Comparing cytokine production and clinical response following vaccination with BCG Moreau and BCG Russia strains in a Brazilian infant population.

INTRODUCTION: BCG is the only licensed vaccine against tuberculosis (TB) and, in Brazil, comprises part of the recommended vaccine schedule within the first month of life. Due to a local manufacturing shortage of BCG Moreau, BCG Russia was introduced in 2017 by the Brazilian Ministry of Health. OBJECTIVE: To evaluate differences in immune responses induced by BCG Moreau and BCG Russia in infants, in addition to scar formation. METHODS: The present case series involved 15 healthy infants who were vaccinated within the first seven days of life with one of two strains of BCG, then followed for 12 weeks or longer. Cytokine levels were measured before and after vaccination in whole blood culture supernatants previously stimulated in vitro with either BCG strain, heat-killed M. tuberculosis H37Rv or in the absence of stimulation. BCG scarring was also documented. RESULTS: Infants vaccinated with BCG Moreau exhibited increased background IL-2, IL-10 and IL-4 production, yet no differences were found in those vaccinated with BCG Russia. Although both strains induced higher levels of IL-2 and IFN-γ, elevated IL-6, TNF and IL-10 production was also seen in response to BCG Russia. In contrast, no specific responses were observed against heat-killed M. tuberculosis H37Rv, with the exception of increased IL-2 following BCG Moreau vaccination. Although documented in both groups, scarring was milder and less frequent following BCG Russia vaccination. CONCLUSIONS: Similar Th1 profiles were found following immunization with either type of BCG vaccine evaluated herein, with more pronounced cytokine production detected in response to the Russia strain. Overall, vaccination was well-tolerated and scarring evolved as expected for both BCG strains.

Efficacy of three BCG strains (Connaught, TICE and RIVM) with or without secondary resection (re-TUR) for intermediate/high-risk non-muscle-invasive bladder cancers: results from a retrospective single-institution cohort analysis.

PURPOSE: (I) To evaluate the clinical efficacy of three different BCG strains in patients with intermediate-/high-risk non-muscle-invasive bladder cancer (NMIBC). (II) To determine the importance of performing routine secondary resection (re-TUR) in the setting of BCG maintenance protocol for the three strains. METHODS: NMIBCs who received an adjuvant induction followed by a maintenance schedule of intravesical immunotherapy with BCG Connaught, TICE and RIVM. Only BCG-naïve and those treated with the same strain over the course of follow-up were included. Cox proportional hazards model was developed according to prognostic factors by the Spanish Urological Oncology Group (CUETO) as well as by adjusting for the implementation of re-TUR. RESULTS: n = 422 Ta-T1 patients (Connaught, n = 146; TICE, n = 112 and RIVM, n = 164) with a median (IQR) follow-up of 72 (60-85) were reviewed. Re-TUR was associated with improved recurrence and progression outcomes (HRRFS: 0.63; 95% CI 0.46-0.86; HRPFS: 0.55; 95% CI 0.31-0.86). Adjusting for CUETO risk factors and re-TUR, BGC TICE and RIVM provided longer RFS compared to Connaught (HRTICE: 0.58, 95% CI 0.39-0.86; HRRIVM: 0.61, 95% CI 0.42-0.87) while no differences were identified between strains for PFS and CSS. Sub-analysis of only re-TUR cases (n = 190, 45%) showed TICE the sole to achieve longer RFS compared to both Connaught and RIVM. CONCLUSION: Re-TUR was confirmed to ensure longer RFS and PFS in intermediate-/high-risk NMIBCs but did not influence the relative single BCG strain efficacy. When routinely performing re-TUR followed by a maintenance BCG schedule, TICE was superior to the other strains for RFS outcomes.

Safety of the Polish BCG-10 Vaccine During a Period of BCG Vaccine Shortage: An Australian Experience.

