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Should a Second Transurethral Resection Be Performed in All Patients with T1 or High-Grade Non–Muscle-Invasive Bladder Cancer?
EUROPEAN UROLOGY SUPPLEMENTS 10 (2011) e8–e11
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Should a Second Transurethral Resection Be Performed in All Patients with T1 or High-Grade Non–Muscle-Invasive Bladder Cancer? Marko Babjuk * Department of Urology, 2nd Faculty of Medicine, Charles University in Praha, Hospital Motol, Czech Republic
Article info
Abstract
Keywords: Bladder cancer TURB Second resection Understaging Tumour persistence
Context: Transurethral resection (TUR) is a critical step in the management of non– muscle-invasive bladder cancer (NMIBC). Because of the high risk of tumour persistence and understaging, the routine second TUR performed after 2–6 wk is recommended by European Association of Urology guidelines in all patients with T1 or high-grade NMIBC. Objective: To summarise arguments that support the recommendation of routine second TUR in all patients with T1 or high-grade NMIBC. Evidence acquisition: Data and arguments were retrieved from a critically selected list of articles and abstracts dealing with the surgical treatment of NMIBC. Evidence synthesis: In patients with T1 tumours, the risk of tumour persistence and tumour understaging detected by the second TUR was 33–78% and 2–28%, respectively. The pathologic finding achieved by second TUR can modify the treatment strategy in a significant number of patients. Correct staging in NMIBC enables the selection of the optimal treatment modality and improves results. Conclusions: The second TUR confirmed the presence of residual cancer and tumour understaging in a significant number of T1 and high-grade tumours. This is a strong argument that supports the recommendation of second TUR in patients with T1 or high-grade NMIBC. # 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved. ´ valu 84, 15006 Praha 5, Czech Republic. Tel. +420224434801; * Department of Urology, FN Motol, V U Fax: +420224434821. E-mail address: [email protected].
1.
Introduction
Worldwide, bladder cancer (BCa) is the seventh most common malignancy in men and the 17th in women. It is estimated that, in 2002, about 357 000 new cases of BCa were diagnosed [1]. Approximately 75–85% of all patients with BCa have disease confined to the mucosa (stage Ta or carcinoma in situ [CIS]) or submucosa (stage T1). This group of tumours is referred to as non–muscle-invasive bladder cancer (NMIBC) as opposed to muscle-invasive disease staged as T2–T4.
Theoretically, NMIBC can be cured using a conservative approach without the need for radical surgery. The treatment strategy is based on complete transurethral resection of the bladder (TURB), individually tailored intravesical chemotherapy, or immunotherapy instillations and careful follow-up. Unfortunately, the expectations are not always fulfilled. We are facing an enormously high recurrence rate and a not-negligible risk of tumour progression [2]. The critical step in the management of NMIBC is TURB. The aim of the procedure is to establish a histologic
1569-9056/$ – see front matter # 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.
doi:10.1016/j.eursup.2011.03.005
e9
EUROPEAN UROLOGY SUPPLEMENTS 10 (2011) e8–e11
diagnosis, determine the tumour stage and grade, and achieve complete removal of papillary non–muscle-invasive tumours. Unfortunately, although TURB is a frequently performed procedure that should be familiar to all urologists, its results are far from optimum, and both the diagnostic and therapeutic purposes are not always completed. Indeed, tumours are frequently overlooked and left behind during initial resection or, more importantly and dangerously, their depth of invasion can be underestimated [3,4]. To overcome these limitations, the second transurethral resection (TUR) performed after 2–6 wk was incorporated into our treatment algorithms. The current version of the European Association of Urology guidelines recommends considering a second TUR if there is a suspicion that the initial resection was incomplete (eg, when multiple or large tumours are present or when the pathologist reported no muscle tissue in the specimen). Furthermore, it should be performed when a high-grade non–muscle-invasive tumour or a T1 tumour was detected at the initial TURB [5]. 2.
Evidence acquisition
This paper is based on the presentation given at the European Section of Oncologic Urology meeting held in London on 21–23 January 2011. The goal was to summarise arguments that supported the recommendation of routine second TUR in all patients with T1 and high-grade NMIBC. Data were retrieved from a critically selected list of articles and abstracts dealing with the surgical treatment of NMIBC. 3.
Evidence synthesis
3.1.
