Adverse events of hyperthermic intravesical chemotherapy for non-muscle invasive bladder cancer patients.

INTRODUCTION: Non-muscle invasive bladder cancer (NMIBC) is one of the most frequent neoplasms in Denmark. Treatment of high-risk NMIBC usually consists of transurethral resection of bladder (TUR-B) followed by intravesical Bacillus Calmette-Guérin (BCG) instillations. Unfortunately, some patients are BCG-unresponsive and will relapse over time. Radical cystectomy is the recommended salvage treatment following BCG-failure or BCG-intolerance. However, not all patients are candidates for surgery and thus, in need of other treatment. This study investigates the adverse events of Hyperthermic Intravesical Chemotherapy (HIVEC) treatment. METHODS: Twenty-three high-risk NMIBC patients, who were BCG-unresponsive or had contraindications for BCG, received HIVEC with Mitomycin C. Prior to each instillation, patients were interviewed by a nurse, using a systematic questionnaire regarding the adverse events. Patients were followed with cytology and cystoscopy every fourth month. The primary outcome was adverse event related to the HIVEC treatment. RESULTS: In general, the adverse events were mild to moderate and often self-limiting. The most common adverse events were urinary frequency (23.6%), incontinence (19.4%) and urinary tract pain (12.2%). CONCLUSION: In the current study, we found that HIVEC was a well-tolerated treatment. HIVEC might be a feasible option for patients, who experienced BCG-failure or BCG-intolerance and could potentially postpone or avoid radical cystectomy.

SPTAN1, APC, and FGFR3 Mutation Status and APOBEC Mutation Signatures are Predictive of Mitomycin C Response in Non-muscle-invasive Bladder Cancer.

BACKGROUND: Currently, no biomarkers of response to mitomycin C have been identified in non-muscle-invasive bladder cancer patients. Predictive biomarkers could improve the treatment outcome and eliminate adverse events from unnecessary treatment. OBJECTIVE: To identify and validate predictive biomarkers of chemoresection with mitomycin C. DESIGN SETTING AND PARTICIPANTS: The intervention group of a randomised controlled trial was identified for analyses. The study was conducted between January 2018 and June 2019 in two major urological departments in Denmark. Patients had a history of Ta low-grade/high-grade disease and were included upon recurrence. The intervention group (58 patients) received chemoresection with mitomycin C. Tumour and reference germline DNA from prior tumours were analysed by whole exome sequencing. Predictive biomarkers were validated in the context of Ta low-grade tumours from the UROMOL study. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Response to chemotherapy (intervention group from the randomised controlled trial) and recurrence-free survival (UROMOL cohort) were measured. Groups were compared using Fisher's exact test and Wilcoxon rank sum test. RESULTS AND LIMITATIONS: Chemoresponse was associated with the mutation status of SPTAN1, APC, and FGFR3, and the level of APOBEC signature contribution (p = 0.035, p = 0.034, p = 0.055, and p = 0.035, respectively). The main limitations include no biopsy for biomarker discovery immediately prior to chemoresection and the unmatched validation cohort. CONCLUSIONS: Mutation status of APC, SPTAN1, and FGFR3 and the level of mutational contribution from APOBEC-related signatures were identified as potential predictive biomarkers for chemoresection with mitomycin C in non-muscle-invasive bladder cancer patients. A prospective validation study is however needed. PATIENT SUMMARY: We investigated DNA from noninvasive bladder tumours in order to predict treatment response to chemotherapy. Four biomarkers showed promising results, which should be tested in future studies.

Novel technique: direct access partial nephrectomy approach through a transperitoneal working space (Roskilde technique).

Objectives: To describe a direct access partial nephrectomy technique through a transperitoneal working space (Roskilde technique).Materials and methods: Prospective single-center descriptive study between April 2015 and January 2017. The surgical outcomes are evaluated according to the Trifecta criteria (negative margins, warm ischemia time < 20 min and a Clavien-Dindo complication score < 3).Surgical procedure: The same access to the transperitoneal cavity as in a Standard transperitoneal Partial Nephrectomy was used. A direct access was established by incision of the peritoneum directly onto the renal fascia. The renal vessels and tumor were identified and the tumor removed with standard technique. The perinephric fat and peritoneum were then closed with a running suture.Results: In total, 122 patients underwent the Roskilde technique. The mean age was 62.2 years, the median Padua score was 12 (IQR = 9-12) and the median tumor size was 32 mm (IQR = 12-90). The median operative time was 101 min (IQR = 90-125). The trifecta achievement criteria goal was achieved in 116/122 (95%), with a median warm ischemia time of 8 min (IQR = 0-12).Conclusions: The Roskilde technique is safe and feasible. It can be performed on complex renal masses, and it seems to result in short operative times and high Trifecta achievement.Trial registration: None.