Bacille Calmete-Guerin vaccine is widely administered to reduce the risk of severe tuberculosis disease in children. Recent global vaccine supply issues have led to the use of alternative products, which may vary in side effect profile. We report on the safety of the Polish (Moreau strain) "Bacille Calmete-Guerin-10" vaccine in an Australian cohort. Using active surveillance, we identified an adverse event rate of 54.6 per 10,000 doses (95% confidence interval: 38.5-75.2), which was comparable to that reported with the Danish Sanofi-Pasteur and Connaught strains.

Bacillus Calmette-Guerin infection following intravesical instillation: Does the strain matter?

PURPOSE: Intravesical BCG is the standard treatment of non-muscle invasive bladder cancer. No difference has yet been reported in the safety profiles of the various BCG strains. METHODS: A nationwide multidisciplinary retrospective survey was conducted between January 2013 and December 2016 to identify cases of BCG infection and differentiate them based on the type of BCG strain used. RESULTS: Forty patients were identified (BCG RIVM 28; other strains 8; unknown 4). Patients treated with BCG RIVM were less severely ill, with fewer occurrences of septic shock (3.6% vs. 50%, P=0.003) and ICU admission (7.1% vs. 62.5%, P=0.003). A higher frequency of pulmonary miliaries (71.4% vs. 12.5%, P=0.005) but lower transaminase levels (mean AST 65 vs. 264 U/L, P=0.001) were observed in these patients. No difference in terms of recovery was reported. CONCLUSION: The type of BCG strain could correlate with the frequency and severity of subsequent BCG infections.

Background and Update for S1602 "A Phase III Randomized Trial to Evaluate the Influence of BCG Strain Differences and T Cell Priming with Intradermal BCG Before Intravesical Therapy for BCG-naïve High-grade Non-muscle-invasive Bladder Cancer.

The S1602 Intergroup trial is a randomized phase III clinical trial that aims to test two important hypotheses: (1) priming with intradermal bacillus Calmette-Guérin (BCG) vaccine prior to standard intravesical BCG improves response to BCG in terms of recurrence-free survival and (2) Tokyo-172 BCG strain is non-inferior to TICE BCG in terms of time to high-grade recurrence. The study was approved by the Cancer Therapy Evaluation Program of the National Cancer Institute and activated in spring 2017. Here, we provide a synopsis of the study background, design, and update of the clinical trial.

Does switching the bacillus Calmette-Guérin strain affect clinical outcome in patients with recurrent non-muscle-invasive bladder cancer after initial bacillus Calmette-Guérin therapy?

PURPOSE: It is still unknown whether switching the bacillus Calmette-Guérin (BCG) strain at the second induction course of BCG therapy has a therapeutic benefit in patients with tumor recurrence after the initial BCG therapy (BCG-relapsing tumor). MATERIALS AND METHODS: We retrospectively reviewed the clinicopathological features of 97 patients treated with a second induction course of BCG therapy between 1986 and 2014. Among the patients initially treated with BCG Tokyo-172, the second course was either BCG Tokyo-172 in 56 (57.8%) or BCG Connaught in 15 (15.5%). Among those who were initially treated with BCG Connaught, the corresponding numbers were 13 (13.4%) or 13 (13.4%), respectively. Twenty-eight (28.9%) patients were given a different BCG strain at the 2 BCG therapies (switching group), and 69 (71.1%) patients were given the same BCG strain (non-switching group). RESULT: The 5-year recurrence-free survival rate of the switching group was 64.7 ± 9.6%, which was not significantly different from that of the non-switching group (54.8 ± 6.9%, P = 0.427). Switching or not switching the BCG strain was not significantly associated with tumor recurrence after the second BCG therapy. The 5-year progression-free survival rate of the switching group was 95.4 ± 2.6%, which was also not significantly different from that of the non-switching group (96.0 ± 3.9%, P = 0.674). Patients treated with BCG Tokyo-172 to Tokyo-172 had significantly higher incidences of side effects during the second BCG therapy. CONCLUSIONS: The results of this study indicate that in patients with a BCG-relapsing tumor after the initial BCG therapy, the same BCG strain as that administered at the initial BCG therapy could be utilized effectively for the second BCG therapy. Patients treated with BCG Tokyo-172 for an initial tumor had a higher incidence of side effects during the second BCG therapy using the same strain.

