Radiofrequency-induced thermo-chemotherapy effect versus a second course of Bacillus Calmette-Guérin or institutional standard in patients with recurrence of non–muscle-invasive bladder cancer following induction or maintenance Bacillus Calmette-Guérin therapy (HYMN): a phase III, open-label, randomised controlled trial

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Radiofrequency-induced thermo-chemotherapy effect versus a second course of Bacillus Calmette-Guérin or institutional standard in patients with recurrence of non–muscle-invasive bladder cancer following induction or maintenance Bacillus Calmette-Guérin therapy (HYMN) : a phase III, open-label, randomised controlled trial. / Tan, Wei Shen; Panchal, Anesh; Buckley, Laura; Devall, Adam J.; Loubière, Laurence S.; Pope, Ann M.; Feneley, Mark R.; Cresswell, Jo; Issa, Rami; Mostafid, Hugh; Madaan, Sanjeev; Bhatt, Rupesh; McGrath, John; Sangar, Vijay; Griffiths, T. R.Leyshon; Page, Toby; Hodgson, Dominic; Datta, Shibendra N.; Billingham, Lucinda J.; Kelly, John D.

In: European urology, 28.09.2018.

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Tan, Wei Shen ; Panchal, Anesh ; Buckley, Laura ; Devall, Adam J. ; Loubière, Laurence S. ; Pope, Ann M. ; Feneley, Mark R. ; Cresswell, Jo ; Issa, Rami ; Mostafid, Hugh ; Madaan, Sanjeev ; Bhatt, Rupesh ; McGrath, John ; Sangar, Vijay ; Griffiths, T. R.Leyshon ; Page, Toby ; Hodgson, Dominic ; Datta, Shibendra N. ; Billingham, Lucinda J. ; Kelly, John D. / Radiofrequency-induced thermo-chemotherapy effect versus a second course of Bacillus Calmette-Guérin or institutional standard in patients with recurrence of non–muscle-invasive bladder cancer following induction or maintenance Bacillus Calmette-Guérin therapy (HYMN) : a phase III, open-label, randomised controlled trial. In: European urology. 2018.

Bibtex

@article{dec776fd08f84668a8b5c248888a0b8c,
title = "Radiofrequency-induced thermo-chemotherapy effect versus a second course of Bacillus Calmette-Gu{\'e}rin or institutional standard in patients with recurrence of non–muscle-invasive bladder cancer following induction or maintenance Bacillus Calmette-Gu{\'e}rin therapy (HYMN): a phase III, open-label, randomised controlled trial",
abstract = "Background: There is no effective intravesical second-line therapy for non–muscle-invasive bladder cancer (NMIBC) when bacillus Calmette-Gu{\'e}rin (BCG) fails. Objective: To compare disease-free survival time (DFS) between radiofrequency-induced thermo-chemotherapy effect (RITE) and institutional standard second-line therapy (control) in NMIBC patients with recurrence following induction/maintenance BCG. Design, settings, and participants: Open-label, phase III randomised controlled trial accrued across 14 centres between May 2010 and July 2013 (HYMN [ClinicalTrials.gov: NCT01094964]). Intervention: Patients were randomly assigned (1:1) to RITE (60 min, 40 mg mitomycin-C, 42 ± 2 °C) or control following stratification for carcinoma in situ (CIS) status (present/absent), therapy history (failure of previous induction/maintenance BCG), and treatment centre. Outcome measurements and statistical analysis: Primary outcome measures were DFS and complete response (CR) at 3 mo for the CIS at randomisation subgroup. Analysis was based on intention-to-treat. Results and limitations: A total of 104 patients were randomised (48 RITE: 56 control). Median follow-up for the 31 patients without a DFS event was 36 mo. There was no significant difference in DFS between treatment arms (hazard ratio [HR] 1.33, 95% confidence interval [CI] 0.84–2.10, p = 0.23) or in 3-mo CR rate in CIS patients (n = 71; RITE: 30% vs control: 47%, p = 0.15). There was no significant difference in DFS between treatment arms in non-CIS patients (n = 33; RITE: 53% vs control: 24% at 24 mo, HR 0.50, 95% CI 0.22–1.17, p = 0.11). DFS was significantly lower in RITE than in control in CIS with/without papillary patients (n = 71; HR 2.06, 95% CI 1.17–3.62, p = 0.01; treatment-subgroup interaction p = 0.007). Disease progression was observed in four patients in each treatment arm. Adverse events and health-related quality of life between treatment arms were comparable. Conclusions: DFS was similar between RITE and control. RITE may be a second-line therapy for non-CIS recurrence following BCG failure; however, confirmatory trials are needed. RITE patients with CIS with/without papillary had lower DFS than control. HYMN highlights the importance of the control arm when evaluating novel therapies. Patient summary: This study did not show a difference in bladder cancer outcomes between microwave-heated chemotherapy and standard of care treatment. Papillary bladder lesions may benefit from microwave-heated chemotherapy treatment; however, more research is needed. Both treatments are similarly well tolerated. Radiofrequency-induced thermo-chemotherapy effect (RITE) had similar oncological outcomes as control. RITE-treated noncarcinoma in situ (CIS) patients reported nonsignificant better disease-free survival (DFS). RITE-treated CIS with/without papillary patients had significantly lower DFS. Control arm is essential when evaluating novel therapies.",
keywords = "BCG failure, Bladder cancer, Chemotherapy, Device-assisted therapy, Hyperthermia, Mitomycin-C, Radiofrequency, Randomised controlled trial, Thermotherapy",
author = "Tan, {Wei Shen} and Anesh Panchal and Laura Buckley and Devall, {Adam J.} and Loubi{\`e}re, {Laurence S.} and Pope, {Ann M.} and Feneley, {Mark R.} and Jo Cresswell and Rami Issa and Hugh Mostafid and Sanjeev Madaan and Rupesh Bhatt and John McGrath and Vijay Sangar and Griffiths, {T. R.Leyshon} and Toby Page and Dominic Hodgson and Datta, {Shibendra N.} and Billingham, {Lucinda J.} and Kelly, {John D.}",
year = "2018",
month = sep,
day = "28",
doi = "10.1016/j.eururo.2018.09.005",
language = "English",
journal = "European urology",
issn = "0302-2838",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Radiofrequency-induced thermo-chemotherapy effect versus a second course of Bacillus Calmette-Guérin or institutional standard in patients with recurrence of non–muscle-invasive bladder cancer following induction or maintenance Bacillus Calmette-Guérin therapy (HYMN)

