Abstract
(1) Background: Intravesical mitomycin-C (MMC) combined with hyperthermia is increasingly used in non-muscle invasive bladder cancer (NMIBC), especially in the context of a relative BCG shortage. We aim to determine real-world data on the long-term treatment outcomes of adjunct hyperthermic intravesical chemotherapy (HIVEC) with MMC and a COMBAT® bladder recirculation system (BRS); (2) Methods: A prospective observational trial was performed on patients with NMIBC treated with HIVEC using BRS in nine academic institutions in Spain between 2012–2020 (HIVEC-E). Treatment effectiveness (recurrence, progression and overall mortality) was evaluated in patients treated with HIVEC MMC 40mg in the adjuvant setting, with baseline data and a clinical follow-up, that comprise the Full Analysis Set (FAS). Safety, according to the number and severity of adverse effects (AEs), was evaluated in the safety (SAF) population, composed by patients with at least one adjunct HIVEC MMC instillation; (3) Results: The FAS population (n = 502) received a median number of 8.78 ± 3.28 (range 1–20) HIVEC MMC instillations. The median follow-up duration was 24.5 ± 16.5 (range 1–81) months. Its distribution, based on EAU risk stratification, was 297 (59.2%) for intermediate and 205 (40.8%) for high-risk. The figures for five-year recurrence-free and progression-free survival were 50.37% (53.3% for intermediate and 47.14% for high-risk) and 89.83% (94.02% for intermediate and 84.23% for high-risk), respectively. A multivariate analysis identified recurrent tumors (HR 1.83), the duration of adjuvant HIVEC therapy <4 months (HR 1.72) and that high-risk group (HR 1.47) were at an increased risk of recurrence. Independent factors of progression were high-risk (HR 3.89), recurrent tumors (HR 3.32) and the induction of HIVEC therapy without maintenance (HR 2.37). The overall survival was determined by patient age at diagnosis (HR 3.36) and the treatment duration (HR 1.82). The SAF population (n = 592) revealed 406 (68.58%) patients without AEs and 186 (31.42%) with at least one AE: 170 (28.72%) of grade 1–2 and 16 (2.7%) of grade 3–4. The most frequent AEs were dysuria (10%), pain (7.1%), urgency (5.7%), skin rash (4.9%), spasms (3.7%) and hematuria (3.6%); (4) Conclusions: HIVEC using BRS is efficacious and well tolerated. A longer treatment duration, its use in naïve patients and the intermediate-risk disease are independent determinants of success. Furthermore, a monthly maintenance of adjunct MMC HIVEC diminishes the progression rate of NMIBC.
Highlights
Bladder cancer is a major urological disease, with more than half a million new cases diagnosed and leading to almost 0.2 million deaths per year worldwide [1]
The Full Analysis Set (FAS) population for the current study focused exclusively on patients receiving adjunct hyperthermic intravesical chemotherapy (HIVEC) mitomycin C (MMC) 40mg and a clinical follow-up was updated in June 2021
The FAS population (n = 502) included patients receiving adjunct HIVEC MMC with follow-up treatment that allowed for the evaluation of primary endpoints
Summary
Bladder cancer is a major urological disease, with more than half a million new cases diagnosed and leading to almost 0.2 million deaths per year worldwide [1]. An increase in bladder cancer incidence but a decrease in mortality has been recently observed in several European countries, possibly related to a better awareness and earlier detection that allows better oncological control [2]. 75% of patients present as having non-muscle invasive bladder cancer (NMIBC), which, despite being a none life-threatening disease, presents the risk of recurrence and of progression to a muscle invasive form, most often leading to metastases [4]. Maintenance BCG is considered to be the best bladder-sparing treatment for high-risk NMIBC patients and as a potential alternative for the intermediate risk group [5]. Recent evidence suggests that maintenance BCG is not a cost-effective alternative for the entire population of patients with intermediate/high risk NMIBC [8]. Shortages in the BCG supply have compromised patient outcomes and left clinicians around the globe without clear effective and reliable alternatives [9,10,11]
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