This document provides information on bladder cancer, including benign bladder tumors, risk factors, symptoms, diagnosis, staging, and treatment of non-muscle-invasive bladder cancer. It discusses various benign bladder tumors such as epithelial metaplasia, leukoplakia, inverted papilloma, and their characteristics. Major risk factors for bladder cancer mentioned are smoking, occupational exposures, infections, and certain genetic factors. Cystoscopy and biopsy are important for diagnosis and staging. Treatment of non-muscle-invasive bladder cancer involves transurethral resection of bladder tumors.

1. Bladder Cancer
Presented by
Dr. Hari Prasad Baral
Dr. Rojan Adhikari
Shahid Dhrma Bhakta National Transplant Center

3. Introduction to Bladder
growth

4. • BENIGN TUMORS OF THE BLADDER
1. Epithelial metaplasia
2. Leukoplakia
3. Inverted papilloma
4. Nephrogenic adenoma
5. Leiomyoma
6. Cystitis cystica
7. Cystitis glandularis.

5. Epithelial Metaplasia
• focal areas of transformed urothelium with normal nuclear and cellular
architecture surrounded by normal urothelium usually located on the trigone.
• Approximately 40% of women and 5% of men have squamous metaplasia of
the bladder, which is usually related to infection, trauma, or surgery (Ozbey et
al, 1999).
• Treatment is unnecessary, and a preventive agent has not been identified.

6. Types of epithelial metaplasia
Squamous metaplasia
- often has a knobby appearance
and is covered by white, flaky,
easily disrupted material lying on
the trigone.
Glandular metaplasia
- appears as clumps of raised red
areas that appear inflammatory
and are often confused for cancer

7. Leukoplakia
• keratin deposition that appears as a white flaky substance floating in the
bladder (Staack et al, 2006).
• occurs in other organs that are covered by squamous epithelium.
• often premalignant (Zhang et al, 2009).
• cytogenetic studies are consistent with a benign lesion.
• no treatment.

8. Inverted Papilloma
• benign proliferative lesion associated with chronic inflammation or BOO
and can be located throughout the bladder but most commonly on the
trigone
• comprising less than 1% of all bladder tumors
• The use FISH to evaluate chromosomal changes can distinguish between
an inverted papilloma and a urothelial cancer (Jones et al, 2007).
• Transurethral resection is the treatment of choice

9. Papilloma
• composed of delicate stalks lined by normal-appearing urothelium
• rarely have mitotic figures and lack markers of aggressive growth such as P53
or RB mutations, but 75% of these tumors have mutations in FGFR-3.
• Papillomas may recur
• but they do not progress or invade.

10. Nephrogenic Adenoma
•
• rare tumor caused by chronic irritation of the urothelium.
• lesion may be vascular, which explains the presence of gross hematuria
(Franke et al, 2011).
• 2 school of thoughts on origin:
1.chronic inflammation causing metaplastic changes to the urothelium lead
to nephrogenic adenoma
2.arises from displaced mesonephric tissue in the urothelium that is
activated with mucosal injury.
• Treatment is transurethral resection and elimination of irritation.

11. Cystitis Cystica and Glandularis
• a common finding associated with inflammation or chronic obstruction.
• cystic nests that are lined by columnar or cuboidal cells and are typically associated with
proliferation.
• Cystitis glandularis can be associated with pelvic lipomatosis and may occupy the majority of
the bladder (Buckley et al, 2007).
• voiding symptoms and hematuria.
• Treatment is transurethral resection and relief of the obstruction or inflammatory condition.

12. Leiomyoma
• most common nonepithelial benign tumor
• Leiomyomas appear as smooth indentations of the bladder and can be
confused with a bladder tumor
• MRI can confirm the diagnosis and spare invasive procedures (Fasih et al,
2008).
• Surgical resection is required if the leiomyoma is large or painful.

13. UROTHELIAL CANCER
• Epidemiology
• American Cancer Society statistics:
- 72,570(54,610 men and 17,960 women) and accounting for 7% of all
cancers.
• 3% of all cancer deaths (Siegelet al, 2013)

14. Gender, Racial, and Age Differences
• M:F::3-4:1
• White> black
• peaks in 8th decade

15. Global Burden of Bladder Cancer
• highest occurring in Southern and
Eastern Europe, parts of Africa,
the Middle East, and North America,
and the lowest occurring in Asia
and underdeveloped areas in Africa.
• In North America and Europe,
- 95% to 97% of cases are urothelial
carcinoma
• Africa 60% to 90% are urothelial and 10% to 40% are squamous cell.

16. Etiology
 Genetic abnormalities
 External risk factors,
• carcinogen exposure,
• smoking
• nutritional factors,
• fluid intake,
• alcohol,
• inflammation,
• infection,
• chemotherapy,
• radiation,
• artificial sweeteners

17. Genetic Factors
• are related to susceptibility to environmental carcinogens.
• N-acetyltransferase (NAT) detoxifies nitrosamines, a known bladder
carcinogen.
• slow NAT-2 polymorphism is related to bladder cancer with an odds ratio
of 1.4 compared with the fast polymorphism (Garcia-Closas et al, 2005).
• Glutathione-S-transferase (GSTM1) conjugates several reactive chemicals,
including arylamines and nitrosamines.
• Null GSTM1 polymorphism is associated with an increased risk with a
relative risk of 1.5 (Garcia-Closas et al, 2005).

18. Hereditary
• First-degree relatives have a twofold increased risk (Kiemeney, 2008).
• risk is higher for women and nonsmokers.
• not associated with bladder cancer formation at an earlier age.
• no clear mendelian inheritance patterns, making classic linkage studies
impossible.
• inherited low penetetrance genes makes a person more susceptible to
carcinogenic exposure, thus of bladder cancer formation.

20. Smoking
• Tobacco(cigratte smoking) accounts for 60% and 30% of all urothelial
cancers in males and females, respectively ( Freedman et al, 2011)
• Relative risk is 2.8 and 2.73 in men and women, respectively
• Two to six times greater chance of developing urothelial cancer with
smoking
• Intensity and duration of smoking are related to the increased risk.
• The risk of secondhand smoke is low and not statistically different from
that for nonsmokers.