Microevolution of BCG substrains.

Tuberculosis was, and still is, one of the main causes of morbidity and mortality in the world. Thus it still remains a public health priority. Nonetheless, without a newly developed vaccine, it is rather unlikely to be easily resolved. The only available vaccine against tuberculosis (BCG) has been used for nearly 100 years. Currently a variety of BCG substrains are used by many manufacturers in the world. All these substrains were obtained from a single parental strain of Mycobacterium bovis. Attempts to explain the complete mechanisms of attenuation, as well as tracing the microevolution resulting from the different distribution time and conditions of production of BCG vaccines in the different parts of the world, might explain the differences in the observed efficacy of vaccines produced with different substrains. The most important marker associated with attenuation of virulent M. bovis is the loss of the RD1 region observed in all BCG substrains. Among other attenuation markers, still not completely identified, accumulation of SNP mutations seems to be an important one. The different number of passages and culture conditions of the parental vaccine strain have led to there being about 50 different sister vaccine BCG substrains throughout the world. Among them, there are "early strains", distributed until 1927, and "later strains" with the RD2 deletion obtained during 1927­1961. It has also been found that 22 regions containing 52 genes were lost during the distribution of sister substrains during the period 1924­1966. Genetic differences due to selection pressure, revealing specific microevolutionary traits, may explain the variability in immunogenicity and residual virulence of each vaccine BCG substrain.

Different effects of BCG strains - A natural experiment evaluating the impact of the Danish and the Russian BCG strains on morbidity and scar formation in Guinea-Bissau.

BACKGROUND: Different Bacillus Calmette-Guerin (BCG) vaccine strains may have different non-specific effects. We assessed the effect of two BCG strains (Danish and Russian) on childhood morbidity and BCG scarification in Guinea-Bissau. METHODS: During 2011-2013, infants in the Bandim Health Project's urban study area received the Danish or Russian BCG in a natural experiment. Health center consultations were registered at point of care and scar status and size at age 4½ months. We assessed the effect of strain on consultation rates between vaccination and age 45days in Cox proportional hazards models. Scar prevalence and size were compared using binomial regression and ranksum tests. RESULTS: Among 1206 children, 18% received Danish BCG (n=215) and 82% Russian BCG (n=991). The adjusted hazard ratio (aHR) for consultations was 0.94 (95% CI 0.60-1.46) for Danish BCG compared with Russian BCG. Girls vaccinated with Danish BCG tended to have lower consultation rates compared with girls vaccinated with Russian BCG (aHR 0.56 (0.25-1.24)), whereas the effect was opposite for boys (aHR 1.24 (0.74-2.11)), p=0.09. Children vaccinated with Danish BCG were more likely to develop a scar (97%) than children vaccinated with Russian BCG (87%), the relative risk (RR) being 1.11 (1.06-1.16). The effect was stronger in girls, and BCG scar size was larger among infants vaccinated with the Danish strain. CONCLUSION: BCG strain influences scar prevalence and scar size, and may have sex differential effects on morbidity. BCG strains are currently used interchangeably, but BCG scarring has been linked to subsequent survival. Hence, more research into the health effects of different BCG strains is warranted. Small adjustments of BCG production could potentially lower childhood morbidity and mortality at low cost.

Molecular analysis of the bacille Calmette-Guérin vaccine strain currently being used in Iran.

