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)

Objective

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.

Results

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.

Discussions

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].

Conclusion

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

Reference

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