21. Nutritional Factors
Most nutrients or other metabolites are excreted in the urine and have
prolonged contact with the urothelium.
Preventive(detoxification.)
• fruits and vegetables(citrus
fruits, apples, berries,
tomatoes, carrots, and
cruciferous)
• Micronutrients (antioxidants)
including vitamins A, C, and E;
selenium; and zinc
causing or promoting
• salted and barbequed meat,
• pork
• total fat
• pickled vegetables
• soy
• spices
• coffee
• tea

22. Analgesic Abuse.
• acetaminophen or phenacetin (5 to 15 kg during a 10-year period) have
been associated with an increased risk of bladder cancer .

23. Infection
• squamous cell carcinoma in patients chronically
infected with Schistosoma haematobium.
• a possible link between human papillomavirus (HPV)
and urothelial cancer formation.
• HPV encodes two oncoproteins, E6 and E7. E6 interacts with TP53, which has a
role in bladder cancer progression and formation (Westenend et al, 2001).
• Potential carcinogens were produced with chronic UTI.

24. Radiation.
• association between radiation exposure and bladder cancer formation is
primarily based on atomic bomb survivors during World War II.
• Further support that radiation can cause bladder cancer is an increased
risk of urothelial cancer in patients with prostate or cervical cancer who
were treated with radiation therapy.

25. Chemotherapy
Chemotherapy destroys malignant cells by causing
• significant DNA and cellular damage on rapidly dividing urothelium.
• The only chemotherapeutic agent that has been proven to cause bladder
cancer is cyclophosphamide ( Nilsson and Ullen, 2008).
• Phosphoramide mustard is the mutagenic metabolite that causes
bladder cancer in patients exposed to cyclophosphamide.

26. Occupational exposure
• second most important risk factor for BC( accounting for about 10%
of all cases)
• The primary culprits are the aromatic amines that bind to DNA.
• benzidine , β-naphthylamine ,aromatic amines, polycyclic aromatic
hydrocarbons, diesel exhaust and chlorinated hydrocarbons.
• mainly in industrial plants, which process paint, rubber, dye, metal
and petroleum products.

27. symptoms
• Gross, painless hematuria is the primary symptom in 85% of patients with a
newly diagnosed bladder tumor, and microscopic hematuria occurs in virtually all
patients (Khadra et al, 2000;Alishahi et al, 2002; Wallard et al,2006).
• Carcinoma in situ with irritative LUTS Vs large mass obstrutive LUTS.
• suprapubic pain, recurrent UTI, pneumaturia
• Urachal adenocarcinomas - a blood or mucus umbilical discharge or a deep sub-
umbilical mass.
• Advanced bladder cancer - lower limb swelling due to lymphatic/ venous
obstruction, bone pain, weight loss, anorexia, confusion.
• anuria (renal failure due to bilateral ureteric obstruction).

28. Signs
• General examination may reveal pallor, indicating anaemia due to blood
loss or chronic renal impairment.
• Abdominal examination may reveal a suprapubic mass in the case of
locally advanced disease; DRE may reveal a pelvic mass above, or
involving, the prostate.
• If this mass is mobile (best assessed on bimanual examination under GA)
• bimanual examination is mandatory before and after bladder tumour
resection to assess size, position, and mobility (i.e. stage)

29. Ultrasound
• Primary screening modality
Permits:
• visualisation of intraluminal mass with vasularity on color doppler
• detection of hydronephrosis(uo or distal ureter involvement)
• ? lymphnode status
• but cannot rule out all potential causes of haematuria

30. Computed tomography
. urography
• detect papillary tumours in the urinary tract, indicated by filling defects
and/or hydronephrosis.
• provides more information (including status of lymph nodes and
neighbouring organs).
• useful for staging

31. magnetic resonance imaging (MRI)
• MRI has not yet been established in BC diagnosis and staging.
• A standardised methodology of MRI reporting in patients with BC was
recently published but requires validation .
• A diagnosis of CIS cannot be made with imaging methods alone (CT
urography, IVU, US or MRI).

32. Urinary cytology
• has high sensitivity in G3 and high-grade tumours (84%), but low sensitivity in
G1/LG tumours (16%)
• The sensitivity in CIS detection is 28-100% .
• Positive voided urinary cytology can indicate an urothelial carcinoma
anywhere in the urinary tract.
• false- positive cytology can arise due to infection, inflammation, stones,
instrumentation, and intravesical instillations such as chemotherapy.
• negative cytology, however, does not exclude its presence.

33. interpretation is user-dependent

34. urinary cytology diagnostic categories
• Urine collection should respect the recommendation.
• In patients with suspicious cytology repeat investigation is advised .
Paris Working Group :2016
• adequacy of urine specimens Adequacy
• negative for high-grade urothelial
carcinoma
Negative
• atypical urothelial cells AUC
• suspicious for high-grade urothelial
carcinoma
Suspicious
high-grade urothelial carcinoma HGUC
low-grade urothelial neoplasia (LGUN).

35. Urine Markers for Urothelial Cancer
• A test able to predict absence of
tumour will have great utility in
daily clinical practice .
• urinary cytology or biomarkers
can be used as an adjunct to
cystoscopy to detect missed
tumours, particularly CIS.

36. Cytology vs biopsy

37. cystoscopy

38. Cystoscopy and biopsy
• The diagnosis of papillary BC ultimately depends on cystoscopic
examination of the bladder and histological evaluation of sampled tissue
by either cold-cup biopsy or resection.
• Carcinoma in situ is diagnosed by a combination of cystoscopy, urine
cytology, and histological evaluation of multiple bladder biopsies .

39. Bladder biopsies
• Biopsies from suspicious urothelium should be taken.
• Carcinoma in situ can present as a velvet-like, reddish area,
indistinguishable from inflammation, or it may not be visible at all.
• patients with positive urine cytology, or with a history of HG/G3 NMIBC
and in tumours with non-papillary appearance, mapping biopsies from
normal-looking mucosa is recommended
• If equipment available, PDD is a useful tool to target the biopsy.
• The resection should be en bloc if <1cm tumour

40. TNM Staging

41. Pathologic
staging of
bladder
carcinoma

42. • Ta: Non invasive,
papillary
• Tis: Carcinoma in situ

43. • STAGE T1: lamina propria
invasion

44. • STAGE T2: Muscularis
propria invasion

45. STAGE 3

46. STAGE 3a:
microscopic
extravesicle
invasion

47. STAGE 3b:
grossly
apparent
extravesicle
invasion

48. STAGE T4:
invades
adjacent
structures

49. • NX- Not accessed
• N0-No LN.
• N1- single LN in
H.O.P.E.
• N2- Multiple LN in
H.O.P.E.
• N3- common iliac LN

50. Prostatic urethral biopsies
• Involvement of the prostatic urethra in men with NMIBC has been reported.
• Palou et al. showed that in 128 men with T1G3 BC, the incidence of CIS in the
prostatic urethra was 11.7% .
-with positive urine cytology but a negative bladder biopsy.
- recurrent bladder cancer after multiple courses of intravesical chemotherapy
-Prostatic urethra involvement is higher if the tumour is located at the trigone or
bladder neck, in the presence of bladder CIS and multiple tumours .
- biopsied if cystectomy with bladder reconstruction is under consideration

51. New methods of tumour visualisation
• As a standard procedure, cystoscopy and TURB are performed
using white light.
• However, the use of white light can lead to missing lesions
that are present but not visible, which is why new
technologies are being developed.