Number of persistent tumours detected by second
[8,11,13] and high-grade lesions [6,8,13] and increases with the size [13] and stage of the original tumour [7,9,11,14,15]. More than 80% of residual tumours were found in the location of the original lesion [7,12]. In patients with T1 tumours, the risk of tumour persistence detected by the second TUR ranged between 33% and 78% [6–15]. Noteworthy is that the high risk can also be observed in patients treated in this decade with modern equipment. Recently, data were published from a Nordic study that enrolled 250 patients with T1 grade 2–3 tumours, and the second resection was a routine part of the protocol. It was demonstrated that using second TUR, residual tumour was detected in 39% of cases [16]. 3.2.
The risk of understaging detected by second transurethral
resection
Underestimation of the depth of tumour invasion is dangerous, especially in cases where the muscle-invasive disease is missed. In tumours staged as T1 by initial TURB, the rate of understaging detected by second TUR varied between 2% and 10% in most series [7–15], except in that of Han et al [15] and Herr [9], who reported a risk of 23% and 28%, respectively (Table 1). Herr [9] recently updated the results with second TUR in 1312 patients with papillary tumours. The risk of tumour upstaging in muscle-invasive disease by second TUR was 0% in Ta low-grade tumours, 5% in Ta high-grade tumours, and 30% in T1 tumours [6]. The most important risk factor and source of error between T1 tumours was the absence of muscle in the initial resection specimen. The risk of tumour understaging increased from 15% to 45% if the muscle was not present in the resected tissue from initial TURB [6].
transurethral resection 3.3.
Many analyses confirmed that the second resection can detect persistent tumours in a significant percentage of patients. The rate of residual tumour detected by second TUR in patients with NMIBC varies between 27% and 78% (Table 1) [6–15]. The risk is higher in multiple tumours
Clinical consequences and prognostic role of second
transurethral resection
The pathologic finding achieved by second TUR can modify the treatment strategy in a significant number of patients. The change in treatment approach is crucial, particularly in
Table 1 – Results of second transurethral resection in patients with Ta and T1 tumours Author
Grimm et al [7] Kla¨n et al [8] Brauers et al [10] Schips et al [11] Herr and Donat [6] Schweibold et al [12] Divrik et al [13] Zurkirchen et al [14] Han et al [15]
Initial stage
Ta (n = 61) T1 (n = 17) T1 (n = 46) T1 (n = 42) Ta (n = 31) T1 (n = 76) Ta high-grade (n = 396) T1 (n = 701) T1 (n = 136) T1 (n = 105) Ta (n = 99) T1 (n = 115) Ta (n = 25) T1 (n = 30)
TUR = transurethral resection; CIS = carcinoma in situ.
Stage in persistent tumours on second TUR CIS, %
Ta, %
T1, %
– – – 19 – – 50 23 11 4 – – – –
– – 15 17 32 11
– – 26 24 6 14 10 25 24 9 – – 4 43
8 13 – – 56 –
T2, % 4 2 5 – 8 5 30 10 8 – – 4 23
Total, % 27 53 44 64 39 33 65 78 53 34 27 37 64 67
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EUROPEAN UROLOGY SUPPLEMENTS 10 (2011) e8–e11
cases where the muscle-invasive tumour was missed by initial resection. There is no doubt that clinical T1 bladder tumours represent a therapeutic challenge. The risk is hidden in their biologic potential, which is difficult to predict in individual cases. The major drawback, however, is inaccuracy in clinical staging. Cystectomy series demonstrated that understaging can be observed in 50% of patients with clinical T1G3 tumours [17]. Indeed, correct staging in T1 tumours is critical, because it enables the selection of appropriate patients for a conservative approach with intravesical bacillus Calmette-Gue´rin (BCG) immunotherapy instillations. Dalbagni et al, in their retrospective analysis of 523 patients, could not detect a difference in survival among patients who underwent immediate cystectomy versus those who were placed on surveillance with or without deferred cystectomy if T1 disease or lower was confirmed on second TUR [18]. The result of second TUR—particularly the persistence of T1 disease—can also provide important prognostic information. Herr presented the outcome of 352 T1 tumours treated with second TUR. Of the 92 patients with residual T1 cancer detected by second TUR, 82% progressed to muscle invasion within 5 yr compared to 19% of 260 without tumour or with Ta disease only [19]. Moreover, in another study, the tumour-free status at the time of second TUR significantly improved the response rate to BCG intravesical immunotherapy and delayed tumour recurrence [20].
