Download MCQ - North West Urology

MCQ
 1) For intravesicle therapy:
 A) Mitomycin C instillation dose is 40mg for 2 hour
 B) Oncotice BCG instillation dose is 81mg for 2hours
 C) ImmuCyst BCG instillation dose is 12.5mg for 1 hours
 D) ImmuCyst BCG instillation dose is 81mg for 2hours
 E) Oncotice BCG instillation dose is 12.5mg for 1 hour
 2) BCG treatment:
A) Lamm’s protocol use 28 doses BCG over a period of 3 years
B) SWOG trial protocol uses maintenance BCG for 1 year only
C) BCG maintenance drop out rate is as high as 84% according to SWOG trial
D) There is good evidence to suggest that Immuncyst BCG is more effective
than Oncotice BCG
E )In superficial bladder cancer BCG reduces progression but not recurrence,
whereas mitomycin C reduces recurrence but not progression
 3) BCG toxicity :
 A) EORTC and CUETO suggest reduced dose BCG reduces the incidence of severe
systemic toxicity compared to standard dose BCG
 B) BCG can be administered in patients with macroscopic haematuria
 C) Patient with microscopic haematuria is a contraindication for BCG instillation
 D) Presence of leukocyte or asymptomatic bacteriuria is not a contraindication for BCG
application
 E) Patient with symptomatic UTI can have BCG provided prophylactic antibiotic is
given
 4) Long term (e.g. 15 years) outcome after BCG for patient
with high risk non-muscle invasive bladder cancer. Which
of the following is the best answer?





A) ~50% progression rate
B) ~27% alive with intact bladder
C) 1/3 die of cancer progression
D) 1/3 develop recurrence in upper tract / prostate
E) All of the above
 1) For intravesicle therapy:
 A) Mitomycin C instillation dose is 40mg for 2 hour -F
 B) Oncotice BCG instillation dose is 81mg for 2hours -F
 C) ImmuCyst BCG instillation dose is 12.5mg for 1 hours-F
 D) ImmuCyst BCG instillation dose is 81mg for 2hours-T
 E) Oncotice BCG instillation dose is 12.5mg for 1 hour-F
 2) BCG treatment:
A) Lamm’s protocol use 28 doses BCG over a period of 3 years-F (27 doses over 3 yrs)
B) SWOG trial protocol uses maintenance BCG for 1 year only-F (used Lamm’s)
C) BCG maintenance drop out rate is as high as 84% according to SWOG trial-T
D) There is good evidence to suggest that Immuncyst BCG is more effective-F than
Oncotice BCG
E )In superficial bladder cancer BCG reduces progression but not recurrence, whereas
mitomycin C reduces recurrence but not progression -F

3) BCG toxicity :

A) EORTC and CUETO suggest reduced dose BCG reduces the incidence of severe systemic toxicity
compared to standard dose BCG –F (CUETO- fewer patients have toxicity but incident of severe
systemic toxicity was similar. EORTC- no difference in toxicity)

B) BCG can be administered in patients with macroscopic haematuria -F

C) Patient with microscopic haematuria is a contraindication for BCG-F instillation

D) Presence of leukocyte or asymptomatic bacteriuria is not a contraindication for BCG application T

E) Patient with symptomatic UTI can have BCG provided prophylactic antibiotic is given -F
 4) Long term (e.g. 15 years) outcome after BCG for patient
with high risk non-muscle invasive bladder cancer. Which
of the following is the best answer?





