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Published in: World Journal of Urology 1/2019

Open Access 01-01-2019 | Original Article

Intravesical BCG treatment causes a long-lasting reduction of recurrence and progression in patients with high-risk non-muscle-invasive bladder cancer

Authors: Tomas Thiel, Charlotta Ryk, Lotta Renström-Koskela, Gunnar Steineck, Martin C. Schumacher, N. Peter Wiklund, Petra J. de Verdier

Published in: World Journal of Urology | Issue 1/2019

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Abstract

Purpose

To analyse if BCG treatment leads to long-term reduction of recurrence, progression, and cancer-specific mortality (CSM) in patients with high-risk NMIBC.

Materials and methods

140 patients with high-risk NMIBC were drawn from a population-based cohort of 538 patients with newly diagnosed bladder cancer in the Stockholm County between 1995 and 1996. Data were collected prospectively, and a final follow-up for recurrence, progression, and CSM was performed after 15 years. Patients that received BCG were compared with patients who did not receive BCG. Survival analysis was done with Kaplan–Meier estimates and Mantel–Cox log-rank test. Multivariable Cox proportional regression with stepwise selection was performed to verify the statistical significance of clinicopathological factors of prognostic importance. Results were displayed in Hazard ratios and a p < 0.05 was considered to be statistically significant.

Results

With a median follow-up of 100 months (2–182), 76 patients recurred; 50 progressed to muscle invasion; and 92 died of whom 38 died from bladder cancer. After 15-year follow-up, there was a statistically significant reduction in rate for recurrence (HR 0.40, p < 0.0001) and progression (HR 0.52, p = 0.038), but not for CSM, in patients that received BCG compared to those who did not.

