NMIBC Urianary Bladder Malignancy

NON-MUSCLE INVASIVE
BLADDER CANCER
DEPT OF UROLOGY
GOVT ROYAPETTAH HOSPITAL AND KILPAUK MEDICAL COLLEGE
CHENNAI 1

MODERATORS:
Professors:
 Prof. Dr. G. Sivasankar, M.S., M.Ch.,
 Prof. Dr.A. Senthilvel, M.S., M.Ch.,
Asst Professors:
 Dr. J. Sivabalan, M.S., M.Ch.,
 Dr. R. Bhargavi, M.S., M.Ch.,
 Dr. S. Raju, M.S., M.Ch.,
 Dr. K. Muthurathinam, M.S., M.Ch.,
 Dr. D.Tamilselvan, M.S., M.Ch.,
 Dr. K. Senthilkumar, M.S., M.Ch.
DEPT OF UROLOGY, GRH AND KMC, CHENNAI. 2

DEFINITION
 Malignant urothelial tumors that have not invaded the detrusor
 Traditionally – superficial bladder cancer
3
DEPT OF UROLOGY, GRH AND KMC, CHENNAI.

NMIBC
 CIS – High grade, flat
malignancy confined to
urothelium
 Ta – papillary tumor
confined to urothelium
 T1 – Papillary tumors
invading lamina propira 4

NON MUSCLE INVASIVE ≠ NON INVASIVE
 T1 and CIS, as compared toTa, have high malignant potential
 “Superficial tumors” – misleading
 T1 – invasive with lamina propria invasion
 Deep lamina propria invasion with muscularis mucosa –
Subcategorised as T1b
 EAU 2018 – do not use the term “superficial bladder cancer”
5

INCIDENCE
 70% - non-muscle invasive at presentation
 70% - Ta
 20% - T1
 10% CIS
6

PATHOLOGIC GRADING
 1973WHO grading
 Grade 1: well differentiated
 Grade 2: moderately differentiated
 Grade 3: poorly differentiated
 2004 WHO grading system (papillary lesions)
 Papillary urothelial neoplasm of low malignant potential (PUNLMP)
 Low-grade (LG) papillary urothelial carcinoma
 High-grade (HG) papillary urothelial carcinoma
7

TUMOR BIOLOGY
 Primarily grade dependent
 Low grade - Ta
 Recurrence – 50 -70%
 Progression – 5%
 High grade -T1, CIS
 Recurrence - >80%
 Progression – 50%
8

OTHER PROGNOSTIC FACTORS
 Tumor size
 Multiplicity
 Papillary versus sessile configuration
 Presence or absence of lymphovascular invasion
 Status of remaining urothelium
9

GENETICS
 Dual molecular lines
 Low grade
 Few chromosomal abnormalities
 Loss of all or part of chromosome 9q
 FGFR3 mutations
 High grade
 Numerous and greatly variable chromosomal gains / losses
 Loss of all or part of chromosome 9q
 Aneuploidy of chromosomes 7,9 and 17
 TP53, RB mutations 10

PUNLMP
 Papillary urothelial neoplasm of low malignant potential
 Low risk
 Unlikely to progress
 Considered benign
 Orderly cellular arrangement, minimal architectural abnormalities, minimal
nuclear atypia
 WHO recommendation for Pathology report
 “Patients with these tumors are at risk of developing new bladder tumors
(‘recurrence”), usually of similar histology; However occasionally these
subsequent lesions manifest as UC, such that follow-up is warranted” 11

HISTOLOGICAL CLASSIFICATION OF FLAT
LESIONS – WHO 2004
 Urothelial proliferation of uncertain malignant potential (flat
lesion without atypia or papillary aspects).
 Reactive atypia (flat lesion with atypia).
 Atypia of unknown significance.
 Urothelial dysplasia.
 Urothelial CIS - always high grade
12

CIS
 Flat, high-grade, non-invasive urothelial carcinoma.
 Precursor of invasive high-grade cancer
 Missed or misinterpreted as an inflammatory lesion during
cystoscopy if not biopsied.
 Often multifocal - in the bladder, but also in the upper urinary
tract (UUT), prostatic ducts, and prostatic urethra
13

CIS – CLASSIFICATION
 Primary: isolated CIS with no previous or concurrent papillary
tumours and no previous CIS
 Secondary: CIS detected during follow-up of patients with a
previous tumour that was not CIS
 Concurrent: CIS in the presence of any other urothelial tumour
in the bladder
14

