(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.
Journal of clinical medicine. 2021 Oct 30*** epublish ***
Ana Plata, Félix Guerrero-Ramos, Carlos Garcia, Alejandro González-Díaz, Ignacio Gonzalez-Valcárcel, José Manuel de la Morena, Francisco Javier Díaz-Goizueta, Julio Fernández Del Álamo, Victoria Gonzalo, Javier Montero, Alejandro Sousa-Escandón, Juan León, Jose Luis Pontones, Francisco Delgado, Miguel Adriazola, Ángela Pascual, Jesús Calleja, Ana Ruano, Luis Martínez-Piñeiro, Javier C Angulo
Urology Department, Hospital Universitario de Canarias, Carretera Ofra s/n, 38320 San Cristóbal de La Laguna, Spain., Urology Department, Hospital Universitario 12 de Octubre, Avenida de Córdoba s/n, 28041 Madrid, Spain., Urology Department, Hospital Universitario Infanta Sofía, Paseo de Europa 34, San Sebastián de los Reyes, 28702 Madrid, Spain., Urology Department, Hospital Universitario Getafe, Carretera de Toledo, Km 12.500, Getafe, 28905 Madrid, Spain., Urology Department, Hospital Universitario de Torrejón, Mateo Inurria, s/n, Torrejón de Ardoz, 28850 Madrid, Spain., Urology Department, Hospital Universitario de Burgos, Avenida Islas Baleares 3, 09006 Burgos, Spain., Urology Department, Hospital Comarcal de Monforte, Rúa Corredoira s/n, 27400 Monforte de Lemos, Spain., Urology Department, Hospital Universitario La Fe, Avinguda de Fernando Abril Martorell 106, 46026 Valencia, Spain., Urology Department, Hospital General Rio Carrión, Avenida Donantes de Sangre s/n, 34005 Palencia, Spain., Urology Department, Hospital Clínico Universitario de Valladolid, Av. Ramón y Cajal 3, 47003 Valladolid, Spain., Urology Department, Hospital Universitario La Paz, Paseo de la Castellana 261, 28046 Madrid, Spain.