«26 Muscle-invasive and Metastatic Bladder Cancer Table 1: 2009 TNM classification of urinary bladder cancer T - Primary tumour TX Primary tumour ...»
MUSCLE-INVASIVE AND METASTATIC
(Text update March 2013)
J.A. Witjes (chair), E. Compérat, N.C. Cowan, G. Gakis,
M. De Santis, T. Lebret, M.J. Ribal, A. Sherif
Eur Urol 2011 Jun;59(6):1009-18
Optimal treatment strategies for MIBC require the involvement of a specialist multidisciplinary team and a model of
integrated care to avoid fragmentation of patient care.
Staging system The UICC 2009 TNM (Tumour, Node, Metastasis Classification) is used for staging.
26 Muscle-invasive and Metastatic Bladder Cancer Table 1: 2009 TNM classification of urinary bladder cancer T - Primary tumour TX Primary tumour cannot be assessed T0 No evidence of primary tumour Ta Non-invasive papillary carcinoma Carcinoma in situ: ‘flat tumour’ Tis T1 Tumour invades subepithelial connective tissue T2 Tumour invades muscle T2a Tumour invades superficial muscle (inner half) T2b Tumour invades deep muscle (outer half) T3 Tumour invades perivesical tissue T3a Microscopically T3b Microscopically (extravesical mass) T4 Tumour invades any of the following: prostate, uterus, vagina, pelvic wall, abdominal wall T4a Tumour invades prostate, uterus or vagina T4b Tumour invades pelvic wall or abdominal wall N - Lymph nodes NX Regional lymph nodes cannot be assessed N0 No regional lymph node metastasis N1 Metastasis in a single lymph node in the true pelvis (hypogastric, obturator, external iliac or presacral) N2 Metastasis in multiple lymph nodes in the true pelvis (hypogastric, obturator, external iliac or presacral) N3 Metastasis in a common iliac lymph node(s) M - Distant metastasis M0 No distant metastasis M1 Distant metastasis Muscle-invasive and Metastatic Bladder Cancer 27 Table 2: WHO grading 1973 and 2004 (Both classifications are used for the current guidelines since most of the retrospective studies were based on the old WHO 1973 grading system).
1973 WHO grading Urothelial papilloma Grade 1: well differentiated Grade 2: moderately differentiated Grade 3: poorly differentiated 2004 WHO grading Urothelial papilloma Papillary urothelial neoplasm of low malignant potential (PUNLMP) Low-grade papillary urothelial carcinoma High-grade papillary urothelial carcinoma Morphological subtypes can be important for helping with prognosis and treatment decisions. Currently the following
differentiation is used:
1. Urothelial carcinoma (more than 90% of all cases)
2. Urothelial carcinomas with squamous and/or glandular partial differentiation
3. Micropapillary urothelial carcinoma
4. Nested carcinoma
5. Some urothelial carcinomas with trophoblastic differentiation
6. Small cell carcinomas
7. Spindle cell carcinomas.
Recommendations for assessing tumour specimens Mandatory evaluations • Histological subtype • Depth of invasion • Resection margins, including CIS 28 Muscle-invasive and Metastatic Bladder Cancer • Extensive lymph-node representation Optional evaluation • Bladder wall blood vessel invasion • CIS, carcinoma in situ.
Specific recommendations for primary assessment of presumably invasive bladder tumours (General information for assessment of bladder tumours, see EAU Guidelines on Non-muscle-invasive Bladder cancer) Recommendations GR Cystoscopy should describe all macroscopic features C of the tumour (site, size, number and appearance) and mucosal abnormalities. A bladder diagram is recommended.
Biopsy of the prostatic urethra is recommended for C cases of bladder neck tumour, when bladder CIS is present or suspected, when there is positive cytology without evidence of tumour in the bladder, or when abnormalities of the prostatic urethra are visible.
If biopsy is not performed during the initial procedure, it should be completed at the time of the second resection.
In women undergoing a subsequent orthotopic neob- C ladder, procedure information is required (including a histological evaluation) of the bladder neck and urethral margin, either prior to, or at the time of cystoscopy.
The pathological report should specify the grade, the C depth of tumour invasion and whether the lamina propria and muscle tissue are present in the specimen.