CIS
 Composed of severely dysplastic urothelium
 Disorderly histology with nuclear atypia characteristic of high
grade malignancy
 40 – 83% - develop muscle invasion if untreated, especially if
associated with papillary tumors
 CIS – second most important prognostic factor after grade
15

TA
 Low grade
 Recurrence common
 Progression rare
 2.9 – 18 % - high grade
16

T1
 Usually papillary with narrow stalk
 Nodular / sessile → deeper invasion
 Increased risk of recurrence/progression with
 Deep penetration involving muscularis mucosae
 Lymphovascular invasion
 Bladder neck involvement
17

RISK OF UNDERSTAGING
 Significant potential for understaging high-grade, apparently
NMIBC
 Many tumors – more extensive / muscle invasive thanTUR
specimen when cystectomy is performed
18

19

CLINICAL FEATURES
 Haematuria - most common finding
 Visible haematuria was found to be associated with higher stage
disease compared to nonvisible haematuria at first presentation
 Carcinoma in situ - lower urinary tract symptoms, especially
irritative voiding.
20

DIAGNOSIS
 Physical examination does not reveal NMIBC
 Transabdominal US
 Permits characterisation of renal masses, detection of hydronephrosis,
and visualisation of intraluminal masses in the bladder
 For detection of obstruction in patients with haematuria.
 Cannot exclude the presence of UTUC and cannot replace CT
urography in bladder cancer detection.
21

CT UROGRAPHY
 Detect papillary tumours in the urinary tract – filling defects
 Tumours located in the trigone
 Multiple tumors
 High-risk tumours
Intravenous urography (IVU) - Alternative
22

CT UROGRAPHY
 Upper tract imaging usually performed beforeTUR
 To identify other sources of hematuria
 To assess the extravesical urothelium because of the field change
nature of UC
 Retrograde pyelography or ureteroscopy can be planned for any
upper tract abnormalities identified.
The diagnosis of CIS cannot be made with imaging methods (CT urography,
IVU or US) 23

URINE CYTOLOGY
 The examination of voided urine or bladder-washing specimens
for exfoliated cancer cells
 High sensitivity in high-grade tumours (84%)
 Low sensitivity in low-grade tumours (16%)
 Sensitivity in CIS detection is 28-100%
24

URINE
CYTOLOGY
Positive voided urinary cytology can
indicate an urothelial tumour anywhere
in the urinary tract
Negative cytology, however, does not
exclude the presence of a tumour.
Evaluation can be
hampered by
Low cellular yield
Urinary tract infections
Stones
Intravesical instillations
25

PARIS REPORTING SYSTEM
 A standardised reporting system redefining urinary cytology diagnostic
categories was published in 2016 by the Paris Working Group
 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).
26

EAU 2018 RECOMMENDATIONS
27

BLADDER DIAGRAM
 1- Trigone
 2,3 – Rt and Lt ureteric orifice
 4,5 – Rt and Lt lateral walls
 6 – Anterior wall
 7 – Posterior wall
 8 – Dome
 9 – Bladder neck
 10 – Prostatic urethra
28

MANAGEMENT
29

RISK
STRATIFICATION
AUA
Low risk Intermediate risk High risk
LG SOLITARYTa <
3CM
LG Ta Recurrence
within 1year
HGT1
PUNLMP SOLITARY LGTa
>3CM
Any recurrent HGTa
LG Ta,
MULITFOCAL
HGTa, >3CM or multifocal
HGTa < 3CM Any CIS
LG T1 Any BCG failure in HG
Any variant histology
Any LVI
Any HG prostatic urethral
involvement
30

RISK
STRATIFICATION
EAU
Low risk Intermediate risk High risk
Primary, solitary
LG/G1 <3cm, No
CIS
All tumors not
defined in two
adjacent categories
T1 tumors
HG/G3 tumors
CIS
Multiple, Recurrent,
>3cm,Ta G1G2
tumors (all
conditions must be
present)
31

TURBT
INITIAL TREATMENT OF
VISIBLE LESIONS
• Remove all visible tumors
• Provide specimens for pathologic examination to accurately
stage and grade
Goal:
32

BIMANUAL EXAMINATION
 Bimanual examination of the bladder is often performed
 with the patient under anesthesia before preparation and draping
 unless the tumor is clearly small and noninvasive
 Repeated after resection.
 Fixation or persistence of a palpable mass after resection suggests locally
advanced disease
 Additional value of this maneuver in the era of modern imaging appears
limited and may even be misleading
33

