In the United States, transitional cell carcinoma of the bladder is the second most common malignancy of the genitourinary tract, and the second most common cause of death of all genitourinary tumors. In 2009, there were an estimated 71,000 new cases of bladder cancer diagnosed in the United States (53,000 in men and 18,000 in women), with approximately 14,000 deaths. Approximately 75% of patients with primary transitional cell carcinoma of the bladder present with low-grade tumors confined to the superficial mucosa. The risk of superficial recurrence in patients with bladder tumors confined to the mucosa is 75%, with the majority of these cancers amenable to initial transurethral resection and selected administration of intravesical immunotherapy or chemotherapy. However, 20% to 40% of all patients with transitional cell carcinoma of the bladder will either present with or develop a high-grade, invasive tumor of the bladder. If left untreated, over 85% of patients with high-grade, muscle invasive bladder cancer will die of the disease within 2 years of diagnosis. This clearly underscores a malignant subset of invasive bladder tumors that is most effectively treated by early radical therapy. Radical cystectomy has traditionally been considered the standard of therapy for high-grade, muscle invasive bladder cancer with the best survival results and lowest local recurrence rates.

Invasive bladder tumors tend to progressively invade from their superficial origin in the mucosa to the lamina propria and sequentially into the muscularis propria, perivesical fat, and contiguous pelvic organs, with an increasing incidence of lymph node involvement at each level. Radical cystectomy, with an appropriate lymphadenectomy, provides the optimal result with regard to accurate pathologic staging, prevention of local recurrence, and overall survival.

With improvements over the past several decades in medical, surgical, and anesthetic techniques, the morbidity and mortality associated with radical cystectomy has dramatically decreased. Prior to 1970, the mortality rate of for cystectomy was nearly 20%. This has significantly diminished to less than 2% to 3% perioperative mortality rate reported in contemporary series. In addition, radical cystectomy with an extended pelvic lymphadenectomy provides optimal local control of the tumor. Pelvic recurrence rates in patients undergoing radical cystectomy are <10% for patients with node-negative bladder tumors, and 10% to 20% for patients with resected pelvic nodal metastases.

Lower urinary tract reconstruction with orthotopic diversion has provided an attractive alternative for patients undergoing radical cystectomy, and has allowed some patients and surgeons to consider this surgery earlier in the disease process when it has the best chance of cure. Currently, most men and women can safely undergo orthotopic lower urinary tract reconstruction to the native urethra following cystectomy. Orthotopic reconstruction most closely resembles original bladder function, providing a continent means to store urine and allowing volitional voiding per urethra. It eliminates the need for a cutaneous stoma or urostomy appliance, and in most cases the need for intermittent catheterization. In our experience, most patients chose this option when presented with the pros and cons of each type of diversion.

The authors from the University of Southern California (USC) have made a dedicated effort to continually improve upon the surgical technique of radical cystectomy and to provide an acceptable form of urinary diversion without compromise of a sound cancer operation. Technical issues regarding radical cystectomy and an extended bilateral pelvic iliac lymphadenectomy are critical in order to minimize local recurrence and positive surgical margins and to maximize cancer-specific survival. Attention to surgical detail is critical in optimizing the successful clinical outcomes of orthotopic diversion, maintaining the rhabdosphincter mechanism and urinary continence in these patients.

A growing body of evidence exists to suggest that a more extended lymphadenectomy may be beneficial in both lymph node-positive and lymph node-negative patients with bladder cancer. Although the ideal limits of the lymphadenectomy for patients with bladder cancer undergoing cystectomy are currently debated, we advocate an extended lymph node dissection with the boundaries to include initiation at the level of the inferior mesenteric artery (superior limits of dissection), extending laterally over the inferior vena cava/aorta to the genitofemoral nerve (lateral limits of dissection), and distally to the lymph node of Cloquet. This bilateral dissection should also include all obturator, hypogastric, and presacral lymph nodes.

This chapter will detail the preoperative evaluation, surgical technique, and clinical results and outcomes of radical cystectomy and orthotopic lower urinary tract reconstruction.

