• This record comes from PubMed

Intravesical thermochemotherapy in the treatment of high-risk and very high-risk non-muscle-invasive urothelial bladder cancer: a single-arm study

. 2024 Jul ; 56 (7) : 2243-2250. [epub] 20240208

Language English Country Netherlands Media print-electronic

Document type Journal Article

Links

PubMed 38329573
PubMed Central PMC11190016
DOI 10.1007/s11255-023-03924-3
PII: 10.1007/s11255-023-03924-3
Knihovny.cz E-resources

AIM: Intravesical thermochemotherapy, also known as HIVEC (Hyperthermic Intra-VEsical Chemotherapy), represents an alternative adjuvant topical treatment for non-muscle-invasive urothelial bladder cancer (NMIBC). High-risk (HR) and very HR tumors carry a substantial risk of recurrence and progression. In this study, we present our own results using HIVEC as an alternative to unavailable Bacillus Calmette-Guérin (BCG) vaccine in the treatment of such groups of patients. METHODS: During the period of November 2014-June 2022, a total of 47 patients with HR and very HR NMIBC underwent treatment with HIVEC after transurethral resection. They were given an induction of 6 instillations with/without a maintenance. The aim was to evaluate the time to recurrence, event-free survival (recurrence or progression), as measured by Kaplan-Meier analysis, the effect of maintenance treatment and other factors on survival (log-rank test and multivariable Cox regression analysis), and complications. RESULTS: The median follow-up for patients who did not experience an event was 32 months. The median time to HR (high grade and/or T1 tumor) recurrence in those who recurred was 15 months. The survival rate without HR recurrence at 12, 24, and 48 months was 84, 70, and 59%, respectively. Progression was detected in 10.6% of patients, which translated to 89% of patients living without progression after 24 months. Maintenance treatment (defined as more than six instillations) and presence of CIS significantly correlated with risk of HR recurrence (Hazard ratio 0.34 and 3.12, respectively). One female patient underwent salvage cystectomy due to contractory bladder, and 19.1% of patients experienced transient lower urinary tract symptoms. CONCLUSION: Based on our experience, HIVEC represents an adequate and safe alternative treatment for HR and very HR NMIBC in situations where BCG is not available or radical cystectomy is not an option for the patient. However, high-quality data from prospective randomized studies are still lacking, and thus, thermochemotherapy should still be regarded as an experimental treatment modality.

See more in PubMed

Sylvester RJ, van der Meijden AP, Oosterlinck W, et al. Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials. Eur Urol. 2006;49(3):466–477. doi: 10.1016/j.eururo.2005.12.031. PubMed DOI

Sylvester RJ, Rodríguez O, Hernández V, et al. European Association of urology (EAU) prognostic factor risk groups for non-muscle-invasive bladder cancer (NMIBC) incorporating the WHO 2004/2016 and WHO 1973 classification systems for grade: an update from the EAU NMIBC guidelines panel. Eur Urol. 2021;79(4):480–488. doi: 10.1016/j.eururo.2020.12.033. PubMed DOI

EAU Guidelines (2022) Edn. presented at the EAU Annual Congress Amsterdam. ISBN 978-94-92671-16-5

Sylvester RJ, van der MEIJDEN AP, Lamm DL (2002) Intravesical bacillus Calmette-Guerin reduces the risk of progression in patients with superficial bladder cancer: a meta-analysis of the published results of randomized clinical trials. J Urol 168(5):1964–1970 PubMed

Kamat AM, Sylvester RJ, Böhle A, et al. Definitions, end points, and clinical trial designs for non-muscle-invasive bladder cancer: recommendations from the international bladder cancer group. J Clin Oncol. 2016;34(16):1935–1944. doi: 10.1200/JCO.2015.64.4070. PubMed DOI PMC

Matulay JT, Li R, Hensley PJ, et al. Contemporary outcomes of patients with nonmuscle-invasive bladder cancer treated with bacillus calmette-guérin: implications for clinical trial design. J Urol. 2021;205(6):1612–1621. doi: 10.1097/JU.0000000000001633. PubMed DOI

Issels RD. Hyperthermia adds to chemotherapy. Eur J Cancer. 2008;44(17):2546–2554. doi: 10.1016/j.ejca.2008.07.038. PubMed DOI

Alvarez-Berríos MP, Castillo A, Mendéz J, Soto O, Rinaldi C, Torres-Lugo M. Hyperthermic potentiation of cisplatin by magnetic nanoparticle heaters is correlated with an increase in cell membrane fluidity. Int J Nanomedicine. 2013;8:1003–1013. PubMed PMC

van der Heijden AG, Dewhirst MW. Effects of hyperthermia in neutralising mechanisms of drug resistance in non-muscle-invasive bladder cancer. Int J Hyperthermia. 2016;32(4):434–445. doi: 10.3109/02656736.2016.1155761. PubMed DOI

Oei AL, Vriend LE, Crezee J, Franken NA, Krawczyk PM. Effects of hyperthermia on DNA repair pathways: one treatment to inhibit them all. Radiat Oncol. 2015;7(10):165. doi: 10.1186/s13014-015-0462-0. PubMed DOI PMC

van der Heijden AG, Hulsbergen-Van de Kaa CA, Witjes JA (2007) The influence of thermo-chemotherapy on bladder tumours: an immunohistochemical analysis. World J Urol 25(3):303–308 PubMed PMC