resection and depends on surgeon experience [22]. Experienced surgeons were more likely to resect detrusor muscle with a lower risk of early recurrence, and the absence of muscle independently predicted a higher risk of early recurrence. It is of interest, however, that even if the TURB was performed by an experienced surgeon and muscle were present in the specimen, the risk of residual disease in T1 and grade 3 tumours reached 30% and 19%, respectively. Another study confirmed that even experienced urologists had a high percentage of persistent carcinomas after an initial TURB [14]. Brausi et al recently introduced a dedicated teaching programme on the surgical treatment of TURB and evaluated its impact on patient outcomes [23]. The programme included the routine use of video-TUR and bipolar resection, the presence of a senior urologist in theatre during the procedure, and regular teaching session meetings on bladder tumours. The programme’s application reduced the 3-mo recurrence rate in patients operated on by resident urologists from 28% to 16%, increased the presence of muscle from 50% to 88%, and decreased the complication rate. These reports clearly demonstrate that even optimally performed TURB using modern equipment is burdened by a high risk of tumour persistence. The frequent failure and absence of clear quality criteria of initial resection strongly underline the role of second TUR in T1 and high-grade NMIBC. 3.5.
3.4.
Can the quality of initial resection be improved?
The recommendation to repeat surgery in a significant number of patients with NMIBC must be focused and critically discussed. We should remember that the indication for repeat resection is just a rescue from an unsuccessful initial procedure, and our effort should be concentrated on improvement of the quality of the first TURB. The essential question is whether the quality of TURB performed with modern equipment by well-trained surgeons justifies withdrawal of the recommendation for a second TUR. The criteria of quality of TURB have never been clearly defined [21]. It is generally accepted, however, that the procedure is successful if the resection is complete and there are no missed lesions. The rate of recurrence at the first follow-up cystoscopy has been attributed to incomplete resection of the tumour. The analysis of 2410 patients from seven phase 3 trials by the European Organisation for Research and Treatment of Cancer showed substantial variations in early recurrence rates among different institutions. The frequency of 3-mo recurrence ranged from 0% to 46%. These differences are not the result of the clinical features of the tumour but probably of the quality of TURB performed by individual surgeons [3]. Mariappan et al assessed patients who were judged to have had a complete first TURB to determine whether the presence or absence of detrusor muscle in the first resection specimen is a suitable surrogate marker of the quality of
Can the selection of patients for second transurethral
resection be improved?
Patients with T1 tumours can be substaged into the T1a and T1b categories according to the depth of invasion into the lamina propria. The prognostic value of substaging has been demonstrated by some retrospective cohort studies [24–26]. In patients with T1a tumours, a lower risk of understaging was confirmed [26]. Results showed that only a limited number of T1a tumours progressed after BCG intravesical immunotherapy, even if no second TUR was performed [27]. As another unfavourable prognostic factor in T1 tumours, the presence of lymphovascular invasion has been recognised [28]. Although these prognostic parameters constitute a promise for the future, their results need further validation. At this time, they cannot be recommended and used for routine clinical decisions concerning second TUR. 4.
Conclusions
Several studies have clearly demonstrated that second TUR confirmed the presence of residual cancer and tumour understaging in a significant number of T1 and high-grade tumours. The pathologic findings achieved by second TUR further modified strategy in a high number of cases. These arguments strongly support the recommendation of second TUR in patients with T1 or high-grade NMIBC.
EUROPEAN UROLOGY SUPPLEMENTS 10 (2011) e8–e11
Conflicts of interest
e11
a must even for experienced urologists. Urol Int 2004;72: 99–102.
The author has received lecturer honorarium from GE Healthcare.
[15] Han KS, Joung JY, Cho KS, et al. Results of repeated transurethral resection for a second opinion in patients referred for nonmuscle invasive bladder cancer: the referral cancer center experience and review of the literature. J Endourol 2008;22:2699–704.
Funding support
[16] Duchek M, Johansson R, Jahnson S, et al. Bacillus Calmette-Gue´rin is superior to a combination of epirubicin and interferon-a2b in the
None.
intravesical treatment of patients with stage T1 urinary bladder cancer. A prospective randomized Nordic study. Eur Urol 2010;57:25–31.
References [1] Wu X, Ros M, Gu J, Kiemeney L. Epidemiology and genetic susceptibility to bladder cancer. BJU Int 2008;102:1207–15.
[17] Fritsche H-M, Burger M, Svatek RS, et al. Characteristics and outcomes of patients with clinical T1 grade 3 urothelial carcinoma treated with radical cystectomy: results from an international cohort. Eur Urol 2010;57:300–9.
[2] Sylvester RJ, van der Meijden APM, Oosterlinck W, et al. Predicting
[18] Dalbagni G, Vora K, Kaag M, et al. Clinical outcome in a contempo-
recurrence and progression in individual patients with stage Ta T1
rary series of restaged patients with clinical T1 bladder cancer. Eur
bladder cancer using EORTC risk tables: a combined analysis of
Urol 2009;56:903–10.
2596 patients from seven EORTC trials. Eur Urol 2006;49:466–77.
