Материал: Oxford American Handbook of Urology ( PDFDrive )
262 CHAPTER 6 Urological neoplasia
Salvage radical cystectomy is technically a more difficult and slightly more morbid procedure. Relatively few patients who have failed primary RT and chemotherapy are suitable for this second chance of a cure.
Efficacy of radical cystectomy 5-year survival rates are as follows:
|
• |
Stage T1/CIS |
+90% |
|
• |
Stages T2, T3a |
63–88% |
|
• |
Stage T3b |
37–61% |
|
• |
Stage T4a (into prostate) |
10% |
|
• |
Stage TxN1–2 |
30% |
|
• |
Salvage T0 |
70% |
|
• |
Salvage T1 |
50% |
|
• |
Salvage T2, 3a |
25% |
|
|
|
|
|
|
|
|
MUSCLE-INVASIVE BLADDER CANCER 263
Muscle-invasive bladder cancer: radical and palliative radiotherapy
Radical external beam radiotherapy (RT)
This is a good option for treating muscle-invasive (pT2/3/4) UC in patients who are not healthy or unwilling to undergo cystectomy. The 5-year survival rates are inferior to those of surgery, but the bladder is preserved and the complications are less significant.
Typically, a total dose of 70 Gy is administered in 30 fractions over 6 weeks. Higher-grade tumors tend to do less well, perhaps because of the undetected presence of disease outside the field of irradiation. Beyond this, prediction of radiotherapy response remains difficult, relying on fol- low-up cystoscopy and biopsy. CIS, SCC, and adenocarcinoma are poorly sensitive to radiotherapy.
Neoadjuvant or adjuvant cisplatin-based combination chemotherapy with RT is used in locally advanced (pT3b/4) disease (see p. 264) and is more commonly performed than RT monotherapy.
Complications
These occur in 70% of patients; they are self-limiting in 90% of cases. Complications include radiation cystitis (LUTS and dysuria) and proctitis (diarrhea and rectal bleeding). These effects usually last only a few months.
Refractory radiation cystitis and hematuria may rarely require measures such as intravesical alum, formalin, hyperbaric oxygen, iliac artery embolization, or even palliative cystectomy.
Efficacy of RT monotherapy
5-year survival rates are as follows:
• |
Stage T1 |
35% |
• |
Stage T2 |
40% |
• |
Stage T3a |
35% |
• |
Stage T3b, T4 |
20% |
• |
Stage TxN1–2 |
7% |
If disease persists or recurs, salvage cystectomy may still be successful in appropriately selected patients; 5-year survival rates are 30–50%.
Otherwise, cytotoxic chemotherapy (see p. 265) and palliative measures may be considered.
Palliative treatment
This includes radiotherapy for metastatic bone pain (30 Gy) or to palliate symptomatic local tumor (40–50 Gy). Intractable hematuria may be controlled by intravesical formalin or alum, hyperbaric oxygen, bilateral internal iliac artery embolization or ligation, or palliative cystectomy.
Ureteral obstruction may be relieved by percutaneous nephrostomy and antegrade stenting (see p. 456). Involvement of a palliative care team can be very helpful to the patient and family.
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.
MUSCLE-INVASIVE BLADDER CANCER 265
Neoadjuvant or adjuvant chemotherapy with RT
The recent meta-analysis also showed a 5% survival advantage with the use of cisplatin-based combination chemotherapy when RT was used as definitive treatment. This may be offered to patients suspected of having locally advanced disease after clinical examination and staging imaging.
Metastatic bladder cancer
Systemic chemotherapy
This modality is routine for patients with unresectable, diffusely metastatic measurable disease. Complete responses are rare with single agents. When chemotherapeutic agents are combined, however, complete responses are observed.
The most active agents include cisplatin, taxanes (docetaxel, paclitaxel), gemcitabine, and cisplatin. Clinical trials have established the MVAC combination as the standard of care.1 This multidrug treatment has been found to be superior to single-agent cisplatin, the combination of docetaxel and cisplatin, and the multidrug regimen CISCA. The median survival of patients treated with MVAC for metastatic disease is 14.2–16.1 months. Using MVAC, 20% of patients develop neutropenia and 3% die of sepsis.
Trials comparing gemcitabine combined with cisplatin to MVAC found similar survival rates. Gemcitabine/cisplatin-treated patients have significantly less neutropenia and fewer hospitalization days for treating infection. Gemcitabine/cisplatin is currently considered an alternative standard of care to MVAC.
Second-line therapy for patients who fail either gemcitabine cisplatin or MVAC is limited. Median time to progression is approximately 3 months, and median survival ranges between 6 and 9 months. Single-agent therapy is used over combination treatment since there are fewer toxicities.
Radiotherapy
Roles for RT include palliation of metastatic pain and spinal cord compression.
Surgery
There is no surgical role in treatment of extravesical metastatic disease. However, some publications suggest that surgical resection of metastatic lesions that have responded to chemotherapy can result in durable responses.
1 Sternberg CN (2007). Chemotherapy for bladder cancer: treatment guidelines for neoadjuvant chemotherapy, bladder preservation, adjuvant chemotherapy, and metastatic cancer. Urology 69(1 Suppl):62.
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.