52. Photodynamic diagnosis
(fluorescence cystoscopy)
• fluorescence-guided biopsy
and resection are more
sensitive for the detection of
malignant tumours,
particularly for CIS .

53. • Patients with positive urine cytology, but normal looking bladder
mucosa, and those with recurrence and a history of high- grade
cancer.
• False-positivity can be induced by inflammation or recent TURB and
during the first three months after BCG instillation.
• One RCT has shown a reduction in recurrence and progression with
fluorescence guided TURB as compared to white light TURB . These
results need to be validated by further studies.
• It has been confirmed that fluorescence-guided biopsy and resection
are more sensitive than conventional procedures for the detection of
malignant tumours, particularly for CIS.

54. Narrow-band imaging
• is an optical image enhancement technology in which the narrow bandwidth
of light is strongly absorbed by Hb and penetrates only the surface of tissue,
increasing the visibility of hypervascular cancer tissue, in contrast to normal
urothelium.
• Improved cancer detection has been demonstrated by NBI flexible cystoscope
and NBI-guided biopsies and resection.

55. Additional technologies
1.Confocal laser micro-endoscopy
high resolution imaging probe designed
to provide endoscopic histological grading
in real time but requires further validation .

56. Additional technologies
2. Storz professional image enhancement
system (IMAGE1 S, formally called SPIES) is an image enhancement
system using four different light spectra but prospective data using this
system are lacking .

57. Non–Muscle-Invasive Bladder
Cancer

58. Epidemiology
• Approximately 70% of bladder tumors are
NMIBC at presentation
Campbell- Walsh Urology 12th edition ; Aldousari and Kassouf, 2010;
Ta: 70%
T1: 20%
CIS: 10%

60. TURBT: transurethral resection of
bladder tumor
• First-line to diagnose, stage, and treat visible tumors.
• Goal: to make the correct diagnosis and completely remove all visible lesions.
• EUA done before & after TURBT to asses disease extent & residual tumor.
• Muscle must be seen in TURBT specimen before ruling out invasive disease
• Biopsies of apparently uninvolved urothelium should be obtained to rule out occult Tis.
• Biopsy from the prostatic urethra is necessary in some cases

61. Steps to achieve a successful TURBT
Identifying the factors required to assign
• disease risk (number of tumurs, size, multifocality, characteristics, concern for the
presence of CIS, recurrent vs. primary tumour),
• clinical stage (bimanual examination under anaesthesia, assignment of clinical tumour
stage),
• adequacy of the resection (visually complete resection, visualisation of muscle at the
resection base), and
• presence of complications (assessment for perforation)

62. Surgical strategy of resection
• Piecemeal resection in fractions (separate
resection of the exophytic part of the tumour, the
underlying bladder wall and the edges of the
resection area) 1
• En-bloc resection using monopolar or bipolar
current, Thulium-YAG or Holmium-YAG laser. It
provides high quality resected specimens with
the presence of detrusor muscle in 96-100% of
cases 2
1. Richterstetter, M., et al. The value of extended transurethral resection of bladder tumour (TURBT) in the treatment of bladder cancer. BJU Int, 2012. 110:
E76.
2. Kramer, M.W., et al. Current Evidence of Transurethral En-bloc Resection of Nonmuscle Invasive Bladder Cancer. Eur Urol Focus, 2017. 3: 567.

63. Pathologist should comment on:
• Size
• tumour grade
• depth of tumour invasion,
• presence of CIS
• whether the detrusor muscle is present in the
specimen.
• specify the presence of LVI or unusual (variant)
histology
• If there is uncertainty over the pathology, a further
early re- resection (2-6 wk.) is indicated.

64. Prostatic urethral biopsies
• Patients with T1G3 Bladder Cancer, the incidence of
CIS in the prostatic urethra was 11.7% 1
• Take the biopsy from abnormal areas in the prostatic
urethra and from the precollicular area (between the 5
and 7 o’clock position) using a resection loop 1, 2
1. Palou, J., et al. Female gender and carcinoma in situ in the prostatic urethra are prognostic factors for recurrence, progression, and disease-specific mortality in T1G3 bladder cancer patients treated with
bacillus Calmette-Guerin. Eur Urol, 2012. 62: 118.
2. Mungan, M.U., et al. Risk factors for mucosal prostatic urethral involvement in superficial transitional cell carcinoma of the bladder. Eur Urol, 2005. 48: 760

65. Take a biopsy of the prostatic urethra
in cases
• bladder neck tumour,
• if bladder carcinoma in situ is present or suspected,
• if there is positive cytology without evidence of tumour in
the bladder,
• if 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.
Brant, A., et al. Prognostic implications of prostatic urethral involvement in non-muscle-invasive bladder cancer. World J Urol, 2019. 37: 2683.

66. Second look TURBT?
Indications
• Residual disease after initial TURBT
• When specimen contained no muscle
• High-grade and/or T1 tumor
• Timing and strategy:
• Most recommend 2-6 weeks after initial TUR
• Should include resection of primary tumor
site
Cumberbatch, M.G.K., et al. Repeat Transurethral Resection in Non-muscle-invasive Bladder Cancer: A Systematic Review. Eur Urol, 2018

70. PREDICTING DISEASE RECURRENCE
AND PROGRESSION
• EORTC Genito-Urinary Cancer Group has
developed a scoring system and risk tables
• The basis for the scoring system are individual
patient data from 2,596 patients diagnosed with
TaT1 tumours, who were randomised into seven
EORTC trials
• Patients with CIS alone, undergo a second TURB
or receive maintenance BCG were not included.
Sylvester RJ, et al: Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables. Eur Urol.2006;