The empty bladder is roughly triangular in shape, with only the top covered by peritoneum. It lies within the true pelvis and the extraperitoneal space around the sides is known as the space of Retzius. The detrusor muscle of the bladder is closely covered by the perivesical fat, which can be removed only with some difficulty. In both males and females, the anterior and anterior-lateral bladder lies free of any attachments to the abdominal wall except through the urachal remnant, which extends up to the umbilical scar in the midline. Deep in the pelvis the endopelvic fascia reflects from the pelvic floor up onto the prostate and bladder. A consolidation of this fascia, the puboprostatic ligament, fixes the prostatic apex to the undersurface of the pubic bone. Levator muscle fibers also attach to the prostatic apex posteriorly. A similar but less well-developed ligament extends between the proximal urethra and pubic bone in the female. In the male, the bladder and prostate are essentially fused at the bladder neck, with the transitional mucosal lining of the bladder extending into the prostatic and bulbar urethra without interruption. Posteriorly, the peritoneal reflection behind the bladder and prostate (Pouch of Douglas) extends down as a fusion fascia between the prostate and rectum (Denonvillier’s fascia). Dissection in the plane behind this fascia (Denonvillier’s space) is required to safely separate the prostate off of the rectum. In the female, the bladder lies on the anterior surface of the uterine cervix, with
the peritoneal fold between the two generally not extending all the way down to the vagina. The bladder is quite densely adherent to the anterior vaginal wall, requiring sharp dissection to separate the two structures.

The blood supply to the bladder arises from the internal iliac artery and vein, which give off the superior vesicle and inferior vesicle branches. The superior vesicle artery and vein course over the top of the ureter as it enters the detrusor muscle. The inferior vesicle artery arises more inferiorly off of the internal iliac trunk, and together with the superior vesicle vessels make up the lateral pedicle. The anterior trunk of the internal iliac artery terminates in the internal pudendal artery. In the male, the inferior vesicle artery supplies the prostate and bladder neck area. In the female, the uterine artery arises off of the superior vesicle artery and courses similarly over the ureter toward the uterus and cervix. There are additional branches from the middle rectal artery and vein that course around the rectum (and vagina in the female) and supply the bladder neck area (the posterior pedicles). A major venous plexus courses along the lateral bladder in both males and females and can be a source of significant bleeding during cystectomy. A second venous plexus courses anteriorly over the urethra (the dorsal venous complex).

The neurovascular bundle in the male carries parasympathetic fibers along with small vessels from the hypogastric plexus toward the penis, coursing along the groove between the posterior prostate and the rectum. Preservation of this bundle during cystectomy is required if erectile function is to be preserved. A similar bundle courses along the lateral vagina in the female, although the role of these nerves in preserving continence or sexual function is somewhat controversial. The main nervous supply to the external urethral sphincter in both males and females appears to course within the levator muscle fibers in the pelvic floor lateral to the urethra itself.

The lymphatic drainage of the bladder follows the primary vessels, coursing to the obturator, internal iliac, and common iliac chains. However, additional drainage includes the external iliacs and presacral nodes. The drainage appears to be bilateral in most cases. From the pelvic nodes, drainage continues up along the periaortic and peri-caval chains. There is not a single identified “sentinal” node for bladder cancer. Node mapping studies have suggested that the primary landing site is in the internal ileac and obturator areas, but solitary positive nodes can occasionally be found in the presacral and common iliac areas as well.

There are few congenital anomalies of bladder formation. However, some vascular variations that are important include the presence of accessory obturator arteries and veins arising from the external iliac vessels in 40% of patients, and accessory pudendal vessels in males, which may be important in preservation of potency. In addition, conditions such as bladder diverticula and prior pelvic surgeries can impact the ease of dissection. Renal anomalies such as horseshoe kidney, duplicated ureters, and others must be recognized as well.

The vast majority of patients with bladder cancer present with gross painless hematuria. Any patient over age 40 with hematuria necessitates evaluation for bladder cancer. Other presenting symptoms may include irritative symptoms (frequency, urgency, incontinence), which are often misdiagnosed as a urinary tract infection, sometimes delaying diagnosis for months. Symptoms of extravesical involvement include flank pain (from upper tract obstruction), bone pain, cough or hemoptysis, and weight loss.

Smoking is the most significant known risk factor for bladder cancer. Often, patients have quit smoking many years before the diagnosis; however, the risk declines only slightly over decades. Up to 30% of men and 50% of women with this disease have never smoked. Other environmental exposures such as industrial chemicals and dyes have also been identified as etiologic agents.

The evaluation of hematuria is very standardized in any patient over age 40. It should include upper tract imaging (generally a CT scan of the abdomen and pelvis with intravenous [IV] contrast) as well as flexible or rigid cystoscopy. Often an ultrasound or non-contrast CT scan is ordered as a preliminary study as part of an emergency room protocol—these are inadequate evaluations for hematuria, with poor sensitivity for detection of both bladder cancer and small renal masses. The ideal CT scan evaluation should include a non-contrast scan followed by an IV contrast scan including the delayed excretion phase (CT Urogram). In patients with contrast allergy or poor renal function, the upper tracts may be evaluated with ultrasound combined with retrograde pyelography or MRI with gadolinium.

