Superficial Bladder Cancer- TCC

Barry Stein, M.D.

2008 data

Prevalence

Total of 68,610 new cases51,230 males17,580 females

Mortality

Total is 14,100

68,000 new pts annually

38,080 will have a recurrence

8160 pts will upgrade or upstage

5,400 pts will develop metastases or die

Year 2 there would be 54,400 + 38,080 pts in the pool This continues on ad infinitumPlus any pts with upper tract tumors + bladder tumor

54,400 pts will have superficial tcc

Breakdown of cases

Cause of TCC

Genetic Issues

• Genetic changes ie. oncogenes play a role

• Suppressor gene mutations ie.– P53- Ch 17– Rb- Ch 13q– 9p21 region of Ch 9

8

Patient Presentation

• Gross Hematuria in 85%• Microscopic hematuria• Pain on voiding• UTI• Incidental finding on CT or US study

The Hematuria “Tattoo”

Upper tract imagingCystoscopyCytologic exam

Work Up• Upper tract imaging

– CT scan – IVU

• Cystoscopy– Flexible– rigid

• Some type of “cytology” test• Then, after dx a tumor, a TURBT

is performed

CT Scan shows papillary lesion

CT Scan of Bladder Ca-solid

Upper Tract Tumor

Office Flexible Cystoscope

Rigid Cystoscopes

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Superficial TCC- 80%

CIS (Flat Lesion)- 1-2%

Invasive Cancer- 20%

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Let’s Talk About “Cytology”

AUA Guidelines 2001

Risk Factors

What’s the Trouble with Cytology?

• The following slides with comments on what’s the trouble with cytology are taken from a recent editorial in the Journal of Urology written by William Murphy

• Reference JU 176: 2343-2346, 2006

What’s the Trouble with Cytology?

• In my opinion the decades long dissatisfaction with UC as a method for detecting urothelial neoplasms can be condensed into the 3 somewhat related themes of

• 1) inaccurate histological classification and terminology

• 2) inappropriate clinical approach to urothelial neoplasms

• 3) lack of confidence among pathologists in general and cytopathologists in particular.

What’s the Trouble with Cytology?

• Many urological pathologists do not claim to have proficiency in cytology and many cytopathologists have not been specifically trained in urinary cytopathology.

• When assessing a urinary specimen, it is not uncommon for cytopathologists to attempt an extrapolation of criteria learned for uterine cervical lesions.

Urology 66, supplement 1, 35-63, 2005

NMP-22

• This paper studied:– 93 pts with known bladder cancer– 42 pts with benign disease– 50 normal volunteers– And compared BTA, NMP 22 and

standard urine cytology

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Results:

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Results- levels vs grade

34

35Compared: NMP22, BTA, telomerase activity, hgb dipstick and voided cytology

Results- compared to cysto and bx findings

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Gupta et al - recurrence rates

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Dogs trained to smell bladder cancer in urine

Man's best friend could help fight disease, scientists say

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New Lab Test in development

Diagnosis Demographics

TCC 79 / 1,331 (6%)

Total Tested Population (1331) vs Patients with TCC (79)

0

16

32

48

64

80

Av Age yr %male %female

TotalTCC

Sensitivity for Detecting TCC: Diagnosis

Cytology = 16%NMP22 Test = 57%

38.5

77.8

11.1

44.4

.0

47.1

20.0

90.9

60.0

80.0

17.2

51.7

6.3

47.1

0

25

50

75

100

Ta T1 Tis T2 + LowGrade

Md Grade

HighGrade

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Improved Detection withNMP22 BladderChek Test and

Cystoscopy

Muscle Invasive All Cancers

Cystoscopy 91% 94%& NMP22 Test (10/11) (74/79)

Cystoscopy 55% 86%alone (6/11) (68/79)

Cancers not seen by cystoscopy but detected by NMP22 Test:Bladder CIS, T2, T3; Ureter T2; Renal Pelvis T1, T3

P=0.014

Monitoring (Surveillance) Demographics

Total population = 668Patients with tumors = 103 (15%)

0

16

32

48

64

80

Av Age yr %male %female

TotalTCC

Sensitivity for Detecting Cancer: Monitoring

Cytology = 12%NMP22 Test = 50%

19.4

75.0

.0

43.8

5.4

31.6

.0

90.9

37.5

50.0

12.5

64.7

6.3

36.0

0

25

50

75

100

Ta T1 Tis T2 + LowGrade

Md Grade

HighGrade

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Improved Detection

Muscle Invasive All CancersCystoscopy 91% 99%& NMP22 Test (10/11) (102/103)

Cystoscopy 64% 91%alone (7/11) (94/103)

Cancers not seen by cystoscopy but detected by NMP22 Test:Ta G1, 2 Cis G3, T1 G3, 2 T2 G3, 2 T4 G3

P=0.005

with NMP22 BladderChek Test and Cystoscopy

Relative Risk- High Grade

Relative Risk- Low Grade

Bladder Cancer Detection AlgorithmResult: >99% Negative Predictive Value

Action: Standard Surveillance

Pathway #1

NMP22 Test(NEG)

Cystoscopy (NEG)

Pathway #4

NMP22 Test(NEG)

Cystoscopy (POS)

Result: Greater likelihood nonmuscle invasive and low grade cancer

Action: Standard biopsy

Pathway #2

NMP22Test (POS)

Cystoscopy (NEG)

Result: Potential for undetected cancer

Action: - More intensive investigation - Review/Schedule upper tract tests - Follow up within shorter interval

Pathway #3

NMP22Test (POS)

Cystoscopy (POS)

Result: - Up to 99% of cancers detected; - Elevated risk of muscle invasive

and/or high grade cancer

Action: Prioritize for biopsy

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TreatmentSuperficial TCC

Initial Treatment

Staging

WHO Classification

Urology 66, supplement 1, 4-34, 2005

Papillary UN of LMP

Papillary Carcinoma LG

High Grade TCC

Progression Rates

• Low risk of progression- 10%

• Ta- Grade 1• Ta- Grade 2• T1- Grade 1

Treatment Paradigm-I

What is the risk of dying of this?

Treatment Paradigm-II

• Moderate risk of progression- 25%

• Ta- Grade 3• T1- Grade 2

Treatment Paradigm-III

• High risk for progression- 50%

• T1- Grade 3• CIS

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Intravesical Chemotherapy

• Indications:– Ablation– Prophylaxis– Prevent progression– CIS

• Agents:– BCG– MMC– Adriamycin– Interferon

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At the end of the day…

• ~80% 5 yr survival rate for superficial ca– Most of the deaths are from Grade 3, T1

• ~60% 5 yr survival rate for invasive ca– We need earlier diagnosis and better

chemotherapy

Barry Stein, M.D.

Thank you for joining me