The patient group with intermediate-risk bladder cancer is heterogeneous and primarily at risk of recurrence rather than progression. As discussed previously, there are tools that a clinician can use, albeit with uncertain accuracy, to estimate if a patient in this group has a higher or lower recurrence risk.37 Therefore, the decision to administer or not administer additional intravesical therapy (distinct from the immediate postoperative dose) and the type of additional intravesical therapy can be based on a clinician’s assessment of recurrence risk, morbidity of subsequent TURBT’s, patient symptomatology and history, and toxicity of therapy. Meta-analyses have demonstrated that BCG (3 trials; RR: 0.56; 95% CI: 0.43 to 0.71; I2=0%), mitomycin C (8 trials; RR: 0.71; 95% CI: 0.57 to 0.89; I2=72%), doxorubicin (10 trials; RR: 0.80; 95% CI: 0.72 to 0.88; I2=46%) and epirubicin (9 trials; RR: 0.63; 95% CI: 0.53 to 0.75; I2=64%) all decrease the risk of recurrence as compared to no intravesical therapy.114 As previously noted, BCG has been shown to be superior to doxorubicin or epirubicin with regard to preventing recurrence.114 More recent comparative data suggest that BCG may also provide better recurrence control than mitomycin C in some intermediate-risk patients.199 However, BCG does have a greater risk of adverse events, both local (granulomatous cystitis, dysuria, hematuria) and systemic (fever), as compared to most intravesical chemotherapies.114 Thus, when the risk of recurrence is moderate and intravesical therapy is felt to be appropriate, a better-tolerated intravesical chemotherapy may have a better risk to benefit ratio than BCG when the primary goal is to prevent recurrence. In this setting, gemcitabine may offer a more favorable adverse event profile than BCG, while maintaining similar recurrence outcomes.200, 201 Additionally, combination intravesical gemcitabine/docetaxel has also shown recurrence outcomes to be comparable to BCG with lower treatment-related toxicity in intermediate-risk patients, although the available data remains sparse to draw a firm conclusion.202, 203 If mitomycin C is the chosen agent, there is evidence from one randomized trial that treatment efficacy can be enhanced by using an optimized administration program that consists of a period of dehydration (no fluids for 8 hours prior to treatment), urinary alkalinization (1.3 g NaHCO3 by mouth, the night prior, the morning of, and 30 minutes prior to the intravesical therapy), confirmed complete bladder drainage prior to intravesical therapy (post-void residual <10 mL by US bladder scanner), and a higher mitomycin C concentration (40 mg in 20 mL of sterile water).204 Primary chemoablation with UGN-102 has been investigated as a non-surgical treatment option for patients with recurrent low-grade, intermediate-risk NMIBC. In the phase 3 ENVISION study, UGN-102 achieved a complete response rate of 80% at 3 months, and among complete responders, the probability of maintaining response 12 months thereafter was 82%.154 Adverse events were generally mild, although serious adverse events were also reported. Interpretation of these findings, however, is tempered by the single-arm design, which precludes direct comparison with standard management approaches. Long-term follow-up is ongoing.