[19] Herr HW, Donat SM, Dalbagni G. Can restaging transurethral resec-
[3] Brausi M, Collette L, Kurth K-H, et al, EORTC Genito-Urinary Tract
tion of T1 bladder cancer select patients for immediate cystec-
Cancer Collaborative Group. Variability in the recurrence rate at
tomy? J Urol 2007;177:75–9.
first follow-up cystoscopy after TUR in stage Ta T1 transitional cell
[20] Guevara A, Salomon L, Allory Y, et al. The role of tumor-free status in
carcinoma of the bladder: a combined analysis of seven EORTC
repeat resection before intravesical bacillus Calmette-Guerin for
studies. Eur Urol 2002;41:523–31. [4] Bostrom PJ, van Rhijn BWG, Fleshner N, et al. Staging and staging errors in bladder cancer. Eur Urol Suppl 2010;9:2–9.
high grade Ta, T1 and CIS bladder cancer. J Urol 2010;183:2161–4. [21] Babjuk M. Transurethral resection of non–muscle-invasive bladder cancer. Eur Urol Suppl 2009;8:542–8.
[5] Babjuk M, Oosterlinck W, Sylvester R, et al. EAU guidelines on non-
[22] Mariappan P, Zachou A, Grigor KM. Detrusor muscle in the first,
muscle-invasive urothelial carcinoma of the bladder. Eur Urol
apparently complete transurethral resection of bladder tumour
2008;54:303–14.
specimen is a surrogate marker of resection quality, predicts risk
[6] Herr HW, Donat MS. Quality control in transurethral resection of bladder tumors. BJU Int 2008;102:1242–6.
of early recurrence, and is dependent on operator experience. Eur Urol 2010;57:843–9.
[7] Grimm M-O, Steinhoff C, Simon X, Spiegelhalder P, Ackermann R,
[23] Brausi MA, Gavioli M, Peracchia G, et al. Dedicated teaching pro-
Vo¨geli TA. Effect of routine repeat transurethral resection for su-
grams can improve the quality of TUR of non-muscle-invasive
perficial bladder cancer: a long-term observational study. J Urol
bladder tumors (NMIBT): experience of a single institution. Eur
2003;170:433–7.
Urol Suppl 2008;7:180.
[8] Kla¨n R, Loy V, Huland H. Residual tumor discovered in routine
[24] Orsola A, Trias I, Ravento´s CX, et al. Initial high-grade T1 urothelial
second transurethral resection in patients with stage T1 transition-
cell carcinoma: feasibility and prognostic significance of lamina
al cell carcinoma of the bladder. J Urol 1991;146:316–8.
propria invasion microstaging (T1a/b/c) in BCG-treated and BCG-
[9] Herr HW. The value of a second transurethral resection in evaluating patients with bladder tumors. J Urol 1999;162:74–6.
non-treated patients. Eur Urol 2005;48:231–8. [25] Faivre d’Arcier B, Celhay O, Safsaf A, et al. T1 bladder carcinoma:
[10] Brauers A, Buettner R, Jakse G. Second resection and prognosis of
prognostic value of the muscularis mucosae invasion (T1a/T1b). A
primary high risk superficial bladder cancer: is cystectomy often
multicenter study by the French Urological Association (CCAFU).
too early? J Urol 2001;165:808–10.
Prog Urol 2010;20:440–9.
[11] Schips L, Augustin H, Zigeuner RE, et al. Is repeated transurethral
[26] Soukup V, Babjuk M, Dusˇkova´ J, et al. Does the expression of fascin-
resection justified in patients with newly diagnosed superficial
1 and tumor subclassification help to assess the risk of recurrence
bladder cancer? Urology 2002;59:220–3.
and progression in T1 urothelial urinary bladder carcinoma? Urol
[12] Schwaibold HE, Sivalingam S, May F, Hartung R. The value of a
Int 2008;80:413–8.
second transurethral resection for T1 bladder cancer. BJU Int
[27] Orsola A, Cecchini L, Raventos CX, et al. Risk factors for positive
2006;97:1199–201. ¨ , et al. Impact of routine second [13] Divrik RT, S¸ahin AF, Yildirim U
findings in patients with high-grade T1 bladder cancer treated
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. [14] Zurkirchen MA, Sulser T, Gaspert A, Hauri D. Second transurethral resection of superficial transitional cell carcinoma of the bladder:
with transurethral resection of bladder tumour (TUR) and bacille Calmette-Gue´rin therapy and the decision for a repeat TUR. BJU Int 2009;105:202–7. [28] Cho KS, Seo HK, Joung JY, et al. Lymphovascular invasion in transurethral resection specimens as predictor of progression and metastasis in patients with newly diagnosed T1 bladder urothelial cancer. J Urol 2009;182:2625–31.