Cystoscopy is mandatory in the evaluation of hematuria because currently available imaging tests have poor sensitivity for small bladder tumors. Cystoscopy is usually performed in the doctor’s office with a flexible or rigid cystoscope under local anesthesia. Papillary tumors are very easily identified on cystoscopy. Carcinoma in situ (CIS) is a flat lesion in the bladder, which has a very aggressive natural history. It may be difficult to identify with cystoscopy, although a patchy, slightly raised erythematous area may be visible. Urinary cytology is nearly always positive in the presence of CIS, and this test is an important adjunct to the initial cystoscopy. Cytology is usually normal in the face of lower grade bladder cancers, so it is not useful alone as a screening test. A number of newer urinary tests are also currently available or in development to diagnose bladder cancer. These are both protein-based tests (NMP22 and BTA Stat) and immumnohistochemical (UroVysion FISH and Immunocyt). However, the ideal use of these tests in both the initial diagnosis and the follow-up of patients with prior bladder cancer is still unclear. No combinations of urinary markers has been proven in clinical studies to be sensitive and specific enough to replace cystoscopy in the initial evaluation of hematuria.

Once a bladder tumor is visualized, the next step is transurethral resection of the bladder tumor (TURBT) to establish histology and grade as well as depth of invasion. A bimanual examination should also be performed under anesthesia during that resection. This is important for clinical staging (Table 1) and for planning the surgical approach for patients with invasive tumors. For patients with low-grade papillary tumors, no further metastatic workup is necessary. However, patients with high-grade or invasive lesions require a full staging evaluation. Standard evaluation should include a CT scan of the chest, abdomen, and pelvis with IV and oral contrast, along with a bone scan. Contrast is necessary to evaluate the upper tract for synchronous lesions, and also for improved evaluation of the retroperitoneal nodes and liver. For patients who cannot receive IV contrast, MRI with gadolinium can be used to evaluate the abdomen and pelvis. Recently, PET scans have been used for staging, but both false negatives and false positives have been seen. It is not yet clear that there is any advantage of FDG-PET over standard contrast-enhanced CT or MRI for staging the localized tumor or metastatic disease.

Despite recent advances in radiographic imaging techniques, errors in clinical staging of the primary bladder tumor are very common. Patients with hydronephrosis, a palpable mass on bimanual examination, or clear extravesical extension on preoperative
imaging generally will have pT3 or greater disease on final pathology (even if clear muscle invasion has not been documented on transurethral biopsy). Table 2 shows the discrepancy between clinical and final pathologic stages for a contemporary group of patients undergoing cystectomy.

Patients undergoing cystectomy often have significant comorbidities, especially heart and lung dysfunction related to smoking. Preoperative optimization is crucial in making this a safe operation. Most patients are evaluated preoperatively by a cardiologist and we routinely employ the use of provocative cardiac testing (stress echocardiogram or similar tests) and pulmonary function testing when indicated to assist in perioperative management. In the past, we have used mechanical and antibiotic bowel preparation beginning 24 hours prior to surgery in these patients, since the small bowel is widely opened as it is refashioned into the neobladder. The right colon may also be opened to use as a continent cutaneous reservoir in the occasion that the urethra is not usable. However, recent data has implicated the bowel preparation in some postoperative complications such as Clostridium difficile bacterial colitis and prolonged ileus. We and many other groups have recently avoided using a full bowel preparation, using instead a clear liquid diet and mild laxative the evening prior to surgery. The most frail, elderly patients are admitted for IV hydration the night before surgery to avoid some of the fluid shifts during the operation. All patients receive perioperative antibiotics according to the recommendations of the AUA Guidelines Committee.

We are fortunate to have a dedicated enterostomal therapist on our team who meets with each patient preoperatively to go over expectations for the perioperative period. He or she also marks the patient for a possible ileal conduit diversion in case that should become necessary during the surgery. We also have a set of written instructions that patients receive going over management of catheters and drains, Kegel exercise techniques, and techniques for self-catheterization. The ideal cutaneous stoma site is determined only after the patient is examined in the supine, sitting, and standing position. In general, incontinent stoma sites are best located higher on the abdominal wall, while stoma sites for a continent cutaneous diversion can be positioned lower on the abdomen (hidden below the belt line) since they do not require an external collecting device. The use of the umbilicus as the site for catheterization may be employed with excellent functional and cosmetic results.