76. INTRAVESICAL THERAPY
Perioperative Intravesical Therapy
• Single-dose intravesical chemotherapy administered
within 6 hours of resection reduces recurrence of low-risk
tumors 1, 2
• Mitomycin C (MMC) appears to be the most effective
adjuvant intravesical chemotherapeutic agent
perioperatively, epirubicin is used in Europe 1, 3
• Average recurrence rate was 54% in the TUR-alone group
versus 38% in the TUR-plus-MMC group 4
1. Bosscheiter et al., 2018,
2. uque and Loughlin, 2000; Isaka et al., 1992; Oosterlinck et al., 1993; Sekine et al., 1994; Solsona et al., 1999
3. Witjes and Hendricksen, 2008
4. Nilsson S, et al . A systematic overview of chemotherapy effects in urothelial bladder cancer. Acta Oncol. 2001

77. Sylvester et al., 2004: THE JOURNAL OF UROLOGY® 2004 ; A single immediate postoperative instillation of chemotherapy decreases the risk of recurrence in patients with stage
ta t1 bladder cancer: a meta-analysis of published results of randomized clinical trials

79. Mitomycin C
• MMC is an alkylating agent that inhibits DNA synthesis.
• The drug is usually instilled weekly for 6 to 8 weeks at
dose ranges from 20 to 60 mg.
• used for Low grade, Ta or T1 tumours, and recurrent
multifocal TCC
• single-​dose Intravesical therapy is equivalent to that
seen using weekly instillations for 6wk, post-​TURBT
Sylvester RJ, et al. (2004). A single immediate postoperative instillation of chemotherapy decreases the risk of recurrence in patients with stage TaT1 bladder cancer: a meta-​analysis. J Urol

80. • most studies shows MMC a viable option for
reduction in recurrence (but not for
progression) in light of its lesser side effects 1
• Adverse effect of MMC include Skin rash-
palmar desquamation, Irritative symptoms
and chemical cystitis (10%) and rarely,
contracted bladder
Huncharek et al., 2001, Anticancer research Journal ; Impact of intravesical chemotherapy on recurrence rate of recurrent superficial transitional
cell carcinoma of the bladder: results of a meta-analysis

81. Intravesical Immunotherapy: Bacille Calmette-Guérin
• Over 30 years’ successful application of
Bacillus Calmette Guerin (BCG) to the clinical
treatment of bladder cancer has proved it one
of the most promising immunotherapies for
cancer 1
• Intravesical BCG results in a robust local
immune response 2
• directly reacts to the tumor cells, causing
apoptosis, necrocytosis, oxidative stress, 1
1. Jiansong Han et al, 2020 ; Mechanisms of BCG in the treatment of bladder cancer-current understanding and the prospect
2. Shen et al., 2008

82. Mechanism of action
• Initial step is direct binding to fibronectin within the bladder wall leading to direct
stimulation of cell-based immunologic response 1
• Numerous cytokines involved in the initiation or maintenance of inflammatory processes
including TNF-α, GM-CSF, IFN-γ, and IL-1, IL-2, IL-5, IL-6, IL-8, IL-10, IL-12, and IL-18 have
been detected in the urine of patients treated with intravesical BCG.1
• cytokine induction with preferential upregulation of IFN-γ, IL-2, and IL-12 reflects
induction of a T-helper type-1 (Th1) response 2
• This immunologic response activates cell-mediated cytotoxic mechanisms believed to
underlie the efficacy of BCG and other agents in the prevention of recurrence and
progression 2
1. Ludwig et al., 2004
2. Bohle and Brandau, 2003

83. Jiansong Han et al, 2020 ; Biomedicine & Pharmacotherapy Journal
Mechanisms of BCG in the treatment of bladder cancer-current understanding and the prospect
The model of mechanisms of BCG in bladder cancer.
When BCG is exposed to tumor microenviroment, it attaches to the cell surface and be internalized by tumor cells to
active different pathways such as NF-KB. Cytokines will be released by some immune cells like nuetrophils and
macrophages to attend immune cascade or kill the tumor cells directly

84. • BCG powdered vaccine 80mg is reconstituted with 50 mL of saline
• typically started 2 to 4 weeks after resection, allowing time for re-
epithelialization of the bladder after TURBT, thereby minimizing the potential
for intravasation of live bacteria
• A urinalysis is usually performed immediately before instillation
• After instillation, the patient should retain the solution for at least 1 to 2 hours
• Fluid, diuretic, and caffeine restriction before instillation limits dilution of the
agent by urine and facilitates adequate retention of the agent for 2 hours
1. Lamm et al. 2011
2. Herr, 2012
3. Lamm et al., 2000b

85. BCG Prophylaxis to Prevent
Recurrence and Progression
Conclusion:
• In NMIBC several intravesical therapies are associated with a decreased risk
of recurrence and Progression vs transurethral bladder tumor resection
alone

86. Conclusion
In 403 patients with CIS, BCG reduced the risk of
progression by 35% compared with intravesical
chemotherapy.

88. Complications of BCG

90. Bacille Calmette-Guérin: Treatment
Schedule
• Several studies and AUA guidelines suggest that a 6-week induction course
• Durations of maintenance therapy based on risk stratification of the tumor 2
• Southwest Oncology Group (SWOG) reported the most significant impact of maintenance
therapy. Patients received a 6-week induction course followed by 3 weekly instillations at 3
and 6 months and every 6 months thereafter for 3 years.1
• intermediate-risk disease, a 1-year course of maintenance BCG was administered at
months 3, 6, and 12 and In patients with high-risk disease, the instillations were continued
every 6 months thereafter up to 3 years. 2
1. Chang et al., 2016
2. Oddens et al. 2013

91. Bohle and Bock,et al 2004, Intravesical bacille Calmette-Guérin versus mitomycin C in superficial bladder cancer: formal meta-analysis of
comparative studies on tumor progression

97. O’Donnell et al: Practical applications of intravesical chemotherapy and immunotherapy in high-risk patients with superficial bladder cancer. Urol Clin North Am 32:121–131, 2005

98. Role of “Early” Cystectomy
• Despite local therapy, many cases of high-grade NMIBC will progress to
invasion 1
• Patients of CIS in whom BCG unresponsiveness will have a 50% chance of
disease progression and potential for disease-specific mortality. 1
• Early (3-month) failure for T1 tumors after BCG is associated with an 82%
progression rate. 2
• Ten-year survival after cystectomy for non–muscle-invasive cancer can
range from 67% to 92%. 3
1. Catalona et al., 1987
2. Herr et al., 2000a
3. Lee et al., 2007; Schrier et al., 2004

99. Cystectomy / Radical cystectomy
consider in NMIBC
• high grade tumour
• invading deeply into lamina propria,
• lymphovascular invasion,
• diffuse CIS,
• Tumour in diverticula,
• Tumour involve the distal ureters or prostatic
urethra,
• Refractory to initial therapy,
• Tumour too large or anatomically inaccessible to
be removed in their entirety endoscopically.