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Should a Second Transurethral Resection Be Performed in All Patients with T1 or High-Grade Non–Muscle-Invasive Bladder Cancer? Marko Babjuk * Department of Urology, 2nd Faculty of Medicine, Charles University in Praha, Hospital Motol, Czech Republic
Article info
Abstract
Keywords: Bladder cancer TURB Second resection Understaging Tumour persistence
Context: Transurethral resection (TUR) is a critical step in the management of non– muscle-invasive bladder cancer (NMIBC). Because of the high risk of tumour persistence and understaging, the routine second TUR performed after 2–6 wk is recommended by European Association of Urology guidelines in all patients with T1 or high-grade NMIBC. Objective: To summarise arguments that support the recommendation of routine second TUR in all patients with T1 or high-grade NMIBC. Evidence acquisition: Data and arguments were retrieved from a critically selected list of articles and abstracts dealing with the surgical treatment of NMIBC. Evidence synthesis: In patients with T1 tumours, the risk of tumour persistence and tumour understaging detected by the second TUR was 33–78% and 2–28%, respectively. The pathologic finding achieved by second TUR can modify the treatment strategy in a significant number of patients. Correct staging in NMIBC enables the selection of the optimal treatment modality and improves results. Conclusions: The second TUR confirmed the presence of residual cancer and tumour understaging in a significant number of T1 and high-grade tumours. This is a strong argument that supports the recommendation of second TUR in patients with T1 or high-grade NMIBC. # 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved. ´ valu 84, 15006 Praha 5, Czech Republic. Tel. +420224434801; * Department of Urology, FN Motol, V U Fax: +420224434821. E-mail address: [email protected].
1.
Introduction
Worldwide, bladder cancer (BCa) is the seventh most common malignancy in men and the 17th in women. It is estimated that, in 2002, about 357 000 new cases of BCa were diagnosed [1]. Approximately 75–85% of all patients with BCa have disease confined to the mucosa (stage Ta or carcinoma in situ [CIS]) or submucosa (stage T1). This group of tumours is referred to as non–muscle-invasive bladder cancer (NMIBC) as opposed to muscle-invasive disease staged as T2–T4.
Theoretically, NMIBC can be cured using a conservative approach without the need for radical surgery. The treatment strategy is based on complete transurethral resection of the bladder (TURB), individually tailored intravesical chemotherapy, or immunotherapy instillations and careful follow-up. Unfortunately, the expectations are not always fulfilled. We are facing an enormously high recurrence rate and a not-negligible risk of tumour progression [2]. The critical step in the management of NMIBC is TURB. The aim of the procedure is to establish a histologic
1569-9056/$ – see front matter # 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.
doi:10.1016/j.eursup.2011.03.005
e9
EUROPEAN UROLOGY SUPPLEMENTS 10 (2011) e8–e11
diagnosis, determine the tumour stage and grade, and achieve complete removal of papillary non–muscle-invasive tumours. Unfortunately, although TURB is a frequently performed procedure that should be familiar to all urologists, its results are far from optimum, and both the diagnostic and therapeutic purposes are not always completed. Indeed, tumours are frequently overlooked and left behind during initial resection or, more importantly and dangerously, their depth of invasion can be underestimated [3,4]. To overcome these limitations, the second transurethral resection (TUR) performed after 2–6 wk was incorporated into our treatment algorithms. The current version of the European Association of Urology guidelines recommends considering a second TUR if there is a suspicion that the initial resection was incomplete (eg, when multiple or large tumours are present or when the pathologist reported no muscle tissue in the specimen). Furthermore, it should be performed when a high-grade non–muscle-invasive tumour or a T1 tumour was detected at the initial TURB [5]. 2.
Evidence acquisition
This paper is based on the presentation given at the European Section of Oncologic Urology meeting held in London on 21–23 January 2011. The goal was to summarise arguments that supported the recommendation of routine second TUR in all patients with T1 and high-grade NMIBC. Data were retrieved from a critically selected list of articles and abstracts dealing with the surgical treatment of NMIBC. 3.
Evidence synthesis
3.1.
Number of persistent tumours detected by second
[8,11,13] and high-grade lesions [6,8,13] and increases with the size [13] and stage of the original tumour [7,9,11,14,15]. More than 80% of residual tumours were found in the location of the original lesion [7,12]. In patients with T1 tumours, the risk of tumour persistence detected by the second TUR ranged between 33% and 78% [6–15]. Noteworthy is that the high risk can also be observed in patients treated in this decade with modern equipment. Recently, data were published from a Nordic study that enrolled 250 patients with T1 grade 2–3 tumours, and the second resection was a routine part of the protocol. It was demonstrated that using second TUR, residual tumour was detected in 39% of cases [16]. 3.2.
