The rationale for postoperative instillation of intravesical chemotherapy includes both destruction of residual microscopic tumor at the site of TURBT and of tumor cells dispersed within the bladder.176, 177 A single postoperative instillation of intravesical chemotherapy after TURBT has been demonstrated in multiple studies to decrease tumor recurrence without effects on progression or survival. SWOG S0337, which was a randomized, controlled double-blinded trial of a single-dose of intravesical gemcitabine (2 g in 100 mL of saline) versus normal saline, reduced recurrences of low-grade Ta bladder cancer with a relative risk reduction of 35% and an absolute risk reduction of 10-15% at 4 years.178 In addition, there were no Grade 4-5 adverse events in any patient in the trial, and the incidence of Grade 3 adverse events between gemcitabine and saline were the same, emphasizing the safety of gemcitabine. Three separate meta-analyses have reported that a single postoperative instillation of chemotherapy significantly decreased tumor recurrence between 10-15% compared to TURBT; however, a recent randomized 3-arm trial with 82 patients on a single-dose of mitomycin C, gemcitabine, or saline failed to demonstrate an improvement in recurrence.178-181 Intravesical mitomycin C and epirubicin are additional agents that have been studied as a single perioperative dose of chemotherapy.182 In the trials, the agents had a dwell time of one to two hours and both had a decrease in recurrence in this setting, but there have been no direct head-to-head comparison trials between these two agents to date. Recently, a trial was published demonstrating the efficacy of using these two agents (epirubicin and mitomycin C) together showing a 31% relative-risk reduction.183 Single instillation postoperative intravesical chemotherapy seems to have the greatest effect in patients with single, small, low-grade tumors184, 185 and may decrease recurrences even when additional adjuvant intravesical therapy is given.186-189 However, in patients with quick recurrent tumors and multiple, larger tumors, this postoperative instillation may not be as helpful.189 Single instillation studies have given the drug within 24 hours, and physiologic rationale exists for this early treatment, as tumor cells implant and are covered by extracellular matrix within a few hours in various in vitro and murine studies.190-192 The most common side effects of single instillation postoperative chemotherapy are irritative lower urinary tract symptoms, but severe complications have been reported in patients with drug extravasation.193, 194 Thus, immediate intravesical chemotherapy should be avoided when TURBT is extensive, perforation is suspected, significant bleeding requires bladder irrigations, or the tumor appears invasive. Given the low toxicity of gemcitabine and case reports of adverse events with mitomycin C, careful consideration should be given to the selection of the best agent for perioperative single-dose chemotherapy.