Elsevier

European Urology

Volume 56, Issue 3, September 2009, Pages 430-442
European Urology

Collaborative Review – Bladder Cancer
Recurrence and Progression of Disease in Non–Muscle-Invasive Bladder Cancer: From Epidemiology to Treatment Strategy

https://doi.org/10.1016/j.eururo.2009.06.028Get rights and content

Abstract

Context

This review focuses on the prediction of recurrence and progression in non–muscle invasive bladder cancer (NMIBC) and the treatments advocated for this disease.

Objective

To review the current status of epidemiology, recurrence, and progression of NMIBC and the state-of-the art treatment for this disease.

Evidence acquisition

A literature search in English was performed using PubMed and the guidelines of the European Association of Urology and the American Urological Association. Relevant papers on epidemiology, recurrence, progression, and management of NMIBC were selected. Special attention was given to fluorescent cystoscopy, the new World Health Organisation 2004 classification system for grade, and the role of substaging of T1 NMIBC.

Evidence synthesis

In NMIBC, approximately 70% of patients present as pTa, 20% as pT1, and 10% with carcinoma in situ (CIS) lesions. Bladder cancer (BCa) is the fifth most frequent type of cancer in western society and the most expensive cancer per patient. Recurrence (in ≤80% of patients) is the main problem for pTa NMIBC patients, whereas progression (in ≤45% of patients) is the main threat in pT1 and CIS NMIBC. In a recent European Organisation for Research and Treatment of Cancer analysis, multiplicity, tumour size, and prior recurrence rate are the most important variables for recurrence. Tumour grade, stage, and CIS are the most important variables for progression. Treatment ranges from transurethral resection (TUR) followed by a single chemotherapy instillation in low-risk NMIBC to, sometimes, re-TUR and adjuvant intravesical therapy in intermediate- and high-risk patients to early cystectomy for treatment-refractory high-risk NMIBC.

Conclusions

NMIBC is a heterogeneous disease with varying therapies, follow-up strategies, and oncologic outcomes for an individual patient.

Introduction

The global incidence of urinary bladder cancer (BCa) was approximately 357 000 cases in 2002 [1]. The vast majority of these cancers are urothelial carcinomas, and it is a disease of the elderly population. The highest incidence rates are observed in North America and Western Europe [1], [2], while the lowest incidence rates are found in the Asian countries (China, Japan, Korea) and central Africa [1], [3]. Variation in registration of pTa (low-grade) tumours may partly be the cause of these differences [4]. Apart from age, the most important risk factors are smoking, occupational exposure, certain medical treatments, and genetic predisposition [4], [5], [6], [7], [8], [9], [10], [11].

Table 1 shows the worldwide incidence, mortality, and prevalence of BCa for males and females and for more- and less-developed countries. Globally, BCa is the 7th most common cancer in men and the 17th in women [1]. In the United States, it is the 4th most common cancer in men and the 10th in women [2]. Most (75–85%) BCa incidences are non–muscle invasive at first diagnosis (pTa, pT1, carcinoma in situ [CIS]) [12]. In non–muscle-invasive bladder cancer (NMIBC), approximately 70% of patients present as pTa, 20% as pT1, and 10% as CIS lesions [13]. Generally, the prognosis of NMIBC is good, although 30–80% of cases will recur and 1–45% of cases will progress to muscle invasion within 5 yr [12], [13], [14], [15], [16]. Consequently, NMIBC is a chronic disease with varying oncologic outcomes requiring frequent follow-up and repeated treatments, making the cost per patient from diagnosis to death the highest of all cancers [17], [18]. At any point in time, 2.7 million people in the world have a history of BCa [19].

Section snippets

Evidence acquisition

A literature search in English was performed using PubMed and the guidelines of the European Association of Urology (EAU) and the American Urological Association (AUA). Relevant papers on epidemiology, recurrence, progression, and management of NMIBC were selected. Next to clinical and pathologic variables for recurrence and progression, special attention has been paid to fluorescence cystoscopy (FC), the new World Health Organisation (WHO) 2004 classification system for grading, and the role

Clinical and pathologic factors of recurrence

Clinical and pathologic factors for NMIBC recurrence have been studied extensively over the years [15], [20], [21], [22], [23], [24], [25], [26]. Although studies vary in the number of patients included, duration of follow-up, variables analysed, and statistical analysis, the most important variables for prediction of recurrence in patients with NMIBC are multiplicity, prior recurrence rate, and tumour size [15], [20], [21], [22], [23], [24], [25], [26]. Sylvester reviewed potential prognostic

