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

(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 intraves...

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Autores principales: Plata, Ana, Guerrero-Ramos, Félix, Garcia, Carlos, González-Díaz, Alejandro, Gonzalez-Valcárcel, Ignacio, de la Morena, José Manuel, Díaz-Goizueta, Francisco Javier, del Álamo, Julio Fernández, Gonzalo, Victoria, Montero, Javier, Sousa-Escandón, Alejandro, León, Juan, Pontones, Jose Luis, Delgado, Francisco, Adriazola, Miguel, Pascual, Ángela, Calleja, Jesús, Ruano, Ana, Martínez-Piñeiro, Luis, Angulo, Javier C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584886/
https://www.ncbi.nlm.nih.gov/pubmed/34768625
http://dx.doi.org/10.3390/jcm10215105
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author Plata, Ana
Guerrero-Ramos, Félix
Garcia, Carlos
González-Díaz, Alejandro
Gonzalez-Valcárcel, Ignacio
de la Morena, José Manuel
Díaz-Goizueta, Francisco Javier
del Álamo, Julio Fernández
Gonzalo, Victoria
Montero, Javier
Sousa-Escandón, Alejandro
León, Juan
Pontones, Jose Luis
Delgado, Francisco
Adriazola, Miguel
Pascual, Ángela
Calleja, Jesús
Ruano, Ana
Martínez-Piñeiro, Luis
Angulo, Javier C.
author_facet Plata, Ana
Guerrero-Ramos, Félix
Garcia, Carlos
González-Díaz, Alejandro
Gonzalez-Valcárcel, Ignacio
de la Morena, José Manuel
Díaz-Goizueta, Francisco Javier
del Álamo, Julio Fernández
Gonzalo, Victoria
Montero, Javier
Sousa-Escandón, Alejandro
León, Juan
Pontones, Jose Luis
Delgado, Francisco
Adriazola, Miguel
Pascual, Ángela
Calleja, Jesús
Ruano, Ana
Martínez-Piñeiro, Luis
Angulo, Javier C.
author_sort Plata, Ana
collection PubMed
description (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.
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spelling pubmed-85848862021-11-12 Long-Term Experience with Hyperthermic Chemotherapy (HIVEC) Using Mitomycin-C in Patients with Non-Muscle Invasive Bladder Cancer in Spain Plata, Ana Guerrero-Ramos, Félix Garcia, Carlos González-Díaz, Alejandro Gonzalez-Valcárcel, Ignacio de la Morena, José Manuel Díaz-Goizueta, Francisco Javier del Álamo, Julio Fernández Gonzalo, Victoria Montero, Javier Sousa-Escandón, Alejandro León, Juan Pontones, Jose Luis Delgado, Francisco Adriazola, Miguel Pascual, Ángela Calleja, Jesús Ruano, Ana Martínez-Piñeiro, Luis Angulo, Javier C. J Clin Med Article (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. MDPI 2021-10-30 /pmc/articles/PMC8584886/ /pubmed/34768625 http://dx.doi.org/10.3390/jcm10215105 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Plata, Ana
Guerrero-Ramos, Félix
Garcia, Carlos
González-Díaz, Alejandro
Gonzalez-Valcárcel, Ignacio
de la Morena, José Manuel
Díaz-Goizueta, Francisco Javier
del Álamo, Julio Fernández
Gonzalo, Victoria
Montero, Javier
Sousa-Escandón, Alejandro
León, Juan
Pontones, Jose Luis
Delgado, Francisco
Adriazola, Miguel
Pascual, Ángela
Calleja, Jesús
Ruano, Ana
Martínez-Piñeiro, Luis
Angulo, Javier C.
Long-Term Experience with Hyperthermic Chemotherapy (HIVEC) Using Mitomycin-C in Patients with Non-Muscle Invasive Bladder Cancer in Spain
title Long-Term Experience with Hyperthermic Chemotherapy (HIVEC) Using Mitomycin-C in Patients with Non-Muscle Invasive Bladder Cancer in Spain
title_full Long-Term Experience with Hyperthermic Chemotherapy (HIVEC) Using Mitomycin-C in Patients with Non-Muscle Invasive Bladder Cancer in Spain
title_fullStr Long-Term Experience with Hyperthermic Chemotherapy (HIVEC) Using Mitomycin-C in Patients with Non-Muscle Invasive Bladder Cancer in Spain
title_full_unstemmed Long-Term Experience with Hyperthermic Chemotherapy (HIVEC) Using Mitomycin-C in Patients with Non-Muscle Invasive Bladder Cancer in Spain
title_short Long-Term Experience with Hyperthermic Chemotherapy (HIVEC) Using Mitomycin-C in Patients with Non-Muscle Invasive Bladder Cancer in Spain
title_sort long-term experience with hyperthermic chemotherapy (hivec) using mitomycin-c in patients with non-muscle invasive bladder cancer in spain
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584886/
https://www.ncbi.nlm.nih.gov/pubmed/34768625
http://dx.doi.org/10.3390/jcm10215105
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