Building on a Solid Foundation: Enhancing Bacillus Calmette-Guérin Therapy.

CONTEXT More than 40 yr ago, bacillus Calmette-Guérin (BCG) was introduced as an adjuvant therapy following transurethral resection of papillary tumours and as a treatment for carcinoma in situ of the bladder. Some 30 yr after its introduction, BCG maintenance therapy was found to be superior to induction therapy alone, representing the most relevant clinical improvement to BCG therapy since its inception. OBJECTIVE To review current efforts and future opportunities to improve BCG immunotherapy. EVIDENCE ACQUISITION English online databases (eg, PubMed and clinicaltrials.gov) were searched for clinical trials and meta-analyses of BCG therapy for bladder cancer. The information retrieved was reviewed and sel ected by all the authors and, while representative of the field, is not necessarily exhaustive. EVIDENCE SYNTHESIS Current knowledge supports the notion that careful patient management from diagnosis to therapy may contribute positively to outcome following BCG immunotherapy. In the future, patient evaluation using predictive immunological or molecular biomarkers will help in identifying those most likely to benefit from BCG therapy. Trials assessing immune modulators in combination with BCG or the use of recombinant BCG are ongoing and results will be forthcoming in the near future. CONCLUSIONS Enhancing BCG to improve patient outcomes is the responsibility of treating physicians and researchers. Future efforts will continue to improve how non-muscle-invasive urothelial carcinoma is evaluated, treated, and ultimately cured. PATIENT SUMMARY Bacillus Calmette-Guérin (BCG) immunotherapy to prevent the recurrence and progression of urothelial carcinoma is invasive and demanding for patients. Meticulous diagnostics, correct application of BCG, and selection of patients likely to respond to therapy will ensure that the highest benefit can be attained from this therapy. Current research is focused on discovering biomarkers to identify patients most likely to benefit from BCG immunotherapy. Biomarker identification, new immune modulators, and genetically modified BCG strains are undergoing clinical trial testing to improve outcomes for bladder cancer patients