100. Follow up
• TaT1 tumurs and carcinoma in situ (CIS) on regular cystoscopy.
• Patients with low-risk Ta tumours should undergo cystoscopy at
three months. If negative, subsequent cystoscopy is advised nine
months later, and then yearly for five years. 1
• Patients with high-risk tumours 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. 2
Palou, J., et al. 2009
Soukup, V., et al. 2012
Holmang, S., et al. 2012

101. • Patients with intermediate-risk Ta tumours should have
an in-between (individualised) follow-up scheme using
cystoscopy. 1, 2
• Regular (yearly) upper tract imaging (computed
tomography-intravenous urography [CT-IVU] ) is
recommended for high-risk tumours. 1
• Cystoscopy under anaesthesia and bladder biopsies
should be performed when office cystoscopy shows
suspicious findings or if urinary cytology is positive 3
1. Holmang, S., et al. 2012
2. Soukup, V., et al. 2012
3. Niwa, N., et al. 2015

102. • During follow-up in patients with positive
cytology and no visible tumour in the bladder,
mapping-biopsies or PDD-guided biopsies and
investigation of extravesical locations (CT
urography, prostatic urethra biopsy) are
recommended.
• In patients initially diagnosed with TaLG bladder
cancer, use ultrasound of the bladder during
surveillance in case cystoscopy is not possible or
refused by the patient.

103. INDEX PATIENT NO. 1:
• ABNORMAL UROTHELIAL GROWTH BUT NOT PROVEN
CANCER
• Standard: Obtain biopsy to confirm grade for all index
patients.
• If possible, eradicate all visible tumors.
• If cancer, periodic cystoscopy.
• Option: Single dose of postoperative intravesical
chemotherapy

104. INDEX PATIENT NO. 2:
• SMALL-VOLUME, LOW-GRADE Ta
• Recommendation: Single dose of
postoperative intravesical chemotherapy.

105. INDEX PATIENT NO. 3:
• MULTIFOCAL OR LARGE LOW-GRADE Ta, OR
RECURRENT LOW-GRADE Ta
• Recommendation: Intravesical BCG or MMC—goal
to prevent/ delay recurrence.
• Option: Maintenance BCG or MMC.

106. INDEX PATIENT NO. 4:
• HIGH-GRADE Ta, T1, OR CIS
• Standard: If T1 disease, but no muscularis in
specimen, repeat resection.
• Recommendation: Intravesical BCG with
maintenance therapy.
• Option: Consider cystectomy for select patients.

107. INDEX PATIENT NO. 5:
• HIGH-GRADE Ta, T1, AND/OR CIS AFTER PRIOR
INTRAVESICAL THERAPY
• Standard: T1 disease but no muscularis in specimen,
repeat resection.
• Recommendation: Consider cystectomy as therapeutic
alternative.
• Option: Further intravesical therapy may be
considered.

108. Bladder biopsies
• biopsies from suspicious urothelium should be
taken
• Patients with positive urine cytology, or with a
history of HG NMIBC and in tumors with non-
papillary appearance, mapping biopsies from
normal-looking mucosa is recommended 1
• biopsies should be taken from the trigone,
bladder dome, right, left, anterior and posterior
bladder wall 1,2
1. Hara, T., et al. Risk of concomitant carcinoma in situ determining biopsy candidates among primary non-muscle-invasive bladder cancer patients: retrospective analysis . Int J Urol, 2009.
2. van der Meijden, A., et al. Significance of bladder biopsies in Ta,T1 bladder tumors: a report from the EORTC Genito-Urinary Tract Cancer Cooperative Group. EORTC-GU Group Superficial Bladder
Committee. Eur Urol, 1999.

109. Intravesical Immunotherapy:
Bacille Calmette-Guérin

110. Introduction
• Over 30 years’ successful application of
Bacillus Calmette Guerin (BCG) to the clinical
treatment of bladder cancer has proved it one
of the most promising immunotherapies for
cancer 1
• Intravesical BCG results in a robust local
immune response 2
• directly reacts to the tumor cells, causing
apoptosis, necrocytosis, oxidative stress, 1
1. Jiansong Han et al, 2020 ; Mechanisms of BCG in the treatment of bladder cancer-current understanding and the prospect
2. Shen et al., 2008

111. • Intravesical BCG is a live, attenuated mycobacteria and therefore has the
potential risk for transmission.
• Urine Routine and culture should be done before installation
• The preparation, handling and disposal should bring with it the same
precautions of other biohazardous materials.
• BCG powdered vaccine 80mg is reconstituted with 50 mL of saline
• Fluid, diuretic, and caffeine restriction before instillation limits dilution
of the agent by urine and facilitates adequate retention of the agent for
2 hours
1. Lamm et al. 2011
2. Herr, 2012
3. Lamm et al., 2000b

112. Administration procedure:
1. Assemble equipment on trolley as above.
2. Reconstitute BCG using closed system equipment as per
manufacturers’ instructions. BCG should always be given within 2
hours of mixing.
3. Place both plastic and linen draw sheet underneath patient’s
buttocks.
4. Insert urethral catheter as per policy and drain bladder
5. A plastic backed sheet should be placed under the catheter
connection and across the patient to prevent the spillage of BCG
onto the patient or bedding if there is a leak.

113. 6. Instil BCG into patient’s bladder in adherence to the
manufacturer’s instructions for using closed system
products.
7. Remove catheter carefully and advise the patient they
are to retain liquid in bladder for up to two hours
following instillation.
8. All efforts should be made to ensure the intravesical
drugs do not come into contact with the skin, clothing or
other surfaces.

114. 9. Following insertion of intravesical therapeutic agents, the patient should lie
prone, supine left lateral and right lateral for 15 minutes each. The drug needs
to remain in the patient’s bladder for at least 1 hour (to a maximum of 2 hours).
10. equipment, in contact with cytotoxic material, should be disposed of into 2
cytotoxic waste bags, labelled and secured closed with cytotoxic tape and
disposed of in the clinical waste for incineration.
11. Following completion of the treatment, the patient should be advised to void
into the designated toilet.
12. The toilet should not be flushed. Two cups of bleach should be poured into the
toilet bowl and left for 20 minutes prior to flushing. Patients should be advised
to continue to use bleach in the toilet bowl with each void for 6 hours following
treatment.

