Focused
Review
© JNCCN—Journal of the National Comprehensive Cancer Network | Volume 11 Number 4 | April 2013
477
Abstract
The role for a single dose of intravesical chemotherapy (IVC) after
transurethral resection (TUR) remains unclear in patients with non–
muscle-invasive bladder cancer (NMIBC). Several recent random-
ized clinical trials (RCTs) have evaluated its effect on recurrence,
prompting this systematic review of RCTs comparing a single im-
mediate postoperative dose of IVC versus placebo within 24 hours
of TUR of NMIBC, and this meta-analysis using a random-effects
model to predict the pooled relative risk (RR) of tumor recurrence.
Subanalyses pooled studies by drug type and a meta-regression
was performed to determine the effect of underlying patient risk
factors on the effcacy of a single dose of IVC. A total of 3103 pa-
tients were randomized in the 18 RCTs that met inclusion criteria.
The recurrence rate in patients receiving perioperative IVC and
TUR was 37% versus 50% in the TUR-alone group. The pooled RR
of recurrence for IVC and TUR was 0.67 (95% CI, 0.56–0.79), cor-
responding to a 13% absolute reduction and a number needed
to treat of 7.2 patients to avoid 1 recurrence. The proportions of
patients with tumor risk factors (T1, high-grade, multifocal, or re-
current) were not associated with IVC effcacy. A single dose of IVC
administered within 24 hours of TUR of NMIBC was found to result
in a reduction in tumor recurrence (RR, 0.67; 95% CI, 0.56–0.79).
Patients with higher-risk tumor features seem to beneft at a simi-
lar rate. (JNCCN 2013;11:477–484)
73,510, with a 3:1 male-to-female ratio, and accounted
for 14,880 deaths.
1
At initial presentation, 75% to 85%
are non–muscle-invasive bladder cancers (NMIBCs),
which include stages Ta, T1, and Tis.
2
Several studies
have shown a beneft of immediate intravesical che-
motherapy (IVC) after transurethral resection (TUR)
in reducing tumor recurrence. In 2004, Sylvester et al
3
performed a meta-analysis of 7 randomized clinical trials
(RCTs) comparing cancer recurrence rates in patients
undergoing TUR alone against a combination of TUR
and a single immediate postoperative dose of IVC. The
study found that over a median follow-up of 3.4 years,
37% of patients in the combined group had experienced
a recurrence compared with 48% in the TUR-alone
group (odds ratio, 0.61; 95% CI, 0.49–0.75).
Since the Sylvester meta-analysis, several addition-
al RCTs have been performed, some with new chemo-
therapeutic agents, showing conficting results regard-
ing the effect of single-dose IVC on NMIBC recurrence.
As a result, existing clinical guidelines provide differing
recommendations to practitioners. For example, the
American Urologic Association does not recommend
the routine use of a single dose of IVC immediately
after TUR for patients without a diagnosis of bladder
cancer because of diagnostic uncertainty and increased
cost.
4
Rather it is listed as optional for men with small-
volume, low-grade Ta bladder cancer. The European
Association of Urology, however, does recommend that
a single dose of immediate postoperative IVC be admin-
istered after TUR of a bladder lesion, with additional
therapy decisions based on EORTC risk category.
2
Fi-
nally, NCCN recommends a single dose of IVC within
24 hours of a “nonextensive” TUR of a bladder tumor
during which the bladder was not perforated.
5
In light of new RCTs and conficting clinical guide-
lines, the authors sought to reassess the effect of im-
From the Division of Urology, Duke University Medical Center,
Durham, North Carolina.
Submitted August 15, 2012; accepted for publication March 21,
2013.
The authors have disclosed that they have no fnancial interests,
arrangements, affliations, or commercial interests with the
manufacturers of any products discussed in this article or their
competitors, nor have they received any fnancial support for the
research presented.
Correspondence: Brant A. Inman, MD, MS, FRCSC, Box 2812, Duke
University Medical Center, Durham, NC 27710. E-mail: brant.
inman@duke.edu
Perioperative Intravesical Chemotherapy in
Non–Muscle-Invasive Bladder Cancer:
A Systematic Review and Meta-Analysis
Michael R. Abern, MD; Richmond A. Owusu, BS; Mark R. Anderson, MD; Edward N. Rampersaud, MD;
and Brant A. Inman, MD, MS, FRCSC
Currently, 2.4% of all people born in the United States
will develop bladder cancer during their lifetime.
1
In
2012, the estimated incidence of bladder cancer was