Conclusions

In this group, BCG in high-risk NMIBC patients reduced the long-term risk of recurrence and progression. The effect on CSM is yet to be clarified.
Literature
1.
go back to reference Morales A, Eidinger D, Bruce AW (1976) Intracavitary Bacillus Calmette-Guerin in the treatment of superficial bladder tumours. J Urol 116(2):180–183CrossRef Morales A, Eidinger D, Bruce AW (1976) Intracavitary Bacillus Calmette-Guerin in the treatment of superficial bladder tumours. J Urol 116(2):180–183CrossRef
2.
go back to reference Babjuk M, Oosterlinck W, Sylvester R et al (2011) EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder, the 2011 update. Eur Urol 59(6):997–1008CrossRef Babjuk M, Oosterlinck W, Sylvester R et al (2011) EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder, the 2011 update. Eur Urol 59(6):997–1008CrossRef
3.
go back to reference Babjuk M, Burger M, Zigeuner R et al (2013) EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: update 2013. Eur Urol 64(4):639–653CrossRef Babjuk M, Burger M, Zigeuner R et al (2013) EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: update 2013. Eur Urol 64(4):639–653CrossRef
4.
go back to reference Sylvester RJ, van der Meijden AP, Oosterlinck W et al (2006) 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 49(3):466–477 (discussion 475–467) CrossRef Sylvester RJ, van der Meijden AP, Oosterlinck W et al (2006) 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 49(3):466–477 (discussion 475–467) CrossRef
5.
go back to reference Larsson P, Wijkstrom H, Thorstenson A et al (2003) A population-based study of 538 patients with newly detected urinary bladder neoplasms followed during 5 years. Scand J Urol Nephrol 37(3):195–201CrossRef Larsson P, Wijkstrom H, Thorstenson A et al (2003) A population-based study of 538 patients with newly detected urinary bladder neoplasms followed during 5 years. Scand J Urol Nephrol 37(3):195–201CrossRef
6.
go back to reference Hudson MA, Herr HW (1995) Carcinoma in situ of the bladder. J Urol. 153(3 Pt 1):564–572CrossRef Hudson MA, Herr HW (1995) Carcinoma in situ of the bladder. J Urol. 153(3 Pt 1):564–572CrossRef
7.
go back to reference Kamat AM, Lamm DL (2000) Intravesical therapy for bladder cancer. Urology. 55(2):161–168CrossRef Kamat AM, Lamm DL (2000) Intravesical therapy for bladder cancer. Urology. 55(2):161–168CrossRef
8.
go back to reference Malmstrom PU, Sylvester RJ, Crawford DE et al (2009) An individual patient data meta-analysis of the long-term outcome of randomised studies comparing intravesical mitomycin C versus bacillus Calmette-Guerin for non-muscle-invasive bladder cancer. Eur Urol 56(2):247–256CrossRef Malmstrom PU, Sylvester RJ, Crawford DE et al (2009) An individual patient data meta-analysis of the long-term outcome of randomised studies comparing intravesical mitomycin C versus bacillus Calmette-Guerin for non-muscle-invasive bladder cancer. Eur Urol 56(2):247–256CrossRef
9.
go back to reference Bohle A, Bock PR (2004) Intravesical bacille Calmette-Guerin versus mitomycin C in superficial bladder cancer: formal meta-analysis of comparative studies on tumour progression. Urology 63(4):682–686 (discussion 686–687) CrossRef Bohle A, Bock PR (2004) Intravesical bacille Calmette-Guerin versus mitomycin C in superficial bladder cancer: formal meta-analysis of comparative studies on tumour progression. Urology 63(4):682–686 (discussion 686–687) CrossRef
10.
go back to reference Millan-Rodriguez F, Chechile-Toniolo G, Salvador-Bayarri J, Palou J, Vicente-Rodriguez J (2000) Multivariate analysis of the prognostic factors of primary superficial bladder cancer. J Urol 163(1):73–78CrossRef Millan-Rodriguez F, Chechile-Toniolo G, Salvador-Bayarri J, Palou J, Vicente-Rodriguez J (2000) Multivariate analysis of the prognostic factors of primary superficial bladder cancer. J Urol 163(1):73–78CrossRef
11.
go back to reference Sylvester RJ, van der MA, Lamm DL (2002) Intravesical bacillus Calmette-Guerin reduces the risk of progression in patients with superficial bladder cancer: a meta-analysis of the published results of randomized clinical trials. J Urol 168(5):1964–1970CrossRef Sylvester RJ, van der MA, Lamm DL (2002) Intravesical bacillus Calmette-Guerin reduces the risk of progression in patients with superficial bladder cancer: a meta-analysis of the published results of randomized clinical trials. J Urol 168(5):1964–1970CrossRef
12.
go back to reference Shang PF, Kwong J, Wang ZP et al (2011) Intravesical Bacillus Calmette-Guerin versus epirubicin for Ta and T1 bladder cancer. Cochrane Database Syst Rev (5):CD006885 Shang PF, Kwong J, Wang ZP et al (2011) Intravesical Bacillus Calmette-Guerin versus epirubicin for Ta and T1 bladder cancer. Cochrane Database Syst Rev (5):CD006885
13.
go back to reference Shelley MD, Court JB, Kynaston H, Wilt TJ, Coles B, Mason M (2003) Intravesical bacillus Calmette-Guerin versus mitomycin C for Ta and T1 bladder cancer. Cochrane Database Syst Rev (3):CD003231 Shelley MD, Court JB, Kynaston H, Wilt TJ, Coles B, Mason M (2003) Intravesical bacillus Calmette-Guerin versus mitomycin C for Ta and T1 bladder cancer. Cochrane Database Syst Rev (3):CD003231
14.
go back to reference Lamm DL (1992) Carcinoma in situ. Urol Clin N Am 19(3):499–508 Lamm DL (1992) Carcinoma in situ. Urol Clin N Am 19(3):499–508
15.
go back to reference Kaasinen E, Wijkstrom H, Rintala E, Mestad O, Jahnson S, Malmstrom PU (2016) Seventeen-year follow-up of the prospective randomized Nordic CIS study: BCG monotherapy versus alternating therapy with mitomycin C and BCG in patients with carcinoma in situ of the urinary bladder. Scand J Urol 50(5):360–368CrossRef Kaasinen E, Wijkstrom H, Rintala E, Mestad O, Jahnson S, Malmstrom PU (2016) Seventeen-year follow-up of the prospective randomized Nordic CIS study: BCG monotherapy versus alternating therapy with mitomycin C and BCG in patients with carcinoma in situ of the urinary bladder. Scand J Urol 50(5):360–368CrossRef
16.