Muscle-invasive and Metastatic Bladder Cancer 29 Recommendations for staging of MIBC GR In patients with confirmed muscle-invasive bladder B cancer, CT of the chest, abdomen and pelvis is the optimal form of staging, including excretory-phase CT urography for complete examination of the upper urinary tracts.
Excretory-phase CT urography is preferred to MR C urography for diagnosing UTUCs in terms of greater diagnostic accuracy, less cost, and greater patient acceptability. MR urography is used when CT urography is contra-indicated for reasons related to contrast administration or radiation dose.
Ureteroscopic-guided biopsy is recommended for C histopathological confirmation of diagnosis in the preoperative assessment of UTUC.
CT or MRI is recommended for staging locally C advanced or metastatic disease in patients in whom radical treatment is being considered.
CT and MRI are generally equivalent in diagnosing C local and distant abdominal metastases but CT is preferred to diagnose pulmonary metastases.
Treatment failure of non-muscle invasive bladder tumours
Recommendations for treatment failure of non-mus- GR cle-invasive bladder cancer In all T1 tumours at high risk of progression (i.e. high B grade, multifocality, carcinoma in situ, and tumour size, as outlined in the EAU guidelines for Non-muscleinvasive bladder cancer), immediate radical treatment is an option.
In all T1 patients failing intravesical therapy, radical B treatment should be offered.
30 Muscle-invasive and Metastatic Bladder Cancer Muscle-invasive bladder cancer - Radical Surgery and Urinary Diversion Conclusions LE For muscle-invasive bladder cancer radical cystec- 3 tomy is the curative treatment of choice.
A higher case load reduces morbidity and mortality of 3 cystectomy.
There is data to support that an extended LND (versus 3 a standard or limited LND) improves survival after radical cystectomy.
Radical cystectomy in both sexes must not include 3 the removal of the entire urethra in all cases, which may then serve as outlet for an orthotopic bladder substitution.
Terminal ileum and colon are the intestinal segments 3 of choice for urinary diversion.
The type of urinary diversion does not affect oncologi- 3 cal outcome.
Laparoscopic and robotic-assisted laparoscopic cys- 3 tectomy is feasible but still investigational.
In patients with invasive bladder cancer older than 80 3 years cystectomy is an option.
Surgical outcome is influenced by comorbidity, age, 2 previous treatment for bladder cancer or other pelvic diseases, surgeon and hospital volumes of cystectomy, and type of urinary diversion.
Surgical complications of cystectomy and urinary 2 diversion should be reported in a uniform grading system. Currently, the best-adapted, graded system for cystectomy is the Clavien grading system.
Contraindications for orthotopic bladder substitution are
Muscle-invasive and Metastatic Bladder Cancer 31 positive margins at the level of urethral dissection, positive margins anywhere on the bladder specimen (in both sexes), if the primary tumour is located at the bladder neck or in the urethra (in women), or if tumour extensively infiltrates the prostate (in men).
Recommendations for radical cystectomy GR Radical cystectomy is recommended in T2-T4a, N0 A* M0, and high risk non-muscle-invasive BC.
Do not delay cystectomy more than 3 months since it B increases the risk of progression and cancer-specific death.
Pre-operative radiotherapy is not recommended in A case of subsequent cystectomy with urinary diversion.
Lymph node dissection should be an integral part of B cystectomy. An extended LND is recommended.
The urethra can be preserved if margins are negative. B If no bladder substitution is attached, the urethra must be checked regularly.
Laparoscopic and robot-assisted laparoscopic cystec- C tomy are both options. However, current data have not sufficiently proven the advantages or disadvantages for both oncological and functional outcomes of laparoscopic and robotic-assisted laparoscopic cystectomy.
Before cystectomy, the patient should be fully B informed about the benefits and potential risks of all possible alternatives, and the final decision should be based on a balanced discussion between patient and surgeon.
32 Muscle-invasive and Metastatic Bladder Cancer The decision regarding bladder sparing or radical cys- B tectomy in the elderly/geriatric patient with invasive bladder cancer should be based on tumour stage and comorbidity best quantified by a validated score, such as the Charlson score.
Pre-operative bowel preparation is not mandatory, C ‘fast track’ measurements may reduce the time of bowel recovery.
An orthotopic bladder substitute should be offered to B male and female patients lacking any contraindications and who have no tumour in the urethra and at the level of urethral dissection.
