Chris Hardy

Consultant in Respiratory Medicine

BCG AND BLADDER CANCER

Bacille Calmette Guerain

- Live attenuated strain of M.Bovis- History

Jean Antoine Villemin first recognised Bovine Tb In 1884 and its transmissibility.

Robert Koch first to distinguish M Bovis from MTB.Since cowpox was used to vaccinate against smallpox successfully in the C18th, Koch wondered if M Bovis may provide protectionAgainst MTb.C19th – clinical trials of Koch’s population in Italy a Disaster.

Albert Calmette & Camille Guerin produced an

Attenuated M Bovis strain in 1908 (potato medium)

BCG launched in 1921.

Lubeck 1930 240 infants

Vaccinated in 1st 10 days of life, almost all

Developed TB, contaminated with a virulent strain.

USA/Netherland never supported the use of BCG.

Doses BCG Intradermal 0.1mg/ml Intravesical BCG 80mg in distillate (2 hrs instillation)

Complications Intradermal BCGParellels with intravesical1. Local ulcerated lesions, lymph nodes osteitis of epiphyses of long bones, local – distantRx? ulcerated lesions – skin care – spontaneous 3/12 recovery ?local steroid ?isoniazid ?anti-TB Rx2. Disseminated immunosuppressed - HIV - immunodeficiency

= children - malignancy

IMMUNOTHERAPY

BCG: Targeted to high risk gps/high prevalence areas/young immigrants

13yr programme abandoned 19893600 vaccinations to prevent single case

Mycobacterium Veccae: in the “augmentation” of non-tuberculous

mycobacterium therapy

Cancer and BCG – my remit

CASE PRESENTATION

Male 76 yr

Normal coronary angiogram 2007Haematuria clinic July 2012.- One episode- Storage, voiding symptoms- P. R 100gm prostate- Cystoscopy – occlusive prostate

- abnormal bladder dome mucosa - biopsy – Ca in situ ?early

papillary tumour

S.M. MDT

Suitable for BCG therapy 6 courses with check cystoscopy

Alternative - cystectomy, Radical Radiotherapy

PATIENT OPTED FOR BCG!!

19/9/2012

- BCG (Medac) administered through a Coloplast Speedicatheter. - felt need to void after one minute (blood stained). flecked blood from penis 30 mins. Major haematuria on catheter withdrawal

- flu like symptoms, night sweats 2/52 later admitted ?bacterial epididymitis RX Gentamicin, Cipro.-

2/52 laterLethargy, weight loss (two stones), fevers, scrotal content discomfortMSSU normal, no growth – CT abdo/pelvis normalUrologist optimistic most settle down?inflammatory ?bacterial. More cipro

24/10/12Referral to CHIncreased malaiseIncreased CRP, Transaminitis ?BCG related - BCG therapy discontinued

“BCG side effects are rare. As a young consultant I confess I have not seen Many during my career”.

Cultured M-Bovis on three E.M.U’s

(Oct-Dec)

E – Sens

R – Sens

Ison – Sens

Pyrazinamide R

Search by Chris Hardy, Chris Bell

Guidance on Tb following

intravesical BCG:-

Feb 13 – Instituted by urologists on

Rifampicin 600mg, Isoniazid 300mg prior to cystoscopy – intention to treat 3 months -

March 13 – Sister Bell – Rifinah 300/150mg 2 daily 9/months

Ethambutol 1400mg 2/months

Jan 2014 – Complete recovery. Weight gain, no sweats

To date Bladder Cancer managed by local measures

Intravesical BCG & Bladder Cancer

- Treatment of superficial TCC, Carcinoma in situ (small% total)

- First trialled in 1976- Lamm 2000- 6 x weekly BCG –every 6 weeks – 3yrs (27

instillations)- Large attrition rate – mean 1yr

15% complete full course ?change vaccine ?change dose ?length of treatment

- 68% Complete Response at check cystoscopies

Complications

LOCAL – 1. Haematuria 35%

2. Cystitis 54%

- ↑ frequency above with repeated instillation

with fever, haematuria, arthralgia

- reducing dose 80 →30mg may help

- co administration of intravesical isoniazid – no effect

3. Granulomatous epidymitis, prostatitis in

most men

Systemic

1. Polyarthritis, conjunctivitis

HLAB27 associated

Isoniazid and corticosteroid dose? ?how long

discontinue BCG

2. Disseminated, miliary BCG infection- Early, continuum after BCG (our case)- Late up to 1yr after BCG- Lung, liver, brain, bone, paraspinal abscess

(no case of lymph node?)

Early fevers lasting >72 hr post any Rx, prompt MSSU – bacterial Tb,

PCR, cystoscopy

Consideration of early Tb Rx

“Miliary Tb affecting lungs, liver, kidneys, brain or high clinical suspicion, the

recommended treatment regime is isoniazid 300mg daily for 3 months,

rifampicin 600mg daily and ethambutol 1200mg daily for 6 weeks and

prednisolone 40mg or greater IV during the acute stages”

Any comments? Chris Hardy

most urologists refer to Chest Physicians