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Bladder Cancer
Figure 1: Summary of the Management of
invasive bladder cancers. The literature suggests that the tumour
Non-muscle-invasive Bladder Cancer
histology will be upstaged to muscle-invasive in a number of cases,
ranging from 2 to 29%, resulting in completely different treatment
TURBT
strategies.
19
Residual cancer was found in 33–76% of cystoscopies.
The reasons for this include incomplete TURs, missed tumours or early
recurrences from circulating tumour cells or previous microscopic
Single-dose intravesical
chemotherapy
lesions. An alternative treatment option for high-risk tumours is early
radical cystectomy. However, there is significant morbidity and
mortality with this procedure, and it is only beneficial to those who will
Low-risk tumour Intermediate-risk tumour High-risk tumour
suffer disease progression.
Second-look TUR may help to identify those who will benefit from
reTUR reTUR
early cystectomy as, in one study, 76% of patients with G3T1 tumours
found at the second TUR progressed to muscle invasion; this prompted
Maintenance BCG
Maintenance BCG Cystectomy
the authors to recommend that the group should be considered for
or chemotherapy
early cystectomy.
20
Radical cystectomy should also be performed if the
patient fails treatment with BCG. This is is defined as disease
recurrence at three and six months or a recurrence of a higher grade,
Cystoscopic surveillance Cystoscopic surveillance Cystoscopic surveillance
T stage or CIS at any time during treatment.
9
TURBT = trans-urethral resection of bladder; reTUR = repeat TUR; BCG = bacillus Calmette-
Guérin. The dotted line represents treatment failure and progression to a higher-risk group as
a result. Based on guidelines laid down by the American Urological Association,
8
the
Guideline Similarities and Differences
European Association of Urology
9
and the British Association of Urological Surgeons/British
The AUA,
8
EAU
9
and BAUS/BUG
10
guidelines all advocate complete
Uro-oncology Group.
10
TUR of the bladder tumour to resect it and to gain histology and
course for medium- to high-risk non-muscle-invasive bladder cancer diagnosis. Additionally, they all agree on the benefit of a single post-
(recurrent and/or multifocal G1Ta, G2-3Ta and G1-3T1).
12
Intravesical operative dose of intravesical chemotherapy. They all divide non-
chemotherapy has no effect on progression. A meta-analysis of several muscle-invasive bladder tumours into three risk categories: low,
randomised clinical trials revealed that TUR and adjuvant chemotherapy intermediate and high. These represent the risk of progression.
had no effect on progression to muscle invasion, progression-free
survival or overall survival compared with TUR alone.
13
Maintenance chemotherapy is
Immunotherapy
Intravesical bacillus Calmette-Guérin (BCG) therapy (immunotherapy) also
recommended for intermediate-risk
reduces the risk of recurrence, with better results than intravesical non-muscle-invasive bladder cancers,
chemotherapy.
14
However, BCG is associated with higher toxicity, which
but the frequency and duration of
can result in poor compliance.
15
The AUA meta-analysis reports that
intravesical maintenance BCG reduces recurrence by 17% compared with treatment remains unclear.
maintenance chemotherapy
8
and that maintenance BCG reduces
recurrence by 31% compared with TUR alone.
Treatment options for the low- and high-risk groups are fairly
Although the AUA panel found that BCG had no statistically significant standard, with a single post-operative dose of intravesical
effect on tumour progression or survival, an alternative meta-analysis of chemotherapy and cystoscopic follow-up recommended for the
24 randomised trials reported a statistically significant 27% reduction in former, and maintenance BCG or early radical cystectomy for the
the risk of progression with BCG treatment.
7
This increased to 37% if the latter, with radical cystectomy for BCG failures (see Figure 1).
trials only giving maintenance BCG therapy were analysed.
7
Analysis
of trials with only a six-week BCG induction course found no difference However, the AUA grades its guidelines as either ‘standards’,
in disease progression compared with controls. ‘recommendations’ or ‘options’, and neither a single dose of
chemotherapy nor maintenance BCG is ‘standard’. Single-dose
The AUA panel also reported that maintenance BCG therapy reduces chemotherapy is an ‘option’ and maintenance BCG is a
recurrence by 14% compared with TUR and BCG induction.
8
Some ‘recommendation’.
8
It is the intermediate category and its management
researchers reduced the dose of BCG and demonstrated reduced toxicity for which guidelines differ.
with similar efficacy. However, a full dose may be better in multiple
tumours.
16,17
In addition to the optimal dose, the optimal maintenance The guidelines also vary in their objectives, with the AUA
8
aiming to
schedule is also unknown. Many people follow the Southwest Oncology reduce recurrence, whereas the EAU
9
and BAUS/BUG
10
aim to reduce
Group (SWOG) three-year regimen.
18
recurrence and progression. This relates to the fact that the AUA
meta-analysis found no statistically significant effect on tumour
Repeat Transurethral Resection progression or survival with maintenance BCG.
8
All three organisations
A repeat TUR (reTUR), two to six weeks after the initial TUR, is also recommend repeat TUR if no muscle is included in the histology
recommended by a number of authors for high-risk non-muscle- specimen, with the AUA suggesting it as a ‘standard’ for high-risk cases,
8
26 EUROPEAN GENITO-URINARY DISEASE 2007
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