BACKGROUND: In developing countries, tuberculosis (TB) infection control remains a challenge. The bacille Calmette-Guérin (BCG) vaccine is the only effective vaccine available for TB control. Iran uses a local BCG vaccine strain with an unknown substrain. OBJECTIVE: To investigate the molecular characteristics of the current BCG strain being used in Iran using comparative genomics of the evolutionarily late strains, including BCG vaccines Pasteur, BCG-Danish, BCG-Glaxo, BCG-Prague, BCG-Frappier, BCG-Connaught and BCG-Moreau. METHODS: A total of 67 different vials of BCG vaccine were cultured. DNA was extracted using the modified cetrimonium bromide (CTAB) method, and multiplex polymerase chain reaction (PCR) was performed to determine four target genomic regions of difference (RD) 1, RD8, RD16 and SenX3-RegX3, and to see whether RD2 and RD14 were present. RESULTS: Our results showed that all studied batches were Mycobacterium bovis; molecular analysis revealed that the Iranian vaccine strains possess RD8, RD16 and SenX3-RegX3 regions but not RD1, RD2 and RD14. All of the vaccine batches analysed were compatible with BCG-Pasteur 1173p2, the original strain. CONCLUSION: All of the BCG strains studied were recognised as the BCG-Pasteur 1173p2 strain. No genetic diversity among stocks and ready-for-use vaccine vials were detected.

Bacillus Calmette-Guérin strain differences have an impact on clinical outcome in bladder cancer immunotherapy.

BACKGROUND: Whether the commonly used bacillus Calmette-Guérin (BCG) strains Connaught and Tice confer different treatment responses in non-muscle-invasive bladder cancer (NMIBC) is unknown. OBJECTIVES: To compare clinical efficacy, immunogenicity, and genetics of BCG Connaught and Tice. DESIGN, SETTING, AND PARTICIPANTS: A prospective randomized single-institution trial with treatment of 142 high-risk NMIBC patients with BCG Connaught or Tice. INTERVENTION: Patients were randomized to receive six instillations of BCG Connaught or Tice. For experimental studies, BCG strains were compared in C57Bl/6 mice. Bladders and lymphoid tissues were analyzed by cytometry and the latter cultivated to detect live BCG. BCG genomic DNA was sequenced and compared with reference genomes. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Recurrence-free survival was the primary end point of the clinical study. The Kaplan-Meier estimator was used for estimating survival and time-to-event end points. Nonparametric tests served for the analysis of the in vivo results. RESULTS AND LIMITATIONS: Treatment with BCG Connaught conferred significantly greater 5-yr recurrence-free survival compared with treatment with BCG Tice (p=0.0108). Comparable numbers of patients experienced BCG therapy-related side effects in each treatment group (p=0.09). In mice, BCG Connaught induced stronger T-helper cell 1-biased responses, greater priming of BCG-specific CD8(+) T cells, and more robust T-cell recruitment to the bladder than BCG Tice. Genome sequencing of the BCG strains revealed candidate genes potentially involved in the differential clinical responses. CONCLUSIONS: BCG strain may have an impact on treatment outcome in NMIBC immunotherapy. PATIENT SUMMARY: We compared the efficacy of two commonly used bacillus Calmette-Guérin (BCG) strains for the treatment of NMIBC and found that treatment with BCG Connaught prevented recurrences more efficiently than BCG Tice. Comparison of the immunogenicity of the two strains in mice indicated superior immunogenicity of BCG Connaught. We also identified genetic differences that may explain the differential efficacy of the Connaught and Tice BCG strains. TRIAL REGISTRATION: NCT00003779.

Genome sequencing and analysis of BCG vaccine strains.

