
Committee V
Bladder Cancer
Prof. Dr. Hassan Abol-Enein Professor of Urology, Mansoura University
Prof. Dr. Mohamed Adel Atta Professor of Urology, Alexandria University
Prof. Dr. Adel Elbakry Professor of Urology, Swiss Canal University
Ass. Prof. Ahmed Moeen Assistant Professor of Urology, Assuit University
Dr. Amr A. Elsawy Lecturer of Urology, Mansoura University
Contents
- V.1 Abbreviations:
- V.2 Introduction:
- V.3 Epidemiology, Etiology and Pathology:
- V.4 Non-muscle invasive bladder cancer (NMIBC)
- V.5 Disease management
- V.6 Muscle invasive bladder cancer (MIBC)
- V.7 Metastatic bladder cancer
- V.8 Summary:
- V.9 References
V.1 Abbreviations:
- BCG - Bacillus Calmette-Guérin
- BC - Bladder cancer
- CIS - Carcinoma in Situ
- CT - Computed tomography
- CT-IVU - Computed Tomography-Intravenous Urography
- FGFR - Fibroblast Growth Factor Receptor
- G-CSF - Granulocyte Colony-Stimulating Factor
- HD - High-Dose
- HG - High-Grade
- IVU - Intravenous Urography
- LG - Low-Grade
- MRI - Magnetic Resonance Imaging
- MVAC - Methotrexate, Vinblastine, Adriamycin plus Cisplatin
- MMT - Multimodality Treatments
- MIBC - Muscle invasive bladder cancer
- NAC - Neoadjuvant Chemotherapy
- NMIBC - Non-muscle invasive bladder cancer
- NMP - Nuclear Matrix Protein
- PUNLMP - Papillary Urothelial Neoplasm of Low Malignant Potential
- QoL - Quality of Life
- RC - Radical Cystectomy
- RT - Radiotherapy
- SREs - Skeletal-Related Events
- TERT - Telomerase Reverse Transcriptase
- US - Ultrasound
- UUT - Upper Urinary Tract
- ZA - Zoledronic Acid
V.2 Introduction:
It must be emphasized that guidelines can never replace clinical expertise when making treatment decisions for individual patients, but rather help to focus decisions and considering the personal values and preferences/individual circumstances of patients into account.
V.2.1 Methods:
• Quality of evidence for this recommendation.
• Impact of this practice on patient and oncological outcomes.
• The balance between this practice and the different aspects of health service in our locality.
V.2.2 Results
V.2.3 Conclusions.
V.3 Epidemiology, Etiology and Pathology:
V.3.1 Epidemiology
Approximately 75% of patients with BC present with a disease confined to the mucosa (stage Ta, CIS) or submucosa (stage T1) (2).
V.3.2 Etiology
Schistosomiasis, a chronic endemic cystitis based on recurrent infection with a parasitic trematode, is also a cause of BC. Exposure to ionizing radiation is connected with increased risk; weak association was also suggested for cyclophosphamide and pioglitazone (6). The impact of metabolic factors (body mass index, blood pressure, plasma glucose, cholesterol and triglycerides) is uncertain (7).
V.3.3 Pathology
V.3.3.1 Staging:
T- Primary tumor |
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N- Lymph Nodes |
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M - Distant metastasis |
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V.3.3.2 Histological grading:
1973 WHO grading |
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2004 WHO/ISUP grading system (papillary lesions) |
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V.3.3.3 Carcinoma in situ and its classification
V.3.3.4 Classification of CIS according to clinical type:
o Primary: isolated CIS with no previous or concurrent papillary tumors and no previous CIS.
o Secondary: CIS detected during follow-up of patients with a previous tumor that was not CIS.
o Concurrent: CIS in the presence of any other urothelial tumor in the bladder.
V.3.3.5 Variants of urothelial carcinoma and lymphovascular invasion
1. Urothelial carcinoma (more than 90% of all cases)
2. Urothelial carcinomas with partial squamous and/or glandular or trophoblastic differentiation
3. Micropapillary urothelial carcinoma
4. Nested variant (including large nested variant) and microcystic urothelial carcinoma
5. Plasmocytoid, giant cell, signet ring, diffuse, undifferentiated
6. Lymphoepithelioma-like
7. Small-cell carcinomas
8. Sarcomatoid urothelial carcinoma
In these pathological variants, the decision of optimal treatment is individualized. Early cystectomy with or without neo-adjuvant or adjuvant therapy is considered according to the decision of multidisciplinary team agreement.