*Upgraded following panel consensus Neoadjuvant chemotherapy Neoadjuvant cisplatin-containing combination chemotherapy improves overall survival, irrespective of the type of definitive treatment (LE: 1a). It has its limitations regarding patient selection, current development of surgical technique, and current chemotherapy combinations. In current routine clinical practice, it is difficult to select patients who will respond to neoadjuvant chemotherapy due to the lack of an applicable test. In the future, genetic markers, in a ‘personalized medicine’ setting, are expected to make it easier to select patients for treatment and to differentiate responders from non-responders.
Recommendations GR Neoadjuvant chemotherapy is recommended for A T2-T4a, cN0M0 bladder cancer and should always be cisplatinum-based combination therapy.
Neoadjuvant chemotherapy is not recommended in B patients with PS ≥ 2 and/or impaired renal function.
In case of progression under neoadjuvant chemotherapy, this treatment should be discontinued.
Direct adjuvant chemotherapy
• Not indicated after cystectomy Bladder-sparing treatments for localised disease Transurethral resection of bladder tumour (TURB) TURB alone is only possible as a therapeutic option if tumour growth is limited to the superficial muscle layer and if re-staging biopsies are negative for residual tumour.
External beam radiotherapy External beam radiotherapy alone should only be considMuscle-invasive and Metastatic Bladder Cancer ered as a therapeutic option when the patient is unfit for cystectomy or a multimodality bladder-preserving approach.
Radiotherapy can also be used to stop bleeding from the tumour when local control cannot be achieved by transurethral manipulation because of extensive local tumour growth (LE: 3).
Surgically non-curable tumours Palliative cystectomy for metastatic disease Primary radical cystectomy in T4b bladder cancer is not a curative option. If there are symptoms, radical cystectomy may be a therapeutic/palliative option. Intestinal or non-intestinal forms of urinary diversion can be used, with or without, palliative cystectomy.
Recommendations LE GR In patients with inoperable locally advanced B tumours (T4b), primary radical cystectomy is a palliative option and cannot be offered as curative treatment.
In patients with symptoms palliative cystectomy may be offered.
Prior to any further interventions, surgery- 3 B related morbidity and quality-of-life should be fully discussed with the patient.
Chemotherapy and best supportive care With cisplatin-based chemotherapy as primary therapy for locally advanced tumours in highly selected patients, complete and partial local responses have been reported. (LE: 2b).
Recommendations GR Transurethral resection of bladder tumour (TURB) B alone cannot be offered as a standard curative treatment option in most patients.
Radiotherapy alone is less effective than surgery and B is only recommended as a therapeutic option when the patient is unfit for cystectomy or a multimodality bladder-preserving approach.
Chemotherapy alone is not recommended as primary A therapy for muscle-invasive bladder cancer.
Surgical intervention or multimodality treatment are B the preferred curative therapeutic approaches since they are more effective than radiotherapy alone.
36 Muscle-invasive and Metastatic Bladder Cancer Multimodality treatment could be offered as an alter- B native in selected, well-informed, well selected and compliant patients, especially for whom cystectomy is not an option.
Metastatic disease Conclusions for metastatic disease LE In a first-line setting, PS and the presence or absence 1b of visceral metastases are independent prognostic factors for survival.
In a second-line setting, prognostic factors are: liver 2 metastasis, PS and haemoglobin ( 10 g/dL) Cisplatin-containing combination chemotherapy can 1b achieve median survival of up to 14 months, with longterm disease-free survival reported in ~15% of patients with nodal disease and good PS.
Carboplatin combination chemotherapy is less 2a effective than cisplatin-based chemotherapy in terms of complete response and survival.
There is no defined standard chemotherapy for unfit 2b patients with advanced or metastatic urothelial cancer.
Vinflunine reached the highest level of evidence ever 1b reported for second-line use.
Post-chemotherapy surgery after partial or complete 3 response may contribute to long-term disease-free survival.
Zoledronic acid and denosumab have been approved 1 for all cancer types including urothelial cancer, because they reduce and delay SREs in metastatic bone disease.
Muscle-invasive and Metastatic Bladder Cancer 37 Recommendations for metastatic disease GR
First-line treatment for fit patients:
Use cisplatin-containing combination chemotherapy A with GC, PCG, MVAC, preferably with G-CSF, or HD-MVAC with G-CSF.
Carboplatin and non-platinum combination chemo- B therapy is not recommended.
First-line treatment in patients ineligible (unfit) for cisplatin: