AUA Experts Release Treatment Guidelines For Bladder
Cancer
BALTIMORE, MD -- October 21, 1999 -- Physicians should consider using
intravesical chemotherapy or immunotherapy as adjuvant therapy following surgery
for non-muscle-invasive bladder cancer, according to new treatment guidelines
released today by the American Urological Association (AUA). Currently, there is
wide variation in the use of adjuvant therapy after transurethral resection of
the bladder.
"For patients who have not had prior intravesical therapy,
adjuvant intravesical chemotherapy or immunotherapy is an option for treatment
after endoscopic removal of low-grade bladder cancers," the AUA guidelines
report states. "All the intravesical agents studied, when used after
transurethral resection, result in lower probability of recurrence than surgery
alone."
Although the data examined by the AUA panel shows that the
intravesical agents decrease bladder cancer recurrence rates, there is no
evidence that they affect long-term progression and they may not be appropriate
in all cases. "The fact that the peer reviewed published data show that the use
of intravesical agents used after surgery lowers the probability of recurrence
but not progression is the most important finding that we made," says panel
Chair Dr. Joseph A. Smith, Jr., of the Vanderbilt University Medical Center.
"It certainly is something that needs to be examined through further
research.
"It also underscores the fact that careful followup is required
because bladder cancer patients are at risk for progression to muscle invasive
cancer which may require bladder removal."
According to Dr. Smith, the
guidelines are especially important because "they establish an objective basis
for physicians to use in determining treatment options to decrease bladder
cancer recurrence."
Chemotherapy and immunotherapy agents reviewed by the
panel include thiotepa, BCG, mitomycin C, and doxorubicin.
Two of the
agents-BCG or mitomycin C-are recommended for treatment after endoscopic removal
of high-grade tumors that have begun to penetrate the superficial bladder wall
but not the muscle because they are superior for reducing recurrence of tumors,
according to the guidelines.
The guidelines report was produced by the AUA
Bladder Cancer Clinical Guidelines Panel, a group of bladder cancer experts that
analyzed published outcomes data to assess potential benefits and possible
adverse effects of treatment interventions and developed practice policy
recommendations. The guidelines were released in the form of a summary article
in the November
Journal of Urology
, the monthly peer-reviewed journal of
the American Urological Association.
According to the American Urological
Association, more than 50,000 new bladder cancer cases are diagnosed each year
in the United States and the incidence rate is slowly rising. Primarily a
disease of middle and old age (more than 70 percent of new cases are diagnosed
in persons 65 and older), the incidence is expected to increase as the U.S.
population ages.
Smoking was cited by the panel as a significant cause of
bladder cancer.
"One half of all bladder cancer cases in the United States
are associated with cigarette smoking," says Salt Lake City urologist Dr.
Richard Labasky, a member of the AUA guidelines panel.
"While not directly
related to the treatment guidelines recommendations for physicians, that fact
should be a key message for the general public about preventing bladder
cancer."
The three types of outcomes the panel determined to be most
important in their analysis are: 1) probability for tumor recurrence; 2) risk
for tumor progression; and 3) complications of treatment.
Once relevant
peer-reviewed published articles were reviewed and data from these articles
analyzed, recommendations were made for three types of patients:
- A patient
who presents with an abnormal growth on the urothelium but has not yet been
diagnosed with bladder cancer.
- A patient with established bladder cancer of
any grade, stages Ta or T1, with or without carcinoma in situ, who has not had
prior intravesical therapy.
- A patient with carcinoma in situ or an
aggressive cancer that has begun to penetrate the bladder wall, who has had at
least one course of intravesical therapy.
Panel policy recommendations were
categorized into three grades of flexibility as determined by the strength of
the available evidence and the expected amount of variation in patient
preferences. The three levels are standards, which have the least flexibility;
guidelines, which have significantly more flexibility; and options, which have
the most flexibility.
The guidelines panel recommended as a standard that
physicians should discuss with all three types of index patients treatment
alternatives and the benefits and risks of each alternative, including side
effects. While the panel's report states that the incidence of serious or life
threatening side effects of any agent are low, all the agents have side effects,
some in common and some unique to a particular agent.
For the index patient
who presents to a physician with an abnormal growth on the urothelium but has
not yet been diagnosed with bladder cancer, the panel recommends as a standard
that a biopsy should be obtained for pathological analysis. Once a diagnosis of
bladder cancer has been established, the panel recommends as a standard that
complete eradication of all tumors should be performed if surgically feasible
and if the patient's medical condition permits.
The panel recommends adjuvant
intravesical chemotherapy or immunotherapy as an option for treating this
patient after endoscopic removal of low-grade bladder cancers because the
outcomes data "show a decreased recurrence probability for all the intravesical
therapies studied, compared to transurethral resection alone." However, based
upon panel opinion, many patients with low- grade tumors do not require adjuvant
intravesical therapy.
There is a low risk of disease progression in this
group and little evidence that adjunct therapy affects the progression rate,
according to the report.
Panel members did recommend, as a guideline,
intravesical use of either BCG or mitomycin C for treatment of carcinoma in situ
and for treatment after removal of tumors that have begun to penetrate the
bladder wall and high-grade Ta tumors. This recommendation is "based on evidence
from the literature and panel opinion that both BCG and mitomycin C are superior
to doxorubicin or thiotepa for reducing recurrence of these tumors."
Because
there is some risk of progression to muscle-invasive disease even after
intravesical therapy, the report stated that, as an option, bladder removal may
be considered as an initial treatment option in certain patients, based on
several factors including large tumor size, high grade of tumor, and tumor
location.
In patients with carcinoma in situ or high-grade tumors who have
had at least one course of intravesical therapy, the panel report states that
cystectomy (a surgical procedure to remove the bladder) and further intravesical
therapy may be considered as options for cancers that have persisted or
recurred.
In concluding its report, the AUA panel recommended several areas
where further research is needed, including dose and frequency of agents used in
adjuvant therapy; the probability of progression; the risk and significance of
urothelial carcinoma outside the bladder, and the role of treatment regimens
using alternative or combined drugs.
