1. Volume 61, Issue 1, Pages 128-145 (January 2012)
Markers Predicting Response to Bacillus Calmette-Guérin Immunotherapy in High-Risk Bladder Cancer Patients: A Systematic Review 
Tahlita C.M. Zuiverloon, Annemieke J.M. Nieuweboer, Hedvig Vékony, Wim J. Kirkels, Chris H. Bangma, Ellen C. Zwarthoff 
European Urology 
Volume 61, Issue 1, Pages (January 2012)
DOI: /j.eururo
Copyright © 2011 European Association of Urology Terms and Conditions

2. Fig. 1
Bacillus Calmette-Guérin (BCG) treatment protocol. After diagnosis of all stages of non–muscle-invasive bladder cancer, patients receive an immediate postoperative instillation of chemotherapy (ie, mytomycin-C, epirubicin, or doxorubicin) within 6h after transurethral resection (TUR). According to European Association of Urology guidelines, a re-TUR is performed within 6 wk when the resection has been incomplete (large and multiple tumours, no muscle in the specimen) or when an exophytic high-grade and/or T1 tumour has been detected. In case of a high-risk T2 tumour, immediate cystectomy is recommended. Patients with non–muscle-invasive tumours (Ta, T1, and carcinoma in situ [Tis]) receive adjuvant intravesical immunotherapy with BCG for 6 wk. If no recurrence is detected after treatment, BCG maintenance schedule is followed for at least 1 yr. In nonresponders, a second course of 6 weekly BCG instillations may be administered after the first one because 40–60% of these patients will respond to additional BCG treatment. In case of Tis BCG failure, a second induction cycle of BCG can be administered. If no or Ta lesions are visible after therapy, maintenance BCG schedule is initiated. Nonresponders (T1, Tis, or T2) receive radical cystectomy.
Chemo=chemotherapy; UCS−=negative urethrocystoscopy; UCS+=positive urethrocystoscopy.
European Urology  , DOI: ( /j.eururo )
Copyright © 2011 European Association of Urology Terms and Conditions

3. Fig. 2
Biomarkers from diagnosis to treatment. Markers to evaluate bacillus Calmette-Guérin (BCG) effectiveness can be measured at different stages during treatment. “Early pretreatment” markers may include the detection of single nucleotide polymorphisms in blood to assess a patient's risk of progression, levels of inflammatory cytokines in urine can serve as “During BCG” markers to estimate the effectiveness of the immune response, and markers derived from the residual tumour in urine can be used as “Post BCG” indicators to detect the response to therapy.
European Urology  , DOI: ( /j.eururo )
Copyright © 2011 European Association of Urology Terms and Conditions

4. Fig. 3
Bacillus Calmette-Guérin (BCG)–induced immune response. After internalisation of fibronectin–BCG complexes by normal urothelial and tumour cells at the transurethral resection (TUR) site, BCG antigens are presented at the cell surface, attracting CD4+ T cells. Urothelial cells start a T helper-1 (Th-1) response by releasing several inflammatory cytokines (ie, interleukin [IL] 2, IL-8, IL-12, interferon [IFN] γ and tumour necrosis factor [TNF] β), which then leads to a cellular response by the recruitment of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. See text for more details.
APC=antigen-presenting cells; DC=dendritic cell; PMN=polymorphonuclear neutrophil; TRAIL=tumour necrosis factor apoptosis-inducing ligand.
European Urology  , DOI: ( /j.eururo )
Copyright © 2011 European Association of Urology Terms and Conditions