264 CHAPTER 6 Urological neoplasia

Muscle-invasive bladder cancer: management of locally advanced and metastatic disease

Locally advanced bladder cancer (pT3b/4)

Many patients treated with primary cystectomy or radiotherapy (RT) with curative intent succumb to metastatic disease due to incomplete tumor excision or micrometastases.

At this stage, 5-year survival is only 5–10%. There is interest in augmenting primary treatment in an effort to improve outcomes.

Neoadjuvant RT

Randomized studies have suggested improvements in local control using RT prior to cystectomy, but no survival benefit has been demonstrated.

Adjuvant RT

The rationale for post-cystectomy RT is that patients with proven residual or nodal disease may benefit from locoregional treatment. However, it leads to unacceptably high morbidity and has no demonstrable advantages. Post-treatment bowel obstruction occurs 4.5 times more commonly in RT patients.

Adjuvant cystectomy

Two studies have demonstrated an improvement in local control and a survival advantage when treating locally advanced disease with cystectomy after RT, compared to RT alone. However, this treatment strategy is associated with increased morbidity of surgery in this setting.

Neoadjuvant chemotherapy

Neoadjuvant chemotherapy with methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) should be considered in all patients with muscle-in- vasive (T2–4a) disease. A randomized trial comparing the median survival among patients assigned to cystectomy alone was 46 months, compared with 77 months among patients assigned to 3 cycles of MVAC combined with cystectomy. Similar findings have been demonstrated using CMV chemotherapy.

For patients with localized disease, pathological complete response (P0) after chemotherapy results in a relapse-free survival at 5 years of 85%. For patients who do not have a complete response to therapy, patients treated with MVAC chemotherapy prior to cystectomy have similar survival rates to those with cystectomy alone.

Adjuvant chemotherapy

The rationale for post-cystectomy chemotherapy is that patients with proven residual or nodal disease may benefit from systemic treatment. Patients with T3–4a, or N+ disease are at high risk for relapse following radical cystectomy.

Adjuvant MVAC or gemcitabine/cisplatin can be considered, although there are no trials demonstrating a survival advantage for adjuvant therapy. Clinical trial enrollment should be encouraged.

266 CHAPTER 6 Urological neoplasia

Bladder cancer: urinary diversion after cystectomy

Ureterosigmoidostomy

This is the oldest form of urinary diversion, whereby the ureters drain into the sigmoid colon, either in its native form or following its detubularization and reconstruction into a pouch (Mainz II). This diversion requires no appliance (stoma bag, catheter) so remains popular in developing countries.

In recreating a cloaca, the patient may be prone to upper UTI with the risk of long-term renal deterioration, metabolic hyperchloremic acidosis, and loose, frequent stools. The low-pressure and capacious Mainz II pouch reduces these complications.

There is a long-term risk of colon cancer with this type of diversion and it is not popular in the United States.

Ileal conduit

This was developed in 1950 and remains the most popular form of urinary diversion. A 15 cm segment of of subterminal ileum is isolated on its mesentery, the ureters are anastomosed to the proximal end, and the distal end is brought out in the right lower quadrant as a stoma. The ileum is anastomosed to gain enteral continuity (ileoileostomy).

Complications

•Prolonged ileus

•Urinary leak

•Enteral leak

•Pyelonephritis

•Ureteroileal stricture

•Stoma problems—skin irritation, stenosis, and parastomal hernia

Patients require stoma therapy support and some find difficulty in adjusting their lifestyle to cope with a stoma bag. Metabolic complications are uncommon.

In post-RT salvage patients, a jejunal or colonic conduit is used because of concerns about the healing of radiation-damaged ileum. The conduit may be brought out in the upper abdomen. Patients require careful electrolyte monitoring due to sodium loss and hyperkalemia.

Continent diversion

The advantage of such a diversion is the absence of an external collection device. A neobladder (pouch) is fashioned from 60–70 cm of detubularized ileum or right hemicolon. The ureters drain into the neobladder, usually through an anti-reflux submucosal tunnel. This may be drained by the patient via a catheterizable stoma, such as the appendix or uterine tube (the Mitrofanoff principle) brought out in the right iliac fossa.

Alternatively, the neobladder may be anastomosed to the patient’s urethra so that natural voiding can be established. Patients void by relaxing their external sphincter and performing a Valsalva maneuver.

BLADDER CANCER: URINARY DIVERSION AFTER CYSTECTOMY 267

This orthotopic neobladder should require no catheter, unless the pouch is too large and fails to empty adequately. In this case, the patient must be prepared to perform intermittent self-catheterization. Initially, bladder irrigations once or twice a day are necessary because of mucous production that gradually diminishes with time.

Popular ileal pouches include those of Studer (Fig. 6.7), Camey II, and Kock; ileocecal pouches include the Indiana and Mainz I. The choice of pouch often comes down to the surgeon’s preference; they all carry similar complication risks.

a

b

c

d

Figure 6.7 (a) The distal 40–44 cm of resected ileum opened along the antimesenteric border with scissors. Spatulated ureters are anastomosed end to side with 4–0 running suture on either side of proximal end of afferent tubular ileal limb. Ureters are stented. (b) The two medial borders of the U-shaped, opened, distal ileal segment are oversewn with a single-layer seromuscular continuous suture. The bottom of the U is folded between the two ends of the U. (c) Before complete closure of the reservoir, an 8–10 mm hole is cut into the most caudal part of the reservoir (left). Six sutures are placed between the seromuscular layer of the anastomotic area of the reservoir and the membranous urethra (right). An 18 Fr urethral catheter is inserted. (d) Before complete closure of the pouch, a cystostomy tube is inserted and brought out suprapubically adjacent to the wound. Reprinted with permission from Studer UE, Danuser H, Hochreiter W, et al. (1996). World J Urol 14(1):29–39.

268 CHAPTER 6 Urological neoplasia

Previously irradiated bowel can be cautiously used to form pouches, though complications are more likely. In orthotopic neobladders, incontinence is more common in men than in women, and women have a higher likelihood of being in retention and requiring long-term intermittent catheterization.

Complications relating to continent diversions and neobladders

•Urinary leakage and peritonitis

•Pelvic abscess

•Stone formation

•Catheterizing difficulties and stomal stenosis

•Urinary incontinence and nocturnal enuresis

•Pouch-ureteral reflux and UTI

•Uretero-pouch anastomotic stricture

•Late neobladder rupture

Metabolic abnormalities

These include early fluid and electrolyte imbalances. Later, urinary electrolyte absorption may cause hyperchloremic acidosis, and loss of the distal small bowel (distal 15 cm of ileum) may result in vitamin B12 deficiency. Metabolic acidosis is less likely in patients with normal renal function; treatment is with sodium bicarbonate and potassium citrate.

Annual B12 and CBC monitoring should be undertaken, with supplementation if necessary.

Adenocarcinoma

Adenocarcinoma may develop (5%) in diversions that involve a segment of colon. While more likely with ureterosigmoidostomy with constant contact of feces with the urinary stream, the cause is the carcinogenic bacterial metabolism of urinary nitrosamines.

This tends to occur near the inflow of urine. It is therefore advisable to perform annual visual surveillance of colon urinary diversions after 10 years. If the urethra is in situ, as with orthotopic neobladder, annual urethroscopy and cytology are suggested.

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