Non-muscle-invasive bladder cancer (NMIBC) is a highly recurrent malignancy whose treatment remains an unmet need in urology. To delay the recurrence of NMIBC tumors, chemotherapy bladder instillations are performed, most commonly with mitomycin C (MMC) or, in high-risk patients, with BCG immunotherapy. However, BCG is often unavailable to these patients. Thermo-chemotherapy, the powerful combination of hyperthermia (up to 45 centigrade that cannot cause burns) and bladder chemotherapy instillation, has been shown to extend the recurrence free interval (RFI) in NMIBC. Its efficacy is both temperature and chemo-concentration dependent.
Uzi Eshel and Jacob Lazarovitz, Elmedical founders, are world pioneers in conductive heat office-based treatments in urology since 1990. They brought to market a bladder wall thermo-chemotherapy (BWT) which provides the highest safe temperature (44.5 centigrade) and most uniform no-burns thermo-chemotherapy delivered over the entire bladder lumen. With this approach the stability of the circulated chemotherapy is guaranteed, and its high concentration is maintained.
Elmedical's UniThermia silicone catheter (flexible and easy to insert at 5.3mm diameter) and the BWT equipment and method are both CE-marked and are used in many medical centers in the EU, as well as in eight Israeli medical centers, where the BWT procedures are reimbursed. BWT is not yet cleared for sale in the USA.
In a clinical trial conducted at two academic medical centers in Israel, a difficult group of 31 highly recurrent NMIBC patients (median RFI was 5 months; more than two recurrences per year) were treated with BWT. All patients had failed BCG instillations, and most were unresponsive to BCG (a highly unmet need within the NMIBC); Ten of them had also failed MMC bladder instillations and 6 had also failed a different form of MMC thermo-chemotherapy. Of the 31, 10 patients were at high risk and 21 at intermediate risk; 18 of the patients had multiple tumors. All patients were treated with the full dose of 40mg MMC in procedures lasting 50-minutes. Each patient's pre-BWT RFI (baseline) and post-BWT RFI were recorded and the patient's individual RFI extension was calculated.
With median eight years follow up, 30 of the 31 patients achieved a 7-fold extension of RFI vs. the patients' prior baselines (range 2X-26X).
In summary:
To date, tens of thousands of BWT procedures have been performed successfully, safely, with good patient tolerance and with good clinical outcomes. The standard BWT protocol comprises 6 weekly induction procedures followed by 10 monthly maintenance procedures with 40mg MMC dissolved in 40ml saline.
Work continues to evaluate this therapy at some medical centers using BWT, where high-risk patients especially, those who are unresponsive to BCG, are being treated with an enhanced BWT, with double the standard dose (80mg MMC in 40ml saline), to reduce their recurrence and their high-risk. In the future, this enhanced protocol will also be evaluated for thermo-chemo-ablation to replace the TURBT surgery (trans urethra resection of bladder tumors) in patients with low-grade intermediate-risk NMIBC.
Partnered with Elmedical
