Recirculating hyperthermic intravesical chemotherapy with mitomycin C (HIVEC) versus BCG in high-risk non-muscle-invasive bladder cancer: results of the HIVEC-HR randomized clinical trial.

PURPOSE: The purpose of the study was to compare the outcomes of high-risk non-muscle-invasive bladder cancer (HR-NMIBC) patients treated with BCG vs recirculating hyperthermic intravesical chemotherapy (HIVEC) with mitomycin C (MMC). METHODS: A pilot phase II randomized clinical trial was conducted including HR-NMIBC patients, excluding carcinoma in situ. Patients were randomized 1:1 to receive intravesical BCG for 1 year (once weekly for 6 weeks plus subsequent maintenance) or HIVEC with 40 mg MMC, administered using the Combat BRS system (once weekly instillations were given for 6 weeks, followed by once monthly instillation for 6 months). Total recirculating dwell time for HIVEC was 60 min at a target temperature of 43° ± 0.5 °C. Primary endpoint was recurrence-free survival. Secondary endpoints were time to recurrence, progression-free survival, cancer-specific survival, and overall survival at 24 months. Adverse events were routinely assessed. RESULTS: Fifty patients were enrolled. Mean age was 73.5 years. Median follow-up was 33.7 months. Recurrence-free survival at 24 months was 86.5% for HIVEC and 71.8% for BCG (p = 0.184) in the intention-to-treat analysis and 95.0% for HIVEC and 75.1% for BCG (p = 0.064) in the per protocol analysis. Time to recurrence was 21.5 and 16.1 months for HIVEC and BCG, respectively. Progression-free survival for HIVEC vs BCG was 95.7% vs 71.8% (p = 0.043) in the intention-to-treat analysis and 100% vs 75.1% (p = 0.018) in the per protocol analysis, respectively. Cancer-specific survival at 24 months was 100% for both groups and overall survival was 91.5% for HIVEC vs 81.8% for BCG. CONCLUSION: HIVEC provides comparable safety and efficacy to BCG and is a reasonable alternative during BCG shortages. TRIAL REGISTRATION: EudraCT 2016-001186-85. Date of registration: 17 March 2016.

Quality of life and adverse events in patients with nonmuscle invasive bladder cancer receiving adjuvant treatment with BCG, MMC, or chemohyperthermia.

INTRODUCTION: Chemohyperthermia (CHT) with mitomycin C (MMC) is together with Bacillus Calmette-Guérin (BCG), and passive MMC, a treatment option for patients with non muscle-invasive bladder cancer. There are no data published about the impact of CHT in quality of life (QoL). We evaluated QoL and adverse events (AE) in this 3-arm observational study. PATIENTS AND METHODS: Prospective observational study from September 2016 to March 2017, we recruited consecutive patients that received adjuvant treatment after transurethral resection of bladder tumor. Patients received induction courses of either BCG, CHT, or passive MMC. Patients filled the questionnaires Functional assessment of cancer therapy for bladder cancer patients (FACT-Bl) and International prostate symptom score (IPSS) before, during, and after the induction course. A urologist documented AE using Common Terminology Criteria for AE (CTCAE criteria). RESULTS: A total of 56 patients, receiving a total of 296 bladder instillations (BCG n = 27, CHT n = 14 and MMC n = 15). FACT-Bl showed statistically significant differences in the fourth week in favor of CHT versus BCG, IPSS did not show statistically significant differences before, during, and after induction course in all 3 arms. All patients recovered their baseline QoL at the end of the induction treatment. Overall 55.5%, 50% and 20% of patients presented any grade of AE in the BCG, CHT and MMC groups respectively. About 7% of patients in BCG and CHT arms had to discontinue treatment due to AE. BCG and CHT showed a similar rate of AE but in CHT were mostly grade I and BCG had grade I, II, and IV. Passive MMC had the safest profile. CONCLUSION: There are no clinically significant differences between BCG, CHT, and passive MMC regarding QoL and lower urinary tract symptoms during the induction course. CHT has a more favorable AE profile when compared with BCG.

[Mitomycin C HIVEC. Update and results in high risk patients.] / HIVEC con mitomicina C. Actualización y resultados en pacientes de alto riesgo.

Adjuvant endovesical treatment is a research field in constant exploration with the aim to minimize the risk of recurrence and progression of non muscle invasive bladder tumors. Over the last years, the administration of chemotherapy in a chemo hyperthermia regimen has been added to the existing regimens. There are various systems for its administration, but this article focus on HIVEC (Hyperthermic IntraVEsical Chemotherapy) and its current status. In this review article we update the results of this system in the case-scenarios it has been used (preoperative with ablative intention and as adjuvant therapy with prophylactic purposes), tolerance and security issues, on-going clinical trials and future perspectives.