BCG for Bladder carcinoma

BCG for Bladder carcinoma

1. BCG for superficial TCC
Dept of Urology
GovtRoyapettahHospital and KilpaukMedical College
Chennai
1

2. 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

3. Natural history of superficial
TCC after TURBT alone
•Risk of recurrence –70%
•Risk of progression –Ta G1 5%
• T1G3 40%
• T1G3 + CIS 50%
3
Dept of Urology, GRH and KMC,
Chennai.

4. Progression Risk
•Ta -11% lifelong risk of dying from TCC
•T1 -30% lifelong risk of dying from TCC
•CIS -up to 50% risk of progression to invasive
disease in untreated cases within 2 years
4
Dept of Urology, GRH and KMC,
Chennai.

5. Studies for adjuvant therapy
•BCG decreases recurrence from 70 –30%
•SWOG –BCG Vs Doxo
• Progression 15% Vs 37%
•Pagano et al –dec progression from 17-
4%
•Various studies confirm superiority of BCG
5
Dept of Urology, GRH and KMC,
Chennai.

6. BCG
•It is an attenuated live mycobacterium
•Used as a vaccine for tuberculosis
•Anti tumor activity against several different
cancers.
6
Dept of Urology, GRH and KMC,
Chennai.

7. Role of BCG
•Effective form of intravesical therapy for
prophylaxis & treatment of superficial
bladder cancer.
•Also effective against treating CIS,
residual papillary disease
•Prophylaxis against recurrent superficial
disease.
7
Dept of Urology, GRH and KMC,
Chennai.

8. Mechanism of action
•BCG contacts tumor cells principally
through a novel fibronectin attachment
protein that is required to initiate any
interaction.
•Expression of IL-2 , IFN –GAMMA as well
as T cell populations noted at the site of
BCG inflammation
8
Dept of Urology, GRH and KMC,
Chennai.

9. •IL-12 ,a strong polarizer of the T-HELPER
CELL (Th1 ) response and inducer of
interferon detected after BCG ,in urine
•Th1 response probably mediates the
therapeutic effect of BCG
9
Dept of Urology, GRH and KMC,
Chennai.

10. Anti tumour effect is associated with
delayed hypersensitivity reaction
•Anti tumor effect also due to induction of
NITRIC ACID SYNTHETASE by BCG
•
•HIGH nitric acid concentration inhibits
bladder tumour growth.
10
Dept of Urology, GRH and KMC,
Chennai.

11. INDICATIONS
•Multiple tumors
•Large tumors
•High grade tumors
•CIS / Concomitant CIS
•Prostatic urethral involvement
•Positive urine cytology
11
Dept of Urology, GRH and KMC,
Chennai.

12. CONTRAINDICATIONS
•Gross haematuria
•Active bacterial infection
•Immune suppressed & Immuno-
compromised patients.
•Poor overall performance status &
advanced age ,
•prior history of TB-relative
contraindications.
12
Dept of Urology, GRH and KMC,
Chennai.

13. Schedule
•Morales –6 weekly administration
•Studies –better response with
maintenance for 1 yr
•Ideal regimen ???
•SWOG regimen
13
Dept of Urology, GRH and KMC,
Chennai.

14. •Effective treatment for low volume G3 and CIS
•Initial course weekly for 6 weeks. Rescope after
4 to 6 weeks
–Complete response -put on maintenance treatment
–Partial response -repeat 6 week course and rescope
–Progression –change to MMC or early cystectomy
14
Dept of Urology, GRH and KMC,
Chennai.

15. PREPARATION &
ADMINISTRATION
•Lyophilized powder
•Stored in 4 degrees C until instillation
•TICE, CONNAUGHT, PASTEUR,
TOKYO,RIVM, DANISH 1331
•Therapeutic efficacy associated with the
ability to deliver approx 10 MILLION
organisms per instillation
15
Dept of Urology, GRH and KMC,
Chennai.

16. •Reconstituted with 50 ml of saline,
administer immediately
•Treatment -min 2-4 weeks after TUR
16
Dept of Urology, GRH and KMC,
Chennai.

17. -Traumatic catheterization;-treatment
should be delayed for several days.
Gravity method of administration
Dwell / Contact time-1-2 hours
•Change in position ??
17
Dept of Urology, GRH and KMC,
Chennai.