A) ~50% progression rate
B) ~27% alive with intact bladder
C) 1/3 die of cancer progression
D) 1/3 develop recurrence in upper tract / prostate
E) All of the above –Best answer (MSKCC –cookson J urol
1997)
Viva Question-EAU guideline
2013 – intravesical therapy
Viva Question-EAU guideline 2013
 Low risk:
 Single dose, immediate post op intravesicle instillation of
chemotherapy, no difference between agents (standard
treatment)
 Absolute recurrence reduction 11.7% (RR 39%) Sylvester 2004 Metaanalysis
 To maximised efficacy immediate instillation is recommended
– all single instillation studies administered within 24 hrs
 Finnbladder group (Kassinen 2002)- suggested by delaying
instillation overnight the risk of recurrence is increased by
two fold
Mitomycin
 MITOMYCIN
 Mechanism of acion - Antitumour antibiotic – DNA
alkylating agent, causes cross links to complementary DNA
strands – inhibits DNA synthesis
 Dose - 40mg in 40ml sterile water
 Side effects – skin rash, storage LUTS, bladder
calcifications, myelosupression
 Evidence – meta-analysis of 7 RCTs, 1476 pts, 36.7% of pts
with one post op dose MMC had recurrence compared to
48.4% treated with TURBT alone (decrease of 39% in odds
of recurrence) (Sylvester J Urol 2004).
 Contraindications
 Bladder perforation
 Bleeding requires irrigation
 Previous allergy
 Intermediate Risk
 One immediate installation of chemotherapy
 Further intravesicle therapy
 BCG or chemotherapy (Optimum schedule not defined)
 For no more than 1 year
 Choice between BCG and mitomycin C for 1 year
 Mitomycin – only prevent recurrence not progression
 BCG- more efficacious than Mitomycin for recurrence,
reduce progression BUT more toxic
 High risk
 BCG reduce recurrence and superior to MMC
(meta-analysis Shelley BJUI 2004; Bohle J Urol 2003)
 BCG reduce progression
 (meta-analysis Sylvester J urol 2002- 4% absolute risk reduction for
progression; 27% RR reduction)
 BCG maintenance is required to achieve effect
(Bohle urology 2004, J urol 2003 at least 1 year of maintenance BCG
is required to obtain superiority of BCG over MMC for prevention of
recurrence or progression)
Methods to improve efficacy of
intravesicle chemo
 Microwave-induced hyperthermia
 Electromotive drug administration (EMDA)
 Considered as experimental treatment, as studies are
small and evidence is limited
What type/ dose of BCG do you
use, what advice do you give and
how do you treat complications
What type/ dose of BCG do you use,
what advice do you give and how do you
treat complications
 Two BCG preparations licensed in the UK
 ImmuCyst (Cambridge)
 BCG Connaught
 81mg dose (contains 0.4-3.7x107 CFU/ml BCG Connaught)
 OncoTICE (Organon)
 BCG-TICE
 12.5mg (contains 0.4-1.6x107 CFU/ml BCG TICE)
 Mechanism – poorly understood, probably immune
response leads to cytokine production
 Both reconstituted with 50mls saline to make a 53ml volume
preparation
 Catheter then inserted
 Ideally full bladder on catheterisation to wash out any lubricant
 Instill BCG slowly via gravity
 Pt should retain the fluid for as long as possible up to 2 hours
 For first 15min, should lie prone, then allowed to get up
 After 2hrs Patient can void in a seated position
 Care should be taken with voiding for the next 4 hours
 Void whilst sitting
 Bleach toilet and leave for 15min
 Condoms should be used within a week of treatment
 BCG – absolute contraindications:




During first 2 weeks after TUR
Macroscopic Haematuria
After traumatic catheterisation
In patient with symptomatic UTI
* WCC or asymptomatic bacteriuria or microscopic haematuria
are not contraindication. Prophylactic antibiotic is not
required
* BCG should be used with caution in immunocompromised
patients
Lamm’s Protocol used in SWOG
&EORTC
 1st year




X6
X3
X3
X3
 2nd year
(induction)
(at 3/12)
(at 6/12)
(at 12/12)
 X3 (at 18/12)
 X3 (at 24/12)
 3rd year
 X3 (at 30/12)
 X3 (at 36/12)
Total= 27 doses
BCG complications
 Local




Cystitis
Haematuria
Prostatitis
Orchitis
 Treatment





Analgesia
+/-Postpone BCG
Culture
Antibiotic
Restart BCG
 Systemic

BCG sepsis

If a systemic BCG infection occurs, an
Infectious Diseases consultation should be
sought.
BCG should be permanently
discontinued
Mulitiple agents anti-tuberculosis
therapy should be initiated promptly.
Commonly, this will comprise
 Treatments



Isoniazid,



Rifampicin,
Ethambutol
Pyrazinamide
BCG complications
 Non specific Symptoms (Malaise, fever, Rash,
arthralgia/ arthritis)
 Anti-histamines or NSAIDs
Final EORTC-GU cancers Group
randomized study -European Urology
2013
 1/3 dose and full dose BCG- no difference in toxicity
 Intermediate-risk patient if BCG is used- should be
treated with full dose for 1 year
 High-risk patient should have full dose 3 years BCG to
reduce recurrence compared with full dose 1 year
BCG. However, there is no benefit in terms of
progressions or deaths using 3 years or 1 year
protocol.
When do you consider radical
treatment in superficial bladder
cancer
When do you consider radical
treatment in superficial bladder
cancer
 Highest risk:





G3T1 with concurrent Bladder CIS
Multiple and /or large (>3cm) G3T1
recurrent G3T1
G3T1 with CIS in prostatic urethra
Micropapillary variant of urothelial ca
 High risk disease unable to tolerate BCG
 consider immediate cystectomy because:
 TURBT staging accuracy: For T1 disease 27-51% of patients being
upstaged to muscle invasive disease at cystectomy
 5 years risk of Disease Progression can be as high as 45%
 Retrospective study shows high risk non muscle invasive disease
undergo early cystectomy has a high survival rate
Others
 Fail BCG
 BCG refractory tumour
1.
2.
3.
If high grade, non muscle invasive tumour present at 3
months
If CIS is present at both 3 and 6 months
If high grade tumour appears during BCG therapy
 BCG recurrence
1.
Recurrence of high grade (G3) tumour after
completion of maintenance BCG, despite initial
response
Alternatives to cystectomy after BCG
failure








Intravesicle Interferon α and BCG
Intravesicle Gemcitabine
Thermochemotherapy
Electromotive drug therapy (EMDA)
Intravesicle Taxane chemo agent
Intravesicle Mitomycin C and gemcitabine
Photodynamic therapy
Sequential therapy- Sequential BCG and EMDA MMC
(Small studies with some promising results but insufficient to formulate definitive
recommendation)
(D Yates European Urology 2012)