PATIENT’S COMPLIANCE TO BCG. DO WE ADEQUATELY CONSIDER IT?

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 Particularly, 32 (8.4%) patients refused it due to personal choice and/or practical limitation, 22 (5.8%) were withdrawn by the urologist before the first planned 3- week cycle due to persistent haematuria or early recurrence and 18 more patients (4.7%) never started and were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) 2618 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.