BACKGROUND: Although the Bacillus Calmette-Guérin (BCG) vaccine against tuberculosis (TB) has been available for more than 75 years, one third of the world's population is still infected with Mycobacterium tuberculosis and approximately 2 million people die of TB every year. To reduce this immense TB burden, a clearer understanding of the functional genes underlying the action of BCG and the development of new vaccines are urgently needed. METHODS AND FINDINGS: Comparative genomic analysis of 19 M. tuberculosis complex strains showed that BCG strains underwent repeated human manipulation, had higher region of deletion rates than those of natural M. tuberculosis strains, and lost several essential components such as T-cell epitopes. A total of 188 BCG strain T-cell epitopes were lost to various degrees. The non-virulent BCG Tokyo strain, which has the largest number of T-cell epitopes (359), lost 124. Here we propose that BCG strain protection variability results from different epitopes. This study is the first to present BCG as a model organism for genetics research. BCG strains have a very well-documented history and now detailed genome information. Genome comparison revealed the selection process of BCG strains under human manipulation (1908-1966). CONCLUSIONS: Our results revealed the cause of BCG vaccine strain protection variability at the genome level and supported the hypothesis that the restoration of lost BCG Tokyo epitopes is a useful future vaccine development strategy. Furthermore, these detailed BCG vaccine genome investigation results will be useful in microbial genetics, microbial engineering and other research fields.

A prospective comparative study of intravesical bacillus Calmette-Guérin therapy with the Tokyo or Connaught strain for nonmuscle invasive bladder cancer.

PURPOSE: We prospectively compared the efficacy and adverse events of the bacillus Calmette-Guérin Tokyo 172 and Connaught strains for nonmuscle invasive bladder cancer. MATERIALS AND METHODS: Between January 2004 and May 2012 patients with pTa/T1 and pTis, multiple tumors and a recurrence-free period of 3 months or less who required intravesical bacillus Calmette-Guérin therapy were prospectively allocated randomly to receive the Tokyo or Connaught strain. The primary study end points were the complete response rate in patients with pTis and concomitant carcinoma in situ (pTa or pT1), recurrence-free survival in patients with pTa, pT1 and carcinoma in situ who achieved a complete response after therapy and the frequency of adverse events. RESULTS: Administration of the Connaught strain ceased because its production was suspended in June 2012. Therefore, analysis was performed using data gathered to date. Overall, 66 and 63 patients who received the Tokyo and Connaught strains, respectively, were included in efficacy analysis. Patient and tumor characteristics were well balanced between the 2 groups. Median followup was 855 days. Adverse events were similar in the groups. The complete response rate was 90.3% and 85.0% in patients given the Tokyo and Connaught strains, respectively, which did not significantly differ (p = 0.896). The 2-year recurrence-free survival rate was 73.2% and 68.8%, respectively. CONCLUSIONS: Results suggest no significant differences between the Tokyo and Connaught strains in the complete response, recurrence-free survival or adverse event rate.

[Efficacy and safety of vaccines against tuberculosis in the relation to genetic variability of Mycobacterium bovis BCG strains]. / Skutecznosc i bezpieczenstwo szczepionek przeciwko gruzlicy a zmiennosc genetyczna szczepów Mycobacterium bovis BCG.

All vaccines against tuberculosis used actually over the world contain Mycobacterium bovis BCG strains (Bacillus Calmette-Guerin) as active substance. Strain BCG, that was obtained in 1921 by Calmette and Guerin after 13 years ofpassaging on the potato-glicerol medium with addition of bile, was distributed to many laboratories for vaccine production. The repeated passages of M. bovis BCG strain in different culture conditions caused the numerous mutations and formation of many BCG substrains that differed according to efficacy and safety. The review of many publications related to genetic differences between BCG substrains was performed for identify the genes responsible for their virulence and protective characteristics. Possibility of development of new generation vaccines against tuberculosis is discussed.

Mapping the global use of different BCG vaccine strains.

