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Chemotherapeutic Prophylaxis of Superficial Bladder Tumors

Chemotherapeutic Prophylaxis of Superficial Bladder Tumors

In a recent issue of ONCOLOGY (15:85-88, 2001), Drs. Edgar C. Baselli and Richard E. Greenberg presented a brief overview of maintenance
intravesical chemotherapy for superficial bladder cancer.[1] Along with two
accompanying reviews,[2,3] this article highlights the continuing controversy
surrounding the management of this disease. While numerous drugs have been and
continue to be used in the treatment of superficial bladder cancer, the true
impact of such treatment on recurrence, progression, and survival remains
unclear. Some investigators (eg, Lamm et al[4]) suggest that intravesical
chemotherapy has only a minor effect on tumor recurrence rates and question the
advisability of its routine use (as opposed to immunotherapy with bacillus
Calmette-Guérin, or BCG). In fact, Lamm et al reported that the addition of
chemotherapy produced only a 14% decrease in the recurrence rate at 1 to 3 years
post-transurethral resection of the bladder (TURB).

Literature Limitations

The literature related to this topic suffers from multiple limitations,
making interpretation problematic. For instance, the summary published by Lamm
et al[4] combined studies in patients with primary and recurrent bladder tumors,
without stratifying this parameter. Biological differences may exist between
primary and recurrent disease, which may be reflected in the response to
chemotherapy. Thus, stratification of this parameter would be informative.
Second, this analysis failed to calculate recurrence rates at specific end
points (eg, 1 or 2 years post-TURB). Third, and most importantly, the analysis
was not performed via standard statistical methods designed specifically for
combining data from multiple randomized clinical trials (ie, meta-analyses).[5]

More Recent Analyses

In an attempt to clarify the ambiguities in the existing published database,
our group performed two meta-analyses using 1-, 2-, and 3-year recurrence rates
as end points.[6,7] The relevant clinical trials were pooled using accepted
meta-analytic techniques.[5] Combined data from 11 trials enrolling over 3,703
patients with primary superficial bladder cancer showed a 30% to 80% reduction
in the incidence of recurrence at 1 to 3 years following TURB plus intravesical
chemotherapy vs TURB alone.[6] Of all the chemotherapeutic agents used,
mitomycin-C (Mutamycin) appeared to be the most effective. Also, long-term
treatment protocols (ie, 2 years) were more effective than short-term or
single-instillation schedules.

Among patients treated for recurrent bladder tumors, intravesical
chemotherapy reduced recurrence by 38% at 1 year compared with TURB alone, while
2- and 3-year recurrence rates were decreased by 54% and 65%, respectively.
Doxorubicin was shown to be significantly less effective than all other drugs
studied.

Heterogeneity across the available studies, in terms of tumor stage, grade,
treatment schedule, chemotherapeutics employed, clinical end points, and
treatment durations, makes the translation of existing information into clinical
practice guidelines difficult. In order to distill clinically useful information
from such data, appropriate statistical techniques must be employed.[5] These
techniques not only allow calculation of a summary estimate of effect but also
enable evaluation of statistical heterogeneity. Such analyses can provide
important insight into potential biases in study design or elucidate confounders
that may produce spurious results.

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