PROSPERO registration number CRD42016042347.

No abstract

What ' s known on the subject? and What does the study add?The standard treatment for non-muscle invasive bladder (NMIBC) is transurethral resection followed by intravesical therapy. Intravesical agents, e.g. bacille CalmetteGu é rin (BCG) or mitomycin C (MMC), have activity in delaying and reducing the incidence of tumour recurrence after surgery but have signifi cant side-effects and are not effective in all patients. Clinical data suggests that gemcitabine has activity in this disease in terms of tumour response and is less toxic, and warrants further study. This systematic review comprehensively presents the available clinical evidence on intravesical gemcitabine for NMIBC. The limited data from randomised trials suggest that gemcitabine may have role in intermediate-risk patients, as an alternative to MMC, and in high-risk, BCG-refractory patients. Data from observational studies indicate that minimal systemic absorption occurs with intravesical administration and that gemcitabine is active in reducing tumour recurrence.Accepted for publication 1 December 2011• Intravesical immunotherapy or chemotherapy for non-muscle invasive bladder cancer is a well-established treatment for preventing or delaying tumour recurrence after tumour resection. However, up to 70% of patients may fail and new intravesical agents with improved effectiveness are needed. Gemcitabine is a relatively new anticancer drug that has shown activity against bladder cancer.• To systematically review the literature on the effectiveness and toxicity of intravesical gemcitabine for non-muscle invasive bladder cancer (NMIBC).• MEDLINE, EMBASE, CINAHL, the Cochrane database of systematic reviews, LILACS, SCOPUS, BNI, Biomed Central, Web of Science and BIOSIS were searched to identify trials of intravesical gemcitabine for the treatment of NMIBC. Also searched were meeting proceedings, international guidelines and trial registries. Data on authors, study design, patient characteristics, interventions and outcome data relating to tumour recurrence, disease progression, survival and adverse events were extracted from relevant studies.• Six relevant randomised trials were identifi ed with the number of patients randomised in each trial varying from 30 to 341 (total 704). All trials compared gemcitabine to active controls and varied in the reporting of outcomes.• The fi rst was a marker lesion study which reported greater tumour response rates when intravesical gemcitabine (2 g) was given as three bi-weekly doses (36%) or six weekly doses (40%) compared with a single dose (9%).• One study compared a single postoperative instillation of intravesical gemcitabine with a saline placebo in 341 patients and found no signifi cant difference in the rates of tumour recurrence (28% vs 39%, respectively) or recurrence-free survival (hazard ratio 0.95, 95% confi dence interval 0.64 -1.39, P = 0.77). The rate of progression to invasive disease was greater with gemcitabine (2.4% vs 0.8%).• A further trial compared gemcitabine with intravesical mitomycin C (MMC) an...