Treatment for carcinoma of the bladder

Noninvasive tumours

Endoscopic surgery

It is not acceptable to take a tiny biopsy from the top of a papillary tumour and apply a fulgurating coagulation current to the rest unless a small recurrence is being dealt with. The tumour should be carefully resected in layers using a resectoscope. The base of the tumour is sent separately for histological examination. Small biopsies are taken near to and distant from the primary lesion to diagnose unsuspected cis. After removal of the tumour, two or three further loops of tissue from the base should be sent separately so that the pathologist can accurately determine whether there is lamina propria or muscle invasion. The base of the tumour is then coagulated, so achieving haemostasis. The appearance of pale yellow glistening fat will indicate a perforation of the bladder. Should this occur before the resection is complete, it may be prudent to stop the resection and place a catheter in the bladder for a few days. In this instance

the procedure could be completed some 2 weeks later. The bimanual examination is repeated at the end of each endoscopic procedure.

Patients with solid tumours should have adequate material resected for histological staging and grading. These patients will usually need some other form of treatment. It is likely that a debulking resection of these tumours is helpful prior to radiotherapy. Following these procedures an irrigating catheter is left in situ for 48 hours to prevent clot retention of urine. There is good evidence that a single dose of mitomycin C (40 mg in 60 ml of fluid) instilled into the bladder prior to catheter removal decreases the risks of recurrence in patients with pTa, PT1 grade 1 and 2 disease.

Follow-up. Most urologists agree that patients with a single, low- or medium-grade pTa tumour can safely be treated by resection alone and followed up by means of regular cystoscopies.

The treatment of patients with multiple low- or medium-grade pTa tumour can be by either means of resection alone or resection followed by a 6-week course of intravesical chemotherapy with mitomycin C, adriamycin or epirubicin.

The treatment of pTl disease is difficult. Many urologists, including many North American and European urologists, would offer immediate cystectomy to a patient with a high-grade pTl tumour — particularly if it was multiple or accompanied by cis, because of the 30—50 per cent risk of progression to muscle invasion. Others will treat such patients by means of endoscopic treatment followed by intravesical immunotherapy with intravesical bacille Calmette—Guérin (BCG) — although there is no firm evidence that this decreases the risk of progression. The treatment of solitary medium-grade pTl disease remains uncertain, but a reasonable approach would be endoscopic resection followed re-resection of the area in 6 weeks followed by intravesical chemotherapy with BCG.

Follow-up cystoscopies are essential; they may be carried out by means of local anaesthesia with a flexible cystoscope on by means of general anaesthesia if the urologist feels that the patient has a high risk of recurrence. They should initially be performed at 3-monthly intervals over the year; following this the time interval between cystoscopies can be determined according to the presence or absence of further disease. Thirty per cent of patients will never develop another tumour, so that after 2 years if the bladder has remained clear annual inspection may be adequate. For patients who go on to develop multiple recurrences within the bladder at each examination, the cystoscopies need to be maintained at frequent intervals so that the growths can be resected. These patients are at a greater risk from developing progression of their disease; whilst intravesical chemotherapy can decrease the recurrence rate, no reduction in progression rates has been found.

Intravesical chemotherapy and immunotherapy

Various agents have been used. These include thiotepa (which may be absorbed because of its low molecular weight and cause blood dyscrasias), mitomycin C, epirubicin and adriamycin. They are of equal efficacy and the cheapest should be chosen. They are administered by means of a urethral catheter and held in the bladder for 1 hour, the patients are turned from side to side and try to hold their urine for as long as possible. Usually the patients are treated weekly for 8—10 weeks and then re-cystoscoped. BCG is now frequently used as intravesical immunotherapy. It carries a greater risk of local side effects such as ‘cystitis-like’ symptoms and also risks of systemic side effects — including systemic BCGosis. Nevertheless, it is probably more effective than intravesical chemotherapy and is the treatment of

choice for cis. Currently, ‘booster’ doses of maintenance BCG treatment are being given in addition to the initial 6-week course.

Open surgical excision

This should be totally avoided. If by some error a bladder containing a tumour is entered, then the tumour may be removed with a diathermy needle and the base coagulated and the bladder closed. Postoperative radiotherapy to the wound will diminish the chance of tumour implantation.

Invasive tumours

The treatment of cancer with proven muscle invasion remains a subject for debate. Whatever the modality of treatment employed, few centres have 5-year survival figures of more than 40 per cent. The controversy is centred around whether primary surgery (radical cystectomy), radical radiotherapy, or a combination of the two, provides the best result. There is a move towards primary surgical treatment in most centres. The use of systemic chemotherapy by means of a combination of agents using cis-platinum, methotrexate, adriamycin and vinblastine (MVAC) in addition to conventional treatment is presently being studied. -

Radiotherapy

Deep external beam X-ray therapy. External beam radiotherapy is usually given by means of high-powered linear accelerators. Radical radiotherapy giving 60 Gy over a 4—6-week period will produce a 40—50 per cent complete response. The difficulty with radiotherapy is in patients who do not respond at all or those who have a partial response, having a bladder with pTa or pTl tumour in it, and who are subject to recurrence. Patients with residual disease after radiotherapy should be offered ‘salvage cystectomy’ if they are fit. The protagonists of radiotherapy would claim that for most patients it saves the need to remove the bladder and allows men to retain potency. Radiotherapy is not always without complications, and during the course of treatment will cause urinary frequency and also diarrhoea. Late complications can leave the bladder contracted and fibrosed, in which case the bladder may need to be removed for palliative reasons. Late complications affecting the rectum should be uncommon, especially if lateral fields of irradiation are employed.