The presence of an element of these variants together with TCC tumors is considered as nonurothelial and should be treated as tumor cell variant.
Revision of the histopathology may be needed by another expert to support the diagnosis
V.4 Non-muscle invasive bladder cancer (NMIBC)
V.4.1 Diagnosis
V.4.1.1 Patient history
V.4.1.1.1 Signs and symptoms
Hematuria is the most common finding in NMIBC. Carcinoma in situ might be suspected in patients with lower urinary tract symptoms, especially irritative voiding. Sometimes, the bladder lesion is detected during routine sonographic survey especially those located in the bladder dome and anterior wall.
V.4.1.1.2 Physical examination
A focused urological examination is mandatory although it does not reveal NMIBC.
V.4.1.1.3 Imaging
V.4.1.1.3.1 Ultrasound
Ultrasound (US) may be performed as an adjunct to physical examination as it has moderate sensitivity to a wide range of abnormalities in the upper and lower urinary tract (12). It permits characterization of associated pathology, detection of hydronephrosis, and visualization of intraluminal masses in the bladder.
V.4.1.1.3.2 Computed tomography urography and intravenous urography
Computed tomography (CT) urography is used to detect papillary tumors in the urinary tract, indicated by filling defects and/or hydronephrosis (13).
Intravenous urography (IVU) is an alternative if CT is not available but particularly in muscle-invasive tumors of the bladder and in UTUCs, CT urography provides more information (including status of lymph nodes and surrounding organs) (14).
The incidence of UTUCs is low (1.8%), but increases to 7.5% in tumors located in the trigone. The risk of UTUC during follow up increases in patients with multiple- and high-risk tumors (15).
CTU or magnetic resonance imaging are an essential tool in the diagnosis, staging and Management
V.4.2 Urinary cytology
Positive voided urinary cytology can indicate an urothelial carcinoma anywhere in the urinary tract; negative cytology, however, does not exclude its presence (17).
Cytological interpretation is user-dependent. Evaluation can be hampered by low cellular yield, urinary tract infections, stones, or intravesical instillations; however, in experienced hands specificity exceeds 90% (18).
V.4.3 Urinary molecular marker tests
The following conclusions can be drawn regarding the existing tests:
• Sensitivity is usually higher at the cost of lower specificity, compared to urine cytology.
• Benign conditions and previous BCG instillations may influence the results of many urinary marker tests.
• The wide range in performance of the markers and low reproducibility may be explained by patient selection and complicated laboratory methods required.
• Positive results of cytology, UroVysion (FISH), Nuclear Matrix Protein (NMP)22R, Fibroblast Growth Factor Receptor (FGFR)3/Telomerase Reverse Transcriptase (TERT) and microsatellite analysis in patients with negative cystoscopy and upper tract work-up, may identify patients more likely to experience disease recurrence and possibly progression.
• If main aim is to avoid unnecessary cystoscopies, rather than looking for markers with a high sensitivity and specificity
Recommendation |
strength rating |
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V.4.4 Cystoscopy
Carcinoma in situ is diagnosed by a combination of cystoscopy, urine cytology, and histological evaluation of multiple bladder biopsies (21).
Cystoscopy is initially performed as an outpatient procedure. A flexible instrument with topical intraurethral anesthetic lubricant instillation results in better compliance compared to a rigid instrument, especially in men (22).
When flexible cystoscopy is not available, provided that the imaging is positive for bladder lesion; formal cystoscopy is required under anesthesia (23). The urologist should be ready to carry out resection or at least biopsy.
V.4.5 Transurethral resection of TaT1 bladder tumors
V.4.5.1 Strategy of the procedure
The operative steps necessary to achieve a successful TURB include identifying the factors required to determine the disease risk (number of tumors, size, multifocality, characteristics, concern for the presence of CIS, recurrent vs. primary tumor), clinical stage (bimanual examination under anesthesia, assignment of clinical tumor stage), adequacy of the resection (visually complete resection, visualization of muscle at the resection base), and presence of complications (assessment for perforation) (24).
V.4.5.2 Surgical and technical aspects of tumor resection
• Piecemeal resection in fractions (separate resection of the exophytic part of the tumor, the underlying bladder wall and the edges of the resection area) provides good information about the vertical and horizontal extent of the tumor (24).
• En-bloc resection using monopolar or bipolar current, Thulium-YAG or Holmium-YAG laser is feasible in selected exophytic tumors. It provides high quality resected specimens with the presence of detrusor muscle in 96-100% of cases (25).
