In 2013, 72,000 new cases of bladder cancer were diagnosed in the United States; almost 17,000 occurred in women, with 4,300 dying from their disease (1
). Although most urothelial carcinomas are noninvasive, up to one-third of patients present with muscle-invasive disease. In addition, 15% to 30% of patients presenting with non-muscle-invasive tumors will eventually progress to muscle invasion. Radical cystectomy remains the most effective single-modality treatment for patients with muscle-invasive bladder cancer, refractory highrisk non-muscle-invasive disease, and especially lymph-node negative disease with reported 10-year recurrence-free survival of organ-confined lymph-node negative (≤pT2N0) disease between 69% and 87% (3
). Improvements in processes of care, particularly at high-volume centers, have led to a reduction in perioperative mortality and long-term survival, further strengthening the role of cystectomy (5
Historically, radical cystectomy in women has posed several technical challenges and concerns, including (a) bleeding from the paravaginal tissues and venous plexus around the urethra, which can be brisk and tedious to control; (b) an intraoperative position change for the surgeon during urethrectomy; and (c) vaginal reconstruction, which can be complex, requiring tissue flaps to maximize organ function.
More recently, additional challenges have related to female organ preservation. Radical cystectomy in women has traditionally been equated with anterior exenteration, including resection of the bladder, urethra, uterus, ovaries, and the anterior one-third of the vagina. This approach is certainly indicated for extensive posterior invasive bladder tumors at risk for reproductive organ involvement. However, tumor involvement of adjacent reproductive organs is rare, suggesting that the routine removal of female reproductive and sex organs is not necessary to achieve local cancer control (9
). Studies have yet to identify female patients with skip lesions involving the urethra, allowing surgeons to proceed with nonstomal diversions when intraoperative frozen-section analysis of the urethral margin is negative (10
). Moreover, the increasing attention to preserving quality of life after cancer surgery provides another incentive to spare part or all of the reproductive organs and urethra when feasible.
INDICATIONS FOR SURGERY
Radical cystectomy is indicated for patients with muscleinvasive urothelial malignancy or non-muscle-invasive disease refractory to transurethral resection and intravesical therapy. Additionally, select patients with high-risk non-muscle-invasive disease may elect to undergo so-called “early cystectomy” at the time of their initial presentation. The presence of intractable local symptoms, failure of bladder preservation strategies, and divergent histology are other indications for radical cystectomy.
The standard therapy for muscle-invasive bladder cancer in women is radical cystectomy. Survival after cystectomy for muscle-invasive disease is closely related to pathologic tumor stage. In patients without lymph node involvement, Stein et al. (4
) reported 10-year recurrence-free survival rates of 87% in T2, 76% in T3, and 45% in T4 disease. Lymph node involvement varies with tumor stage, ranging from 18% of patients
with T2a disease to 45% of patients with T3/T4 disease, and the 10-year recurrence-free survival rate in these patients was reported to be 34%.
Radical cystectomy should seriously be considered as an alternative to intravesical therapy in patients with high-grade T1 disease which is (a) recurrent, (b) associated with carcinoma in situ, and/or (c) combined with adverse histologic features (mixed histology, lymphovascular invasion, inverted growth pattern, or nested variant). Patients with non-muscle-invasive disease resistant or refractory to endoscopic resection and intravesical therapy (particularly bacille Calmette-Guérin) are at significant risk of progression, and repeated courses of intravesical therapy can compromise overall survival (12
). This may be due to the 30% incidence of understaging in patients with noninvasive disease (13
). Divergent histology is identified on 25% of transurethral resection of bladder tumor specimens and has been shown to correlate with high-grade and invasive disease (14
Failure of Alternative Therapies
Alternatives to cystectomy can include systemic chemotherapy, radiation therapy, and aggressive transurethral resection of the tumor, ideally in combination. Although there are no randomized trials comparing bladder-sparing regimens with radical cystectomy, these bladder-sparing modalities have historically been offered to patients who have a solitary tumor <5 cm in size, clinical stage T2 disease without hydronephrosis, minimal or no carcinoma in situ, and no evidence of extravesical disease. Patients who are poor surgical candidates (due to age or medical comorbidities) or refuse cystectomy are also considered for organ preservation strategies.
