Availability and Patterns of Intravesical BCG Instillations Sławomir Poletajew*, Aleksandra Majek, Piotr Magusiak, Katarzyna Śledzikowska, Bartosz Dybowski, Piotr Radziszewski Purpose: Intravesical BCG instillations improve recurrence free survival in patients with non-muscle-invasive bladder cancer (NMIBC). Methods: This is a national survey study, covering 223 urological centres, aimed at reliable identification of BCG availability and implemented treatment patterns. Results: Response rate was 93.7%. BCG was used in 56.5% of urological departments. Another 22.7% referred patients to other hospitals for instillations, while 20.8% did not recommend BCG at all. The most common in- dications for BCG instillations were as follows: T1 tumours (88.5%), carcinoma in situ (83.6%) and high grade tumours (73.8%). Maintenance therapy was routinely abandoned in 16.4% of centres or was scheduled for <1 year, 1 year, 3 years and 1-3 years in 6.6%, 19.7%, 21.3% and 31.2% of centres, respectively. Continuation of BCG despite treatment failure in carcinoma in situ cases was considered in 21.3% of departments. Conclusion: Our findings indicate that BCG is underused, while patterns of maintenance and follow-up are sub- optimal. Keywords: Bacillus Calmette-Guerin; Bladder cancer; Intravesical instillation; Physician survey; Recurrence. Department of Urology, Medical University of Warsaw, Warsaw, Poland. *Correspondence: Department of Urology, Medical University of Warsaw 4 Lindleya St., 02005 Warsaw, Poland. Tel: +48225021702. Fax: +48225022148. E-mail: slawomir.poletajew@wum.edu.pl. Received November 2016 & Accepted May 2017 INTRODUCTION Intravesical Bacillus Calmette-Guerin therapy (BCG) improves recurrence-free, as well as may prolong progression-free survival in patients with high- and intermediate-risk non-muscle-invasive bladder can- cer (NMIBC) after transurethral resection of bladder tumour (TURBT). However, BCG is associated with important limitations. First, half of patients does not complete full BCG course due to toxicity, discomfort, deterioration in quality of social life or disease recur- rence.(1) Second, urological community has to face re- duced availability of BCG strains. Finally, adherence to EAU guidelines on BCG therapy and monitoring of NMIBC patients vary between institutions and coun- tries in Europe.(2) These factors can lead to underuse of intravesical immunotherapy. Despite clear clinical significance, reliable real-life data on usage of BCG in Europe is limited. This data would be of special atten- tion in the region of Central Europe, where survival of patients with bladder cancer was reported to be signif- icantly lower than in Western Europe(3,4) and where the incidence of high-risk NMIBC is relatively high.(5) In this context, we decided to perform a national anal- ysis of availability and patterns of BCG therapy in Po- land. METHODS Based on National Health Fund registry, we identi- fied 223 urological centres in Poland. Afterwards, we contacted these departments electronically and/or by telephone in the period from December 2015 to March 2016. Urologists working in these centres were asked to complete a unified survey. It consisted of 23 ques- tions in five blocks, concerning availability of BCG, indications for therapy, technique of instillations, dura- tion and scheme of treatment, and follow-up protocols. Questions applied to hospital policy regarding BCG instillations and did not incorporate any patient clini- cal data. Before answering the questions, all respond- ers were informed about the character of the study and were ensured about anonymous publication of data. RESULTS Response rate was 93.7% (n=209/223). Among the re- sponders, there were 55 highly specialized or one-day surgery centres, which did not take care of patients with bladder cancer. They were excluded from further analysis, limiting the study group to 154 urological de- partments routinely performing TURBTs. BCG was available in 56.5% of these departments (n=87/154). In 22.7% of cases urologists declared to routinely refer pa- tients to other centres for BCG (n=35/154). In 20.8% of departments BCG was not recommended irrespective- ly of oncological characteristics of individual patient (n=32/154) (Figure 1). Full data regarding indications, preparation of patient, BCG strains and follow-up was available for 70.1% of centres (n=61/87; Table 1). In patients with high-risk NMIBC, follow-up cystoscopy was scheduled 3 and 6 months after TURBT in 95.1% and 78.7% of cases, BRIEF COMMUNICATION Vol 14 No 06 November-December 2017 5068 therapy was continued in 59.0% and 21.3% of depart- ments, respectively. Urinary cytology complemented endoscopic assessment only in 32.8% of departments. DISCUSSION This is a unique national survey study, presenting real pattern of BCG treatment in Poland. As the study cov- ered 94% of urological centres in the country, it pre- sents fully reliable data. The importance of our findings are highlighted by the fact that mortality rate from blad- der cancer in Europe is the highest among Latvian and Polish patients.