The technique selected is dependent on the size and location of th tumor, experience of the surgeon and the availability of the facilities as well.
V.4.5.3 Evaluation of resection quality
The resected tissues should be identified in specific well labelled containers (tumor, base, random biopsies) (27)
V.4.5.3.1 Bladder biopsies
V.4.5.3.2 Prostatic urethral biopsies
It is preferable to obtain biopsy from the prostatic urethra if the patient would receive orthotopic diversion (29).
V.4.5.3.2.1 Second resection
Second TURB is indicated in the following situations (31):
After incomplete initial TURB, or in case of doubt about completeness of a TURB)
If there is no muscle in the specimen after initial resection, with the exception of Ta LG/G1 tumors and primary CIS in T1 tumors
V.4.6 Predicting disease recurrence and progression
The scoring system is based on the six most significant clinical and pathological factors which are shown in Table-4. It also illustrates the weights applied to various factors for calculating the total scores for recurrence and progression.
Factor |
Recurrence |
Progression |
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Number of tumors | ||
Tumor diameter | ||
Prior recurrence rate | ||
Category | ||
Concurrent CIS | ||
Grade | ||
Total Score |
10-17 | 0-23 |
V.4.6.1 Prognosis of Carcinoma in situ
The response to intravesical treatment with BCG or chemotherapy is an important prognostic factor for subsequent progression and death caused by BC. Approximately 10-20% of complete responders eventually progress to muscle-invasive disease, compared with 66% of non-responders (35).
V.4.6.2 Patient stratification into risk groups
Risk group stratification |
Characteristics |
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• T1 tumor • G3 (HG) tumor • carcinoma in situ (CIS) • Multiple, recurrent and large (> 3 cm) TaG1G2/LG tumors (all features must be present) |
Recommendation |
strength rating |
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V.5 Disease management
V.5.1 Adjuvant treatment
Although TURB by itself can eradicate a TaT1 tumor completely, these tumors commonly recur and can progress to MIBC. It is therefore necessary to consider adjuvant therapy in all patients.
V.5.1.1 Intravesical chemotherapy
V.5.1.1.1 A single, immediate, post-operative intravesical instillation of chemotherapy
V.5.1.1.2 Additional adjuvant intravesical chemotherapy instillations
V.5.1.1.3 Intravesical bacillus Calmette-Guérin (BCG) immunotherapy
Induction BCG instillations are given according to the empirical 6-weekly schedule. For optimal efficacy, BCG must be given in a maintenance schedule. Many different maintenance schedules have been used, ranging from a total of ten instillations given in eighteen weeks to 27 over three years (42).
BCG intravesical treatment is associated with more side effects compared to intravesical chemotherapy (43). However, serious side effects are encountered in < 5% of patients and can be treated effectively in almost all cases (44). The patient should be counseled about the possible adverse events of BCG instillations up to severe form of contracted bladder which may obligate cystectomy and urinary diversion.
To reduce BCG toxicity, instillation of a reduced dose was proposed. However, it has been suggested that a full dose of BCG is more effective in multifocal tumors (45).
Risk Category |
Criteria |
Treatment Recommendation |
---|---|---|
• T1 tumours; • G3 (High Grade) tumour; • CIS; • Multiple, recurrent and large (> 3 cm) TaG1G2/Low Grade tumours (all features must be present). |
Recommendation |
strength rating |
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• During the first two weeks after TURB; • In patients with visible haematuria; • After traumatic catheterisation; • In patients with symptomatic urinary tract infection. |
V.5.1.2 Treatment of carcinoma in situ
V.5.1.3 Treatment of failure of intravesical therapy
V.5.1.3.1 Failure of intravesical chemotherapy
V.5.1.3.2 Recurrence and failure after intravesical BCG immunotherapy
Non-muscle-invasive BC presenting after BCG can be categorized into BCG refractory, BCG unresponsive and BCG relapse (48).
