deep regional Hyperthermia in Bladder Conservation

Deep regional hyperthermia (RHT) is performed with devices that are technically capable of delivering selective and controlled heating to a predefined target volume, for example, the bladder, while causing minimal heating of normal tissue at the same time (see Fig. 2). Technically the most indicated method to achieve such preferential heating is by using radiating and focusing electromagnetic waves to the target volume. The target temperature in the bladder usually ranges between 40 and 43°C.

Toxicity of Additional Hyperthermia

In their randomized HIVEC trial, Colombo et al. reported of a higher pain sensation and a heat-specific posterior wall thermal reaction for intravesical hyperthermia in addition to instillation chemotherapy with Mitomycin C, compared to the control group with chemotherapy alone. No patient discontinued hyperthermia because of pain and the posterior wall reactions were usually asymptomatic and resolved spontaneously within a few days.6 No additional treatment-related toxicity was evident at the

Who Benefits the Most From Additional RHT?

The presented data showed that additional RHT has the potential as a clinically relevant sensitizer to standard radio- and/or chemotherapy with no or negligible additional toxicity. Now the question arises, which patients with bladder cancer may have the pronounced benefit? Exploring the data of the Dutch deep hyperthermia trial15 and the retrospective results from Erlangen,8 there is a 20% overall survival benefit in the Erlangen data compared to no significant overall survival benefit in the

Conclusions

For decades, it has been a well-known fact that additional mild hyperthermia with 40-43°C combined with standard chemotherapy and/or radiotherapy may improve oncological outcomes such as local control, survival, and organ preservation rates in both superficial and muscle-invasive bladder cancer. The gain in efficacy is not related to a significant increase of early or late toxicity rates, which makes hyperthermia an attractive radio- and chemosensitizer. Although numerous clinical trials

Acknowledgments

This project (Hyperboost; www.Hyperboost-h2020.eu) was supported in part from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 955625.

View full text

© 2022 Elsevier Inc. All rights reserved.