Long-term versus short-term introvesical chemotherapy in patients with non-muscle-invasive bladder cancer: A systematic review and meta-analysis of the published results of randomized clinical trials

Abstract

In order to assess the effect of long-term versus short-term intravesical chemotherapy in preventing the recurrence of patients with non-muscle-invasive bladder cancer, we searched several databases with words as mesh terms and free text words to find all eligible randomized clinical trials (RCTs) for the comparison of the two strategies of instillation durations. “Observed-Expected events research (O-E)” and “Variance (V)” for calculating hazard ratio (HR) were used in Revman 5.2 software recommended by Cochrane Collabration for data analysis. Sensitivity and subgroup analysis were selected to minish heterogeneity. GRADEpro 3.6 profile recommended by Cochrane Collabration was employed for quality assessment of analyses. Finally, 13 eligible RCTs with 4216 patients were included in this review and 16 comparisons from 13 trials were involved for analysis. The pooled analysis revealed no significant difference between long-term and short-term duration [HR=0.99, 95% CI (0.89, 1.11), P=0.89]. Within the subgroup analysis, patients benefited from long-term instillations with a start regimen of one immediate instillation [HR=0.83, 95% CI (0.69, 1.00), P=0.05]. But patients were not suitable to receive long-term instillations with epirubicin (EPI) [HR=1.01, 95% CI (0.91, 1.13), P=0.78]. The progression rate was not reduced after long-term instillations [HR=0.96, 95% CI (0.66, 1.39), P=0.82]. From our results, patients should not receive introvesical chemotherapy more than half a year. In contrast, patients with one immediate instillation are preferred to have a long-term duration at least one year. Long-term instillations can not reduce the progression rate.

Keywords

duration / non-muscle-invasive bladder cancer / intravesical administration / adjuvant chemotherapy / meta-analysis

References

[1] MRC Working Party on Urological Cancer.. The effect of intravesical thiotepa on the recurrence rate of newly diagnosed superficial bladder cancer. An MRC study. Br J Urol, 1985, 57(6): 680-685

[2] ThrasherJB, CrawfordED. Complications of intravesical chemotherapy. Urol Clin North Am, 1992, 19(3): 529-539 PMID: 1636237

[3] Medical Research Council Working Party on Urological Cancer, Subgroup on Superficial Bladder Cancer.. The effect of intravesical thiotepa on tumour recurrence after endoscopic treatment of newly diagnosed superficial bladder cancer. A further report with long-term follow-up of a Medical Research Council randomized trial. Br J Urol, 1994, 73(6): 632-638

[4] ShelleyMD, JonesG, ClevesA, et al. . Intravesical gemcitabine therapy for non-muscle invasive bladder cancer (NMIBC): a systematic review. BJU Int, 2012, 109(4): 496-505 PMID: 22313502

[5] JonesG, ClevesA, WiltTJ, et al. . Intravesical gemcitabine for non-muscle invasive bladder cancer. Cochrane Database Syst Rev, 2012, 1: CD009294 PMID: 22259002

[6] BabjukM, BurgerM, ZigeunerR, et al. . Table 8: risk group stratification, Guidelines on Non-muscle-invasive Bladder Cancer (TaT1 and CIS). European Association of Urology Text Update March, 2013, 2013: 19

[7] SylvesterRJ, OosterlinckW, van der MeijdenAP. A single immediate postoperative instillation of chemotherapy decreases the risk of recurrence in patients with stage Ta T1 bladder cancer: a meta-analysis of published results of randomized clinical trials. J Urol, 2004, 171(6Pt1): 2186-2190 PMID: 15126782

[8] GudjonssonS, AdellL, MerdasaF, et al. . Should all patients with non-muscle-invasive bladder cancer receive early intravesical chemotherapy after transurethral resection? The results of a prospective randomised multicentre study. Eur Urol, 2009, 55(4): 773-780 PMID: 19153001

[9] American Urological Association Education and Research. In: MC Hall, Sam SC, Guido Dalbagni, et al. eds. Guideline for the Management of Nonmuscle-Invasive-Bladder Cancer: (StagesTa, T1, andTis): 2007. Update 2014.

[10] TolleyDA, ParmarMK, GrigorKM, et al. . The effect of intravesical mitomycin C on recurrence of newly diagnosed superficial bladder cancer: a further report with 7 years of follow up. J Urol, 1996, 155(4): 1233-1238 PMID: 8632538

[11] BouffiouxC, KurthKH, BonoA, et al. . Intravesical adjuvant chemotherapy for superficial transitional cell bladder carcinoma: results of 2 European Organization for Research and Treatment of Cancer randomized trials with mitomycin C and doxorubicin comparing early versus delayed instillations and short-term versus long-term treatment. J Urol, 1995, 153(3Pt2): 934-941 PMID: 7853578

[12] SylvesterRJ, OosterlinckW, WitjesJA. The schedule and duration of intravesical chemotherapy in patients with non-muscle-invasive bladder cancer: a systematic review of the published results of randomized clinical trials. Eur Urol, 2008, 53(4): 709-719 PMID: 18207317 PMCID: 2587437

[13] European Association of Urology. In: Babjuk M, Zigeuner R, Shariat S, et al. eds. Recommendations for stratification of NMIBC, Guidelines on Non-muscle-invasive Bladder Cancer (TaT1 and CIS), Chapter 6.3.1:19. Update 2013.

