Bcg Case Study

Orihuela and Smith [139] found a recurrence rate of
80% among patients who did not receive supplemental
BCG versus a recurrence rate of 16.6% among those who
did. However, an update of their series could not ultimately
demonstrate a survival advantage with the addition
of adjuvant BCG [111]. Rastinehad et al. [122]
retrospectively studied 133 renal units treated by percutaneous
resection for UTTCC. Eighty‐nine renal units
treated primarily by percutaneous resection were then
analyzed. Fifty renal units received adjuvant BCG therapy
two weeks after endoscopic management for a total
of six courses. Recurrence was defined as a positive
biopsy result after the third‐look nephroscopy. Overall
median follow‐up was 40.8 months. There was no statistical

difference with regard to tumor grade or stage
between treated and nontreated groups. Recurrence,
time to recurrence, and progression of disease among
renal units treated with BCG were subselected by grade
and compared with the corresponding nontreated group.

There was no statistical significance demonstrated
between any of the treated and nontreated groups. The
authors concluded that there is no overall oncologic benefit
in the administration of adjuvant BCG with regard to
disease recurrence, interval to recurrence, and progression
of disease in the treatment of UTTCC. The latest
analysis of this retrospective series from Smith’s group
included 141 patients with median follow‐up of 66
months [143]. Nephroureterectomy was avoided in 87%
of patients. Recurrence occurred in 37% of low‐grade
UTTCC patients and 63% of high‐grade UTTCC
patients, with a median time to recurrence of 71.4 versus
36.4 months, respectively. On multivariate analysis,
grade was the only predictor of recurrence (HR 2.12,
P = 0.018). Disease in one patient recurred after 116
months of surveillance, emphasizing the importance of
long‐term follow‐up after endoscopic management of
UTTCC. Similar to their previous analysis, BCG and
mitomycin did not protect against recurrence, progression
to nephroureterectomy, or death over resection
alone

[143].
Similarly, Martinez‐Pineiro et al. [114] have shown
reduction in recurrence rates with addition of BCG or
mitomycin C following endoscopic treatment of UTTCC.
The authors reported a recurrence rate of 50% among
patients with grade 2 or 3 disease who were not treated
with adjuvant therapy, versus a recurrence rate of 27.7%
among a similar group of patients who received some
form of adjuvant therapy. They used several drugs in that
study, including BCG, mitomycin C, 5‐fluorouracil, thiotepa,
and interferon‐α, from which only BCG and mitomycin
C were promising. Finally, Katz et al. [121]
published their initial experience with BCG plus
interferon‐α2b. With a median follow‐up of 24 months,
80% demonstrated a complete response, while 20% had a
partial response (decrease in tumor size, number, or
both). The authors reported that the treatment was well
tolerated in the office setting and did not note any
complications.
In contrast, other studies have not shown a significant
difference between patients treated with adjuvant
mitomycin
C or BCG compared to those undergoing
endoscopic treatment alone [112, 144]. Hayashida et al.
[145] reported a 50% disease recurrence rate after a
follow‐
up of 50.9 months using intrarenal perfusion of
BCG with endoscopic treatment. This high recurrence
rate occurred despite an initial return of cytology results
to normal and all of these patients suffered cancer‐specific
mortality.
There are several known complications of cavitary
BCG therapy. Persistent fever after BCG administration
has been reported in 3 out of 59 (5.1%) patients in a combined
series. However, this resolved in all cases with
appropriate antimicrobial therapy [111, 114, 144].
Granulomatous involvement of the upper urinary tract
may occur in up to 25% of patients after BCG administration
[146]. Therefore, it is important to obtain percutaneous
biopsy of renal masses that develop in patients
who have received intracavitary BCG prior to deciding
on their management [147]. In addition, these renal
granulomas could be observed in asymptomatic
patients and they may resolve without antituberculous
medications [147].
The controversy and variability among studies addressing
intracavitary use of BCG as an adjuvant therapy for
UTTCC are likely the result of lack of prospective randomized
studies and reliance on retrospective case series
with their inherent biases in patient selection. Some
authors treat all patients with adjuvant therapy while
others treat only high‐risk patients. Furthermore, it is
important to note that there are several products containing
different substrains of BCG. There is variability
of BCG organisms per milligram of vaccine with different
substrains and variability from lot to lot within the
same substrain [148, 149]. Thus, the true efficacy of
adjuvant BCG therapy for UTTCC has yet to be adequately
evaluated. However, secondary effects of therapy
seem to be generally well tolerated among patients.
Mitomycin C
Less information is available on the use of intracavitary
mitomycin C topical treatment compared with BCG.
Mitomycin C is a 334 kDa alkylating agent that inhibits
DNA synthesis. Because of its moderately high molecular
weight, there are few problems with transurothelial
absorption. Therefore, side‐effects such as myelosuppression
are rare with mitomycin C. The typical dosage
varies from 20 to 60 mg per instillation, and the most