Cystectomy is most often performed for aggressive bladder cancer that has invaded into the muscular layer of the bladder. In males, the procedure usually includes removal of the prostate; in such cases, the operation is known as cystoprostatectomy. A nerve-sparing technique originally described for radical prostatectomy to preserve the neurovascular bundle for erectile function may be used in cystoprostatectomy in younger patients. In women, the traditional radical cystectomy includes hysterectomy, oophrectomy, and removal of the anterior vaginal wall, which is also 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 is usually performed to complete the surgical staging, though more recent reports have also demonstrated a therapeutic role for lymphadenectomy in patients with node-positive disease showing improved survival when the 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 third spacing 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, reconstruction of the urinary tract is performed.