Conclusions

NMIBC is a frequent and heterogeneous disease with varying oncologic outcomes. FC is a valuable add-on to WLC, as FC allows a more complete TUR, resulting in lower recurrence rates. It is not clear yet whether FC also results in lower progression rates. Multiplicity, tumour size, and prior recurrence rate are the most important variables for recurrence. Grade, stage, and CIS are the most important variables for progression. The new WHO 2004 classification system for grade precludes a one-on-one

References (141)

  • Ferlay J, Bray F, Pisani P, Parkin DM. GLOBOCAN 2002: cancer incidence, mortality and prevalence worldwide. IARC Cancer...
  • A. Jemal et al.

    Cancer statistics, 2008

    CA Cancer J Clin

    (2008)
  • M. Colombel et al.

    Epidemiology, staging, grading, and risk stratification of bladder cancer

    Eur Urol Suppl

    (2008)
  • X. Wu et al.

    Epidemiology and genetic susceptibility to bladder cancer

    BJU Int

    (2008)
  • M.P. Zeegers et al.

    The impact of characteristics of cigarette smoking on urinary tract cancer risk: a meta-analysis of epidemiologic studies

    Cancer

    (2000)
  • C. Murta-Nascimento et al.

    Epidemiology of urinary bladder cancer: from tumor development to patient's death

    World J Urol

    (2007)
  • L.A. Kiemeney et al.

    Sequence variant on 8q24 confers susceptibility to urinary bladder cancer

    Nat Genet

    (2008)
  • K.K. Aben et al.

    Familial aggregation of urothelial cell carcinoma

    Int J Cancer

    (2002)
  • J.M. Kaldor et al.

    Bladder tumours following chemotherapy and radiotherapy for ovarian cancer: a case-control study

    Int J Cancer

    (1995)
  • A.M. Nieder et al.

    Radiation therapy for prostate cancer increases subsequent risk of bladder and rectal cancer: a population based cohort study

    J Urol

    (2008)
  • M. García-Closas et al.

    NAT2 slow acetylation, GSTM1 null genotype, and risk of bladder cancer: results from the Spanish Bladder Cancer Study and meta-analyses

    Lancet

    (2005)
  • M. Babjuk et al.

    EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder

    Eur Urol

    (2008)
  • Z. Kirkali et al.

    Bladder cancer: epidemiology, staging and grading, and diagnosis

    Urology

    (2005)
  • L.A. Kiemeney et al.

    The clinical epidemiology of superficial bladder cancer. Dutch South-East Cooperative Urological Group

    Br J Cancer

    (1993)
  • R.J. Sylvester et al.

    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

    (2006)
  • M.C. Hall et al.

    Guideline for the management of nonmuscle invasive bladder cancer (stages Ta, T1, and Tis): 2007 update

    J Urol

    (2007)
  • M.F. Botteman et al.

    The health economics of bladder cancer

    Pharmacoeconomics

    (2003)
  • G.F. Riley et al.

    Medicare payments from diagnosis to death for elderly cancer patients by stage at diagnosis

    Med Care

    (1995)
  • M. Ploeg et al.

    The present and future burden of urinary bladder cancer in the world

    World J Urol

    (2009)
  • J. Fernandez-Gomez et al.

    Prognostic factors in patients with non–muscle-invasive bladder cancer treated with bacillus Calmette-Guérin: multivariate analysis of data from four randomized CUETO trials

    Eur Urol

    (2008)
  • K.H. Kurth et al.

    Factors affecting recurrence and progression in superficial bladder tumours

    Eur J Cancer

    (1995)
  • K.-H. Kurth et al.

    Prognostic factors in non–muscle-invasive bladder tumors: I. Clinical prognostic factors: a review of the experience of the EORTC Genito-Urinary group II: biologic prognostic markers

    Eur Urol Suppl

    (2007)
  • F. Millan-Rodriguez et al.

    Primary superficial bladder cancer risk groups according to progression, mortality and recurrence

    J Urol

    (2000)
  • K. Zieger et al.

    Long-term follow-up of non-invasive bladder tumours (stage Ta): recurrence and progression

    BJU Int

    (2000)
  • F. Millán-Rodríguez et al.

