Role of re-staging transurethral resection for T1 non-muscle invasive bladder cancer: a systematic review and meta-analysis

Angelo Naselli1, Rodolfo Hurle2, Stefano Paparella1, Nicolò Maria Buffi2, Giovanni Lughezzani2, Giuliana Lista2, Paolo Casale2, Alberto Saita2, Massimo Lazzeri2, Giorgio Guazzoni3
  • 1 Ospedale San Giuseppe, Gruppo Multimedica (Milano)
  • 2 Istituto Clinico Humanitas IRCCS (Rozzano)
  • 3 Istituto Clinico Humanitas IRCCS, Humanitas University (Rozzano)


Repeated transurethral resection of bladder tumor (reTUR), the fourth most common cancer [1], has been advocated as an essential step to obtain a complete tumor clearance in T1 stage and an appropriate staging. Several standardized national and international guidelines recommend the procedure, especially in patients with high grade and/or T1 bladder cancer [2]. The main reason is the high prevalence of residual tumor found after reTUR and its clinical implications [2]. However, experts’ opinion on the topic is not concordant. Some suggest that reTUR may be not useful when an adequate first TUR has been performed [3]. Moreover, to our knowledge, the last meta-analysis were published respectively in 2011 and 2014 [4,5]. Since then many series, including a great number of cases, properly stratified upon the status of detrusor muscle of the first TUR, have been reported. Therefore, we believe it is necessary to re assess the impact of the procedure by means of a systematic review of literature and meta-analysis of available datasets, distributed in a period of 30 years, to find out potential discrepancies and support guidelines commitment.

Materials and Methods

The whole process of evidence acquisition and synthesis has been carried in order to accomplish to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Checklist [6]. After definition of the population and of the outcome a systematic search of available literature in English from 1980 to 2016 was performed. Articles included in the study [7-35] were assessed for risk of bias using two domains of the Quality in Prognosis Studies tool (QUIPS) relevant to observational studies (study participation and outcome measurement). Pooled prevalence of residual tumor and of upstage at reTUR was assessed and computed by means of random effects model to take into account heterogeneity showed by I squared and Cochran’s Q values. A sensitivity analysis was conducted to exclude excessive influence by a single study.


Among papers identified, 29 items were selected. A total of 3566 and 2556 cases formed the study population to assess the prevalence of residual tumor and upstaging respectively. The respective figures for the subgroup with detrusor muscle in the specimen of TUR were respectively 1565 and 1187. Pooled residual tumor prevalence at reTUR and upstaging to T2 were 0.56 (95% CI 0.48 – 0.63) and 0.1 (95% CI 0.06 – 0.14). Respective figures for the subgroup were 0.47 (95% CI 0.33 – 0.62) and 0.1 (95% CI 0.06 – 0.14). Analysis of series at low risk of bias disclosed a limited impact of heterogeneity, especially in regards to up staging. Pooled prevalence of residual disease was 0.42 (95% CI 0.27 – 0.58) and of upstaging to invasive disease 0.11 (95% CI 0.06 – 0.18). Sensitivity analysis excluded excessive influence from each of the study examined.


Findings from our systematic review and meta-analysis showed that the rate of persistence of disease in T1 cases is really high and stable among studies belonging to different decades. Pooled prevalence of persistent disease is about 50% whereas pooled prevalence of upstaging to invasive disease is about 10% overall or about one third of the cases with residual cancer. Intriguingly, results are similar including only cases with a sample of muscle in the specimen of the initial TUR or including only series at low risk of bias. A meta-analysis, published in 2011, came to similar findings analyzing a group of 2248 patients, including 1432 T1 cases [4]. Interestingly, Authors observed similar pooled prevalence rate among cases with single and multiple primary lesion [4]. Another meta-analysis, including 3 randomized trials and 4 prospective clinical studies on reTUR for Ta and T1 tumors, showed a rate of residual disease of about one third, raging from 3.7 to 17.6% for cases with a complete first TUR [6].


The rate of residual disease and of upstaging also in prospective nowadays series including cases with a “clinically and pathologically” complete previous TUR suggest that reTUR should remain a cornerstone in the treatment of non muscle invasive bladder cancer as recommended in guidelines