18. CIS
•Initial tumour free response-76%
•BCG replaced cystectomy in initial form of
therapy.
•In CIS -failure to respond to 6 week
course, early recurrence of high-risk
disease requires more aggressive therapy
18
Dept of Urology, GRH and KMC,
Chennai.

19. RESIDUAL TUMOUR
•Effectively treat residual papillary disease
•Response rate around 60%
19
Dept of Urology, GRH and KMC,
Chennai.

20. TUMOUR PROPHYLAXIS
•T1 & HIGH GRADE Ta treated
prophylactically after TUR
•DECREASED TUMOUR RECURRENCE
OF AROUND 40%
•DOSE -6 WEEK induction course is
insufficient
20
Dept of Urology, GRH and KMC,
Chennai.

21. SWOG-6+3 REGIMEN
•6 WEEK INDUCTION COURSE followed by 3
weekly instillations at 3 & 6 monthes,then every
6 monthes for 3 years.
•5 year survival of non maintainance group is
78%, maintainance group is 83%
•16% only tolerated full dose regimen
•Post therapy p53 over expression is an
independent marker of disease progression.
21
Dept of Urology, GRH and KMC,
Chennai.

22. SIDE EFFECTS OF BCG
THERAPY
•Fever 3%
•Haematuria 1%
•Granulomatous Prostatitis1%
•Pneumonitis / Hepatitis <1%
•Epididymitis
•Sepsis
•Rash
•Ureteral Obstruction
•Contracted bladder
22
Dept of Urology, GRH and KMC,
Chennai.

23. •Low grade fever or slight malaise;-fever
>38.5’c >24 hours not resolve with
antipyretic ,,fever >39.5’c ;-treated with
INH 300 mg for 3 months
•Systemic BCGosis ;-treatment INH –RIFX
6 MONTHS
•BCG SEPSIS;-0-4% ;-TREAT;-LIFE
SUPPORT , TRIPLE DRUG THERAPY
23
Dept of Urology, GRH and KMC,
Chennai.

24. •Carcinoma of mucosa & superficial ducts
of prostate can be treated with BCG.
•TUMOUR free rate around 50% is
ATTAINED.
24
Dept of Urology, GRH and KMC,
Chennai.

25. •Response rates to treatment up to 70%
disease free at 36 months
–40 % response to first course
–30% more respond to a second course
–Problems relate to patients managing to
remain on maintenance therapy
25
Dept of Urology, GRH and KMC,
Chennai.

26. Advantages
•Persistent activity
•Deeper activity
•Panurothelial effect
26
Dept of Urology, GRH and KMC,
Chennai.

27. Combination therapy
•High dose Vit A,B6,E & Zn
•IFN Alpha
•Increased panurothelial effect and
decreased dose
27
Dept of Urology, GRH and KMC,
Chennai.

28. Treatment for BCG Failures
•6
 Repeat BCG treatment
 20 -40% CR
 Toxicity BCG-systemic mycobacterial
infection
•(1% disseminated M bovis, 6% anti-TB
meds),
28
Dept of Urology, GRH and KMC,
Chennai.

29. •cystitis, hematuria, fever, dysuria and
frequency,
•malaise, and nausea
 Interferon + BCG
 50% CR in patients failing BCG
induction
 Only Phase 2 data available
 No significant long term data reported
29
Dept of Urology, GRH and KMC,
Chennai.

30. Treatment for BCG Failures
 Valrubicin
 21% CR in patients who have failed at
•least one previous treatment with BCG
 Only FDA approved treatment for BCG
• failures
 GM-CSF
 CR observed in 6/11
patients following
• intravesical treatment
 Single study only
30
Dept of Urology, GRH and KMC,
Chennai.

31. Treatment for BCG Failures
 Cystectomy
 2 -4% treatment-related mortality
 10 -30% post-operative complication
rate
 infection, lymphedema (ADD)
 Neobladder or urostomy-life-long
•consequence
 Negative impact on QOL
31
Dept of Urology, GRH and KMC,
Chennai.

32. CONCLUSIONS
•BCG is effective in decreasing the
recurrence and progression of sup TCC
•Toxicity is a important criteria
•Ineffective in muscle invasive disease
•Atleast 1 yr maintanence is reqd.
•Ideal regimen still found wanting
32
Dept of Urology, GRH and KMC,
Chennai.