Abern MR, Owusu RA, Anderson MR, Rampersaud EN, Inman BA. Perioperative intravesical chemotherapy in non-muscle-invasive bladder cancer: a systematic review and meta-analysis. J Natl Compr Canc Netw. 2013;11(4):477–484. doi: 10.6004/jnccn.2013.0060. PubMed DOI

Chiancone F, Carrino M, Fedelini M, Meccariello C, Fedelini P. Intravesical thermo-chemotherapy using the combined antineoplastic thermotherapy bladder recirculation system for BCG-failure patients: a single center experience. Eur Urol Supp. 2019;18:e3248. doi: 10.1016/S1569-9056(19)33634-6. DOI

van der Heijden AG, Verhaegh G, Jansen CF, Schalken JA, Witjes JA. Effect of hyperthermia on the cytotoxicity of 4 chemotherapeutic agents currently used for the treatment of transitional cell carcinoma of the bladder: an in vitro study. J Urol. 2005;173(4):1375–1380. doi: 10.1097/01.ju.0000146274.85012.e1. PubMed DOI

Chiancone F, Fabiano M, Fedelini M, Meccariello C, Carrino M, Fedelini P. Outcomes and complications of Hyperthermic IntraVesical Chemotherapy using mitomycin C or epirubicin for patients with non-muscle invasive bladder cancer after bacillus Calmette-Guérin treatment failure. Cent European J Urol. 2020;73(3):287–294. PubMed PMC

Soukup V, Babjuk M, Bellmunt J, et al. Follow-up after surgical treatment of bladder cancer: a critical analysis of the literature. Eur Urol. 2012;62(2):290–302. doi: 10.1016/j.eururo.2012.05.008. PubMed DOI

Angulo JC, Álvarez-Ossorio JL, Domínguez-Escrig JL, et al. Hyperthermic mitomycin C in intermediate-risk non-muscle-invasive bladder cancer: results of the HIVEC-1 trial. Eur Urol Oncol. 2023;6(1):58–66. doi: 10.1016/j.euo.2022.10.008. PubMed DOI

Tan WS, Prendergast A, Ackerman C, et al. Adjuvant intravesical chemohyperthermia versus passive chemotherapy in patients with intermediate-risk non-muscle-invasive bladder cancer (HIVEC-II): a phase 2, open-label. Randomised Controlled Trial Eur Urol. 2023;83(6):497–504. PubMed

Plata Bell A, et al. Chemohyperthermia with mitomycin C (MMC) and COMBAT system in high risk non muscle invasive bladder cancer (HR NMIBC): a new alternative? Presented: AUA 18–21 May 2018 San Francisco, CA, USA. J Urol. 2018;199(4):e1119.

Cambier S, Sylvester RJ, Collette L, et al. EORTC Nomograms and risk groups for predicting recurrence, progression, and disease-specific and overall survival in non-muscle-invasive stage Ta-T1 urothelial bladder cancer patients treated with 1–3 years of maintenance Bacillus Calmette-Guérin. Eur Urol. 2016;69(1):60–69. doi: 10.1016/j.eururo.2015.06.045. PubMed DOI

Guerrero-Ramos F, González-Padilla DA, González-Díaz A, et al. Recirculating hyperthermic intravesical chemotherapy with mitomycin C (HIVEC) versus BCG in high-risk non-muscle-invasive bladder cancer: results of the HIVEC-HR randomized clinical trial. World J Urol. 2022;40(4):999–1004. doi: 10.1007/s00345-022-03928-1. PubMed DOI PMC

Conroy S, Pang K, Jubber I, et al. Hyperthermic intravesical chemotherapy with mitomycin-C for the treatment of high-risk non-muscle-invasive bladder cancer patients. BJUI Compass. 2022;4(3):314–321. doi: 10.1002/bco2.203. PubMed DOI PMC

Oddens J, Brausi M, Sylvester R, et al. Final results of an EORTC-GU cancers group randomized study of maintenance bacillus Calmette-Guérin in intermediate- and high-risk Ta, T1 papillary carcinoma of the urinary bladder: one-third dose versus full dose and 1 year versus 3 years of maintenance. Eur Urol. 2013;63(3):462–472. doi: 10.1016/j.eururo.2012.10.039. PubMed DOI

Plata A, Guerrero-Ramos F, Garcia C, et al. Long-term experience with hyperthermic chemotherapy (HIVEC) using mitomycin-C in patients with non-muscle invasive bladder cancer in Spain. J Clin Med. 2021;10(21):5105. doi: 10.3390/jcm10215105. PubMed DOI PMC

Pierconti F, Straccia P, Emilio S et al (2017) Cytological and histological changes in the urothelium produced by electromotive drug administration (EMDA) and by the combination of intravesical hyperthermia and chemotherapy (thermochemotherapy) [published correction appears in Pathol Res Pract. Pathol Res Pract 213(9):1078–1081 PubMed

Find record

Citation metrics

Loading data ...

Archiving options

Loading data ...