Page 9 - Management of non-muscle invasive bladder cancer

Kassouf et al.

Table 1. BCG side effects and treatments 132,133
Side effects
Grade 1 (mild to moderate Grade 2 (moderate to severe Grade 3 (regional and systemic) Grade 4 (generalized BCGitis
symptoms ≤48 hours) and/or (>48 hours) or BCG sepsis)
a) Allergic reactions
b) Persistent high-grade fever (>38.5 C and
o
>48 hours)
a) Symptoms of non- a) Symptoms of non-bacterial c) Epididymo-orchitis; symptomatic a) Multi-organ failure and
bacterial cystitis; fever cystitis granulomatous prostatitis septic shock
≤38.5 C b) Prolonged cystitis
o
d) Caseous abscesses; granulomatous
masses of the kidney; hepatitis;
pneumonitis; osteomyelitis
Treatments
a) Antihistamines and NSAIDs; consider
suspending BCG instillations. If
a) Symptomatic treatment symptoms are severe or persistent, a) Emergent hospital
with phenazopyrdine, discontinue BCG instillations and admission; discontinue
anticholinergics and consider INH + RFP +/- corticosteroids for BCG instillations; INH
NSAIDs; suspend BCG 3 months
a) Symptomatic instillations until resolution b) Discontinue BCG instillations, start + RFP + ethambutol
treatment with of symptoms then consider treatment with 2 or more antimicrobials for 6 month, high-
phenazopyrdine, BCG dose reduction to (INH, RFP, quinolones) for 3-6 months dose quinolones,
anticholinergics and 1/3 upon continuation of while awaiting blood work, urine culture high-dose steroids,
NSAIDs additional antimicrobial
therapy and chest X-ray results; consult infectious
b) Consider quinolone diseases specialist coverage for Gram
negative bacteria and/or
antibiotics or treat according c) High-dose quinolones (for Gram negative enterococcus
to urine culture results bacteria), INH + RFP for 3-6 months;
suspend BCG instillations
d) INH + RFP + ethambutol for 6 months
BCG: bacillus Calmette-Guerin; INH: Isoniazid; NSAIDS: nonsteroidal anti-inflammatory drugs; RFP: Rifampicin.
BCG failure is defined as the presence of high-grade NMIBC BCG (without maintenance) who later develop recurrence
at 6 months from time of TURBT (or at 3 months if the of disease (BCG relapse), a second induction course may
initial tumour is T1G3/T1HG) or any worsening of the dis- achieve up to 30 to 50% response rates. 118,137 Beyond 2
ease (higher grade, stage or appearance of CIS) while on induction courses with BCG, further courses are not recom-
134
BCG therapy despite initial response to BCG. In fact, any mended, as there is a 7% actuarial risk of progression with
tumour recurrence after BCG therapy can be defined as BCG each additional course. 138 The impact of re-induction on
failure. However, not all failures under this definition have patients receiving maintenance is unknown.
a similar prognosis. Unfortunately, most of the literature After BCG failure, second-line intravesical therapy with
did not differentiate the type of BCG failure when evalu- combined low-dose BCG and interferon alpha 2b (induc-
ating various salvage intravesical regimens. BCG failure tion followed by maintenance therapy) is a viable option
can be stratified into several categories: BCG intolerance; with lower toxicity, but may be associated with significant
BCG resistance; BCG relapse; and BCG refractory (Table 2). oncologic risk (Level of Evidence 3). In a recent large multi-
Among patients with BCG failure, BCG intolerance has the centre phase II trial, 467 BCG failure patients receiving low-
best prognosis, whereas BCG refractory disease portrays the dose BCG and interferon alpha 2b were followed in parallel
worst prognosis. 134,135 with 536 BCG-naïve patients receiving standard dose BCG
For patients with high-risk NMIBC who fail BCG, the with interferon alpha 2b. After a median follow-up of 24
139
option of radical cystectomy should be recommended and months, 45% of the BCG failure patients and 59% of BCG-
140
discussed with the patient (Grade B recommendation). naïve patients were disease-free. Response was only seen
Herr and colleagues compared the outcome of 2 groups in patients with BCG relapse. Patients with BCG refractory
of patients with NMIBC who received a radical cystectomy disease demonstrated no benefit from BCG with interferon.
due to recurrence of disease within 2 years from initial BCG Dalbagni’s phase II trial evaluated the efficacy of gem-
therapy, with patients who received radical surgery after citabine on 30 patients with NMIBC refractory or intoler-
2 years. Early radical cystectomy was associated with sig- ant to intravesical BCG. Patients received 2 courses, each
nificantly improved survival in patients with non-muscle course consisting of 2000 mg/100 mL of gemcitabine twice
invasive recurrence as well as muscle-invasive recurrence. 136 weekly for 3 consecutive weeks, with each course separated
In patients with NMIBC treated with an induction course of by 1 week. In total, 50% of patients achieved a complete

E698 CUAJ • September-October 2015 • Volume 9, Issues 9-10