Long-term efficacy of hyperthermic intravesical chemotherapy for BCG-unresponsive non-muscle invasive bladder cancer.

BACKGROUND: The recommended treatment for patients with Bacillus Calmette-Guérin (BCG) unresponsive non-muscle invasive bladder cancer (NMIBC) is radical cystectomy (RC). However, many patients refuse, or are unfit for RC. Therefore, alternative bladder-sparing treatment modalities are needed for BCG-unresponsive NMIBC. In this study we sought to assess the long-term efficacy of hyperthermic intravesical chemotherapy (HIVEC) as alternative to radical cystectomy in BCG-unresponsive non-muscle invasive bladder cancer patients. METHODS AND MATERIALS: Retrospectively collected data from 56 patients with BCG-unresponsive NMIBC who received ≥5 HIVEC instillations between October 2014 and March 2020 was analyzed. All patients met the BCG-unresponsive criteria according to the current EAU guideline on NMIBC 2020. Patients were followed-up with cystoscopy and/or bladder biopsies, urine cytology and annually CT-urography. The Primary outcome was the high grade (HG) recurrence-free survival (RFS), defined as the time from the first HIVEC instillation until histologically confirmed intravesical recurrence or last follow-up. The Kaplan Meier method was used to estimate survival outcomes. Secondary outcomes were: complete response rate (CR), adverse events (AE), assessed by the Common Terminology Criteria for Adverse Events v5.0 (CTCAE) and tumor progression to muscle invasive disease or distant metastases. RESULTS: The median follow-up was 32.2 months (IQR 13.7-44.8). The 1- and 2-year HG-RFS was 53% (SE:6.8) and 35% (SE:6.9), respectively. The CR for patients with CIS was 70% (21/30) at 6 months. Overall, 80% of the population developed an AE, only 1 was classified as CTCAE ≥3. Limitation of this study was the small sample size. CONCLUSION: HIVEC resulted in a 2-year HG-RFS of 35% for BCG-unresponsive NMIBC patients without severe side-effects and therefore HIVEC seems to be an alternative treatment option for patients who refuse or are unfit for RC.

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

BACKGROUND: 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. OBJECTIVE: To assess the effectiveness of Hyperthermic IntraVEsical Chemotherapy (HIVEC®) in BCG unresponsive NMIBC patients. METHODS: A post-hoc analysis was conducted of prospectively included intermediate-and high-risk NMIBC patients who were planned to receive HIVEC® treatment between October 2014 and November 2017. For the present analysis, only patients who met the BCG unresponsive definition were included. Patients were followed by cystoscopy and cytology every 3 months and a CT-urography scan yearly. The primary outcome was the disease-free survival (DFS). The Common Terminology Criteria for Adverse Events (CTCAE) was used to assess side-effects. RESULTS: The study population consisted of 55 BCG unresponsive NMIBC patients of whom 52 underwent≥5 HIVEC® treatments. The median age and follow-up were 73 years and 14.0 months (IQR 7.6 - 24.6). The median DFS was 17.7 months (SE 6.72) and progression occurred in four patients. The 1-year cumulative incidence rate of disease recurrence/progression was 53%. Two patients experienced severe side-effects (CTCAE≥3). CONCLUSIONS: HIVEC® seems a valid treatment option for BCG unresponsive NMIBC patients. We report a median DFS of 17.7 months (SE 6.72), potentially avoiding or postponing the need for radical surgery in a proportion of these patients.