Long-Term Experience with Hyperthermic Chemotherapy (HIVEC) Using Mitomycin-C in Patients with Non-Muscle Invasive Bladder Cancer in Spain

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.

Hyperthermic intravesical chemotherapy with mitomycin‐C for the treatment of high‐risk non‐muscle‐invasive bladder cancer patients

“…Overall, the 12-month RFS, PFS and OS rates were promising, with slightly higher rates than other high-risk HIVEC studies. 17,18 Higher RFS, PFS and OS have been reported in one randomised trial of BCG versus HIVEC, 16 which excluded patients with CIS, enrolled fewer patients with recurrent tumours or prior treatment, and had a lower median age; and the second, a large prospective observational cohort in Spain, 30 For example, transport challenges to and from the department, finding the treatment too time consuming, other life commitments, opting for a watch and wait approach.…”

Device-assisted intravesical chemotherapy treatment for nonmuscle invasive bladder cancer: 2022 update

“…Six new studies reported AEs after HIVEC with four reporting after first-line treatment [13 ▪▪ ,14 ▪▪ ,17 ▪▪ ,18 ▪▪ ]. The majority reported only grade 1–2 AEs, with only one study that reported grade 3–4 AEs for 2.7% of patients [18 ▪▪ ]. The reported rates for grade 1–2 AEs varied from 31.4% to 50%.…”

Urological Cancer Panorama in the Second Year of the COVID-19 Pandemic

“…Miyake et al [21] present a retrospective study of a very large series of patients with T1 high-grade urothelial carcinoma and evaluate the prognostic role of divergent differentiation and variant morphologies when Bacillus Calmette-Guérin (BCG) endovesical treatment is used. This topic presents the clinical implications of urothelial cancer heterogeneity and is of particular interest in this era of BCG shortage, where new treat modalities such as chemo-hyperthermia to optimize adjuvant treatment after transurethral resection are being investigated [22,23] or even early cystectomy [24] are controversial. With the limitations of the study design using inverse probability of treatment weighting analysis, the authors found that not only recurrence-free or progression-free rates are affected, but also cancer-specific mortality was affected by variant morphologies (nested, microcystic, micropapillary, lympho-epithelioma-like, plasmacytoid, giant cell, sarcomatoid, lipid-rich and clear cell variants), but not for urothelial cancer with divergent (squamous, glandular and trophoblastic) differentiation.…”