Bacille Calmette-Guérin (BCG) vaccine is one of the oldest and most commonly administered vaccines worldwide. Different BCG vaccine strains exist as a result of genetic changes that occurred during repeated subculture in different countries before lyophilisation was introduced for storage of seed lots in the 1960s. Increasing evidence suggests that these genetically divergent BCG vaccine strains are associated with different protective efficacy against tuberculosis (TB), different rates of adverse events and variable susceptibility to anti-tuberculous drugs. Information on which BCG vaccine strains are used in each country worldwide has not previously been collated. This report summarises data from the EuroTB network and from WHO/UNICEF in the first map depicting the BCG vaccine strains used globally. In 83 (44%) of 188 countries, more than one BCG vaccine strain was used during the five year period. In the countries that used only one strain, BCG Denmark was used in 32, BCG Russia/Bulgaria in 30, BCG Japan in eight, BCG Connaught in two. Twelve countries used their locally-produced BCG vaccine strains. The considerable variation in BCG vaccine strains used worldwide highlights the importance of documenting the particular vaccine strain used on an individual, local and national level. This is important for the interpretation of changes in the epidemiology of adverse events after BCG immunisation, for the management of adverse events after BCG immunisation, to interpret differences in the protective efficacy of BCG, and to inform the design of trials investigating novel TB vaccines.

Phenotypic differences between BCG vaccines at the proteome level.

To contribute to Mycobacterium bovis BCG characterization, two substrains were analyzed using two-dimensional gel electrophoresis (2D-PAGE) and mass spectrometry (MS), based on their protective efficacy in a pulmonary-tuberculosis mouse model. Cell-fraction proteins of BCG Denmark and Phipps substrains were separated into approximately 500 spots in 2D-PAGE. The proteomes were similar in protein number, and isoelectric point (pI) and molecular mass (MM) distribution. Statistical analysis, resulted in 72 spots with no change, and 168 and 90 unique for BCG Phipps or Denmark, respectively. Two hundred and fourteen spots showed changes in intensity of >1-fold, 138 of Denmark, and 76 of Phipps. Seventeen spots were selected for MS-based identification (13 from Phipps and 4 from Denmark), including unique, as well as proteins with changes in intensity. The proteins identified participate in virulence, detoxification, adaptation, lipid metabolism, information pathways, cell wall and cell processes, intermediary metabolism and respiration, or still hypotheticals. Our findings contribute to phenotype characterization of BCG substrains and provide new elements to consider for the design of diagnostic tools, drug targets and a new vaccine against tuberculosis based upon protein expression through quantitative statistical analysis.

Manipulation of immune responses to Mycobacterium bovis by vaccination with IL-2- and IL-18-secreting recombinant bacillus Calmette Guerin.

Bacillus Calmette Guerin (BCG) has been reported to show variable efficacy as a vaccine against tuberculosis. We demonstrated that the secretion of biologically active IL-2 (rBCG/IL-2),but not IL-18 (rBCG/IL-18), by BCG improves its ability to induce and maintain a strong type 1 immune response in BALB/c mice. rBCG/IL-2 induced significantly higher Ag-specific proliferative responses, high IFN-gamma production and serum titres of IgG2a 16 weeks after vaccination. This immune profile was correlated to an increased rate of clearance of non-pathogenic mycobacteria (live BCG delivered intranasally). Surprisingly, however,this strong type 1 immune profile induced no greater protective immunity against aerosol challenge with virulent Mycobacterium bovis than that induced by normal BCG (nBCG). By comparison,vaccination with rBCG/IL-18 was found to induce significantly less IFN-gamma production in splenic lymphocytes than nBCG. This impaired induction of IFN-gamma was correlated to a significantly lower protective efficacy against M. bovis challenge, as compared to nBCG. The data suggest that manipulation of the immune response to tuberculosis and tuberculosis vaccines will require a more complete understanding of the factors that are important in generating a protective immune response.

[Intravesical BCG-therapy: comparison of side effects of Connaught (Toronto) and Pasteur (Paris) strains]. / BCG-thérapie intravésicale: comparaison des effets secondaires des souches Connaught (Toronto) et Pasteur (Paris).