Local radiotherapy. For small invasive lesions, local radiotherapy can be delivered by open placement of a radioactive tantalum wire (iB2Ta) or iridium wire or the implantation of gold grains (t98Au). It is used infrequently today.

Surgery

Partial cystectomy. This should be limited to the treatment of small adenocarcinomas of the bladder.

Radical cystectomy and pelvic lymphadenectomy. This is now standard treatment for localised pT2—pT3 disease without evidence of secondary spread or of cis which has nor responded to BCG. Before contemplating radical surgery to remove the bladder, it is important to have evidence that surgical cure is attainable. A CT scan of the pelvis may over-stage the bladder if a recent resection has been carried out, although the finding of grossly enlarged pelvic, iliac or para aortic nodes on liver metastases will alter the decision for cystectomy. A bone scan [technetium-99m (S9mTc)] will help to show whether there is spread to bone.

Operation

Alternative drainage for the urine is necessary following removal of the bladder. The standard procedure is to perform an ileal conduit. Patients should be counselled about the onset of erectile impotence and absent ejaculation following the operation; they should also be told about alternative forms of urinary diversion which include continent urinary diversions and orthotopic bladder replacement.

Patients should be seen by a stoma care therapist who will help to advise the patient and will try different ileostomy bags to ensure that the correct site is chosen avoiding skin creases so that one does not end up with the disaster of a leaking urinary ileostomy. A decision is made about whether the male urethra is to be removed (depending on the estimated risk of recurrence within the urethra); a urethrectomy is usually indicated in patients with primary cis or those with tumour invading the prostate stroma. Many surgeons are now offering total replacement of the bladder after cystectomy (Fig. 65.53).

Preoperatively, the bowel is prepared with a balanced solution of polyethylene glycol (Golytely or Kleanprep). The patient should receive prophylactic antibiotics including metronidazole, cefuroxime and amoxycillin, and low-dose heparin.

The abdomen is opened through a long lower midline incision extending down to the symphysis pubis. The liver and the retroperitoneum are checked for evidence of metastases and the operability of the bladder is assessed. A bilateral pelvic lymphadenectomy is performed removing external iliac nodes, internal iliac nodes and the nodes in the obturator fossae. The vessels passing to the bladder from the side wall are ligated in continuity; these include the obliterated hypogastric vessels, the superior vesical artery, the middle vesical veins, and the inferior vesical arteries and veins. The ureters are then divided. The posterior ligaments extending from the pararectal area to the back of the bladder are ligated and divided, and the layer posterior to Denonvillier’s fascia is opened up. The endopelvic fascia is then divided on each side and the puboprostatic ligaments are divided. A ligature is passed between the dorsal vein complex and the urethra, and the former is ligated and divided. The urethra is then mobilised and divided. The ligaments lateral to the prostate are divided and the bladder is removed. In women, the uterus and anterior vaginal wall need to be included. Women must be counselled about the loss of ovarian and uterine function. -

An isolated loop of ileum is then prepared on its own mesentery, and continuity of the small bowel restored. The ureters are then implanted into the bowel and the ileostomy is created. Meticulous care must be taken to close all mesenteric windows, thus avoiding internal hernias. If the bladder is to be replaced orthotopically, a reservoir made from detubularised bowel (usually an ileocaecal segment or ileum) is created and anastomosed to the urethra after implantation of the ureters.

The operative mortality associated with cystectomy used to be considerable, but should be in the order of 2 per cent. Late complications include urethral recurrence (about 5—8 per cent) which is increased in the presence of multifocal tumours, cis and, particularly, invasion of prostatic stroma (Fig. 65.54).

Leukoplakia

This condition is simply squamous metaplasia of the bladder. Profuse production of keratin may result in the passing of white particles in the urine. It cannot be treated easily. Localised areas may be resected endoscopically. Diffuse leucoplakia of the bladder is premalignant and results in squamous bladder cancer. Careful cystoscopic assessment is required. The condition may require cystectomy.

Endometriosis

Endometriosis within the bladder wall is rare, but can have the appearance of a vascular bladder tumour or a tumour which contains chocolate-coloured or bluish cysts. The swelling enlarges and bleeds during menstruation. If medical management fails, by means of danazol or luteinising hormone-releasing agonists (LHRH), further treatment is usually by means of partial cystectomy or full-thickness endoscopic resection, depending on its site. The condition may be part of more widespread disease. Endometriosis is also a cause of ureteric stricture.