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Radical Cystectomy As Early Primary Therapy for T1G3 Bladder Cancer. Karim Touijer and Bernard H. Bochner. Memorial Sloan-Kettering Cancer Center . T1G3 Bladder Cancer “THE FACTS”. Is a potentially lethal tumor This is NOT a superficial tumor Understaging occurs frequently

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radical cystectomy as early primary therapy for t1g3 bladder cancer

Radical Cystectomy As Early Primary Therapy for T1G3 Bladder Cancer

Karim Touijer and Bernard H. Bochner.

Memorial Sloan-Kettering Cancer Center

t1g3 bladder cancer the facts
T1G3 Bladder Cancer“THE FACTS”
  • Is a potentially lethal tumor
  • This is NOT a superficial tumor
  • Understaging occurs frequently
  • High recurrence rate and progression despite intravesical therapy
  • Poor markers available to accurately identify high risk lesions
  • Can be effectively CURED by early definitive surgery (radical cystectomy)
bladder cancer two pathways of progression

9qDel

Ta

Ta

RAS

9pDel

(INK4A)

NORMAL

UROTHELIUM

N+/M+

T1

T2-4

10qDel, 11pDel, 18qDel

Tis

TP53

RB

5qDel, 3pDel

14qDel

N+/M+

T1

T2-4

(Presti et al, Ca Res 91; Cordon-Cardo et al, JNCI 92; Dalbagni et al, Lancet 93; Sarkis et al, JNCI 93; Cairns et al, Science 94; Orlow et al, JNCI 95; Li et al, Am J Path 96; Rabbani et al, JNCI 99; McShane et al, Ca Res 2000; Hernando et al, Int J Ca 2001; Sanchez et al, Ca Res, 2002; Veltman et al Ca Res, 2003 )

BLADDER CANCER:TWO PATHWAYS OF PROGRESSION
t1g3 and tis bladder cancer clinical understaging
T1G3 And TIS Bladder CancerClinical Understaging

10 - 15% have positive nodes at cystectomy

risk of understaging is influenced by presence of muscle in tur specimen
Risk Of Understaging Is Influenced By Presence Of Muscle In TUR Specimen

N=78

Dutta, J Urol 166:490, 2001

Herr, HW J Urol 162:74, 1999

A second TURBT required to identify extent of disease.

t1g3 bladder cancer outcome of understaged patients disease specific outcomes
T1G3 Bladder CancerOutcome Of Understaged PatientsDisease Specific Outcomes
  • 179 patients (71% with T1 tumors)
  • 53% failed intravesical therapy
  • Understaged lesions do significantly worse
  • Understaged lesions WILL NOT respond to bladder sparing approaches

Freeman et al, Cancer, 1995

repeat turbt may help reduce understaging
Repeat TURBT May Help Reduce Understaging

Dalbagni et al, UROLOGY 2002

t1g3 bladder cancer natural history recurrence and progression risk
T1G3 Bladder CancerNatural HistoryRecurrence and Progression Risk
  • Recurrence Risk
    • Following TURBT, 69-80% risk of recurrence
    • Intravesical immunotherapy can delay recurrence and progression, but long-term will not alter natural history
  • Progression Risk
    • 33-50% will progress to muscle invasion
bcg can delay recurrence but may not impact ultimate cancer specific survival
BCG Can Delay Recurrence But May Not Impact Ultimate Cancer-specific Survival

Recurrence-free survival

Cancer-specific survival

Orsola et al Eur Urol 48:231, 2005

t1g3 bladder cancer long term results with bcg
T1G3 Bladder CancerLong-term Results With BCG

Cookson, J Urol 158:62, 1997

Pansodoro, Urology 59:227, 2002

Shahin, J Urol 169:96, 2003

t1g3 bladder cancer long term outcome conservative bcg and progression of disease
T1G3 Bladder CancerLong-Term Outcome ConservativeBCG and Progression of Disease
  • 1978-1981 86 patients with high risk non-muscle invasive disease (36 patients T1)
  • Randomized to TURBT +/- BCG
  • Followed q3-6 months for 3 years then annually
  • Evaluated progression and disease specific survival
t1g3 bladder cancer long term outcome conservative disease specific survival
T1G3 Bladder CancerLong-Term Outcome ConservativeDisease Specific Survival

People not treated by cystectomy continue to die of bladder cancer!

Cookson J Urol 158:62, 1997

t1 bladder cancer characteristics associated with recurrence and progression
T1 Bladder CancerCharacteristics Associated with Recurrence and Progression
  • Pathologic
    • High grade, multifocality, associated CIS, prostatic urethral involvement, size, sessile growth pattern, (Others unreliable and controversial: aneuplody, p53 alteration, lymphovascular invasion)
  • Clinical
    • Failure of intravesical therapy (80% with disease at 3 months progress), endoscopically uncontrollable disease, disease within diverticuli

MAJORITY