Cystectomy is most often performed for bladder cancer, either superficially invasive disease that has failed to respond to topical chemotherapy, or more aggressive disease that has invaded into the muscular layer of the bladder. In males, the procedure will usually include removal of the prostate, thus the term cystoprostatectomy is used. In women, the traditional radical cystectomy would include hysterectomy, oophorectomy, and removal of the anterior vaginal wall, which would also be referred to as anterior pelvic exenteration. More recently, there has been a trend towards preservation of the anterior vaginal wall.

When dealing with bladder cancer, pelvic lymphadenectomy has a therapeutic role, showing improved survival when more lymph nodes are removed. Thus, a more extensive dissection to include the common iliac nodal tissue has become routine. With such extended dissections in the pelvis/retroperitoneum, there is more risk for lymph leak, bleeding, and fluid losses in the early postoperative period.

Other indications for cystectomy include neurogenic bladder, pyocystis from defunctionalized bladder, salvage cystoprostatectomy for radiation therapy failure for prostate cancer, radiation cystitis, and refractory interstitial cystitis.

Once the bladder has been removed, the reconstruction of the urinary tract is performed. The ideal bladder replacement would fill and empty without leakage, would protect the kidneys from reflux or obstruction, would have no metabolic or nutritional consequences, would not require an appliance or instrumentation, and would have low risk of infection or stones. There have been numerous types of urinary diversions, each with advantages and unique disadvantages, but none have attained that ideal. There are several options for permanent urinary diversion.