The risk of understaging detected by second transurethral
resection
Underestimation of the depth of tumour invasion is dangerous, especially in cases where the muscle-invasive disease is missed. In tumours staged as T1 by initial TURB, the rate of understaging detected by second TUR varied between 2% and 10% in most series [7–15], except in that of Han et al [15] and Herr [9], who reported a risk of 23% and 28%, respectively (Table 1). Herr [9] recently updated the results with second TUR in 1312 patients with papillary tumours. The risk of tumour upstaging in muscle-invasive disease by second TUR was 0% in Ta low-grade tumours, 5% in Ta high-grade tumours, and 30% in T1 tumours [6]. The most important risk factor and source of error between T1 tumours was the absence of muscle in the initial resection specimen. The risk of tumour understaging increased from 15% to 45% if the muscle was not present in the resected tissue from initial TURB [6].
transurethral resection 3.3.
Many analyses confirmed that the second resection can detect persistent tumours in a significant percentage of patients. The rate of residual tumour detected by second TUR in patients with NMIBC varies between 27% and 78% (Table 1) [6–15]. The risk is higher in multiple tumours
Clinical consequences and prognostic role of second
transurethral resection
The pathologic finding achieved by second TUR can modify the treatment strategy in a significant number of patients. The change in treatment approach is crucial, particularly in
Table 1 – Results of second transurethral resection in patients with Ta and T1 tumours Author
Grimm et al [7] Kla¨n et al [8] Brauers et al [10] Schips et al [11] Herr and Donat [6] Schweibold et al [12] Divrik et al [13] Zurkirchen et al [14] Han et al [15]
Initial stage
Ta (n = 61) T1 (n = 17) T1 (n = 46) T1 (n = 42) Ta (n = 31) T1 (n = 76) Ta high-grade (n = 396) T1 (n = 701) T1 (n = 136) T1 (n = 105) Ta (n = 99) T1 (n = 115) Ta (n = 25) T1 (n = 30)
TUR = transurethral resection; CIS = carcinoma in situ.
Stage in persistent tumours on second TUR CIS, %
Ta, %
T1, %
– – – 19 – – 50 23 11 4 – – – –
– – 15 17 32 11
– – 26 24 6 14 10 25 24 9 – – 4 43
8 13 – – 56 –
T2, % 4 2 5 – 8 5 30 10 8 – – 4 23
Total, % 27 53 44 64 39 33 65 78 53 34 27 37 64 67
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EUROPEAN UROLOGY SUPPLEMENTS 10 (2011) e8–e11
cases where the muscle-invasive tumour was missed by initial resection. There is no doubt that clinical T1 bladder tumours represent a therapeutic challenge. The risk is hidden in their biologic potential, which is difficult to predict in individual cases. The major drawback, however, is inaccuracy in clinical staging. Cystectomy series demonstrated that understaging can be observed in 50% of patients with clinical T1G3 tumours [17]. Indeed, correct staging in T1 tumours is critical, because it enables the selection of appropriate patients for a conservative approach with intravesical bacillus Calmette-Gue´rin (BCG) immunotherapy instillations. Dalbagni et al, in their retrospective analysis of 523 patients, could not detect a difference in survival among patients who underwent immediate cystectomy versus those who were placed on surveillance with or without deferred cystectomy if T1 disease or lower was confirmed on second TUR [18]. The result of second TUR—particularly the persistence of T1 disease—can also provide important prognostic information. Herr presented the outcome of 352 T1 tumours treated with second TUR. Of the 92 patients with residual T1 cancer detected by second TUR, 82% progressed to muscle invasion within 5 yr compared to 19% of 260 without tumour or with Ta disease only [19]. Moreover, in another study, the tumour-free status at the time of second TUR significantly improved the response rate to BCG intravesical immunotherapy and delayed tumour recurrence [20].
resection and depends on surgeon experience [22]. Experienced surgeons were more likely to resect detrusor muscle with a lower risk of early recurrence, and the absence of muscle independently predicted a higher risk of early recurrence. It is of interest, however, that even if the TURB was performed by an experienced surgeon and muscle were present in the specimen, the risk of residual disease in T1 and grade 3 tumours reached 30% and 19%, respectively. Another study confirmed that even experienced urologists had a high percentage of persistent carcinomas after an initial TURB [14]. Brausi et al recently introduced a dedicated teaching programme on the surgical treatment of TURB and evaluated its impact on patient outcomes [23]. The programme included the routine use of video-TUR and bipolar resection, the presence of a senior urologist in theatre during the procedure, and regular teaching session meetings on bladder tumours. The programme’s application reduced the 3-mo recurrence rate in patients operated on by resident urologists from 28% to 16%, increased the presence of muscle from 50% to 88%, and decreased the complication rate. These reports clearly demonstrate that even optimally performed TURB using modern equipment is burdened by a high risk of tumour persistence. The frequent failure and absence of clear quality criteria of initial resection strongly underline the role of second TUR in T1 and high-grade NMIBC. 3.5.