115. 13.The patient should be encouraged to drink 2-3 litres of
fluid for the first 24 hours following treatment to
encourage elimination of absorbed drugs.
14.Urine samples should not routinely be sent to the
laboratory within 72 hours of treatment.
15.The patient should be given instructions on after care,
their next appointment and contact details should they
encounter any problems prior to leaving the
department.

116. Mechanism of action
• Initial step is direct binding to fibronectin within the bladder wall leading to direct
stimulation of cell-based immunologic response 1
• Numerous cytokines involved in the initiation or maintenance of inflammatory processes
including TNF-α, GM-CSF, IFN-γ, and IL-1, IL-2, IL-5, IL-6, IL-8, IL-10, IL-12, and IL-18 have
been detected in the urine of patients treated with intravesical BCG.1
• cytokine induction with preferential upregulation of IFN-γ, IL-2, and IL-12 reflects
induction of a T-helper type-1 (Th1) response 2
• This immunologic response activates cell-mediated cytotoxic mechanisms believed to
underlie the efficacy of BCG and other agents in the prevention of recurrence and
progression 2
1. Ludwig et al., 2004
2. Bohle and Brandau, 2003

117. Jiansong Han et al, 2020 ; Biomedicine & Pharmacotherapy Journal
Mechanisms of BCG in the treatment of bladder cancer-current understanding and the prospect
The model of mechanisms of BCG in bladder cancer.
When BCG is exposed to tumor microenviroment, it attaches to the cell surface and be internalized by tumor cells to
active different pathways such as NF-KB. Cytokines will be released by some immune cells like nuetrophils and
macrophages to attend immune cascade or kill the tumor cells directly

118. BCG Prophylaxis to Prevent
Recurrence and Progression
Conclusion:
• In NMIBC several intravesical therapies are associated with a decreased risk
of recurrence and Progression vs transurethral bladder tumor resection
alone

119. Conclusion
In 403 patients with CIS, BCG reduced the risk of
progression by 35% compared with intravesical
chemotherapy.

121. Adverse effect
• Local
• Systemic

122. Symptoms of cystitis and LUTS
• frequency, dysuria and occasional mild haematuria. These
symptoms usually subside within 24 to 48 hours
• Phenazopyridine, or non-steroidal anti-inflammatory drugs
(NSAIDs).
• If symptoms improve within a few days: continue
instillations.
• If symptoms persist or worsen:
• Postpone the instillation
• Perform a urine culture
• Start empirical antibiotic treatment

123. If symptoms persist even with antibiotic treatment:
• With positive culture: adjust antibiotic treatment
according to sensitivity
• With negative culture: quinolones and potentially
analgesic anti-inflammatory instillations once daily for
5 days (repeat cycle if necessary) .
• If symptoms persist: anti-tuberculosis drugs +
corticosteroids.
• If no response to treatment and/or contracted bladder:
radical cystectomy.

124. Haematuria
• Perform urine culture to exclude
haemorrhagic cystitis, if other symptoms
present.
• If haematuria persists, perform cystoscopy to
evaluate presence of bladder tumour

125. Symptomatic granulomatous
prostatitis
• Symptoms rarely present: perform urine culture.
• Quinolones is treatment of choice
• If quinolones are not effective: isoniazid (300
mg/day) and rifampicin (600 mg/day) for three
months.
• Cessation of intravesical therapy.

126. Epididymo-orchitis
• Perform urine culture and administer
quinolones.
• Cessation of intravesical therapy.
• Orchidectomy if abscess or no response to
treatment.

127. Arthritis
• Rare complication and considered
autoimmune reaction.
• Arthralgia and arthritis : treatment with
NSAIDs.
• If no/partial response, proceed to
corticosteroids, high-dose quinolones or
antituberculosis drugs.

128. Persistent high-grade fever
• (> 38.5°C for > 48 h)
• Permanent discontinuation of BCG instillations.
• Immediate evaluation: urine culture, blood tests, chest
X-ray.
• Prompt treatment with more than two antimicrobial
agents while diagnostic evaluation is conducted.
• Consultation with an infectious diseases specialist.

129. BCG sepsis
• Evaluation: total count, urine culture, chest X-ray, ESR, CRP
• Cessation of BCG.
• For severe infection:
• High-dose quinolones or isoniazid, rifampicin and
ethambutol
• Start ATT for 6 months
• Early, high-dose corticosteroids as long as symptoms
persist.
• Consider an empirical non-specific antibiotic to cover
Gram-negative bacteria and/or Enterococcus.

130. Allergic reactions
• Antihistamines and anti-inflammatory agents.
• Consider high-dose quinolones or isoniazid
and rifampicin for persistent symptoms.
• Delay therapy until reactions resolve

131. Bacille Calmette-Guérin: Treatment
Schedule
• Several studies and AUA guidelines suggest that a 6-week induction course 1
• Durations of maintenance therapy based on risk stratification of the tumor 2
• Southwest Oncology Group (SWOG) reported the most significant impact of
maintenance therapy. Patients received a 6-week induction course followed by 3
weekly instillations at 3 and 6 months and every 6 months thereafter for 3
years.1
• intermediate-risk disease, a 1-year course of maintenance BCG was administered
at months 3, 6, and 12. 2
1. Chang et al., 2016
2. Oddens et al. 2013

134. BCG-refractory tumour
• If T1G3/HG tumour is present at 3 months . Further
conservative treatment with BCG is associated with an
increased risk of progression
• If TaG3/HG tumour is present after 3 months and/or at 6
months, after either re-induction or first course of
maintenance.
• If CIS (without concomitant papillary tumour) is present at
3 months and persists at 6 months after either re-induction
or first course of maintenance. If patients with CIS present
at 3 months, an additional BCG course can achieve a
complete response in > 50% of cases
• If HG tumour appears during BCG maintenance therapy

135. BCG-relapsing tumour
• Recurrence of G3/HG tumour after
completion of BCG maintenance, despite an
initial response
• Radical cystectomy or repeat BCG course
according to individual situation.
• Bladder-preserving strategies

136. BCG unresponsive tumour
• BCG refractory or T1Ta/HG BCG recurrence
within 6 months of completion of adequate
BCG exposure
• or
• Development of CIS within 12 months of
completion of adequate BCG exposure
• Radical cystectomy or bladder preservation
strategy

138. Muscle invasive bladder cancer

139. MUSCLE INVASIVE

140. Overview
• 20% to 30% of patients will present with muscle-invasive bladder cancer
at the time of initial presentation.
• 20% will progress to muscle-invasive disease after an initial diagnosis of
non–muscle-invasive bladder cancer.
• 30% of patients diagnosed with MIBC have undetected metastasis at the
time of treatment of primary tumor.
• 25% of patients submitted to radical cystectomy present with lymph node
involvement at the time of surgery.

