1

Superficial Bladder Cancer-TCC

Barry Stein, M.D.Professor Emeritus

Alpert Medical School ofBrown University

2009 data

Total of 70,980 new cases52,810 males18,170 females

Prevalence

Total is 14,300Men: 10,180Women: 4,150

Mortality

70,980 new pts annually

56,784 pts will have superficial tcc

39,750 will have a recurrence

7950 pts will upgrade or upstage

4,000 pts will develop metastases or die

Year 2 there would be 56,784 + 39,750 pts in the poolThis continues on ad infinitum

Plus any pts with upper tract tumors + bladder tumor

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

16

Superficial TCC- 80%

CIS (Flat Lesion)- 1-2%

Invasive Cancer- 20%

20

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

• 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

29

Results:

30

Results- levels vs grade

31

32Compared: NMP22, BTA, telomerase activity, hgb dipstick and voided cytology

Results- compared to cysto and bx findings

33

34

Gupta et al – recurrence rates

35

Dogs trained to smell bladder cancer in urineMan's best friend could help fight disease,

scientists say

37

New Lab Test in development

Diagnosis DemographicsTotal Tested Population (1331) vs Patients with TCC (79)

TCC 79 / 1,331 (6%)

Sensitivity for Detecting TCC: Diagnosis

Cytology = 16%NMP22 Test = 57%

40

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%)

Sensitivity for Detecting Cancer: Monitoring

Cytology = 12%NMP22 Test = 50%

43

Improved Detection withNMP22 BladderChek Test and Cystoscopy

Muscle Invasive All Cancers

Cystoscopy 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

Relative Risk- High Grade

Relative Risk- Low Grade

Bladder Cancer Detection AlgorithmResult: >99% Negative Predictive Value

Action: Standard SurveillancePathway

#1NMP22 Test(NEG)

Cystoscopy (NEG)

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

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

47

TreatmentSuperficial TCC

Initial Treatment

Staging

WHO Classification

Urology 66, supplement 1, 4-34, 2005

Papillary UN of LMP

Papillary Carcinoma LG

High Grade TCC

Progession Rates

Treatment Paradigm-IWhat is the risk of dying of this?

• Low risk of progression- 10%

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

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

58

Intravesical Chemotherapy

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

• Agents:– BCG– MMC– Adriamycin– Interferon

60

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

61

Thank you for joining me.