3.4.
Can the quality of initial resection be improved?
The recommendation to repeat surgery in a significant number of patients with NMIBC must be focused and critically discussed. We should remember that the indication for repeat resection is just a rescue from an unsuccessful initial procedure, and our effort should be concentrated on improvement of the quality of the first TURB. The essential question is whether the quality of TURB performed with modern equipment by well-trained surgeons justifies withdrawal of the recommendation for a second TUR. The criteria of quality of TURB have never been clearly defined [21]. It is generally accepted, however, that the procedure is successful if the resection is complete and there are no missed lesions. The rate of recurrence at the first follow-up cystoscopy has been attributed to incomplete resection of the tumour. The analysis of 2410 patients from seven phase 3 trials by the European Organisation for Research and Treatment of Cancer showed substantial variations in early recurrence rates among different institutions. The frequency of 3-mo recurrence ranged from 0% to 46%. These differences are not the result of the clinical features of the tumour but probably of the quality of TURB performed by individual surgeons [3]. Mariappan et al assessed patients who were judged to have had a complete first TURB to determine whether the presence or absence of detrusor muscle in the first resection specimen is a suitable surrogate marker of the quality of
Can the selection of patients for second transurethral
resection be improved?
Patients with T1 tumours can be substaged into the T1a and T1b categories according to the depth of invasion into the lamina propria. The prognostic value of substaging has been demonstrated by some retrospective cohort studies [24–26]. In patients with T1a tumours, a lower risk of understaging was confirmed [26]. Results showed that only a limited number of T1a tumours progressed after BCG intravesical immunotherapy, even if no second TUR was performed [27]. As another unfavourable prognostic factor in T1 tumours, the presence of lymphovascular invasion has been recognised [28]. Although these prognostic parameters constitute a promise for the future, their results need further validation. At this time, they cannot be recommended and used for routine clinical decisions concerning second TUR. 4.
Conclusions
Several studies have clearly demonstrated that second TUR confirmed the presence of residual cancer and tumour understaging in a significant number of T1 and high-grade tumours. The pathologic findings achieved by second TUR further modified strategy in a high number of cases. These arguments strongly support the recommendation of second TUR in patients with T1 or high-grade NMIBC.
EUROPEAN UROLOGY SUPPLEMENTS 10 (2011) e8–e11
Conflicts of interest
e11
a must even for experienced urologists. Urol Int 2004;72: 99–102.
The author has received lecturer honorarium from GE Healthcare.
[15] Han KS, Joung JY, Cho KS, et al. Results of repeated transurethral resection for a second opinion in patients referred for nonmuscle invasive bladder cancer: the referral cancer center experience and review of the literature. J Endourol 2008;22:2699–704.
Funding support
[16] Duchek M, Johansson R, Jahnson S, et al. Bacillus Calmette-Gue´rin is superior to a combination of epirubicin and interferon-a2b in the
None.
intravesical treatment of patients with stage T1 urinary bladder cancer. A prospective randomized Nordic study. Eur Urol 2010;57:25–31.
References [1] Wu X, Ros M, Gu J, Kiemeney L. Epidemiology and genetic susceptibility to bladder cancer. BJU Int 2008;102:1207–15.
[17] Fritsche H-M, Burger M, Svatek RS, et al. Characteristics and outcomes of patients with clinical T1 grade 3 urothelial carcinoma treated with radical cystectomy: results from an international cohort. Eur Urol 2010;57:300–9.
[2] Sylvester RJ, van der Meijden APM, Oosterlinck W, et al. Predicting
[18] Dalbagni G, Vora K, Kaag M, et al. Clinical outcome in a contempo-
recurrence and progression in individual patients with stage Ta T1
rary series of restaged patients with clinical T1 bladder cancer. Eur
bladder cancer using EORTC risk tables: a combined analysis of
Urol 2009;56:903–10.
2596 patients from seven EORTC trials. Eur Urol 2006;49:466–77.
