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Bladder Cancer
New Treatments for Non-muscle-invasive Bladder Cancer
Antoine G van der Heijden
1
and J Alfred Witjes
2
1. Resident; 2. Professor of Oncological Urology, Department of Urology, Radboud University Nijmegen Medical Centre
Abstract
Non-muscle-invasive bladder cancer (NMIBC) is characterised by a high risk of recurrence after transurethral resection of the initial tumour.
The one-year recurrence rate is 15–61% and the five-year recurrence rate is 31–78%. Despite this high risk of recurrence, the five-year
survival rate is 85–90%. Unfortunately, after one year up to 17% and after five years up to 45% of the non-muscle-invasive tumours will
progress to a muscle-invasive tumour, which has a much poorer prognosis. The priorities in patients with non-muscle-invasive transitional
cell carcinoma are therefore two-fold: to lower the number of recurrences and to prevent progression. However, current treatment options
are still far from optimal. In the last decade several new treatment options have been introduced, including combination therapy and the
application of medical devices. In this article, developments in the treatment of NMIBC are reviewed. New chemotherapeutic and
immunotherapeutic agents are studied, as well as new agent delivery devices.
Keywords
Non-muscle-invasive bladder cancer, intravesical chemotherapy, gemcitabine, apaziquone, taxanes, immunotherapy, mycobacterial cell-wall DNA
complex, Lactobacillus casei, interferon-α, microwave-induced thermotherapy, electromotive drug administration, photodynamic therapy
Disclosure: The authors have no conflicts of interest to declare.
Received: 22 May 2009 Accepted: 10 July 2009
Correspondence: Antoine G van der Heijden, Department of Urology, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
E: t.vanderheijden@uro.umcn.nl
Non-muscle-invasive bladder cancer (NMIBC) is characterised by a high an estimated cost of US$96,000–187,000 per patient from diagnosis to
risk of recurrence after transurethral resection of the initial tumour. The death in the US.
8
So, from both a patient and an economic point of view
one-year recurrence rate is 15–61% and the five-year recurrence rate is it is important to reduce the number of recurrences. In this article new
31–78%.
1,2
Clinical prognostic factors for recurrence and progression are treatment options for NMIBC are reviewed.
size, multiplicity, reaction to intravesical therapy, grade, stage and the
presence of carcinoma in situ (CIS). Nevertheless, recurrence anywhere Chemotherapy
in the bladder at first follow-up cystoscopy after transurethral resection The recurrence rate of NMIBC after intravesical chemotherapy
(TUR) is one of the most important prognostic factors for time to decreases in the short term, but in the long run this benefit disappears.
progression.
3,4
It is possible to identify three groups of patients. A In addition, progression is not prevented by chemotherapy use. There
minority of patients have a relatively benign type of transitional cell is still a role for chemotherapy in the treatment of NMIBC, but it is
carcinoma (TCC) with a low recurrence rate. In such patients, refraining reserved for patients with low- and intermediate-risk disease and BCG-
from adjuvant treatment is an option, but one immediate instillation with refractory disease.
a chemotherapeutic agent significantlylowers the recurrence rate in
the first few years
5–7
and therefore is the treatment of choice. The Gemcitabine
largest group consists of patients who frequently develop a non- Gemcitabine is a novel deoxycytidine analogue with a broad spectrum
muscle-invasive recurrence but seldom progression. In an attempt to of antitumour activity. It has a molecular weight of 300, and after
reduce the number of recurrences, adjuvant therapy after TUR has intracellular activation the active metabolite is incorporated into DNA,
become common practice. Guidelines advise additional intravesical resulting in inhibition of further DNA synthesis. It has been proved to be
chemotherapy or intravesical bacillus Calmette-Guerin (BCG). Finally, a efficacious in advanced bladder cancer, with acceptable adverse
small group of patients have a relatively malignant non-muscle-invasive effects.
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Animal studies showed conflicting results concerning systemic
tumour at presentation and, despite maximum intravesical treatment, absorption. Dalbagni et al. found significant systemic absorption in
which is maintenance BCG, up to 45% of all patients will develop dogs, whereas our study with pigs did not show any systemic
invasive cancer. These high-risk patients must be selected as soon as absorption.
10–12
A possible explanation is the difference in instillation
possible. Thus, the major goals in treating patients with NMIBC are to schedule (three times a week versus weekly).
prevent the high number of recurrences and to prevent muscle-invasive
progression. This high number of recurrences is also reflected in the In the last decade gemcitabine has been investigated for intravesical
high cost, which makes NMIBC the most expensive disease to treat, with use in patients. Dalbagni et al. studied gemcitabine in BCG-refractory
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