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European Urology
Volume 58, issue 2, pages e19-e28, August 2010Bladder Cancer
Second Resection for Non-Muscle-Invasive Bladder Carcinoma: Current Role and Future Perspectives
Marko Babjuk 
.
Published online 21 April 2010, pages 191 - 192
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Refers to article:
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
Accepted 3 March 2010
August 2010 (Vol. 58, Issue 2, pages 185 - 190)
Article Outline
1. Introduction
The success of treatment in non-muscle-invasive bladder cancer (NMIBC) depends on the biologic characteristics of the tumor and on the treatment strategy, which must be appropriately selected and correctly performed.
Transurethral resection of the bladder (TURB) is the initial and critical step in the management of bladder tumors. The aim of the procedure is to establish the histologic diagnosis, to determine the tumor stage and grade, and to achieve complete removal of papillary non-muscle-invasive tumors. Although TURB is a frequently performed procedure that should be familiar to all urologists and is based on principles that have not changed for decades, its results are far from optimum, and the diagnostic and therapeutic purposes are not always achieved. Tumors are frequently overlooked and left behind during initial resection, or, more dangerously, their depth of invasion can be underestimated.
To overcome these limitations, a second transurethral resection (TUR) performed after 2–6 wk was incorporated into our treatment algorithms. The current version of the European Association of Urology (EAU) guidelines recommends considering a second TUR if there is suspicion that the initial resection was incomplete (eg, when multiple or large tumors are present, when the pathologist reported no muscle tissue in the specimen). Furthermore, second TUR should be performed when a high-grade non-muscle-invasive tumor or a T1 tumor is detected at initial TUR [1].
This relatively strict recommendation, which affects a large proportion of NMIBC patients, was a matter of sharp discussion within the guidelines group as well as with reviewers of European Urology and at many meetings afterward. To target the essence of the problem, many points should be mentioned and discussed.
2. Detection of residual tumor and correction of staging error
The rate of residual tumor detected by second TUR varies between 33% and 76% [2]. The risk is higher in multiple tumors and high-grade lesions and increases with the stage of the original tumor. In four studies that separately evaluated Ta and T1 tumors, disease persistence was detected for 27–72% of Ta tumors and for 33–78% of T1 tumors [2]. This observation was confirmed recently in a trial managed by the Urothelial Cancer Group of the Nordic Association of Urology, in which 39% of patients with T1 tumors had persistent disease after initial resection [3].
Underestimation of the depth of tumor invasion is critical, particularly when muscle-invasive disease is missed. In tumors staged as T1 by initial TURB, the rate of understaging varied between 4% and 10% in most series, but in one report, the risk was as high as 29%. The most important risk factor and source of error was the absence of muscle in the initial resection specimen [2].
These data were the basis for the EAU guidelines [1], and results in T1 tumors provided by Divrik et al. [4] in this issue of European Urology, with 33.3% persistent and 7.6% understaged tumors after initial TURB, support guidelines recommendations.
3. Can the second transurethral resection reverse the unfavorable course of disease?
Divrik et al confirmed that after second TUR, patients had a lower risk of tumor recurrence and progression compared with those for whom second TUR was not performed [4]. We should remember, however, that nearly 8% of patients who were upstaged by second TUR were excluded from the study after randomization. Patients in this arm were better selected, and it is not a great surprise that their outcomes were better. To support the role of second TUR even more impressively, future authors should provide data about disease-specific survival in both arms including those patients who were excluded after randomization.
4. Areas of future effort and interest
It must be emphasized that the second TUR is only emergency rescue of an ineffective initial procedure. It is not easy to persuade the patient that the surgery will be repeated simply because of the uncertain quality of the initial procedure. For years, the urologic community was exceedingly satisfied with the low invasiveness of transurethral procedures and the low mortality of NMIBC. Today we should change our attitude and critically challenge unsatisfactory results regarding recurrence and progression rates.
4.1. The quality and improvement of initial transurethral resection of the bladder
The analysis of seven phase 3 trials by the European Organization for Research and Treatment of Cancer showed substantial variation in early recurrence rates among different institutions. The frequency of 3-mo recurrence ranged from 0% to 46%. These differences are due to the quality of TURB performed by individual surgeons [5]. Each institution should be aware of the quality of its own TURB, and the second TUR is a good tool for evaluation. I personally believe that we can reach better results for initial resection than those seen in published series by strict application of teaching programs for our residents and by utilization of modern equipment [2], and [6]. New imaging methods like photodynamic diagnosis (PDD) are available. The systematic review of prospective studies showed only 15% risk of tumor persistence in patients for whom PDD was used during initial resection [2], and [7].
