As discussed previously, the available data supports the use of mitomycin C, doxorubicin, and epirubicin as choices for induction intravesical therapy in patients with intermediate-risk NMIBC. Relatively few studies directly test the benefit of maintenance therapy for those patients who completely respond (defined as a normal cystoscopy and cytology, with no evidence of cancer on pathology if a bladder biopsy is performed) to an induction course of intravesical chemotherapy.188 If a bladder biopsy or TURBT is performed, to meet a complete response definition, no evidence of cancer is detected. Although the specific best maintenance regimen is unknown, common maintenance regimens include full-dose chemotherapy given at monthly intervals for a 6-12 month time period. Available studies are difficult to generalize due to variability of the tumor characteristics in the populations treated and the dosing regimens chosen for each trial. For mitomycin C, there is a single trial that focused on patients with intermediate- and high-risk disease (recurrent or multifocal low- to high-grade Ta or T1) that reported the addition of 3 years of maintenance therapy compared to a 6-week induction only course of mitomycin C (20 mg) reduced the recurrence rate in half (RR: 2.5; 95% CI: 1.5 to 4.2) without any clear difference in adverse events.221 Conversely, for epirubicin, two studies that compared induction therapy with and without a maintenance regimen failed to find any significant improvement in recurrence rates.222, 223 A study of 395 patients by Serretta et al. found no significant difference in the 4-year recurrence rate when they compared an induction course of 6 weekly instillations of epirubicin (80 mg) to the same induction course plus monthly maintenance for 1 year (recurrence rate of 46% versus 50%; p=0.26).223 Similarly, a study of 148 patients by Okamura et al. compared a 6-week induction course of epirubicin (40 mg) to the same induction course plus once monthly maintenance for 1 year and reported no difference in recurrence-free survival at 3 years (75% versus 77%; p=0.62).222 In both trials, there was no significant difference in the rate of adverse events between the two study groups. Importantly, however, there are five trials that compared differing induction plus maintenance regimens and demonstrated a benefit of increased dosing intensity of epirubicin on disease recurrence.224-228 While these trials varied considerably in their patient inclusion criteria and dosing regimens, the analysis conducted for this review114 found that, in general, more intensive exposure to intravesical epirubicin was associated with decreased risk of recurrence. For doxorubicin, two trials that compared induction intravesical therapy to induction plus maintenance therapy for either one year229 or two years,230 demonstrated that maintenance was not associated with any significant improvement in recurrence rates. For all three of these agents, there was no evidence to suggest that where it was analyzed, maintenance therapy decreased disease progression or cancer-related mortality in NMIBC. Therefore, the Panel felt that although there was some evidence to support the use of maintenance intravesical chemotherapy in those with a complete response after induction therapy, its routine use could not be supported and more trials are needed to assess this question. An important exception is the recently approved agent UGN-102 for intermediate-risk NMIBC. As discussed previously, UGN-102 is a reverse thermal hydrogel formulation containing mitomycin.152, 153, 231 The clinical trials supporting its approval utilized a six-week induction regimen without maintenance therapy; therefore, evidence supporting the role of maintenance treatment with UGN-102 is currently lacking.