 Resection is performed using a 12- or 30-degree lens
 Continuous irrigation with the bladder filled only enough to
visualize its contents
 Minimizes bladder wall movement
 Lessens thinning of the detrusor through overdistention
 Reduce the risk of perforation
34

 Resection is performed piecemeal, delaying transection of any
stalk until most tumor has been resected, to maintain
countertraction.
 Friable, low-grade tumors can often be removed without the
use of electrical energy because the nonpowered cutting loop
will break off many low-grade tumors.
35

TURBT
 Higher-grade, more solid tumors and the base of all tumors require
the use of cutting current
 Lifting the tumor edge away from detrusor lessens the chance of
perforation
 Cautery yields hemostasis once the entire tumor has been
resected.
 Repeated slow fulguration may complicate the ability of the
pathologist to determine grade or invasion status.
36

MUSCLE BIOPSY
 After all visible tumor has been resected, an additional pass of
the cutting loop or a cold-cup biopsy can be obtained to send
to pathology separately to determine the presence of muscle
invasion of the tumor base.
37

OBTURATOR REFLEX
 Obturator nerve passes near the inferolateral bladder wall,
bladder neck and lateral prostatic urethra.
 Stimulated by lateral wall resection
 Minimised by
 TUR in saline
 Use of general anesthesia with muscle-paralyzing agents
 Obturator block - by direct injection of 20 to 30 mL of local
anesthetic (lidocaine) into the obturator nerve and its canal
38

OBTURATOR BLOCK
39

TURBT IN DIVERTICULAR
TUMORS Significant risk of bladder wall perforation
Accurate staging is difficult to achieve - underlying
detrusor is absent.
Invasion beyond the diverticular lamina propria
immediately involves perivesical fat (stageT3a by
definition)
40

DIVERTICULARTUMORS
• Combination of resection and fulguration of the base
• Conservative resection can be followed with subsequent repeat
resection if the final pathologic interpretation is high grade.
Low-grade
diverticular tumors
• Require adequate sampling of the tumor base, often including
perivesical fat, despite the near certainty of bladder perforation.
• Partial or radical cystectomy should be strongly considered for
high-grade diverticular lesions.
High-grade
diverticular tumors
An indwelling catheter usually allows healing within a few days.
41

ANTERIOR WALL TUMORS
 Anterior wall tumors and tumors at the dome in patients with large bladders can
be difficult to reach.
 Maneuvers to facilitate resection
 Minimal bladder filling combined with manual compression of the lower
abdominal wall
 Long resectoscopes
 Temporary perineal urethrostomy - rarely necessary except in the obese
patient with an inaccessible tumor.
 Digital manipulation through the rectum or vaginal wall
42

ADJACENTTO URETERAL ORIFICE
 Care to prevent obstruction from scarring after fulguration.
 Pure cutting current causes minimal scarring and may be safely
performed, including resection of the orifice if necessary.
 Resection of the intramural ureter can sometimes lead to
complete eradication of the tumor but risks reflux of malignant
cells.
43

RESECTION WITH COLD CUP BIOPSY FORCEPS
 Small tumors
 In elderly women, who are predisposed to perforation owing
to their thin-walled bladders.
 If perforation occurs, the cup causes a smaller hole than does
the cutting loop.
44

HEMOSTASIS AFTER TURBT
 A Bugbee electrode facilitates hemostasis.
 Involves placing the Bugbee electrode inside the biopsy site with the bladder under minimal
distention.
 Electrical energy will cause the mucosa to contract around the electrode unless the bladder is full.
 Light irrigation clears the area of blood and vaporization bubbles created during fulguration.
 Visualizing a small (1 to 2 mm) ring of white coagulation confirms hemostasis and yields less
damage to the bladder than that occurring when the biopsy area is “painted” with cautery.
 Removing the electrode from the site before discontinuing the energy current lessens the chance
of pulling the fresh clot off as the Bugbee electrode separates from the urothelium.
45

MUSCLE BIOPSY
 If a tumor appears to be muscle invasive, biopsies of the
borders and base to establish invasion may be performed in lieu
of complete resection
 Failure to demonstrate invasion necessitates repeat resection
unless the decision is made to proceed to cystectomy based on
factors other than muscle invasion.
46

EVALUATION OF RESECTION
 Detrusor muscle in the specimen is considered as the surrogate
criterion of the resection quality and is required (except of
TaG1/LG tumours).
47

