Mitomycin C allergy after passive and device-assisted hyperthermia for non-muscle invasive bladder cancer treatment: A retrospective cohort from a high-volume center.

INTRODUCTION: Mitomycin C (MMC) is one of the most frequently utilized intravesical chemotherapy drugs for the management of non-muscle-invasive bladder cancer (NMIBC). Allergic reactions (Type 4 delayed hypersensitivity) are seldomly reported in the literature but not so infrequent in daily practice, its incidence has been increasing with the use of device-assisted hyperthermia. This study aims to identify the incidence, risk factors, and clinical characteristics of patients with allergic reactions to MMC. PATIENTS AND METHODS: Single-center retrospective cohort from June 2014 to August 2018. Patients with intermediate or high-risk NMIBC were included. Patients received passive MMC (4 weekly and eleven monthly instillations of 40mg of MMC) or Chemohyperthermia (CHT) with MMC (6 weekly and 6-monthly instillations, heated at 43°C [+/- 0.5°C] using Combat BRS). RESULTS: We included 258 patients (MMC = 157, CHT = 101) and found 7 (4.4%) suspected and 4 confirmed (2.4%) allergies in the passive MMC group and 11 suspected (10.9%) and 7 confirmed (6.9%) in the CHT group. The mean number of instillations received before developing the allergy was 6 in the passive MMC and 5 in the CHT group. Seven out of 18 suspected allergy cases were pseudo-allergic reactions with negative allergy tests. Early postoperative MMC instillation was associated with an increased risk of allergy (OR 2.47 [CI 1.39-4.36], P = 0.001), while neither history of atopy nor history of other medications allergy was found to increase the risk. CONCLUSION: MMC allergy risk is increased with the use of device-assisted hyperthermia with an incidence of 2.4% for passive MMC and 6.9% for CHT. History of prior allergies does not seem to increase the risk of developing MMC allergy. In this series 38% of suspected cases were found to be pseudo-allergic reactions, highlighting the need to confirm the diagnosis before definitively stopping the treatment.

Carcinoma in situ of the bladder: why is it underdetected?

PURPOSE OF REVIEW: The standard diagnosis of carcinoma in situ (CIS) of the bladder, based on white light cystoscopy and urine cytology, is limited because CIS can vary from normal-appearing mucosa to a lesion indistinguishable from an inflammatory process. Intravesical instillation of Bacillus Calmette-Guerin (BCG) remains first-line therapy; however, a significant proportion of cases persist or recur after BCG treatment. This review summarizes recent improvements in the detection and treatment of CIS. RECENT FINDINGS: The new optical technologies improve CIS detection, with a potential positive impact on oncological outcomes. The usefulness of MRI-photodynamic diagnosis fusion transurethral resection in CIS detection is unclear and further studies are needed. BCG instillation remains the first-line therapy in CIS patients and seems to improve recurrence and progression rates, especially with the use of maintenance. Intravesical device-assisted therapies could be effective in both BCG-naïve and BCG-unresponsive CIS patients, but further studies are ongoing to clarify their clinical benefit. A phase II clinical trial with pembrolizumab has shown the potential effectiveness of immune checkpoint inhibitors in BCG-unresponsive CIS patients and further trials are ongoing. SUMMARY: New optical techniques increase the CIS detection rate. BCG instillation remains the first-line treatment. Immune checkpoint inhibitors could be a future alternative in BCG-naïve and BCG-unresponsive CIS patients.