141. IMAGING IN MIBC
• optimal to obtain cross-sectional imaging before TUR.
• if imaging is obtained subsequently, it should be delayed approximately 7
days post-procedure to minimize inflammatory artifact, which can be mistaken
for T3 disease (Kim et al, 2004).
• Both CT & MRI cannot accurately diagnose microscopic invasion of perivesical
fat (T2 vs T3a).
• aim of CT or MRI is therefore to detect T3b disease or higher.
• pelvis nodes > 8mm and abdominal nodes >10mm in maximum short-axis
diameter is regarded as enlarged on CT or MRI.

143. ROLE OF PET IN DISTANT METS
• Evidence is accruing in the literature suggesting that 18F-
fluorodeoxyglucose (FDG)-positron emission tomography
(PET)/CT might have potential clinical use for staging
metastatic BC but there is no consensus yet.
• The results of further trials are awaited before a
recommendation can be made.

144. Magnetic resonance imaging is more sensitive and
specific for diagnosing bone metastases than bone
scintigraphy.
• Conclusion: Whole-body MR imaging for the evaluation of metastases
compared well with the reference techniques for cerebral, pulmonary, and
hepatic lesions. Whole-body MR imaging was more sensitive in the
detection of hepatic and osseous metastases than were the reference
techniques.

145. NEOADJUVANT CHEMOTHERAPY FOR MUSCLE-
INVASIVE BLADDER CANCER
• Advantages
1. chemotherapy is often better tolerated before
surgery-delay in chemotherapy after surgery
due to complications or debilitation.
2. Patients with micrometastatic disease.
3. downstage bulky and locally advanced tumors
increasing likelihood for negative surgical
margins.
4. allows the clinician to assess each individual’s
response to therapy.

146. NAC
Disadvantage:
- chemotherapy is a delay in definitive local
therapy for patients who do not respond to
chemotherapy and thus experience disease
progression.

147. NEOADJUVANT CHEMOTHERAPY FOR
MUSCLE-INVASIVE BLADDER CANCER
• 50% of patients with muscle-invasive bladder cancer treated with
cystectomy alone will progress to metastatic disease (Stein et al, 2001;
Ghoneim et al, 2008).
•

148. Is NAC really beneficial for T2 or
less???
• 526 patients in 3 arms
- No NAC
- partial NAC
- complete NAC

149. •
• Cisplatin-based neoadjuvant chemotherapy is associated with an overall
survival advantage of 5% to 6% and a pathologic complete response rate
of 30% to 40%.

150. RADICAL CYSTECTOMY AND PELVIC LYMPH
NODE DISSECTION
• Patients with clinical T2-T4a, N0, M0 disease, remains the gold standard
therapy.
• Time from diagnosis MIBC to cystectomy likely impacts oncologic
outcomes, particularly if there is a delay of greater than 12 weeks
Sanchez-Ortiz and colleagues (2003)

151. Radical cystectomy in NMIBC
1. are high grade and invading deeply into lamina propria
2. exhibit lymphovascular invasion
3. associated with diffuse CIS
4. diverticula
5. substantially involve the distal ureters or prostatic urethra
6. refractory to initial therapy
7. too large or anatomically inaccessible to be removed entirety
endoscopically.

152. Radical cystectomy indications
in MIBC and others
• MUSCLE INVASIVE
• T2-T4a.N0, N0, M0 disease
• OTHERS
• Non urothelial carcinomas (squamous, adeno)
• non responders to conservative therapy
• Recurrences after bladder sparing treatments
• Palliative intervension- fistula formation,pain,recurrent visible
haematuria

153. CONTRAINDICATIONS-
CYSTECTOMY
1. Unresectable - lymph node metastases.
2. Bulky lymph node with extensive periurethral disease.
3. Bladder is fixed to the pelvic sidewall, or invading the recto sigmoid
colon.

154. RADICAL CYSTECTOMY
• Technique-removal of bladder and adjacent organs
• Male- removal of prostate, seminal vesicles
• Female- removal of uterus,cervix,vagina and ovary

155. URETHRECTOMY INDICATIONS
• Positive margin at the level of urethral dissection.
• Primary tumor is located at bladder neck or in urethra.
• Extensive infiltration of prostate.

156. Consent
• Pt is explained about his/her disease and the
diagnosis MIBC
• The need for surgery
• The prognosis (5 yr survival 50-60%)
• Organ removed – bladder, - prostate, seminal vesicles
• Pt is explained about ileal conduit & complication & stoma
care
• VAS deferens ligation
• Erectile dysfn
• Gen complications: infection,bleeding,trauma and others

157. Pre Op
Prep
1. Blood reservation
2. Only liquid diet from morning on the day before
surgery
3. Oval peglec at 12 to noon
4. NBM 12:00 midnight
5. Ileostomy site marking
6. Inform pathology dept for frozen section preparation
7. Part preparation nipple to knee.
On the day of sx
Morning - serum electrolytes, pulse /BP/RBS
- Antibiotics -cephalosporin +Metronidazole

158. Pre Op Prep
1. Blood reservation
2. Only liquid diet from morning on the day before
surgery
3. Oral peglec at 12 to noon
4. Nil By Mouth,12:00 midnight
5. Ileostomy site marking
6. Inform pathology dept for frozen section preparation
7. Part preparation nipple to knee.
- On the day of surgery serum electrolytes, RBS
- Antibiotics - Cephalosporin +Metronidazole

159. MAIN STEPS
• POSITION
• INCISION
• ABDOMINAL EXPLORATION
• BOWEL MOBILIZATION
• URETERAL DISSECTION
• PELVIC LYMPHADENECTOMY
• LIGATION OF LATERAL VASCULAR PEDICLE
• LIGATION OF POSTERIOR VASCULAR PEDICLE
• ANTERIOR ,APICAL DISSECTION

160. Position
• Hyper extended supine position with iliac crest
located below the fulcrum of operating table
• The legs are slightly abducted