COMPLICATIONS
 Immediate postoperative period – minor bleeding and irritative
symptoms
 Major – 5%
 Uncontrolled hematuria
 Bladder perforation
 As long as resection of the ureteral orifice is performed with pure
cutting current, scarring is minimal and obstruction unlikely.
48

REPEAT TURBT
 High-grade tumor
 T1 tumors
 No evidence of muscle invasion is identified on the initial resection
in pT1 and many high-gradeTa tumors
 Timing: 1 to 6 weeks after the initial resection
 Residual tumor is identified at the site of the initial resection at
least 40% of the time
49

50

RANDOM / ADDITIONAL BIOPSIES
 Biopsies from normal looking mucosa / abnormal epithelium
 Indications:
 CIS indistinguishable from inflammation/ not visible
 Multiple tumors
 Positive cytology / High risk tumor (non- papillary appearance) – trigone,
bladder dome and right, left, anterior and posterior bladder wall
 Tumors in trigone / bladder neck, CIS – prostatic urethra / duct
involvement higher
 Prostatic urethral biopsy - if neobladder creation is anticipated for high-
risk disease
51

LASER THERAPY
 Laser coagulation allows minimally invasive ablation of tumors up to 2.5 cm
in size.
 The neodymium : yttrium-aluminum-garnet (Nd :YAG) laser has the best
properties for use in bladder cancer.
 Lesions can be coagulated until nonviable through protein denaturation
using a straight or 90-degree noncontact “free beam” laser using power
output of up to 60W.
 No tissue available for pathologic inspection - the optimal candidate is
patient with recurrent, low-grade lesions whose biology is already known. 52

COMPLICATIONS OF LASER
 Injury to Adjacent Structures
 Due to forward scatter of laser energy to adjacent structures,
resulting in perforation of a hollow, viscous organ such as
overlying bowel.
 Rare but most commonly occurs with the Nd :YAG laser
because of its deeper tissue penetration than with holmium
(Ho):YAG and potassium titanyl phosphate (KTP) lasers
53

 Bladder wall perforation
 Unless higher energy is necessary for a very large tumor,
limiting energy to 35W precludes exceeding 60°C on the
outer bladder wall, minimizing the risk of perforation
 The most efficient delivery appears to be an end-fire
noncontact fiber with a 5- to 15-degree angle of divergence,
which allows variable penetration depth up to 5 mm
54

 Extravesical injury
 Treatment should be under direct visualization and should
discontinue as soon as protein denaturation is evident by the
white appearance of the treated tissue. Persistence after this
occurs, risks extravesical injury.
55

LASER THERAPY
 More expensive - cost of laser fibers
 Bleeding is negligible
 No risk of obturator reflex.
 Small lesions can be treated easily using intravesical anesthesia.
56

SUMMARY
57

INTRAVESICAL
THEREAPY
58

PERIOPERATIVE INTRAVESICALTHERAPY
 Rationale
 Tumor cell implantation immediately after resection is
responsible for many early recurrences
 Explains the observation that initial tumors are most
commonly found on the floor and lower sidewalls of the
bladder, whereas recurrences are often located near the
dome as a result of “flotation” (Heney et al, 1981).
 Intravesical chemotherapy kill such cells before implantation
59

INTRAVESICAL CHEMOTHERAPY
 Single dose administered within 6 hours lessens recurrence
rates, whereas a dose 24 hours later does not
 The number needed to treat (NNT) to prevent one recurrence
in the meta-analysis was 8.5
60

PERIOPERATIVE
ADMINISTRATION
OF INTRAVESICAL
CHEMOTHERAPY
Confirm absence of clinical perforation
Place three way catheter into bladder while patient is still in operating
room
Attach inflow port to saline infusion bag and clamp inflow
Administer chemotherapeutic agent through catheter outflow port in
recovery room within 6 hrs of surgery and clamp outflow tubing to allow
retention
Open outflow 1 hour after administration and for irrigation, to be opened
to gravity drainage for next 30 to 60 mins
Remove foley’s catheter and discard in biohazard container
61

COMPLICATIONS
 Local irritative symptoms
 Chemical cystitis
 Cutaneous desquamation,
 Decreased bladder capacity as a result of contractures, calcified
eschars
 Added difficulty of subsequent cystectomy
 Serious sequelae and rare deaths have occurred, especially in
patients with perforation during resection 62