V.5.1.3.3 Treatment of BCG failure
V.5.1.3.4 Radical cystectomy for non-muscle-invasive bladder cancer
Treatment options |
strength rating |
|
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Late BCG relapsing: T1Ta/High Grade Recurrence > 6 months or CIS > 12 months of last BCG exposure |
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Low Grade recurrence after BCG for primary intermediate risk tumour |
V.5.2 Critical consideration in management of NMIBC
V.5.3 Follow up of patients with NMIBC
Patients with low-risk Ta tumors should undergo cystoscopy at three months. If negative, subsequent cystoscopy is advised nine months later, and then yearly for five years (51). Patients with high-risk tumors should undergo cystoscopy and urinary cytology at three months. If negative, subsequent cystoscopy and cytology should be repeated every three months for a period of two years, and every six months thereafter until five years, and then yearly (52). Patients with intermediate-risk Ta tumors should have an in-between (individualized) follow-up scheme using cystoscopy. Regular (yearly) upper tract imaging (computed tomography-intravenous urography [CT-IVU] or IVU) is recommended for high-risk tumors.
Endoscopy under anesthesia and bladder biopsies should be performed when office cystoscopy shows suspicious findings or if urinary cytology is positive.
Recommendation |
strength rating |
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V.6 Muscle invasive bladder cancer (MIBC)
V.6.1 Diagnosis
V.6.1.1 Symptoms
V.6.1.2 Physical examination
V.6.1.3 Bladder imaging
V.6.1.4 Cystoscopy
A careful description of the cystoscopic findings is necessary. This should include documentation of the site, size, number, and appearance (papillary or solid) of the tumors, as well as a description of any mucosal abnormalities. The use of a bladder diagram is recommended (56).
Biopsy from the prostatic urethra (or bladder neck in female) is required especially when orthotopic diversion is planned (57)
V.6.1.5 Transurethral resection of invasive bladder tumors
At least the deeper part of the resection specimen must be referred to the pathologist in a separate labelled container to enable them to make a correct diagnosis. In cases in which radiation therapy is considered, CIS is to be excluded (58).
If the plan of treatment is to utilize definitive/palliative chemo-radiotherapy, safe maximum resection should be tried during the first look biopsy to avoid further need to re-anesthesia.
V.6.1.6 Imaging for staging of MIBC
• Extent of local tumor invasion
• Involvement of LNs
• Tumor spread to the upper tract and other distant organs (e.g., liver, lungs, bones, peritoneum, pleura, and adrenal glands)
Timing of radiological staging is preferred either before TURB or at least two weeks after resection biopsy to avoid radiological overstating (59).
V.6.1.7 Evaluation of comorbidity
Age carried the highest risk for other-cause mortality but not for increased cancer-specific death, while the stage of locally advanced tumor was the strongest predictor for decreased cancer specific survival. Stratifying elderly patients according to their risk-benefit profile using a multidisciplinary approach will help selecting patients most likely to benefit from radical surgery and to optimize treatment outcomes (61).
V.6.2 Disease management
V.6.2.1 Neoadjuvant therapy (NAC)
There are theoretical advantages and disadvantages of administering chemotherapy before planned definitive surgery to patients with resectable muscle-invasive urothelial carcinoma of the bladder and cN0M0 disease (62):
• Chemotherapy is delivered at the earliest time-point, when the burden of micro metastatic disease is expected to be low.
• Potential reflection of in-vivo chemo sensitivity.
• Tolerability of chemotherapy and patient compliance are expected to be better pre-cystectomy.
• Patients might respond to NAC and reveal a favorable pathological status, determined mainly by achieving pT0, pN0 and negative surgical margins.
• Delayed cystectomy might compromise the outcome in patients not sensitive to chemotherapy, although published studies on the negative effect of delayed cystectomy only include chemo-naïve patients (63).
Diabetes, hypertension, pulmonary and cardiac diseases are prevalent in this age group, preoperative medical assessment and correction are a must, and the operation should be performed in well-equipped hospital
V.6.2.2 Pre-operative radiotherapy
V.6.2.3 Post-operative radiotherapy
Recommendation |
strength rating |
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V.6.3 Intravesical instillation treatment in MIBC
V.6.3.1 Radical surgery and urinary diversion
A delay in radical cystectomy of more than twelve weeks since diagnosis has a negative impact on outcome and should be avoided (65).
V.6.3.2 Radical cystectomy: indications
Salvage cystectomy is indicated in non-responders to conservative therapy, recurrence after bladdersparing treatment, and non-UC (these tumors respond poorly to chemotherapy and RT) (63). It is also used as a purely palliative intervention, including for fistula formation, pain and recurrent visible hematuria. When there are positive LNs, in the case of N1 involvement (metastasis in a single node in the true pelvis) orthotopic neobladder can still be considered, but not preferable option in N2 or N3 tumors (63).
