Can We Prevent Bladder Cancer Recurrences?

Abstract

Non–muscle-invasive bladder cancer (NMIBC), oft noted to be among the most expensive cancers on a per capita basis, is burdened by frequent recurrences and rarer occurrences of disease progression. Given the length of time patients spend with bladder cancer, this disease lends itself to consideration of chemoprevention strategies. In this issue of European Urology, Kelly and colleagues [1] present the results of BOXIT, a phase 3 randomized controlled trial in which they compared daily preventive celecoxib for secondary chemoprevention with placebo among patients with initial or recurrent intermediateor high-risk NMIBC. Among all patients, time to recurrence did not differ between the treatment groups. Among a subgroup of patients with stage T1 high-grade cancers, there was benefit of celecoxib in delaying recurrences, although this subset analysis was underpowered and not a preplanned subgroup. However, any potential value is counterbalanced by the much higher rate of adverse cardiovascular events in the celecoxib arm (5.2% vs 1.7%). This contrasts with a recent trial among rheumatologic patients that found no increase in the risk of cardiovascular events among patients taking celecoxib versus naproxen or ibuprofen; there was no placebo arm [2]. BOXIT exemplifies an important new direction in scientific presentation: the importance of the negative result. We cannot correct mistaken clinical directions without acknowledgment of what does not work. Despite compelling preclinical and observational data, randomized trials refute causality. Other chemoprevention strategies that failed when confronted with a randomized trial include vitamin B6, retinoids, difluoromethylornithine, megadose vitamins, and selenium [3]. Until data demonstrate a therapeutic option for bladder cancer chemoprevention, clinicians should continue to educate patients on the