MITOMYCIN C
 Alkylating agent
 Inhibits DNA synthesis
 Instilled weekly for 6 to 8 weeks at dose ranges from 20 to 60 mg
 Optimisation of delivery by:
 Eliminating residual urine
 Fasting overnight
 Sodium bicarbonate to reduce drug degradation
 Increasing concentration to 40 mg in 20 ml
 Local microwave therapy
 Electromotive intravesical therapy
63

DOXORUBICIN
 Anthracyline antibiotic
 Binds to DNA base pairs → inhibits topoisomerase II & protein synthesis
 Principal AE: chemical cystitis
 Derivatives
 Epirubicin – available only in Europe for UC treatment
 Valrubicin – semisynthetic analog
 Approved by FDA for BCG refractory CIS in patients who
cannot tolerate cystectomy
64

THIOTEPA
 Triethylenethiophosphoramide
 Only chemotherapeutic approved by FDA specifically for intravesical
treatment of papillary bladder cancer
 Alkylating agent
 Not cell cycle specific
 Systemic side effects – low molecular weight (half of administered
doses being absorbed) risking hemopoietic toxicity
65

NOVEL AGENTS
 Gemcitabine
 Intravesically – either weekly or twice weekly for 6 to 8
treatments
 Reduction of recurrence
 Taxanes – paclitaxel, docetaxel
 Modest efficacy
 Data limited to preclinical studies 66

COMBINATION THERAPY
 MMC (20mg) – day 1 + Doxorubicin (40mg) – day 2 / week X 5
weeks
 Chemotherapy + BCG
 No clear advantage
67

IMMUNOTHERAPY
 BCG
 Interferon alpha
 Investigational agents – KLH, IL 2, Mycobacterial cell wall DNA
68

BCG
Attenuated mycobacterium
Antitumor activity in several different cancers including UC
STANDARD DOSE: 120 mg
LOW DOSE: 40 / 80 mg
Reconstituted with 50 mL of saline
Administered through a urethral catheter under gravity.
Retain the solution for atleast 2 hours
69

INTRAVESICAL
BCG
2 to 4 weeks after tumor resection
Allowing time for re-epithelialization
Urinalysis is usually performed
immediately before instillation
In the event of a traumatic
catheterization, the treatment should be
delayed for several days to 1 week
70

MECHANISM
OF ACTION
71

BCG
 In carcinoma in situ
 Intital tumor free response rate – 84%
 50% - durable response for median period of 4 years
 30% free of progression or recurrence – over 10 years
 AUA – BCG as the preferred initial treatment in CIS
 Residual tumor
 Effectively treat residual papillary lesions
 Should not be used as a substitute for surgical resection
 60% response rate
72

BCG
 To prevent recurrence
 Maintenance BCG
 3years maintenance therapy
 Intermediate risk – 1 year
 Impact on progression
 Delay progression of high risk cancer
 No chemotherapy trials achieved significant reduction in
progression when compared to BCG
73

LAMMS/SWOG REGIMEN
 Induction therapy – 6 weeks
 Maintenance therapy – 3 years
 3 weekly instillations at 3 and 6 months and every 6 months
thereafter
74

CONTRAINDICATIONS
TO BCGTHERAPY
75

MANAGEMENT
OF BCG
TOXICITY
76

BCG
TOXICITY
77

BCG
TOXICITY
78

BCG FAILURE
 Recurrent or persistent disease after an initial 6 week course of BCG = BCG
failure
 BCG REFRACTORY - non improving or worsening despite BCG
 BCG RESISTANT – recurrence or persistence of lesser degree, stage, or grade
after an initial course, which then resolves with further BCG
 BCG RELAPSING – recurrence after initial resolution with high risk group
 Should be strongly considered for immediate cystectomy if young and in
generally good health
79

 Declaring failure may take upto 6 months
 Response rate for patients with high grade with BCG rose
from 57 to 80% 3 to 6 months after therapy
 Tumoricidal activity continued after cessation of therapy for
some period
80

INTERFERON
 Glycoproteins produced in response to antigenic stimuli
 Anti-tumor Actions:
 Inhibition of nucleotide synthesis
 Upregulation of tumor antigens
 Antiangiogenic properties
 Stimulation of cytokine release with enhancedT and B cell activation
 Enhanced natural killer cell activity
81

