Intravesical Therapy in Patients with Intermediate-risk Non-muscle-invasive Bladder Cancer: A Systematic Review and Network Meta-analysis of Disease Recurrence

TY - JOUR

T1 - Intravesical Therapy in Patients with Intermediate-risk Non-muscle-invasive Bladder Cancer: A Systematic Review and Network Meta-analysis of Disease Recurrence

AU - Laukhtina, Ekaterina

AU - Abufaraj, Mohammad

AU - Al-Ani, Abdallah

AU - Ali, Mustafa Rami

AU - Mori, Keiichiro

AU - Moschini, Marco

AU - Quhal, Fahad

AU - Sari Motlagh, Reza

AU - Pradere, Benjamin

AU - Schuettfort, Victor M

AU - Mostafaei, Hadi

AU - Katayama, Satoshi

AU - Grossmann, Nico C

AU - Fajkovic, Harun

AU - Soria, Francesco

AU - Enikeev, Dmitry

AU - Shariat, Shahrokh F

AU - European Association of Urology – Young Academic Urologists (EAU-YAU), Urothelial Carcinoma Working Group

N1 - Copyright © 2021. Published by Elsevier B.V.

PY - 2022/3

Y1 - 2022/3

N2 - CONTEXT: Patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC) may pose a clinical dilemma without an agreed evidence-based decision tree for personalized treatment.OBJECTIVE: To perform a systematic review and network meta-analysis (NMA) to summarize available evidence on the oncologic outcomes of intravesical therapy in patients with intermediate-risk NMIBC.EVIDENCE ACQUISITION: The MEDLINE, EMBASE, and ClinicalTrials.gov databases were searched in October 2020 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Studies were deemed eligible if they reported on oncologic outcomes in patients with intermediate-risk NMIBC treated with transurethral resection of bladder tumor with and without intravesical chemotherapy or bacillus Calmette-Guérin (BCG) immunotherapy.EVIDENCE SYNTHESIS: Twelve studies were included in a qualitative synthesis (systematic review); three were deemed eligible for a quantitative synthesis (NMA). An NMA of five different regimens was conducted for the association of treatment with the 5-yr recurrence risk. Chemotherapy with maintenance was associated with a lower likelihood of 5-yr recurrence than chemotherapy without maintenance (odds ratio [OR] 0.51, 95% credible interval [CI] 0.26-1.03). Immunotherapy, regardless of whether a full- or reduced-dose regimen, was not associated with a significantly lower likelihood of 5-yr recurrence when compared with chemotherapy without maintenance (OR 0.90, 95% CI 0.39-2.11 vs OR 0.93, 95% CI 0.40-2.19). Analysis of the treatment ranking revealed that chemotherapy with maintenance had the lowest 5-yr recurrence risk (P score 0.9666).CONCLUSIONS: Our analysis indicates that chemotherapy with a maintenance regimen confers a superior oncologic benefit in terms of 5-yr recurrence risk compared to chemotherapy without maintenance in patients with intermediate-risk NMIBC. Regardless of the dose regimen, immunotherapy with BCG does not appear to be superior to chemotherapy in patients with intermediate-risk NMIBC in term of disease recurrence. However, owing to the lack of comparative studies, there is an unmet need for well-designed, large-scale trials to validate our findings and generate robust evidence on disease recurrence and progression.PATIENT SUMMARY: A maintenance schedule of chemotherapy reduces the rate of long-term recurrence of bladder cancer that has not invaded the bladder muscle. Chemotherapy inserted directly into the bladder and immunotherapy without maintenance schedules seem to have limited benefit in preventing cancer recurrence.

AB - CONTEXT: Patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC) may pose a clinical dilemma without an agreed evidence-based decision tree for personalized treatment.OBJECTIVE: To perform a systematic review and network meta-analysis (NMA) to summarize available evidence on the oncologic outcomes of intravesical therapy in patients with intermediate-risk NMIBC.EVIDENCE ACQUISITION: The MEDLINE, EMBASE, and ClinicalTrials.gov databases were searched in October 2020 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Studies were deemed eligible if they reported on oncologic outcomes in patients with intermediate-risk NMIBC treated with transurethral resection of bladder tumor with and without intravesical chemotherapy or bacillus Calmette-Guérin (BCG) immunotherapy.EVIDENCE SYNTHESIS: Twelve studies were included in a qualitative synthesis (systematic review); three were deemed eligible for a quantitative synthesis (NMA). An NMA of five different regimens was conducted for the association of treatment with the 5-yr recurrence risk. Chemotherapy with maintenance was associated with a lower likelihood of 5-yr recurrence than chemotherapy without maintenance (odds ratio [OR] 0.51, 95% credible interval [CI] 0.26-1.03). Immunotherapy, regardless of whether a full- or reduced-dose regimen, was not associated with a significantly lower likelihood of 5-yr recurrence when compared with chemotherapy without maintenance (OR 0.90, 95% CI 0.39-2.11 vs OR 0.93, 95% CI 0.40-2.19). Analysis of the treatment ranking revealed that chemotherapy with maintenance had the lowest 5-yr recurrence risk (P score 0.9666).CONCLUSIONS: Our analysis indicates that chemotherapy with a maintenance regimen confers a superior oncologic benefit in terms of 5-yr recurrence risk compared to chemotherapy without maintenance in patients with intermediate-risk NMIBC. Regardless of the dose regimen, immunotherapy with BCG does not appear to be superior to chemotherapy in patients with intermediate-risk NMIBC in term of disease recurrence. However, owing to the lack of comparative studies, there is an unmet need for well-designed, large-scale trials to validate our findings and generate robust evidence on disease recurrence and progression.PATIENT SUMMARY: A maintenance schedule of chemotherapy reduces the rate of long-term recurrence of bladder cancer that has not invaded the bladder muscle. Chemotherapy inserted directly into the bladder and immunotherapy without maintenance schedules seem to have limited benefit in preventing cancer recurrence.

U2 - 10.1016/j.euf.2021.03.016

DO - 10.1016/j.euf.2021.03.016

M3 - SCORING: Review article

C2 - 33762203

VL - 8

SP - 447

EP - 456

JO - EUR UROL FOCUS

JF - EUR UROL FOCUS

SN - 2405-4569

IS - 2

ER -