Retinoids in the chemoprevention of bladder cancer

Bladder cancer is strongly related to tobacco use and is estimated to cause 54,500 new cancer cases and 11,700 deaths in the United States in 1998. Approximately two thirds of new US cases will be superficial tumors, predominantly low-grade papillary. After standard therapeutic resection (with or without intravesical therapy), the superficial bladder tumor recurrence rate is 30% to 70% within 12 months of resection. Morbidity is substantial, with frequent cystoscopy, recurrence, resections, and possible cystectomy for progression to invasive cancers. Therefore, new approaches, including chemoprevention, are needed. Data suggest that bladder carcinogenesis is a multi-step, multifocal (field effect) process, possibly involving the spread of premalignant clones--all of which are prerequisites for effective chemopreventive approaches. To date, retinoids are the best-studied chemopreventive agents in this site, achieving mixed clinical results (with 13-cis-retinoic acid and etretinate) in superficial bladder tumors. This review includes the epidemiology and biology of bladder carcinogenesis in addition to preclinical and clinical retinoid data, and focuses on the most promising avenue of current retinoid chemoprevention in the bladder: the potent apoptosis-inducing retinoid fenretinide (4-HPR), which currently is in three phase III trials.