V.6.3.3 Urinary diversion after radical cystectomy
• Abdominal diversion, such as an uretero-cutaneostomy, ileal or colonic conduit, and various forms of a continent pouch;
• Urethral diversion, which includes various forms of gastrointestinal pouches attached to the urethra as a continent, orthotopic urinary diversion.
• Rectosigmoid diversions, such as uretero-(ileo-) rectostomy. Different types of segments of the intestinal tract have been used to reconstruct the urinary tract, including the stomach, ileum, colon and appendix.
Ideal urinary diversion method should be selected for each patient considering the patient, urinary tract, oncological and anesthetic factors to minimize the perioperative morbidity and maintain long term oncological and functional outcomes (68).
V.6.3.4 Lymphadenectomy: role and extent
Standard lymphadenectomy in BC patients involves removal of nodal tissue cranially up to the distal inch of the common iliac artery, with the ureter being the medial border, and including the internal iliac, obturator fossa and external iliac nodes down to the lymph node of Cloquet.
The number of lymph nodes removed during radical cystectomy is ranged from 15-20 nodes from both sides. Lymphadenectomy should be bilateral. Less than 10 LN is considered inadequate procedure.
The number of lymph nodes removed during radical cystectomy is ranged from 15-20 nodes from both sides. Lymphadenectomy should be bilateral. Less than 10 LN is considered inadequate procedure.
Extended lymphadenectomy includes all LNs in the region of the aortic bifurcation, and presacral and common iliac vessels medial to the crossing ureters. The lateral borders are the genitofemoral nerves, caudally the circumflex iliac vein, the lacunar ligament and the LN of Cloquet, as well as the area described for standard lymphadenectomy.
A super-extended lymphadenectomy extends cranially to the level of the inferior mesenteric artery.
No difference in outcome was reported between extended and super-extended LND. Removal of at least ten LNs has been postulated as sufficient for evaluation of LN status (69).
Recommendation |
strength rating |
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V.6.4 Unrespectable tumors
V.6.4.1 Palliative cystectomy for muscle-invasive bladder carcinoma
Palliative cystectomy carries the greatest morbidity and should be considered for symptom relief only if there are no other options (70). Urinary diversion in this occasion should be as simple as required to alleviate the symptoms and minimize the morbidities.
V.6.4.1.1 Obstruction of the upper urinary tract
Another possible solution is a urinary diversion with, or without, a palliative cystectomy; supravesical diversion using uretero-cutanous anastomosis or palliative ileal conduit diversion (71).
V.6.4.1.2 Bleeding and pain
V.6.5 Bladder-sparing treatments for localized disease
V.6.5.1 Transurethral resection of bladder tumor
TURB alone should only be considered as a therapeutic option for muscle-invasive disease after radical TURB, when the patient is unfit for cystectomy, or refuses open surgery, or as part of a multimodality bladder-preserving approach (73).
Recommendation |
strength rating |
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V.6.5.2 External beam radiotherapy
EBRT can be an alternative treatment in patients unfit for radical surgery, as it can be used to control bleeding (75).
V.6.5.3 Systemic chemotherapy
Response to chemotherapy is a prognostic factor for treatment outcome and eventual survival although it may be confounded by patient selection (77).
Several groups have reported the effect of chemotherapy on resectable tumors (neoadjuvant approach), as well as unresectable primary tumors.
V.6.5.4 Multimodality bladder-preserving treatment
V.6.6 Adjuvant therapy
V.6.6.1 Role of adjuvant platinum-based chemotherapy
No delay in definitive surgical treatment
Delay or intolerability of chemotherapy, due to post-operative morbidity
V.6.6.2 Role of adjuvant immunotherapy
V.6.6.3 Critical consideration in management of MIBC
Laparoscopic and robotic radical cystectomy may be utilized but never replace the standard open approach, The use of such techniques is still in its infancy in Egypt and should be restricted to a well experienced surgeon who would be able to treat any unexpected complications.
The patient should be well informed about the technique without any bias from the surgeon and the operation should be performed in a well-equipped place.
Radical cystectomy and urinary diversion should be strictly performed by a high volume surgeon, (at least 30-50 cystectomy per year) in a well-equipped hospital, high caliber anesthetic team, ICU, Blood transfusion, well trained nursing staff, stoma therapist, nutritionist, and preferably social or psychiatric support team.
V.7 Metastatic bladder cancer
The patient and his family should be informed about such natural history of metastatic outcome, QoL and survival rate.