(4) Our survey study indicated significant shortcomings in the adjuvant treatment of patients with NMIBC. The most important findings can be summa- rized as a “triple one-fifth rule”. One fifth of patients has no access to BCG therapy, thus it is advocated to state this therapy is underused. One fifth of patients are not considered for maintenance therapy or its duration is inadequate, thus BCG therapy is suboptimal. Finally, in patients with Cis, in one fifth of cases the therapy is continued despite BCG failure. Our data allowed us to formulate several possible rea- sons for unsatisfactory survival of bladder cancer pa- tients in Poland. It can be assumed that both limited use of BCG and suboptimal follow-up, as well as delaying the decision for radical treatment could be the contrib- uting factors. However, it is of utmost importance to establish whether these findings are a kind of regional phenomenon or they rather present global trend. This question is particularly relevant if one considers high toxicity related to the treatment, BCG shortage, data on decreased effectiveness in elderly and limited compli- ance of bladder cancer patients.(1,6,7) However, none of these facts eventually advocate intentional underuse of BCG therapy. The use of BCG in patients with high-risk NMIBC varies between institutions. Recent study by Witjes et respectively. In patients with history of carcinoma in situ (Cis), 19.7% of departments routinely performed random bladder biopsy during follow-up. In case of presence of Cis at 3 and 6 months after TURBT, BCG Patterns of intravesical BCG instillations-Poletajew et al. Table 1. Adopted indications, patient preparation and BCG strains in Polish departments applying BCG treatment. Indications T1 tumours 88.5% High grade or G3 tumours 73.8% Carcinoma in situ 83.6% Intermediate-risk NMIBC 44.3% Patient preparation Urine alkalisation before instillation 4.9% Changing position after instillation 73.8% Limitation of fluid intake before instillation None 29.5% For 2-3 hours 50.8% For > 3 hours 14.8% Unspecified time 4.9% Limitation of fluid intake after instillation None 59.0% For 1-2 hours 26.2% For 2-3 hours 14.8% BCG strain used RIVM 60.7% Moreau 26.2% Tice 3.3% Different / unspecified 9.8% Duration of maintenance therapy None (only induction course) 16.4% < 1 year 6.6% 1 year 19.7% 1-2 years 4.9% 3 years 21.3% 1-3 years, depending on patient individual risk 31.2% Abbreviations: NMIBC – non muscle-invasive bladder cancer. Figure 1. Flowchart presenting constitution of study group and availability of BCG in Polish urological centres. NMIBC – non muscle-invasive bladder cancer; TURBT – transurethral resection of the bladder tumour. Brief Communication 5069 al. demonstrated significant non-adherence to clini- cal guideline recommendations for BCG use in North America and Europe. In their study only 29% of in- termediate-risk patients received intravesical therapy, while in the group of high-risk patients BCG induc- tion and maintenance was offered to 50% of patients. (8) In contrast, based on survey study among American urologists, Nielsen et al. reported routine use of BCG induction and maintenance therapy in over 80% of pa- tients with high-grade NMIBC. However, despite high number of responders included, the response rate in the study was only 6.9%.(9) Gontero et al. showed that 22% of high-risk NMIBC patients receive no further treat- ment after TURBT in referral Italian centres, while BCG maintenance is implemented in 57% of cases.(10) Historical analysis of SEER database by Chamie et al. presented the rate of implementation of maintenance BCG therapy in 26% of high-risk patients.(11) All pa- pers cited above analysed individual patient data from selected urological centres or presented clinical practice of individual urologists. None of them present fully re- liable regional schemes of BCG treatment. Our study presents strategies of bladder cancer treatment adopted in all Polish centres. It avoids individual preferences of urologists, as majority of centres usually have unified policy of BCG therapy. The most important limitation of our survey is the lack of questions on further treat- ment in departments that routinely do not recommend BCG therapy. CONCLUSIONS To conclude, BCG therapy in Poland is underused and treatment schemes are frequently suboptimal. There are significant differences in the policy of intravesical treatment of NMIBC patients between institutions. Im- provement of adherence to guideline recommendations should become a priority for urologists treating patients with bladder cancer. REFERENCES 1. Serretta V, Scalici Gesolfo C, Alonge V, Cicero G, Moschini M, Colombo R. Does the Compliance to Intravesical BCG Differ between Common Clinical Practice and International Multicentric Trials? Urol Int. 2016;96:20-4. 2. Aziz A. BP, Chun FK, Dobruch J, et al. Discrepancy between guidelines and daily practice in the management of non-muscle- invasive bladder cancer (NMIBC): Results of a European survey. Eur Urol Suppl. 2016;15:e216. 3. 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