INTRODUCTION: Urologists have felt that the adverse effects of intravesical BCG-therapy have been more serious and more frequent since the use of the Connaught strain. The objective of this retrospective study was to compare the toxicity of this new strain with that previously used in France (Pasteur strain). MATERIAL AND METHODS: After endoscopic resection, 89 patients with stage Ta grade 1-2 recurrent or T1 grade 3 and/or CIS bladder tumour were treated with 6 instillations of 150 mg of BCG Pasteur from 1992 to 1996 (50 patients: group 1) or 81 mg of BCG Connaught from January 1997 to December 1998 (39 patients: group 2). Adverse effects were classified as minor, lasting less than 48 hours (bladder irritation syndrome and/or macroscopic haematuria and/or fever less than 38 degrees C), moderate (requiring symptomatic treatment, reduction of the dose or an increased interval between instillations), and major (contraindication to continuation of treatment). RESULTS: 74% of patients in group 1 presented at least one adverse effect versus 77% in group 2. The reasons for permanent discontinuation of BCG-therapy in groups 1 and 2, respectively, were as follows: malaise during instillation (1 vs 0), bladder irritation syndrome not controlled by symptomatic treatment (4 vs 5) and epididymitis (0 vs 1). Pulmonary tuberculosis was diagnosed in one patient from group 2, one year after the last instillation. The frequency and severity of adverse effects were not statistically different between the two groups. The number of patients discontinuing BCG-therapy because of severe complications was also not statistically different between the two groups. CONCLUSION: This study did not reveal any difference of toxicity between Connaught and Pasteur strain in intravesical BCG-therapy of superficial bladder tumours.

The immunogenicity of single and combination DNA vaccines against tuberculosis.

DNA immunization is a promising new approach for the development of novel tuberculosis vaccines. In this study, the immune responses following the administration of single and combination tuberculosis DNA vaccines were evaluated. Single DNA vaccines encoding the MPT-63 and MPT-83 tuberculosis antigens evoked partial protection against an aerogenic challenge with M. tuberculosis Erdman in the mouse model of pulmonary tuberculosis. Immunization with a multivalent combination DNA vaccine (containing the ESAT-6, MPT-64, MPT-63, and KatG constructs) generated immune responses that indicated an absence of antigenic competition since antigen-specific cell-mediated and humoral responses were detected to each component of the mixture. More importantly, the combination vaccine elicited a strong protective response relative to the protection evoked by live BCG vaccine.

[Results of BCG in the treatment of pTa and pT1 bladder tumors. Evaluation of a long protocol using 75 mg of Pasteur strain BCG]. / Résultats du BCG dans le traitement des tumeurs de vessie pTa et pT1. Evaluation d'un protocole long utilisant 75 mg de BCG de souche Pasteur.

OBJECTIVES: Evaluation of a protocol of intravesical BCG therapy using 75 mg of Pasteur strain BCG with 2 years of maintenance treatment, and a follow-up of up to 60 months. MATERIAL AND METHODS: 189 patients treated by transurethral resection (TUR) for a pTa (N = 80) or pT1 (N = 109) bladder tumour were included in the study. The local and general safety was excellent. We retrospectively compared this series to a group of patients treated by TUR alone (N = 42) another group treated with TUR and Mitomycin C (MMC) (N = 81). The 3 groups were statistically comparable. RESULTS: At 48 months, 62% of patients treated with BCG were recurrence-free, versus only 18% for patients treated with TUR alone and 38% for patients treated with TUR and MMC (p = 0.001). At 42 months, 11% of pT1 tumours treated with BCG had progressed to invasive carcinoma, and this progression occurred during the first 18 months in every case. In comparison, this progression was observed in 25% of pT1 tumours treated by TUR alone and 21% of tumours treated with TUR and MMC. CONCLUSIONS: Our study confirms the efficacy of our BCG protocol ro reduce the potential for recurrence and progression of superficial bladder tumours, despite reduction of the dose to 75 mg. It also suggests the superiority of BCG compared to MMC in terms of recurrence and progression.