[1] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016; 66:7-30
[2] Burger M, Oosterlinck W, Konety B, et al. ICUD-EAU International Consultation on Bladder Cancer 2012: Non-muscle-invasive urothelial carcinoma of the bladder. Eur Urol 2013; 63:36-44
[3] Brausi MA. Challenging the EAU Guidelines Regarding Early Repeat Transurethral Resection. Eur Urol Suppl 2011;3:e5 – e7
[4] Vianello A, Costantini E, Del Zingaro M, et al. Repeated white light transurethral resection of the bladder in nonmuscle-invasive urothelial bladder cancers: systematic review and meta-analysis. J Endourol 2011; 25:1703-12
[5] Dobruch J, Borówka A, Herr HW. Clinical value of transurethral second resection of bladder tumor: systematic review. Urology 2014; 84:881-5
[6] Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009; 21:339:b2535
[7] Klan R, Loy V, Huland H. Residual tumor discovered in routine second transurethral resection in patients with stage T1 transitional cell carcinoma of the bladder. J Urol 1991;146:316–18
[8] Herr HW. The value of a second transurethral resection in evaluating patients with bladder tumors. J Urol 1999; 162:74–76
[9] Brauers A, Buttner R, Jakse G. 2nd Resection and prognosis in primary high risk superficial bladder cancer. J Urol 2001; 165:808–10
[10] Ozen H, Ekici S, Uygur MC, Akbal C, Sahin A. Repeated transurethral resection and intravesical BCG for extensive superficial bladder tumors. J Endourol 2001; 15:863-7
[11] Schips L, Augustin H, Zigeuner RE, et al. Is repeated transurethral resection justified in patients with newly diagnosed superficial bladder cancer? Urology 2002; 59:220–23
[12] Dalbagni G, Herr HW, Reuter VE. Impact of a second transurethral resection on the staging of T1 bladder cancer. Urology 2002; 60:822-824
[13] Grimm M, Steinhoff C, Simon X, Spiegelhalder P, Ackermann R, Vogeli TA. Effect of routine repeat transurethral resection for superficial bladder cancer: a long-term observational study. J Urol 2003; 170:433-37
[14] Zurkirchen MA, Sulser T, Gaspert A, Hauri D. Second transurethral resection of superficial transitional cell carcinoma of the bladder: a must even for experienced urologists. Urol Int 2004; 72:99–102
[15] Schwaibold HE, Sivalingam S, May F, Hartung R. The value of a second transurethral resection for T1 bladder cancer. BJU Int 2006; 97:1199-1201
[16] Divrik T, Yildirim U, Ero─člu AS, Zorlu F, Ozen H. Is a second transurethral resection necessary for newly diagnosed pT1 bladder cancer? J Urol 2006; 175:1258–61
[17] Han KS, Joung JY, Cho KS, et al. Results of repeated transurethral resection for a second opinion in patients referred for non muscle invasive bladder cancer: the referral cancer center experience and review of the literature. J Endourol 2008; 22:2699-2704
[18] Herr HW, Donat MS. Quality control in transurethral resection of bladder tumors. BJU Int 2008; 102:1242–46
[19] Divrik RT, Sahin AF, Yildirim U, Altok M, Zorlu F. Impact of routine second transurethral resection on the long-term outcome of patients with newly diagnosed pT1 urothelial carcinoma with respect to recurrence, progression rate and disease-specific survival: a prospective randomised clinical trial. Eur Urol 2010; 58:185–90
[20] Parkin J, O’Keefe K, Bhatt RI, et al. G3T1 bladder cancer: Is early re-resection necessary? Br J Med Surg Urol 2011; 4:13–17
[21] Ali MH, Ismail IY, Eltobgy A, Gobeish A. Evaluation of second-look transurethral resection in restaging of patients with non-muscle- invasive bladder cancer. J Endourol 2010; 24:2047-2050
[22] Yucel M, Hatipoglu NK, Atakanli C, et al. Is repeat transurethral resection effective and necessary in patients with T1 bladder carcinoma? Urol Int 2010; 85:276-80
[23] Katumalla FS, Devasia A, Kumar R, Kumar S, Chacko N, Kekre N. Second transurethral resection in T1G3 bladder tumors – Selective avoidable? Indian J Urol 2011; 27:176-79
[24] Aning JJ, Hotston M, Pisipatti S, et al. Early re-resction for T1 transitioanl cell carcinoma of the bladder-A study of current practice in the South West of England. Br J Med Surg Urol 2011; 4:18-23
[25] Fujikawa A, Yumura Y, Yao M, Tsuchiya F, Iwasaki A, Moriyama M. An evaluation to define the role of repeat transurethral resection in a treatment algorithm for non-muscle-invasive bladder cancer. Indian J Urol. 2012 Jul; 28:267-70
[26] Vasdev N, Dominguez-Escrig J, Paez E, Johnson MI, Durkan GC, Thorpe AC. The impact of early re-resection in patients with pT1 high-grade non-muscle invasive bladder cancer. Ecancermedicalscience 2012; 6:269
[27] Takaoka E, Matsui Y, Inoue T, et al. Risk factors for intravesical recurrence in patients with high-grade T1 bladder cancer in the second TUR era. Jpn J Clin Oncol 2013; 43:404-9
[28] Gontero P, Sylvester R, Pisano F, et al. The impact of re-transurethral resection on clinical outcomes in a large multicentre cohort of patients with T1 high-grade/Grade 3 bladder cancer treated with bacille Calmette-Guérin. BJU Int 2016; 118:44-52
[29] Shim JS, Choi H, Noh TI, et al. The clinical significance of a second transurethral resection for T1 high-grade bladder cancer: Results of a prospective study. Korean J Urol 2015; 56:429-34
[30] Cao M, Yang G, Pan J, et al. Repeated transurethral resection for non-muscle invasive bladder cancer. Int J Clin Exp Med 2015; 8:1416-9
[31] Angulo JC, Palou J, García-Tello A, de Fata FR, Rodríguez O, Villavicencio H. Second transurethral resection and prognosis of high-grade non-muscle invasive bladder cancer in patients not receiving bacillus Calmette-Guérin. Actas Urol Esp 2014; 38:164-71
[32] Do─čantekin E, Girgin C, Görgel SN, Soylemez H, Dinçel Ç. Can immediate second resection be an alternative to standardized second transurethral resection of bladder tumors? Kaohsiung J Med Sci 2016; 32:147-5
[33] Sanseverino R, Napodano G, Campitelli A, Addesso M. Prognostic impact of ReTURB in high grade T1 primary bladder cancer. Arch Ital Urol Androl 2016; 88:81-5
[34] Hashine K, Ide T, Nakashima T, Hosokawa T, Ninomiya I, Teramoto N. Results of second transurethral resection for high-grade T1 bladder cancer. Urol Ann; 8:10-5
[35] Gendy R, Delprado W, Brenner P, et al. Repeat transurethral resection for non-muscle-invasive bladder cancer: a contemporary series. BJU Int 2016; 117 Suppl 4:54-9