Introduction

Adjuvant intravesical instillations with bacillus Calmette-Guérin (BCG) is the recommended treatment option for patients with intermediate-and high-risk non-muscle invasive bladder cancer (NMIBC). Despite adequate BCG treatment, a large proportion of patients experience a recurrence. Although radical cystectomy is the gold standard for BCG unresponsive NMIBC, some patients are unfit or unwilling to consider this option.
The optimal therapy in such cases is unknown, as established and effective salvage intravesical therapies are not yet available [15]. The European Association of Urology and International Consultation on Urologic Diseases (EAU-ICUD) does not endorse salvage intravesical gemcitabine, valrubicin, or IFNα, in patients who fail BCG, but chemo-hyperthermia is recommended as a promising treatment modality.

Objective
The objective of the present study was to assess the effectiveness and safety of hyperthermic intravesical chemotherapy (HIVEC®) in BCG unresponsive NMIBC patients.

Materials/Methods
Between 2018-2019, 6 patients underwent HIVEC for BCG unresponsive NMIBC at Centro Hospitalar Universitário Lisboa Central. Patients were eligible for inclusion in the present study if the criteria for BCG unresponsive disease were met and/or had histologically confirmed high-grade NMIBC or a combination of CIS and papillary disease.

Results
The study population consisted of 6 BCG unresponsive NMIBC patients of whom 6 underwent HIVEC®.  The median age and follow-up were 74 years and 12 months.
Four patients showed recorrence after 5,5 months (75% were pT1 and 25% CIS). The other two patients are still tumor free after 9 months. All patients were followed by cystoscopy and cytology every 3 months and biopsies were performed if cystoscopy showed a recurrence or cytology showed a suspicion of the presence of urothelial carcinoma. The primary outcome was the disease-free survival (DFS), defined as the time from start of first HIVEC® treatment until disease recurrence, which was 5.5 months.


Conclusion 
Despite HIVEC® seems to be a valid treatment option for BCG unresponsive NMIBC patients, we report a median DFS of 5.5 months, postponing the need for radical surgery in a proportion of these patients. Our sample is small and we require a longer follow up period.

Hyperthermic Intravesical Chemotherapy for BCG Unresponsive Non-Muscle Invasive Bladder Cancer Patients