[14] Collaboration T.C. Table 7.3.a: Checklist of items to consider in data collection or data extraction. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0, 2011, Chapter 7:7

[15] TierneyJF, StewartLA, GhersiD, et al. . Practical methods for incorporating summary time-to-event data into meta-analysis. Trials, 2007, 8: 16 PMID: 17555582 PMCID: 1920534

[16] GuyattGH, OxmanAD, KunzR, et al. . GRADE guidelines: 7. Rating the quality of evidence—inconsistency. J Clin Epidemiol, 2011, 64(12): 1294-1302 PMID: 21803546

[17] IsbarnH, BudausL, PichlmeierU, et al. . Comparison of the effectiveness between long-term instillation of mitomycin C and short-term prophylaxis with MMC or bacille Calmette-Guerin. Study of patients with non-muscleinvasive urothelial cancer of the urinary bladder. Urologe A, 2008, 47(5): 608-615 PMID: 18317718

[18] SylvesterRJ, van der MeijdenAP, OosterlinckW, 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): 466-465 PMID: 16442208

[19] HulandH, KloppelG, OttoU, et al. . Cytostatic intravesical instillation in patients with superficial bladder carcinoma for the prevention of recurrent tumors. Eur Urol, 1988, 14(3): 202-206 PMID: 3133216

[20] HulandH, KloppelG, FeddersenI, et al. . Comparison of different schedules of cytostatic intravesical instillations in patients with superficial bladder carcinoma: final evaluation of a prospective multicenter study with 419 patients. J Urol, 1990, 144(1): 68-72 PMID: 2113590

[21] SchwaiboldH, PichlmeierU, KlingenbergerHJ, et al. . Long-term follow-up of cytostatic intravesical instillation in patients with superficial bladder carcinoma. Is short-term, intensive instillation better than maintenance therapy?. Eur Urol, 1997, 31(2): 153-159 PMID: 9076457

[22] FriedrichMG, PichlmeierU, SchwaiboldH, et al. . Long-term intravesical adjuvant chemotherapy further reduces recurrence rate compared with short-term intravesical chemotherapy and short-term therapy with Bacillus Cal mette-Guerin (BCG) in patients with non-muscle-invasive bladder carcinoma. Eur Urol, 2007, 52(4): 1123-1129 PMID: 17383080

[23] AkazaH, IsakaS, KoisoK, et al. . Comparative analysis of short-term and long-term prophylactic intravesical chemotherapy of superficial bladder cancer. Prospective, randomized, controlled studies of the Japanese Urological Cancer Research Group. Cancer Chemother Pharmacol, 1987, 20(Supp1): S91-S96 PMID: 3117403

[24] KogaH, KuroiwaK, YamaguchiA, et al. . A randomized controlled trial of short-term versus long-term prophylactic intravesical instillation chemotherapy for recurrence after transurethral resection of Ta/T1 transitional cell carcinoma of the bladder. J Urol, 2004, 171(1): 153-157 PMID: 14665865

[25] OkamuraK, KinukawaT, TsumuraY, et al. . A randomized study of short-versus long-term intravesical epirubicin instillation for superficial bladder cancer. Nagoya University Urological Oncology Group. Eur Urol, 1998, 33(3): 285-289 PMID: 9555553

[26] SerrettaV, MorgiaG, AltieriV, et al. . A 1-year maintenance after early adjuvant intravesical chemotherapy has a limited efficacy in preventing recurrence of intermediate risk non-muscle-invasive bladder cancer. BJU Int, 2010, 106(2): 212-217 PMID: 20070299

[27] MitsumoriK, TsuchiyaN, HabuchiT, et al. . Early and large-dose intravesical instillation of epirubicin to prevent superficial bladder carcinoma recurrence after transurethral resection. BJU Int, 2004, 94(3): 317-321 PMID: 15291859

[28] HendricksenK, WitjesWP, IdemaJG, et al. . Comparison of three schedules of intravesical epirubicin in patients with non-muscle-invasive bladder cancer. Eur Urol, 2008, 53(5): 984-991 PMID: 18248876

[29] KurodaM, NiijimaT, KotakeT, et al. . Effect of prophylactic treatment with intravesical epirubicin on recurrence of superficial bladder cancer—The 6th Trial of the Japanese Urological Cancer Research Group (JUCRG): a randomized trial of intravesical epirubicin at dose of 20 mg/40ml, 30 mg/40ml, 40 mg/40ml. Eur Urol, 2004, 45(5): 600-605 PMID: 15082202

[30] NomataK, NoguchiM, KanetakeH, et al. . Intravesical adjuvant chemotherapy for superficial transitional cell bladder carcinoma: results of a randomized trial with epirubicin comparing short-term versus long-term maintenance treatment. Cancer Chemother Pharmacol, 2002, 50(4): 266-270 PMID: 12357299

[31] FlammJ. Long-term versus short-term doxorubicin hydrochloride instillation after transurethral resection of superficial bladder cancer. Eur Urol, 1990, 17(2): 119-124 PMID: 2178939

[32] RubbenH, LutzeyerW, FischerN, et al. . Natural history and treatment of low and high risk superficial bladder tumors. J Urol, 1988, 139(2): 283-285 PMID: 3339726

[33] SegawaN, NishidaT, TakaharaK, et al. . Intravesical instillation with epirubicin as a prophylactic treatment for superficial bladder cancer—using two different schedules. Hinyokika Kiyo, 2008, 54(11): 711-716 PMID: 19068724

[34] KurthKH, DenisL, BouffiouxC, et al. . Factors affecting recurrence and progression in superficial bladder tumours. Eur J Cancer, 1995, 31a(11): 1840-1846 PMID: 8541110

[35] AuJL, BadalamentRA, WientjesMG, et al. . Methods to improve efficacy of intravesical mitomycin C: results of a randomized phase III trial. J Natl Cancer Inst, 2001, 93(8): 597-604 PMID: 11309436

[36] GuyattG, OxmanAD, AklEA, et al. . GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol, 2011, 64(4): 383-394 PMID: 21195583