title: Results of a Randomised Controlled Trial Comparing Intravesical Chemohyperthermia with Mitomycin C Versus Bacillus Calmette-Guérin for Adjuvant Treatment of Patients with Intermediate- and High-risk Non-Muscle-invasive Bladder Cancer.
abstract: Despite adjuvant intravesical therapy, recurrences in non-muscle-invasive bladder cancer (NMIBC) are still high; therefore, new treatment options are needed. The use of chemohyperthermia (CHT) as an alternative treatment is expanding in Europe. To date, however, there has been a lack of prospective randomised data.
  
  
  
  To compare CHT using mitomycin C (MMC) with bacillus Calmette-Guérin (BCG) as adjuvant treatment for intermediate- and high-risk NMIBC.
  
  
  
  Between 2002 and 2012, 190 NMIBC patients were randomised in this controlled, open-label, multicentre trial for 1-yr CHT (six weekly treatments and six maintenance treatments) and 1-yr BCG immunotherapy (six weekly treatments and three weekly maintenance treatments at months 3, 6, and 12). Patients and physicians giving the interventions were aware of assignment. This study is registered with ClinicalTrials.gov (NCT00384891).
  
  
  
  The primary end point was 24-mo recurrence-free survival (RFS) in the intention-to-treat (ITT) and per-protocol (PP) analyses in all papillary NMIBC patients (n=147). Analyses were done with the log-rank test and Fisher exact test. All tests were two-sided.
  
  
  
  The 24-mo ITT RFS was 78.1% in the CHT group compared with 64.8% in the BCG group (p=0.08). The 24-mo RFS in the PP analysis was 81.8% in the CHT group compared with 64.8% in the BCG group (p=0.02). Progression rates were <2% in both groups. Regarding the side-effects, no new safety concerns were identified. A concern is that this study closed prematurely and thus is underpowered. Furthermore, blinding of treatment for patients and physicians was impossible; this may have resulted in unavoidable bias.
  
  
  
  CHT is a safe and effective treatment option in patients with intermediate- and high-risk papillary NMIBC. A significantly higher 24-mo RFS in the CHT group was seen in the PP analysis. Based on the results above, CHT is an option for BCG therapy as adjuvant treatment for intermediate- and high-risk papillary NMIBC.
  
  
  
  Recurrences in non-muscle-invasive bladder cancer are common, despite adjuvant therapies. We compared 24-mo recurrence-free survival (RFS) with chemohyperthermia (CHT) versus bacillus Calmette-Guérin (BCG) therapy. According to these data, CHT therapy appears to be safe and has higher 24-mo RFS than BCG therapy.
authors.affiliation: Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Tom J H
authors.initials: TJ
authors.lastname: Arends
authors.affiliation: Bnai-Zion Hospital, Haifa, Israel.
authors.forename: Ofer
authors.initials: O
authors.lastname: Nativ
authors.affiliation: Ente Ospedaliero Ospedali Galliera, Genova, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Maffezzini
authors.affiliation: Istituto Europeo di Oncologia, Milan, Italy.
authors.forename: Ottavio
authors.initials: O
authors.lastname: de Cobelli
authors.affiliation: Ente Ospedaliero Ospedali Galliera, Genova, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Canepa
authors.affiliation: IRCCS Multimedica, Milan, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Verweij
authors.affiliation: Bnai-Zion Hospital, Haifa, Israel.
authors.forename: Boaz
authors.initials: B
authors.lastname: Moskovitz
authors.affiliation: Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Antoine G
authors.initials: AG
authors.lastname: van der Heijden
authors.affiliation: Radboud University Medical Centre, Nijmegen, The Netherlands. Electronic address: Fred.witjes@radboudumc.nl.
authors.forename: J Alfred
authors.initials: JA
authors.lastname: Witjes
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000283:Administration, Intravesical; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D001500:BCG Vaccine / Q000627:therapeutic use*; D002278:Carcinoma in Situ / Q000473:pathology / Q000628:therapy*; D002291:Carcinoma, Papillary / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D006979:Hyperthermia, Induced; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000627:therapeutic use*; D009130:Muscle, Smooth / Q000473:pathology; D009361:Neoplasm Invasiveness; D011446:Prospective Studies; D012307:Risk Factors; D001749:Urinary Bladder Neoplasms / Q000473:pathology / Q000628:therapy*
chemical_list: D000276:Adjuvants, Immunologic; D000903:Antibiotics, Antineoplastic; D001500:BCG Vaccine; D016685:Mitomycin
keywords: BCG; Device-assisted therapy; Hyperthermia; Intravesical chemotherapy; Mitomycin-C; Non–muscle-invasive bladder cancer; Radiofrequency; Randomised controlled trial; Recurrence rate; Thermochemotherapy