Introduction: Several studies and meta-analysis demonstrated
that BCG is the best treatment for conservative management of
high-risk NMI-BC with a net benefit in terms of both
recurrence-free and progression-free survival (1, 2).
Maintenance lasting minimum one year is recommended. In
spite of the effectiveness, the amount of patients who complete
the manteinance schedule does not exceed 50% (3). The
reasons of BCG maintenance interruption remain still unclear.
The aim of our study was to investigate the causes of low
adherence to 1-year full dose maintenance BCG in a large
series. Patients and Methods: The clinical files of consecutive
patients affected by T1 HG NMI-BC and undergoing adjuvant
BCG for one year, between 2000 and 2012, were reviewed.
Main exclusion criteria were presence of Tis, previous T1 HG,
number of tumors more than 3 and diameter greater than 3 cm,
genitourinary tract infections or other disease potentially
impacting tolerability and compliance to BCG. One-year BCG
maintenance was scheduled according to the South West
Oncology Group (SWOG) including 3 weekly instillations at
3, 6 and 12 months starting 21-40 days after TUR. No dose
reduction was considered. Both local and systemic side effects
and any reason of treatment suspension were recorded. BCG
tollerability was classified in four grades: 0. no need of
postponement, 1. one-week postponement, 2. two-week
postponement, 3. one single instillation omitted, 4. definitive
stop. Results: The files of 545 consecutive patients with HG
NMI-BC, selected for conservative management at two tertiary
referral centers were reviewed. Out of them, 411 patients
(75.4%) satisfied the inclusion criteria. The induction cycle was
completed and suspended by 380 (92.5%) and 31 (7.5%)
patients respectively. Suspension was due to toxicity in 20
(4.8%) and to no toxicity-related reasons in 11 (2.6%) patients.
Maintenance was initiated by 308 (74.9%) patients while 72
(17.5%) never started. Particularly, 32 (8.4%) patients refused
it due to personal choice and/or practical limitation, 22 (5.8%)
were withdrawn by the urologist before the first planned 3-
week cycle due to persistent haematuria or early recurrence and
18 more patients (4.7%) never started and were lost at followup.
Out of the 308 patients starting the 1-year maintenance, 215
(52.3%) patients completed it, while 93 (30.2%) did not. The
manteinance regimen was interrupted by 9 patients (9.7%) due
to recurrence, while 14 (15.1%) experienced grade 3 toxicity
and 55 (59.1%) refused it in absence of grade 2-3 toxicity or
other evident causes. Grade-I toxicity and/or mild side effects,
not responsible for maintenance treatment modification, were
recorded in 193 (62.7%) patients. Discussion and Conclusion:
The European Association of Urology (EAU) and the National
Comprehensive Cancer Network (NCCN) recommend one year
BCG maintenance as the elective intravesical adjuvant regimen
in intermediate- and high-risk NMI-BC, conservatively treated.
The scientific urologic community does not consider BCGrelated
toxicity as the major limiting factor. In the present study
patient’s compliance during the induction cycle reached 92%.
However during the interval between the induction course and
the first maintenance instillation, 50 patients (13%) became
reluctant to treatment while 22 (6%) were excluded after
cystoscopy for suspicious bladder lesion. Toxicity (moderate to
severe) was responsible for the interruption of BCG
maintenance only in a low number of patients. The high rate
of patients who abandoned the treatment could be attributable
to the persistency of mild symptoms causing consistent
discomfort that justified the reluctance to carry on the therapy.
Moreover the inadequate counseling in everyday clinical
practice when compared to multi-institutional trials should be
taken into account. A structured periodical counseling and a
timely recognition and treatment of symptoms, might
significantly ameliorate the acceptance of BCG maintenance.
Acknowledgements: We wish to thank the GSTU Foundation for
administrative support.
1 Sylvester RJ et al: Intravesical bacillus Calmette-Guerin
reduces the risk of progression in patients with superficial
bladder cancer: a meta-analysis of the published results of
randomized clinical trials. J Urol 168: 1964-1970, 2002.
ANTICANCER RESEARCH 34: 2593-2686 (2014)
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2 Malmstrom PU et al: An individual patient data metaanalysis
of the long-term outcome of randomised studies
comparing intravesical mitomycin c versus bacillus
Calmette-Guerin for non–muscle-invasive bladder cancer.
Eur Urol 56: 247-256, 2009.
3 Oddens J et al: Final results of an EORTC-GU of EORTC
genito-urinary cancers group randomized study of
maintenance bacillus comparing intravesical instillations of
Calmette-Guerin in intermediate- and high-risk Ta, T1
papillary carcinoma of the urinary bladder: one-third dose
versus full dose and 1 year versus 3 years of maintenance.
Eur Urol 63: 462-472, 2013