161. Incision
• Vertical midline incision
• Incision should be carried
lateral to umbilicus on the
contralateral side of stoma
site
• While opening of posterior
rectus sheath ,care should
be taken to remove the
urachus en bloc with
bladder

162. Abdominal Exploration
• Look for extent and resectability
• Hepatic metastasis
• Gross regional and retroperitoneal
lymphadenopathy

163. Ureteral resection
• Ureters are dissected in to deep pelvis(several
cm beyond the iliac vessels) and divided
between two large hemo clips
• Proximal cut end of ureteral segment is send for
frozen section
• Leaving the proximal hemo clip on divided
ureter allows for hydro static ureteral dilation
and facilitates uretero enteric anastomoses

164. Pelvic Dissection
Blood supply of bladder
• lateral pedicle
- Superior vesicle artery
- Inferior vesicle artery
• Posterior pedicle
• Superior & inferior vesicle
arteries are branch of
anterior division of Int iliac
Artery.
• Posterior pedicle is
branch of posterior
division of Internal
iliac Artery.

166. Control DVC
vicryl 1-0 or 1 number
and apply “figure of
eight suture” on DVC
complex and fix it to
pubic
symphysis

167. Anatomic Extent of Pelvic Lymph Node Dissection
and Landing Zones

168. Standard LN dissection

169. Extended LN dissection
• Completed extended pelvic lymph node
dissection

170. • 5-year recurrence-free survival of patients with lymph node positive
disease was
- 7% for limited
- 35% for extended node dissection
• It is recommend that an adequate pelvic lymph node dissection at a
minimum includes all lymphatic tissue around the common iliac,
intercommon iliac, internal iliac, and obturator packets bilaterally.
• It has also been suggested that frozen-section analysis be performed for
the lymph nodes in the true pelvis, and if metastasis is not identified, a
more superior dissection can be omitted.

172. Number of Lymph Nodes Removed at
the Time of Cystectomy
• -50% if 15-25 nodes
• -75% if 25 nodes
• - 90% if 45 nodes
• (suggesting 25 node
minimum).

173. Lymph Node Density and
Extracapsular Nodal Extension
• Lymph node density refers to the percentage of positive nodes relative to
the total number of nodes removed.
• Herr (2003) and colleagues) In their study of 162 patients with lymph node
positive bladder cancer patients who had a lymph node density of less
than 20%, these patients experienced a significantly better 5-year disease-
specific survival following radical cystectomy.
• Seiler and colleagues (2011) reported an extranodal extension to be an
independent predictor of overall survival and disease-specific survival in a
smaller cohort (n=162) of lymph node positive patients.

174. Intraoperative Decision Making
A. Grossly Positive Nodes and T4b Disease
-Cystectomy is not performed
1. when lymph node metastases are unresectable because of bulk,
2. when there is evidence of extensive periureteral disease,
3. when the bladder is fixed to the pelvic sidewall
4. when the tumor is invading the rectosigmoid colon

175. Intraoperative Decision Making
B.Intraoperative Frozen Sections of the Ureter
• The incidence of involvement of the distal ureter with tumor on final
pathology at the time of radical cystectomy was 6% to 8% (Gakis et al,
2011).
• Final ureteral margin status has proven to be an independent predictor of
upper tract recurrence following cystectomy (Tran et al, 2008; Volkmer et
al, 2009).
• role of intraoperative frozen-section analysis of the ureters at the time of
cystectomy remains somewhat controversial.

177. Urinary diversion after radical cystectomy
Orthotopic
Orthotopic bladder substitution
Heterotopic
• Continent
Right colonic pouches-Indiana,Florida,Miami,Penn Ileal pouches-
Kock,Mainz Caecum & ascending colon-Mainz I
• Non continent
Ileal/colonic conduit Cutaneous ureterostomy
• Diversion in to GIT
Uretrosigmoidostomy/Rectal bladder-Manz II,Mansuora rectal bladder

178. Ileal conduit urinary diversion
Originally described by Zaayer in 1911, popularised by Bricker in early 1950s
Reliable, easily performed procedure which has stood test of time
Typically 10-15 cm of ileum, 10-15cm from ileocaecal valve
Contraindications:
Short bowel syndrome
Inflammatory bowel disease
Pelvic irradiation

179. Oncologic Outcomes following
Radical Cystectomy
.
• Lymph node status appears to be the single
greatest predictor of disease outcome.

180. ADJUVANT CHEMOTHERAPY FOR
MUSCLE-INVASIVE BLADDER CANCER
• Patients with pT3-T4 or node-positive disease are known to be at high
risk for failure following cystectomy.
• A major limitation of adjuvant chemotherapy is that it is often difficult or
impossible for patients to undergo systemic therapy following cystectomy
secondary to surgical deconditioning, deteriorating renal function, or
perioperative complications (Donat et al, 2009).

181. Randomised trails of adjuvant chemo
• The EUA guidelines currently recommend
adjuvant chemotherapy within clinical trials but
not as a routine therapeutic option

182. Partial cystectomy
• First, a full pelvic lymphadenectomy can be performed that allows for
complete staging. Second, the full thickness of bladder wall and associated
perivesical fat can be removed.
• Ideal candidates for partial cystectomy include those with small, solitary
tumors amenable to wide resection with 2-cm margins. Ideally the tumor
should be away from the ureteral orfices to avoid reimplantation.
• complete resection while maintaining adequate functional bladder
capacity
• The presence of CIS is considered by most to be a contraindication to
partial cystectomy, and random bladder biopsies can be performed
preoperatively.
• The MSKCC group has also recommended the routine use of
intraoperative frozen sections and proceeding with radical cystectomy if a
negative margin cannot be achieved (Holzbeierlein et al, 2004).

183. Multimodality bladder-preserving
treatment
• trimodality treatment combines TURB, chemotherapy and RT
• The aim of MMT is to preserve the bladder and QoL without
compromising oncological outcome.
• Patients who are medically unfit for surgery or who refuse surgery can be
considered for bladder preservation.

184. Metastatic urothelial cancer

186. Time schedule for surveillance
• EAU Guidelines
- CT scan (every 6 months) until the third year, followed by annual imaging
thereafter.
- CT scan of the UUT(Patients with multifocal disease, NMIBC with CIS or
positive ureteral margins are at higher risk of developing UTUC, which can
develop late (> 3 years)).

187. Follow-up of functional outcomes and
complications
• The functional complications are diverse :
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
emptying dysfunction risk of fractures