Synergo presented at the SWDGU (Südwestdeutsche Gesellschaft für Urologie e.V.), Offenburg 2018

45-year-old patient suffering from a multifocal, recurrent non-muscle invasive transitional cell carcinoma of the urinary bladder since 2012.The patient had multiple transurethral resections of the bladder (max. Tumor Stage pTA, high-grade).

The patient received instillations therapy with Mitomycin (8x), 2013 followed BCG instillations, which was aborted due to BCGitis with pulmonary and hepatic infection.
In 2015, following repeated recurrences of tumors, the patient was recommended cystectomy which the patient rejected.
Synergo® treatment was performed at the patient's request. A total of 8 induction cycles (11/2015 -01/2016, 2x40 mg Mitomycin weekly) and 6 maintenance cycles (04 – 12/2016, 2x20 mg Mitomycin 6-weekly) were given.

Since 03/17 the patient receives a maintenance therapy (2x20 mg Mitomycin, once every 3 months) and has been remaining free of tumour for 2 years.
With overall good therapy compatibility, a unique Intradetrusorale Botox injection was required to treat the increasingly pronounced urge symptoms.

RF-Induced hyperthermia and chemotherapy after failure of previous instillation therapies with Mitomycin and BCG can be an effective therapy option in individual cases before offering cystectomy.

Hyperthermiegestützte Mitomycininstillation nach Versagen der herkömmlichen Instillationstherapien bei rezidivierendem, nicht muskelinvasivem Harnblasenkarzinom als Alternative zur Zystektomie 

Presentation given by Maxim Kochergin; Ulrich Witzsch; Joseph Bcheraoui; Stefan Tietz; Eduard Walter Becht from Krankenhaus Nordwest

"Knowledge of drug diffusion mechanisms into the tissue and cellular cytoplasm following bladder

instillation is a key to understand the safety profile and clinical activity of chemotherapy."

Intravesical Chemotherapy and Chemohypherthermia in Non-Muscle-Invasive Bladder
Cancer; An Overview on Drug Administration Technologies and Pharmacokinetics
Campodonico F, Di Stasi S, Lev GM, Terrone C, Bongiovanni L, Mattioli F, Pagliarulo V and Introini C
Current Drug Metabolism, 2017

https://doi.org/10.2174/1389200218666170427092421

Despite the widely adopted international guidelines’ recommendations, and recent clinical trials of device-assisted chemotherapy instillations showing markedly enhanced recurrence-free survival compared even to the standard of care, clinicians and pharmacologists are not familiar with the in-depth physical aspects, pharmacokinetics and systemic absorption of chemotherapeutic drugs following their intravesical
administration. This paper gives a comprehensive review covering various aspects of different treatments with intravesical drugs.
Device-assisted therapies have set a goal to potentiate the drug’s effect and efficacy. The Radiofrequency-Induced Thermochemotherapeutic Effect (RITE) and the Electromotive-Drug Administration (EMDA) are the two most relevant modalities used to increase the activity of intravesical chemotherapy.

This new published study examined whether RF-CHT (using Synergo system) results in higher MMC drug tissue concentrations as compared to cold MMC instillation.

Intravesical radiofrequency induced hyperthermia enhances mitomycin C accumulation in tumour tissue,
F. Johannes P. van Valenberg, Antoine G. van der Heijden, Rianne J. M. Lammers, Johannes Falke, Tom J. H. Arends, Egbert Oosterwijk & J. Alfred Witjes
International Journal of Hyperthermia

https://doi.org/10.1080/02656736.2017.1406618

Patients received either (1) cold drug instillation (Mitomycin) or (2) RF-CHT (Synergo) before a planned transurethral resection operation. After instillation, three biopsy tests were taken of both normal and tumour tissue. The results showed that the median drug concentration in tumour tissue was higher in the RF-CHT (Synergo) group (median 665.00ng/g vs. 63.75ng/g, U¼51.0, p¼0.018). Moreover, in both techniques the MMC concentration was lower in normal tissue compared to tumour tissue. They concluded that Intravesical RF-CHT results in higher tumour MMC concentrations vs. cold MMC instillation which contributes to its superior efficacy.

virtual London (EAU 2017)

Enjoyed meeting all urology specialists at the last EAU conference!