4.2. Selection of patients for second transurethral resection
Patients with T1 tumors do not represent a homogenous group, and perhaps not all of them really need a second TUR. A promising approach is the stratification of T1 tumors according to the depths of invasion into the lamina propria mucosae. Soukup et al showed that patients with only superficial T1 invasion have more favorable prognosis and lower risk of tumor understaging and progression [8]. For an individual indication of second TUR also additional parameters can be used. Data provided by Divrik et al showed that the risk of tumor persistence or understaging was dependent on the size and grade of the T1 tumor [4]. To be able to change guidelines recommendation and routinely select only a subgroup of T1 tumors for second TUR, the prognostic factors must be systematically evaluated and related with the results of second TUR.
4.3. Modifications of surgical technique
As mentioned previously, the principles of TURB have not changed for decades. The technique of piecemeal resection of the lesion ignores the parameter of negative surgical margins, which is usual in other oncologic procedures. This approach liberates tumor cells into the irrigation fluid, which facilitates their implantation and early recurrence. Some first efforts to change the technique and to provide en block resection were reported [9]. In my opinion, we should draw much more attention to this area in the future and should comprehensively consider all possible ideas and solutions.
5. Conclusions
In conclusion, second TUR is currently an unavoidable component of the treatment strategy for NMIBC. In the future, we must endeavor to replace this rescue surgery with a more effective initial procedure.
Conflicts of interest
Marko Babjuk has received honoraria from GE Healthcare for lectures at meetings on bladder cancer.
References
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- [2] M. Babjuk. Transurethral resection of non-muscle-invasive bladder cancer. Eur Urol Suppl 8 (2009) (542 - 548) Abstract, Full-text, PDF, Crossref.
- [3] M. Duchek, R. Johansson, S. Jahnson, et al.. Bacillus Calmette-Guérin is superior to a combination of epirubicin and interferon-α2b in the intravesical treatment of patients with stage T1 urinary bladder cancer. A prospective, randomized, Nordic study. Eur Urol 57 (2010) (25 - 31) Abstract, Full-text, PDF, Crossref.
- [4] R.T. Divrik, A.F. Şahin, Ü. Yildirim, M. Altok, F. Zorlu. 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 58 (2010) (185 - 190) Abstract, Full-text, PDF, Crossref.
- [5] M. Brausi, L. Collette, K. Kurth, et al.. EORTC Genito-Urinary Tract Cancer Collaborative Group. Variability in the recurrence rate at first follow-up cystoscopy after TUR in stage Ta T1 transitional cell carcinoma of the bladder: a combined analysis of seven EORTC studies. Eur Urol 41 (2002) (523 - 531) Abstract, Full-text, PDF, Crossref.
- [6] M.A. Brausi, M. Gavioli, G. Peracchia, et al.. Dedicated teaching programs can improve the quality of TUR of non-muscle-invasive bladder tumours (NMIBT): experience of a single institution. Eur Urol Suppl 7 (2008) (180) Abstract, Full-text, PDF, Crossref.
- [7] I. Kausch, M. Sommerauer, F. Montorsi, et al.. Photodynamic diagnosis in non–muscle-invasive bladder cancer: a systematic review and cumulative analysis of prospective studies. Eur Urol 57 (2010) (595 - 606) Abstract, Full-text, PDF, Crossref.
- [8] V. Soukup, M. Babjuk, J. Duskova, et al.. Does the expression of fascin-1 and tumor subclassification help to assess the risk of recurrence and progression in T1 urothelial urinary bladder carcinoma?. Urologia Internationalis 80 (2008) (413 - 418) Crossref.
- [9] K. Thomas, T. O’Brien. Improving transurethral resection of bladder tumour: the gold standard for diagnosis and treatment of bladder tumours. Eur Urol Suppl 7 (2008) (524 - 528) Abstract, Full-text, PDF, Crossref.
Footnotes
Departments of Urology, 2nd and 1st Faculty of Medicine, Charles University, Praha, Czech Republic
Department of Urology, FN Motol, V Úvalu 84, 15006 Praha 5, Czech Republic. Tel. +420224434801; Fax: +420224434821.
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