T2 - a phase III, open-label, randomised controlled trial

AU - Tan, Wei Shen

AU - Panchal, Anesh

AU - Buckley, Laura

AU - Devall, Adam J.

AU - Loubière, Laurence S.

AU - Pope, Ann M.

AU - Feneley, Mark R.

AU - Cresswell, Jo

AU - Issa, Rami

AU - Mostafid, Hugh

AU - Madaan, Sanjeev

AU - Bhatt, Rupesh

AU - McGrath, John

AU - Sangar, Vijay

AU - Griffiths, T. R.Leyshon

AU - Page, Toby

AU - Hodgson, Dominic

AU - Datta, Shibendra N.

AU - Billingham, Lucinda J.

AU - Kelly, John D.

PY - 2018/9/28

Y1 - 2018/9/28

N2 - Background: There is no effective intravesical second-line therapy for non–muscle-invasive bladder cancer (NMIBC) when bacillus Calmette-Guérin (BCG) fails. Objective: To compare disease-free survival time (DFS) between radiofrequency-induced thermo-chemotherapy effect (RITE) and institutional standard second-line therapy (control) in NMIBC patients with recurrence following induction/maintenance BCG. Design, settings, and participants: Open-label, phase III randomised controlled trial accrued across 14 centres between May 2010 and July 2013 (HYMN [ClinicalTrials.gov: NCT01094964]). Intervention: Patients were randomly assigned (1:1) to RITE (60 min, 40 mg mitomycin-C, 42 ± 2 °C) or control following stratification for carcinoma in situ (CIS) status (present/absent), therapy history (failure of previous induction/maintenance BCG), and treatment centre. Outcome measurements and statistical analysis: Primary outcome measures were DFS and complete response (CR) at 3 mo for the CIS at randomisation subgroup. Analysis was based on intention-to-treat. Results and limitations: A total of 104 patients were randomised (48 RITE: 56 control). Median follow-up for the 31 patients without a DFS event was 36 mo. There was no significant difference in DFS between treatment arms (hazard ratio [HR] 1.33, 95% confidence interval [CI] 0.84–2.10, p = 0.23) or in 3-mo CR rate in CIS patients (n = 71; RITE: 30% vs control: 47%, p = 0.15). There was no significant difference in DFS between treatment arms in non-CIS patients (n = 33; RITE: 53% vs control: 24% at 24 mo, HR 0.50, 95% CI 0.22–1.17, p = 0.11). DFS was significantly lower in RITE than in control in CIS with/without papillary patients (n = 71; HR 2.06, 95% CI 1.17–3.62, p = 0.01; treatment-subgroup interaction p = 0.007). Disease progression was observed in four patients in each treatment arm. Adverse events and health-related quality of life between treatment arms were comparable. Conclusions: DFS was similar between RITE and control. RITE may be a second-line therapy for non-CIS recurrence following BCG failure; however, confirmatory trials are needed. RITE patients with CIS with/without papillary had lower DFS than control. HYMN highlights the importance of the control arm when evaluating novel therapies. Patient summary: This study did not show a difference in bladder cancer outcomes between microwave-heated chemotherapy and standard of care treatment. Papillary bladder lesions may benefit from microwave-heated chemotherapy treatment; however, more research is needed. Both treatments are similarly well tolerated. Radiofrequency-induced thermo-chemotherapy effect (RITE) had similar oncological outcomes as control. RITE-treated noncarcinoma in situ (CIS) patients reported nonsignificant better disease-free survival (DFS). RITE-treated CIS with/without papillary patients had significantly lower DFS. Control arm is essential when evaluating novel therapies.