[19] Herr HW, Donat SM, Dalbagni G. Can restaging transurethral resec-
[3] Brausi M, Collette L, Kurth K-H, et al, EORTC Genito-Urinary Tract
tion of T1 bladder cancer select patients for immediate cystec-
Cancer Collaborative Group. Variability in the recurrence rate at
tomy? J Urol 2007;177:75–9.
first follow-up cystoscopy after TUR in stage Ta T1 transitional cell
[20] Guevara A, Salomon L, Allory Y, et al. The role of tumor-free status in
carcinoma of the bladder: a combined analysis of seven EORTC
repeat resection before intravesical bacillus Calmette-Guerin for
studies. Eur Urol 2002;41:523–31. [4] Bostrom PJ, van Rhijn BWG, Fleshner N, et al. Staging and staging errors in bladder cancer. Eur Urol Suppl 2010;9:2–9.
high grade Ta, T1 and CIS bladder cancer. J Urol 2010;183:2161–4. [21] Babjuk M. Transurethral resection of non–muscle-invasive bladder cancer. Eur Urol Suppl 2009;8:542–8.
[5] Babjuk M, Oosterlinck W, Sylvester R, et al. EAU guidelines on non-
[22] Mariappan P, Zachou A, Grigor KM. Detrusor muscle in the first,
muscle-invasive urothelial carcinoma of the bladder. Eur Urol
apparently complete transurethral resection of bladder tumour
2008;54:303–14.
specimen is a surrogate marker of resection quality, predicts risk
[6] Herr HW, Donat MS. Quality control in transurethral resection of bladder tumors. BJU Int 2008;102:1242–6.
of early recurrence, and is dependent on operator experience. Eur Urol 2010;57:843–9.
[7] Grimm M-O, Steinhoff C, Simon X, Spiegelhalder P, Ackermann R,
[23] Brausi MA, Gavioli M, Peracchia G, et al. Dedicated teaching pro-
Vo¨geli TA. Effect of routine repeat transurethral resection for su-
grams can improve the quality of TUR of non-muscle-invasive
perficial bladder cancer: a long-term observational study. J Urol
bladder tumors (NMIBT): experience of a single institution. Eur
2003;170:433–7.
Urol Suppl 2008;7:180.
[8] Kla¨n R, Loy V, Huland H. Residual tumor discovered in routine
[24] Orsola A, Trias I, Ravento´s CX, et al. Initial high-grade T1 urothelial
second transurethral resection in patients with stage T1 transition-
cell carcinoma: feasibility and prognostic significance of lamina
al cell carcinoma of the bladder. J Urol 1991;146:316–8.
propria invasion microstaging (T1a/b/c) in BCG-treated and BCG-
[9] Herr HW. The value of a second transurethral resection in evaluating patients with bladder tumors. J Urol 1999;162:74–6.
non-treated patients. Eur Urol 2005;48:231–8. [25] Faivre d’Arcier B, Celhay O, Safsaf A, et al. T1 bladder carcinoma:
[10] Brauers A, Buettner R, Jakse G. Second resection and prognosis of
prognostic value of the muscularis mucosae invasion (T1a/T1b). A
primary high risk superficial bladder cancer: is cystectomy often
multicenter study by the French Urological Association (CCAFU).
too early? J Urol 2001;165:808–10.
Prog Urol 2010;20:440–9.
[11] Schips L, Augustin H, Zigeuner RE, et al. Is repeated transurethral
[26] Soukup V, Babjuk M, Dusˇkova´ J, et al. Does the expression of fascin-
resection justified in patients with newly diagnosed superficial
1 and tumor subclassification help to assess the risk of recurrence
bladder cancer? Urology 2002;59:220–3.
and progression in T1 urothelial urinary bladder carcinoma? Urol
[12] Schwaibold HE, Sivalingam S, May F, Hartung R. The value of a
Int 2008;80:413–8.
second transurethral resection for T1 bladder cancer. BJU Int
[27] Orsola A, Cecchini L, Raventos CX, et al. Risk factors for positive
2006;97:1199–201. ¨ , et al. Impact of routine second [13] Divrik RT, S¸ahin AF, Yildirim U
findings in patients with high-grade T1 bladder cancer treated
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. [14] Zurkirchen MA, Sulser T, Gaspert A, Hauri D. Second transurethral resection of superficial transitional cell carcinoma of the bladder:
with transurethral resection of bladder tumour (TUR) and bacille Calmette-Gue´rin therapy and the decision for a repeat TUR. BJU Int 2009;105:202–7. [28] Cho KS, Seo HK, Joung JY, et al. Lymphovascular invasion in transurethral resection specimens as predictor of progression and metastasis in patients with newly diagnosed T1 bladder urothelial cancer. J Urol 2009;182:2625–31.