Alternate‐day administration of intravesical gemcitabine and docetaxel to improve clinic utilisation

Sequential intravesical gemcitabine-docetaxel (Gem/Doce) has emerged as a legitimate treatment option for patients with non-muscle-invasive bladder cancer (NMIBC) after BCG failure. Studies of Gem/Doce have demonstrated 1-year high-grade recurrence-free survival (RFS) of 65–79%, which decreases to 31% at 5-year follow-up [1, 2]. As a result, Gem/Doce may be given to patients with BCG-unresponsive disease or BCG-naïve disease during BCG shortages. The efficacy of Gem/Doce has given the practicing urologist another tool to combat BCG-unresponsive disease, yet it presents its own set of challenges. A survey of 198 urological oncologists in the USA and Canada found 44% reported at least one barrier to Gem/Doce administration [3]. Over 30% of those surveyed said clinical workflow, including space for administration, was a significant barrier. The time burden of this regimen for both practitioners and patients has also been described with a median office visit duration of 87 min and induction instillation duration of 221 min [4]. The clinic resources required and the frequency and duration of visits (six induction and 24 monthly maintenance treatments) are a significant drawback to Gem/Doce, potentially limiting utilisation. In our clinic, we have introduced a protocol for Gem/Doce administration on alternating days in order to improve workflow and reduce the duration of clinic visits. In this protocol gemcitabine and docetaxel are administered separately over two visits per week (usually Tuesday and Friday). After patient rooming a Foley catheter is placed, and chemotherapy is instilled into the bladder. The catheter is subsequently removed, and patients are discharged from clinic with instructions to hold for ≥90 min. Here we describe our initial experience with an alternating-day administration protocol to provide practicing urologists a potential solution to the logistical challenges of Gem/Doce treatment. We conducted a retrospective analysis of patients in our urological oncology clinic with NMIBC who received either alternate-day (n = 21) or same-day (n = 22) Gem/Doce and had a follow up of at least 5 months. Patients received an induction course of six cycles followed by monthly maintenance therapy with a goal duration of 2 years of maintenance. The median (interquartile range [IQR]) follow-up was 12 (7–21) months. Patients received a median of one prior BCG induction while 17 patients received more than one. This quality improvement study was deemed exempt by the Cedars-Sinai Institutional Review Board. Alternate-day administration of Gem/Doce had comparable RFS to same-day administration in Kaplan–Meier analysis (P = 0.52) (Fig. 1). Recurrence was associated with the number of prior BCG induction courses (P < 0.001). In a Cox proportional hazards model controlling for age, gender, race, smoking, and presence of carcinoma in situ (CIS) the alternate-day protocol was associated with lower risk for recurrence (hazard ratio [HR] 0.13, 95% CI 0.02–0.90; P = 0.04) while the number of prior BCG treatments was associated with higher risk (HR 7.6, 95% CI 1.7–10; P = 0.007). Side effects were similar between the two treatment protocols overall. Clinic visit duration was defined as the time between patient rooming and administration of the last medication, after which the patient's catheter was removed and they were discharged from clinic. Only visits for chemotherapy administration were included (no cystoscopy or follow-up). The median (IQR) visit duration for alternate-day administration was 32 (27–40) min while same-day visit duration was 117 (98–129) min. Our protocol of alternate-day Gem/Doce administration can improve clinical efficiency by reducing treatment visit durations while providing comparable oncological outcomes. The median visit time of 32 min twice per week is a noticeable improvement from same-day treatments. When intravesical chemotherapy treatments are performed at the start of the day, as in our clinic, a large number of patients can be treated before return to a typical clinic schedule. This regimen may present its own challenges, especially for patients travelling long distances, as they will likely not be amenable to multiple visits per week. In our anecdotal experience, local patients report substantial logistical benefits to their personal schedules with alternate-day administration. Other groups have studied modifications to instillation techniques to improve Gem/Doce treatment. McElree et al. [5] have reported the use of a split-dosing regimen and temporary instillation drainage as methods to improve chemotherapy dwell times in patients with diminished bladder capacity or bladder spasms during treatment. Alternatively in the BRIDGE trial (NCT05538663), comparing BCG and Gem/Doce, chemotherapy dwell times of 60 min are used compared to the traditional 90–120 min protocol [6]. This approach may be an improvement; however, not to the same degree as an alternative-day protocol. Finally, a discussion of NMIBC treatment after BCG would not be complete without mention of novel agents. These treatments may require fewer clinic visits than Gem/Doce, but at the trade-off of tremendous financial toxicity [7]. Our study is limited by the small size of this pilot cohort. In order to definitively determine equivalent efficacy of alternate-day Gem/Doce a randomised controlled trial will be needed. Until then we plan to continue use of this protocol and study its effectiveness through collaborations with additional institutions. The authors have no conflicts of interest to disclose. None. The datasets analysed during the present study are not publicly available but de-identified data can be made available from the corresponding author on reasonable request.