V.7.1 First line systemic therapy for metastatic disease
V.7.1.1 Standard first-line chemotherapy for fit patients
High-dose intensity MVAC (HD-MVAC) combined with granulocyte colony-stimulating factor (GCSF) is less toxic and more efficacious than standard MVAC in terms of dose density, complete response (CR), and survival rate (84).
Carboplatin-containing chemotherapy is not equivalent to cisplatin combinations, and should not be considered interchangeable or standard (85).
V.7.1.2 Non-platinum combination chemotherapy
V.7.1.3 Single-agent chemotherapy
V.7.1.4 Immunotherapy in first-line treatment
V.7.2 Second-line systemic therapy for metastatic disease
V.7.2.1 Second-line chemotherapy
A reasonable strategy has been to re-challenge former cisplatin-sensitive patients if progression occurred at least six to twelve months after first-line cisplatin-based combination chemotherapy.
Second-line response rates of single agent treatment with paclitaxel (weekly), docetaxel, nab-paclitaxel oxaliplatin, ifosfamide, topotecan, pemetrexed, lapatinib, gefitinib and bortezomib have ranged between 0% and 28% (90). Gemcitabine has also shown good response rates in second-line use but most patients receive this drug as part of their first-line treatment.
V.7.3 Post-chemotherapy surgery and oligometastatic disease
The role of surgery of residual LNs after chemotherapy is still unclear. Although some studies suggest a survival benefit and QoL improvement, the level of evidence supporting this practice is mainly anecdotal (92).
in the absence of data from RCTs, patients should be evaluated on an individual basis and discussed by an interdisciplinary tumor board.
V.7.4 Treatment of patients with bone metastases
Bisphosphonates such as zoledronic acid (ZA) reduce and delay skeletal-related events (SREs) due to bone metastases by inhibiting bone resorption, as shown in a small pilot study (94).
V.7.5 Follow-up in metastatic bladder cancer
V.7.5.1 Site of recurrence
V.7.5.1.1 Local recurrence
Risk factors described are pathological stage, LNs, positive margins, extent of LND and peri-operative chemotherapy (96). Patients generally have a poor prognosis after pelvic recurrence.
V.7.5.1.2 Distant recurrence
The most likely sites for distant recurrence are LNs, lungs, liver and bone. Nearly 90% of distant recurrences appear within the first three years after RC, mainly in the first two years, although late recurrence has been described after more than 10 years (97).
V.7.5.1.3 Urethral recurrence
There is limited data, and agreement, about urethral follow-up, with some authors recommending routine surveillance with urethral wash and urine cytology and others doubting the need for routine urethral surveillance.
However, there is a significant survival advantage in men with urethral recurrence diagnosed asymptomatically vs. symptomatically, so follow-up of the male urethra is indicated in patients at risk of urethral recurrence.
V.7.5.1.4 Metachronus upper urinary tract urothelial carcinoma
V.7.5.2 Time schedule for surveillance
A schedule suggested by the EAU Guidelines Panel includes a CT scan (every 6 months) until the third year, followed by annual imaging thereafter. Patients with multifocal disease, NMIBC with CIS or positive ureteral margins are at higher risk of developing UTUC, which can develop late (> 3 years) (100). In those cases, monitoring of the UUT is mandatory during follow-up. Computed tomography is to be used for imaging of the UUT.
The exact time to stop follow-up is not well known and recently a risk-adapted schedule has been proposed, based on the interaction between recurrence risk and competing health factors that could lead to individualized recommendations and may increase recurrence detection (101). Elderly and very low-risk patients (those with NMIBC or pT0 disease at final cystectomy report) showed a higher competing risk of non-BC mortality when compared with their level of BC recurrence risk. On the other hand, patients with locally advanced disease or LN involvement are at a higher risk of recurrence for more than 20 years (101).
V.7.6 Follow-up of functional outcomes and complications
The functional complications are diverse (102) and include: vitamin B12 deficiency, metabolic acidosis, worsening of renal function, urinary infections, urolithiasis, stenosis of uretero-intestinal anastomosis, stoma complications in patients with ileal conduit, neobladder continence problems, and emptying dysfunction. Especially in women approximately two-thirds need to catheterize their neobladder, while almost 45% do not void spontaneously at all. Recently a 21% increased risk of fractures was also described as compared to no RC, due to chronic metabolic acidosis and subsequent long-term bone loss. Since low vitamin B12 levels have been reported in 17% of patients with bowel diversion, in case of cystectomy and bowel diversion, vitamin B12 levels should be measured annually.
V.8 Summary:
V.9 References
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