Long-Term Experience with Radiofrequency-Induced Hyperthermia Combined with Intravesical Chemotherapy for Non-Muscle Invasive Bladder Cancer

SIMPLE SUMMARY: Non-muscle invasive bladder cancer is a disease that frequently recurs, despite standard bladder instillations with chemotherapeutic agents or immunotherapy. When the disease recurs despite treatment with standard bladder instillations, urology guidelines recommend surgical removal of the bladder. This major operation often comes with complications or even death. Therefore, patients are often unfit or unwilling to undergo this operation. In this study, we present the treatment outcome of “radiofrequency-induced hyperthermia combined with intravesical chemotherapy”, which are bladder instillations with a chemotherapeutic agent, while simultaneously heating the bladder wall with microwave radiation to fever temperature. We compare the outcomes of two tumor subtypes of non-muscle invasive bladder cancer and two doses of chemotherapeutic agent. We conclude that this therapy is effective and safe in both types of non-muscle invasive bladder cancer patients in whom standard bladder treatments have failed. The high dose should be used if patients have a tumor at therapy onset. ABSTRACT: Background: The recurrence rate of non-muscle invasive bladder cancer (NMIBC) is high, despite intravesical treatments. Importantly, patients are frequently unfit or unwilling to undergo a recommended radical cystectomy when standard intravesical treatments fail, due to the substantial risk of morbidity and mortality. For these patients, radiofrequency-induced hyperthermia combined with intravesical chemotherapy (RF-CHT) has shown promising results. We aim to determine treatment outcomes and assess the effect of (ablative) dose. Methods: 299 intensively pretreated patients treated with RF-CHT were included in safety analysis. Of these, 274 patients who fulfilled induction treatments were included in efficacy analysis. Six-month complete response (CR) and durable response were reported for (concomitant) carcinoma in situ (CIS) patients and recurrence-free survival (RFS) for papillary patients. Results: For CIS, six-month CR-rate was 56.0%; and durable response rates were 79.7%, 66.5%, and 40.3% at one-, two- and five-year, respectively. RFS rates for papillary patients were 77.9%, 57.5%, and 37.2%, respectively. Patients treated with ablative dose are less likely to develop recurrence (adjusted Hazard Ratio 0.54, p = 0.01), compared to adjuvant dose. Conclusions: RF-CHT is effective in NMIBC patients in whom standard intravesical treatments have failed and should be considered in patients who are unwilling or unfit to undergo radical cystectomy. Patients with CIS or residual papillary tumor at baseline benefit from ablative dose.