Thirty-five years of intravesical bacillus Calmette-Guérin for bladder cancer: where now?

It is 35 yr since Morales described the use of intravesical bacillus Calmette-Guérin (BCG) for non–muscle invasive bladder cancer (BC). In the interveningyearswehave learned much about this treatment. Although BCG is one of the most studied medicines in urology, many questions regarding its use remain [1]. In this month’s European Urology, Herr et al report their use of induction BCG for high-risk BC [2]. The authors demonstrate excellent outcomes in BCG complete responders and suggest the need for a new trial to reevaluate induction andmaintenance BCG. Their findings andsuggestionhighlight thegaps inourknowledgeandpoint to issues that need resolving with BCG in this context. The current dilemmas with BCG are well illustrated using a historical perspective. In 1991, Lamm et al reported that BCG was more effective than intravesical doxorubicin at reducing BC recurrence [3]. When compared, 20% more patients were disease free, and the time to recurrence was around 1 yr longer for BCG-treated patients. In 2000, the Southwest Oncology Group (SWOG) reported a comparison of induction and maintenance BCG [4]. In 348 randomised patients, maintenance BCG reduced the 5-yr recurrence, worsening disease (including cystectomy), and death rates by a further 19%, 6%, and 5%, respectively, when compared with induction BCG. These data were the largest trial included in key meta-analyses (eg, Sylvester et al [5]), whose findings are central to our current use of BCG and require exploration. First, maintenance BCG reduced progression and death by 4% and 2.1%, respectively, when compared with induction BCG and other treatments. Second, the natural history of highand intermediate-risk non–muscle-invasive BC appeared relatively indolent. By 2.5 yr (median follow-up), progression to invasive disease had occurred in only 9.8–13.8% and death from BC in only