INTERFERON
 Most active in doses of at least 100 million units
 Optimal dose and administration schedule – unclear
 Expensive
 Less effective than BCG or Intravesical chemotherapy (in residual disease,
preventing recurrence and in CIS)
 Occasionally be effective in BCG failure
 Additive effects with epirubicin or MMC
 Trials – BCG + IFN → superiority with possibility of dose reduction of BCG
82

INVESTIGATIONAL IMMUNOTHERAPEUTIC AGENTS
 KLH
 Keyhole limpet hemocyanin
 From hemolymph of mollusk Megathura crenulata
 Non specific immune stimulant
 No clear superiority to available agents
 Mycobacterial cell wall DNA extract
 Good tolerability with success rates less than BCG
 IL 2
 Highly expressed after BCG stimulation
 Key component of Th1 immune response
 Trials – potential benefit; less toxicity
83

REFRACTORY HIGH GRADE DISEASE
Initial 6 week course of
intravesical therapy for
high risk
(BCG / chemotherapy)
Persistent after first
course
Initial chemotherapy –
BCG
Initial BCG – 2nd course
Cannot tolerate BCG →
salvage chemotherapy
(risk of progression &
failure high)
Further courses beyond
two are not
recommended
Fail 80% of the time
Salvage chemotherapy
Investigational protocols
IFN alone or in
combination with BCG
84

ALTERNATIVE OPTIONS FOR REFRACTORY
DISEASE
 Photodynamic therapy
 Administering photosensitizing agent (porfimer sodium iv or HAL, hypericin, radachlorin
intravesically)
 2 to 3 days after the substance cleared from normal tissue (for Photofrin), intravesical
treatment with red laser light (630nm) for 12 to 20 mins
 After excitation by light, the photosensitiser reacts with molecular oxygen to form free
radical and reactive singlet oxygen → cytotoxic
 Side effects: bladder contracture, irritative LUTS, dermal sensitivity
 Radiation therapy
 Restricted to patients who refuse cystectomy after failure of intravesical therapy or who
are unsuitable for major surgery
 Limited role other than palliative purpose 85

86

ROLE OF EARLY CYSTECTOMY
 “Early” cystectomy - performed before traditional surgical indication of documented muscle
invasion
 Considered in
 High grade NMIBC
 Deep invasion into lamina propria
 Lymphovascular invasion
 Associated with diffuse CIS
 Tumors in diverticula, distal ureters, prostatic urethra
 Tumors refractory to initial therapy
 Too large or anatomically inaccessible to be removed in their entirety endoscopically 87

RATIONALE FOR EARLY CYSTECTOMY
 Early (3 month) failure for T1 tumors after BCG – 82% progression rate
 Upto 20% of CIS – die of UC within 10 years
 Each occurrence ofT1 tumors associated with 5-10% chance of metastasis
 Residual tumor on repeat TUR – associated with 82% chance of muscle
invasion
 50% of presumed high grade NMIBC who undergo cystectomy – muscle
invasion+
 Delay in cystectomy even by 12 weeks – poorer survival
 Pts who progress to muscle invasion have poorer prognosis than with muscle
invasiveness at presentation
 More accurate pathological staging
88

SURVEILLANCE
89

EORTC SCORING SYSTEM
90

EORTC SCORING SYSTEM
91

CUETO
SCORING
SYSTEM
(CLUB UROLÓGICO ESPAÑOL
DE TRATAMIENTO
ONCOLÓGICO)
FACTOR RECURRENCE PROGRESSION
GENDER MALE
FEMALE
0
3
0
0
AGE LESSTHAN 60
60-70
>70
0
1
2
0
0
2
RECURRENTTUMOR NO
YES
0
4
0
2
NO. OF TUMORS 3 OR LESS
GREATERTHAN 3
0
2
0
1
T CATEGORY Ta
T1
0
0
0
2
ASSOCIATES CIS NO
YES
0
2
0
1
GRADE G1
G2
G3
0
1
3
0
2
6
TOTAL SCORE 0-16 0-14
Spanish Urological Club for OncologicalTreatmentTable for NMIBC
treated with BCG
92

SECONDARY PREVENTION STRATEGIES
 Smoking cessation
 Increased fluid intake
 Low fat diet
 Chemoprevention – retinoids, pyridoxine, alphatocopherol,
difluoromethyl ornithine
93

94

THANK YOU
95

96

97

98

 Stomach
 Jejunum
 Colon / Ileum
Electrolyte Disturbances
Hyperammonemia
Hypomagnesemia
Hypocalcemia
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NMIBC Urianary Bladder Malignancy

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