PMID- 34768625
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211118
IS  - 2077-0383 (Print)
IS  - 2077-0383 (Electronic)
IS  - 2077-0383 (Linking)
VI  - 10
IP  - 21
DP  - 2021 Oct 30
TI  - Long-Term Experience with Hyperthermic Chemotherapy (HIVEC) Using Mitomycin-C in 
      Patients with Non-Muscle Invasive Bladder Cancer in Spain.
LID - 10.3390/jcm10215105 [doi]
LID - 5105
AB  - (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(R) 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 naive 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.
FAU - Plata, Ana
AU  - Plata A
AD  - Urology Department, Hospital Universitario de Canarias, Carretera Ofra s/n, 38320 
      San Cristobal de La Laguna, Spain.
FAU - Guerrero-Ramos, Felix
AU  - Guerrero-Ramos F
AUID- ORCID: 0000-0002-0767-3465
AD  - Urology Department, Hospital Universitario 12 de Octubre, Avenida de Cordoba s/n, 
      28041 Madrid, Spain.
FAU - Garcia, Carlos
AU  - Garcia C
AD  - Urology Department, Hospital Universitario de Canarias, Carretera Ofra s/n, 38320 
      San Cristobal de La Laguna, Spain.
FAU - Gonzalez-Diaz, Alejandro
AU  - Gonzalez-Diaz A
AUID- ORCID: 0000-0002-3581-7200
AD  - Urology Department, Hospital Universitario 12 de Octubre, Avenida de Cordoba s/n, 
      28041 Madrid, Spain.
FAU - Gonzalez-Valcarcel, Ignacio
AU  - Gonzalez-Valcarcel I
AD  - Urology Department, Hospital Universitario Infanta Sofia, Paseo de Europa 34, San 
      Sebastian de los Reyes, 28702 Madrid, Spain.
FAU - de la Morena, Jose Manuel
AU  - de la Morena JM
AD  - Urology Department, Hospital Universitario Infanta Sofia, Paseo de Europa 34, San 
      Sebastian de los Reyes, 28702 Madrid, Spain.
FAU - Diaz-Goizueta, Francisco Javier
AU  - Diaz-Goizueta FJ
AD  - Urology Department, Hospital Universitario Getafe, Carretera de Toledo, Km 
      12.500, Getafe, 28905 Madrid, Spain.
FAU - Del Alamo, Julio Fernandez
AU  - Del Alamo JF
AD  - Urology Department, Hospital Universitario de Torrejon, Mateo Inurria, s/n, 
      Torrejon de Ardoz, 28850 Madrid, Spain.
FAU - Gonzalo, Victoria
AU  - Gonzalo V
AD  - Urology Department, Hospital Universitario de Burgos, Avenida Islas Baleares 3, 
      09006 Burgos, Spain.
FAU - Montero, Javier
AU  - Montero J
AD  - Urology Department, Hospital Universitario de Burgos, Avenida Islas Baleares 3, 
      09006 Burgos, Spain.
FAU - Sousa-Escandon, Alejandro
AU  - Sousa-Escandon A
AD  - Urology Department, Hospital Comarcal de Monforte, Rua Corredoira s/n, 27400 
      Monforte de Lemos, Spain.
FAU - Leon, Juan
AU  - Leon J
AUID- ORCID: 0000-0001-8162-0313
AD  - Urology Department, Hospital Comarcal de Monforte, Rua Corredoira s/n, 27400 
      Monforte de Lemos, Spain.
FAU - Pontones, Jose Luis
AU  - Pontones JL
AD  - Urology Department, Hospital Universitario La Fe, Avinguda de Fernando Abril 
      Martorell 106, 46026 Valencia, Spain.
FAU - Delgado, Francisco
AU  - Delgado F
AD  - Urology Department, Hospital Universitario La Fe, Avinguda de Fernando Abril 
      Martorell 106, 46026 Valencia, Spain.
FAU - Adriazola, Miguel
AU  - Adriazola M
AD  - Urology Department, Hospital General Rio Carrion, Avenida Donantes de Sangre s/n, 
      34005 Palencia, Spain.
FAU - Pascual, Angela
AU  - Pascual A
AD  - Urology Department, Hospital General Rio Carrion, Avenida Donantes de Sangre s/n, 
      34005 Palencia, Spain.
FAU - Calleja, Jesus
AU  - Calleja J
AD  - Urology Department, Hospital Clinico Universitario de Valladolid, Av. Ramon y 
      Cajal 3, 47003 Valladolid, Spain.
FAU - Ruano, Ana
AU  - Ruano A
AD  - Urology Department, Hospital Clinico Universitario de Valladolid, Av. Ramon y 
      Cajal 3, 47003 Valladolid, Spain.
FAU - Martinez-Pineiro, Luis
AU  - Martinez-Pineiro L
AD  - Urology Department, Hospital Universitario La Paz, Paseo de la Castellana 261, 
      28046 Madrid, Spain.
FAU - Angulo, Javier C
AU  - Angulo JC
AD  - Urology Department, Hospital Universitario Getafe, Carretera de Toledo, Km 
      12.500, Getafe, 28905 Madrid, Spain.
AD  - Clinical Department, Facultad de Ciencias Biomedicas, Universidad Europea de 
      Madrid, Carretera de Toledo, Km 12.500, Getafe, 28905 Madrid, Spain.
LA  - eng
PT  - Journal Article
DEP - 20211030
PL  - Switzerland
TA  - J Clin Med
JT  - Journal of clinical medicine
JID - 101606588
PMC - PMC8584886
OTO - NOTNLM
OT  - bladder neoplasia
OT  - bladder recirculation system
OT  - hyperthermic intravesical chemotherapy
OT  - mitomycin-C
COIS- The authors declare no conflict of interest. The funders had no role in the 
      design of the study; in the collection, analyses, or interpretation of data; in 
      the writing of the manuscript, or in the decision to publish the results.
EDAT- 2021/11/14 06:00
MHDA- 2021/11/14 06:01
PMCR- 2021/10/30
CRDT- 2021/11/13 01:02
PHST- 2021/10/17 00:00 [received]
PHST- 2021/10/27 00:00 [revised]
PHST- 2021/10/29 00:00 [accepted]
PHST- 2021/11/13 01:02 [entrez]
PHST- 2021/11/14 06:00 [pubmed]
PHST- 2021/11/14 06:01 [medline]
PHST- 2021/10/30 00:00 [pmc-release]
AID - jcm10215105 [pii]
AID - jcm-10-05105 [pii]
AID - 10.3390/jcm10215105 [doi]
PST - epublish
SO  - J Clin Med. 2021 Oct 30;10(21):5105. doi: 10.3390/jcm10215105.