    Multivariate analysis of the prognostic factors of primary superficial bladder cancer

    J Urol

    (2000)
  • R.J. Sylvester

    Natural history, recurrence and progression in superficial bladder cancer

    TSW Urology

    (2006)
  • S.F. Shariat et al.

    Nomograms including nuclear matrix protein 22 for prediction of disease recurrence and progression in patients with Ta, T1 or CIS transitional cell carcinoma of the bladder

    J Urol

    (2005)
  • S.F. Shariat et al.

    Nomograms for bladder cancer

    Eur Urol

    (2008)
  • M.-O. Grimm et al.

    Effect of routine repeat transurethral resection for superficial bladder cancer: a long-term observational study

    J Urol

    (2003)
  • M. Brausi et al.

    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

    (2002)
  • H.B. Grossman et al.

    A phase III, multicenter comparison of hexaminolevulinate fluorescence cystoscopy and white light cystoscopy for the detection of superficial papillary lesions in patients with bladder cancer

    J Urol

    (2007)
  • Y. Fradet et al.

    A comparison of hexaminolevulinate fluorescence cystoscopy and white light cystoscopy for the detection of carcinoma in situ in patients with bladder cancer: a phase III, multicenter study

    J Urol

    (2007)
  • C.S.D. Lee et al.

    The past, present, and future of cystoscopy: the fusion of cystoscopy and novel imaging technology

    BJU Int

    (2008)
  • J. Schmidbauer et al.

    Improved detection of urothelial carcinoma in situ with hexaminolevulinate fluorescence cystoscopy

    J Urol

    (2004)
  • E. Hungerhuber et al.

    Seven years’ experience with 5-aminolevulinic acid in detection of transitional cell carcinoma of the bladder

    Urology

    (2007)
  • D.I. Daniltschenko et al.

    Long-term benefit of 5-aminolevulinic acid fluorescence assisted transurethral resection of superficial bladder cancer: 5-year results of a prospective randomized study

    J Urol

    (2005)
  • S. Denzinger et al.

    Clinically relevant risk of reduction in risk of recurrence of superficial bladder cancer using 5-aminolevulinic acid induced fluorescence diagnosis: 8-years results of prospective randomized study

    Urology

    (2007)
  • A. Karl et al.

    Positive urine cytology but negative white-light cystoscopy: an indication for fluorescence cystoscopy?

    BJU Int

    (2009)
  • E.R. Ray et al.

    Hexylaminolaevulinate ‘blue light’ fluorescence cystoscopy in the investigation of clinically unconfirmed positive urine cytology

    BJU Int

    (2009)
  • M. Burger et al.

    Photodynamic diagnostics and noninvasive bladder cancer: is it cost-effective in long-term application? A Germany-based cost analysis

    Eur Urol

    (2007)
  • S. Denzinger et al.

    Does photodynamic transurethral resection of bladder tumour improve the outcome of initial T1 high-grade bladder cancer? A long-term follow-up of a randomized study

    BJU Int

    (2008)
  • J.P. Stein et al.

    Prognostic markers in bladder cancer: a contemporary review of the literature

    J Urol

    (1998)
  • J.A. Karam et al.

    Genomics: a preview of genomic medicine

    BJU Int

    (2008)
  • M.A. Knowles

    Molecular subtypes of bladder cancer: Jekyll and Hyde or chalk and cheese

    Carcinogenesis

    (2006)
  • B.W. van Rhijn et al.

    Molecular grading of urothelial cell carcinoma with fibroblast growth factor receptor 3 and MIB-1 is superior to pathologic grade for the prediction of clinical outcome

    J Clin Oncol

    (2003)
  • C.H. Spruck et al.

    Two molecular pathways to transitional cell carcinoma of the bladder

    Cancer Res

    (1994)
  • M. Burger et al.

    Prediction of progression of non–muscle-invasive bladder cancer by WHO 1973 and 2004 grading and by FGFR3 mutation status: a prospective study

    Eur Urol

    (2008)
  • S. Hernández et al.

    Prospective study of FGFR3 mutations as a prognostic factor in nonmuscle invasive urothelial bladder carcinomas

    J Clin Oncol

    (2006)
  • Mostofi FK, Sobin LH, Torloni H. Histological typing of urinary bladder tumours. In: International Histological...
  • E.C. Ooms et al.

    Analysis of the performance of pathologists in the grading of bladder tumors

    Hum Pathol

    (1983)
  • Cited by (589)

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