Bacillus Calmette-Guerin therapy after the second transurethral resection significantly decreases recurrence in patients with new onset high-grade T1 bladder cancer

The median age was 72.0 years (range: from 39 to 93 years). The patients were followed
up until March 2014 and the median follow-up period was 33.5 months (range: from 2.9
to 69.5 months). Patients’ characteristics are shown in Table 1. Of the 207 patients who were diagnosed with high-grade T1 bladder cancer, 65 received
a second TUR (31 %) and 142 (69 %) did not (Table 1). BCG induction instillations after the second TUR were performed in 42 patients
(group 1) and not in 23 patients (group 2). Of the 142 patients who were treated without
a second TUR, 72 patients received BCG induction instillations after the initial TUR
(group 3) and 70 patients did not (group 4). Patients in group 4 were older than patients
in the other three groups. Patients in group 1 and group 3, who received BCG therapy,
had more concomitant CIS and higher EAU recurrence risk score than patients in the
two non-BCG treated groups.

Table 1. Patients’ characteristics in four groups

The median interval between the initial TUR and the second TUR was 6.4 weeks (range:
from 1.6 to 11.0 weeks, standard deviation 0.53). Of the 65 patients who underwent
a second TUR, residual tumors were detected in 34 patients (52 %). Histopathological
findings were pT0 in 31 cases (48 %), dysplasia in 2 cases (3 %), atypical gland in
2 cases (3 %), low-grade urotherial carcinoma in 5 cases (8 %), high-grade urotherial
carcinoma pTis/a/1 in 25 cases (38 %). There was no upstaged case. Kaplan–Meier curves
of the intravesical RFS of the four groups are shown in Fig. 2. The 1- and 3-year RFS rates of the four groups were 83 %, 77 % (group 1), 60 %,
32 % (group 2), 68 %, 56 % (group 3), and 56 %, 48 % (group 4). Group 1 had longer
RFS than the other three groups (group 1 vs group 2, 3, 4, p?=?0.002, p?=?0.045, p??0.001, respectively).

Fig. 2. Kaplan–Meier curve of the RFS in the four groups (group 1: BCG induction instillations
after the second TUR, group 2: a second TUR alone, group 3: BCG induction instillations
alone, group 4: neither a second TUR nor BCG induction instillations). RFS: recurrence-free
survival; BCG: Bacillus Calmette-Guerin; TUR: transurethral resection

Table 2 shows the risk factors for intravesical recurrence after a second TUR determined
by univariate and multivariate analyses. BCG induction instillation was the strongest
factor to predict intravesical RFS after the second TUR in both univariate and multivariate
analyses.

Table 2. Risk factors for intravesical recurrence after a second TUR

Table 3 shows the characteristics and outcome of the recurrent cases in the four groups.
Recurrent cases within one year in group 1, 2, 3 and 4 were 7 (17 %), 9 (39 %), 22
(31 %) and 31 (44 %), respectively. With regard to the location of the recurrence
in group 1, 2, 3 and 4, recurrence occurred in the same location as the initial TUR
in 3 (14 %), 3 (23 %), 20 (69 %) and 29 (41 %) cases, respectively; on the other hand,
recurrence occurred in a different location in 7 (33 %), 10 (77 %), 12 (41 %) and
22 (31 %) cases, respectively. On the basis of the RFS in each group and of the location
of intravesical recurrence, patients in group 2, who were treated with the second
TUR without BCG, had more recurrence at a different site from the initial tumor; patients
in group 3, who were treated by BCG induction instillation without a second TUR, had
more recurrence at the same site of the initial tumor. These data indicate that either
BCG alone or a second TUR alone did not prevent intravesical recurrence.

Table 3. Patients’ characteristics and outcome of the recurrent cases in the four groups

Then, among a total of 31 patients whose pathology of the second TUR was pT0, we administered
BCG induction instillation in 12 patients who were treated with a second TUR and in
19 who were not. Only one of the 12 patients (8 %) after BCG induction instillation
following the second TUR had recurrence, and the location of the recurrent tumor was
the same as the initial tumor. On the other hand, 11 of 19 patients (58 %) after the
second TUR without BCG had recurrence (Table 4). Ten of these 11 cases had recurrence at a different site from the initial tumor;
only one had recurrence at the same site of the initial tumor. These results indicate
that high-grade T1 bladder cancer can recur even after the tumor has been completely
resected, and that BCG induction instillation can prevent ectopic intravesical recurrence
after complete resection.

Table 4. Characteristics and outcome of patients whose pathology of the second TUR was pT0