go back to reference Thorstenson A, Schumacher MC, Wiklund NP et al (2010) Diagnostic random bladder biopsies: reflections from a population-based cohort of 538 patients. Scand J Urol Nephrol 44(1):11–19CrossRef Thorstenson A, Schumacher MC, Wiklund NP et al (2010) Diagnostic random bladder biopsies: reflections from a population-based cohort of 538 patients. Scand J Urol Nephrol 44(1):11–19CrossRef
17.
go back to reference International Union against Cancer, Harmer MH, International Union against Cancer (1978) Committee on TNM Classification. TNM classification of malignant tumours, 3rd edn. The Union, Geneva International Union against Cancer, Harmer MH, International Union against Cancer (1978) Committee on TNM Classification. TNM classification of malignant tumours, 3rd edn. The Union, Geneva
18.
go back to reference Reuter VE, Epstein JI, Amin MB, Mostofi FK (1999) The “WHO/ISUP consensus classification of urothelial (transitional cell) neoplasms”: continued discussion. Hum Pathol 30(7):879–880CrossRef Reuter VE, Epstein JI, Amin MB, Mostofi FK (1999) The “WHO/ISUP consensus classification of urothelial (transitional cell) neoplasms”: continued discussion. Hum Pathol 30(7):879–880CrossRef
19.
go back to reference Persad R, Lamm D, Brausi M et al (2008) Current approaches to the management of non-muscle invasive bladder cancer: comparison of current guidelines and recommendations. Eur Urol Suppl 7(10):637–650CrossRef Persad R, Lamm D, Brausi M et al (2008) Current approaches to the management of non-muscle invasive bladder cancer: comparison of current guidelines and recommendations. Eur Urol Suppl 7(10):637–650CrossRef
20.
go back to reference Patard JJ, Rodriguez A, Leray E, Rioux-Leclercq N, Guille F, Lobel B (2002) Intravesical Bacillus Calmette-Guerin treatment improves patient survival in T1G3 bladder tumours. Eur Urol 41(6):635–641 (discussion 642) CrossRef Patard JJ, Rodriguez A, Leray E, Rioux-Leclercq N, Guille F, Lobel B (2002) Intravesical Bacillus Calmette-Guerin treatment improves patient survival in T1G3 bladder tumours. Eur Urol 41(6):635–641 (discussion 642) CrossRef
21.
go back to reference Gontero P, Sylvester R, Pisano F et al (2015) Prognostic factors and risk groups in T1G3 non-muscle-invasive bladder cancer patients initially treated with Bacillus Calmette-Guerin: results of a retrospective multicenter study of 2451 patients. Eur Urol 67(1):74–82CrossRef Gontero P, Sylvester R, Pisano F et al (2015) Prognostic factors and risk groups in T1G3 non-muscle-invasive bladder cancer patients initially treated with Bacillus Calmette-Guerin: results of a retrospective multicenter study of 2451 patients. Eur Urol 67(1):74–82CrossRef
22.
go back to reference Shahin O, Thalmann GN, Rentsch C, Mazzucchelli L, Studer UE (2003) A retrospective analysis of 153 patients treated with or without intravesical bacillus Calmette-Guerin for primary stage T1 grade 3 bladder cancer: recurrence, progression and survival. J Urol 169(1):96–100 (discussion 100) CrossRef Shahin O, Thalmann GN, Rentsch C, Mazzucchelli L, Studer UE (2003) A retrospective analysis of 153 patients treated with or without intravesical bacillus Calmette-Guerin for primary stage T1 grade 3 bladder cancer: recurrence, progression and survival. J Urol 169(1):96–100 (discussion 100) CrossRef
23.
go back to reference Cambier S, Sylvester RJ, Collette L et al (2016) EORTC nomograms and risk groups for predicting recurrence, progression, and disease-specific and overall survival in non-muscle-invasive stage Ta-T1 urothelial bladder cancer patients treated with 1-3 years of maintenance Bacillus Calmette-Guerin. Eur Urol 69(1):60–69CrossRef Cambier S, Sylvester RJ, Collette L et al (2016) EORTC nomograms and risk groups for predicting recurrence, progression, and disease-specific and overall survival in non-muscle-invasive stage Ta-T1 urothelial bladder cancer patients treated with 1-3 years of maintenance Bacillus Calmette-Guerin. Eur Urol 69(1):60–69CrossRef
24.
go back to reference Baniel J, Grauss D, Engelstein D, Sella A (1998) Intravesical bacillus Calmette-Guerin treatment for Stage T1 grade 3 transitional cell carcinoma of the bladder. Urology 52(5):785–789CrossRef Baniel J, Grauss D, Engelstein D, Sella A (1998) Intravesical bacillus Calmette-Guerin treatment for Stage T1 grade 3 transitional cell carcinoma of the bladder. Urology 52(5):785–789CrossRef
25.
go back to reference Hurle R, Losa A, Manzetti A, Lembo A (1999) Intravesical bacille Calmette-Guerin in Stage T1 grade 3 bladder cancer therapy: a 7-year follow-up. Urology 54(2):258–263CrossRef Hurle R, Losa A, Manzetti A, Lembo A (1999) Intravesical bacille Calmette-Guerin in Stage T1 grade 3 bladder cancer therapy: a 7-year follow-up. Urology 54(2):258–263CrossRef
26.
go back to reference Mariappan P, Zachou A, Grigor KM, Edinburgh Uro-Oncology G (2010) Detrusor muscle in the first, apparently complete transurethral resection of bladder tumour specimen is a surrogate marker of resection quality, predicts risk of early recurrence, and is dependent on operator experience. Eur Urol 57(5):843–849CrossRef Mariappan P, Zachou A, Grigor KM, Edinburgh Uro-Oncology G (2010) Detrusor muscle in the first, apparently complete transurethral resection of bladder tumour specimen is a surrogate marker of resection quality, predicts risk of early recurrence, and is dependent on operator experience. Eur Urol 57(5):843–849CrossRef
Metadata
Title
Intravesical BCG treatment causes a long-lasting reduction of recurrence and progression in patients with high-risk non-muscle-invasive bladder cancer
Authors
Tomas Thiel
Charlotta Ryk
Lotta Renström-Koskela
Gunnar Steineck
Martin C. Schumacher
N. Peter Wiklund
Petra J. de Verdier
Publication date
01-01-2019
Publisher
Springer Berlin Heidelberg
Published in
World Journal of Urology / Issue 1/2019
Print ISSN: 0724-4983
Electronic ISSN: 1433-8726
DOI
https://doi.org/10.1007/s00345-018-2375-7

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