A significant proportion of these patients will have a complete response to maximal endoscopic resection with chemoradiation (15
). More recently, newer chemoradiation regimens have been proposed, even for clinical T1 tumors, in an effort to provide greater sexual and urinary quality of life in bladder cancer patients (16
). Concurrent chemoradiation does appear to be more effective than radiotherapy alone, with a phase 3 trial showing 48% 5-year survival in a cohort receiving fluorouracil and mitomycin compared to 35% 5-year survival in a cohort receiving radiation alone (17
). Lifelong routine surveillance is critical in this cohort, and 30% to 40% of patients will ultimately require salvage radical cystectomy for disease recurrence (15
Intractable Local Symptoms
Side effects of intravesical therapies are generally mild and managed conservatively. More serious side effects including severe bladder contracture are rare, occurring in <1% of patients treated with intravesical therapy; however, these can also be managed with cystectomy (19
). This decision requires an active discussion between the physician and patient to balance the risks of surgical intervention with the impact of patient symptoms on quality of life.
Optimization of preoperative performance and nutritional status helps reduce the risk of perioperative complications and may be associated with improved perioperative as well as overall survival (2
). Patients are encouraged to augment their diet with protein and caloric supplements if they have anorexia or significant unintended weight loss. Although mechanical bowel preparation was formerly the standard of care, increasing evidence over the past 10 years has suggested that this is likely unnecessary and can be safely omitted in patients undergoing urinary diversion with small intestine. Large et al. (26
) showed that a GoLYTELY (polyethylene
glycol/electrolytes) bowel prep did not appear to impact rates of perioperative infection or bowel complications. In another study, where patients were prospectively randomized to undergo or not undergo mechanical bowel preparation prior to radical cystectomy and ileal urinary diversion, a nonstatistically significant increase in complication rate was observed in the group receiving a bowel preparation (27
). Wound prophylaxis is achieved in the perioperative period with a second-generation cephalosporin antibiotic administered over a 24-hour period.
TABLE 20.1 INDICATIONS FOR SURGICAL EXTENT OF RADICAL CYSTECTOMY IN WOMEN
Cystectomy alone Preserve reproductive organs/vagina/urethra (for neobladder)
≤ T2 Childbearing potential desired Potentially sexually active
Cystectomy plus TAHa/BSOb (if uterus and ovaries are present) Preserve vagina/urethra (for neobladder)
Postchildbearing Postmenopausal Potentially sexually active
Cystectomy plus TAH (if organs present) Preserve vagina/urethra (for neobladder)
≤ T2 Postchildbearing Premenopausal; grossly normal ovaries Potentially sexually active
Cystectomy plus TAH/BSO (if organs present) plus anterior vaginectomy Preserve urethra for neobladder
T2 or T3 Posterior wall tumor away from bladder neck
Cystectomy plus TAH (if organs present) plus anterior vaginectomy Preserve urethra for neobladder
T2 or T3 Posterior wall tumor away from bladder neck Premenopausal; grossly normal ovaries
Cystectomy plus TAH/BSO (if organs present) plus anterior vaginectomy and urethrectomy
T2 or T3 Tumor at bladder neck or urethra
Cystectomy plus TAH (if organs present) plus anterior vaginectomy and urethrectomy
T2 or T3 Tumor at bladder neck or urethra Premenopausal; grossly normal ovaries
a TAH, total abdominal hysterectomy.
b BSO, bilateral salpingo-oophorectomy.
Reprinted with permission from Lee CT, Montie JE. Orthotopic bladder replacement in women. In: Kreder KJ, Stone AR, eds. Urinary Diversion, 2nd ed. Oxfordshire, United Kingdom: Taylor & Francis, 2005:191. Copyright © 2005 by Taylor & Francis. Reproduced by permission of Taylor & Francis Books UK.
The authors of this chapter have also begun short-term perioperative administration of alvimopan (Cubist Pharmaceuticals, Inc, Lexington, Massachusetts) for most patients because it has been shown to reduce the time to return of bowel function and is well tolerated by patients (28
). Alvimopan is contraindicated in patients who have taken opioids for more than a week prior to surgery and patients with end-stage renal disease. Patients should be counseled regarding a potential increase in the risk of myocardial infarction, although this has not been observed with short-term alvimopan use. Pneumatic compression stockings and 5,000 units of low-dose unfractionated subcutaneous heparin are administered prior to induction of anesthesia for deep venous thrombosis prophylaxis. Enhanced Recovery After Surgery pathways have been used to reduce complications and length of stay after colorectal surgery and are being studied for cystectomy patients to optimize perioperative care (29