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

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