AB - Background: There is no effective intravesical second-line therapy for non–muscle-invasive bladder cancer (NMIBC) when bacillus Calmette-Guérin (BCG) fails. Objective: To compare disease-free survival time (DFS) between radiofrequency-induced thermo-chemotherapy effect (RITE) and institutional standard second-line therapy (control) in NMIBC patients with recurrence following induction/maintenance BCG. Design, settings, and participants: Open-label, phase III randomised controlled trial accrued across 14 centres between May 2010 and July 2013 (HYMN [ClinicalTrials.gov: NCT01094964]). Intervention: Patients were randomly assigned (1:1) to RITE (60 min, 40 mg mitomycin-C, 42 ± 2 °C) or control following stratification for carcinoma in situ (CIS) status (present/absent), therapy history (failure of previous induction/maintenance BCG), and treatment centre. Outcome measurements and statistical analysis: Primary outcome measures were DFS and complete response (CR) at 3 mo for the CIS at randomisation subgroup. Analysis was based on intention-to-treat. Results and limitations: A total of 104 patients were randomised (48 RITE: 56 control). Median follow-up for the 31 patients without a DFS event was 36 mo. There was no significant difference in DFS between treatment arms (hazard ratio [HR] 1.33, 95% confidence interval [CI] 0.84–2.10, p = 0.23) or in 3-mo CR rate in CIS patients (n = 71; RITE: 30% vs control: 47%, p = 0.15). There was no significant difference in DFS between treatment arms in non-CIS patients (n = 33; RITE: 53% vs control: 24% at 24 mo, HR 0.50, 95% CI 0.22–1.17, p = 0.11). DFS was significantly lower in RITE than in control in CIS with/without papillary patients (n = 71; HR 2.06, 95% CI 1.17–3.62, p = 0.01; treatment-subgroup interaction p = 0.007). Disease progression was observed in four patients in each treatment arm. Adverse events and health-related quality of life between treatment arms were comparable. Conclusions: DFS was similar between RITE and control. RITE may be a second-line therapy for non-CIS recurrence following BCG failure; however, confirmatory trials are needed. RITE patients with CIS with/without papillary had lower DFS than control. HYMN highlights the importance of the control arm when evaluating novel therapies. Patient summary: This study did not show a difference in bladder cancer outcomes between microwave-heated chemotherapy and standard of care treatment. Papillary bladder lesions may benefit from microwave-heated chemotherapy treatment; however, more research is needed. Both treatments are similarly well tolerated. Radiofrequency-induced thermo-chemotherapy effect (RITE) had similar oncological outcomes as control. RITE-treated noncarcinoma in situ (CIS) patients reported nonsignificant better disease-free survival (DFS). RITE-treated CIS with/without papillary patients had significantly lower DFS. Control arm is essential when evaluating novel therapies.

KW - BCG failure

KW - Bladder cancer

KW - Chemotherapy

KW - Device-assisted therapy

KW - Hyperthermia

KW - Mitomycin-C

KW - Radiofrequency

KW - Randomised controlled trial

KW - Thermotherapy

UR - http://www.scopus.com/inward/record.url?scp=85054013219&partnerID=8YFLogxK

U2 - 10.1016/j.eururo.2018.09.005

DO - 10.1016/j.eururo.2018.09.005

M3 - Article

AN - SCOPUS:85054013219

JO - European urology

JF - European urology

SN - 0302-2838

ER -