Intravesical Immunotherapy with BCG

An Expert Explanation by Dr. Janet Kukreja and Dr. Ashish Kamat

Introduction Who is eligibile for BCG?

A large majority of patients Intravesical immunotherapy with BCG is effective if the tumor
Fig. 1 Bladder

who develop bladder cancer is non-muscle invasive. These tumors are often divided into risk
have what is known as ‘non Lamina
groups (low-risk, intermediate-risk and high-risk) based on
propria Muscle

muscle invasive bladder cancer’ Urothelium

the risk of recurrence (the likelihood the tumor will return) and
or ‘NMIBC’. This terminology the risk of progression (the likelihood the tumor will get worse
comes from the fact that the and potentially become
tumor has not yet invaded into invasive or spread).
the true muscle layer of the Fat
[1] There are various
bladder. When detected at this relatively early stage it is often factors that your
possible, with the appropriate combination of treatments, to urologist will consider
save the patient’s bladder. when making this risk
Normal Low grade High grade assessment – such as
The first step is complete removal of all visible disease within
on how big the tumor is,
the bladder. This is achieved with a transurethral resection
if it is a first time tumor
of the tumor, also called TURBT. For some patients, this may
or a tumor that has
require more than one surgery, especially if the tumor is high
regrown, the length of time it took for the tumor to regrow, if
grade and involving more than the very first layer of the
the bladder cancer is pure urothelial cancer, as well as as the
bladder. After this has been achieved and the bladder has
location of the tumor and the grade of the tumor.
healed, the appropriate treatment may be with intravesical
instillation of Bacillus Calmette-Guerin or BCG. BCG is a form In general, bladder cancer tumors can be low grade and high
of the tuberculosis bacteria and originated as a vaccination grade. Low grade cancers can recur often, but are less likely to
against tuberculosis. After decades of detailed investigation progress. Thus the goal of therapy with these tumors is mainly
including large trials in multiple countries that have tested BCG to reduce the frequency of recurrence. The high grade tumors
against various other agents, it currently remains the most can progress and become muscle invasive or metastasize.
effective therapy for NMIBC. However, as with any treatment, In treating this type of tumor the goal is to not only prevent
it works best when used appropriately – i.e for the right patient recurrence but especially to prevent progression.
in the right manner.
Most patients with the intermediate-risk and high-risk non-
It is instilled into the bladder with a urethral catheter muscle invasive bladder cancers will be candidates for
(intravesical) in the office for several treatments. BCG works immunotherapy with BCG. However, based on individualized
locally in the bladder to stimulate the body’s own immune risk assessment, other intravesical treatments or even bladder
system to fight off the cancer cells removal (cystectomy) may be recommended.
in the bladder. Because it stimulates
the immune system, it is considered What are the benefits of BCG for patients?
an immunotherapy (as opposed to BCG is relatively non-invasive and used to directly treat the
chemotherapy). It works to activate bladder lining. BCG intravesical treatment for non-muscle
the body’s immune system to kill invasive bladder cancer is the most effective treatment that
cancer cells without harming the exists for reducing the recurrence and progression of bladder
normal cells. In addition, BCG is tumors. [1] In patients who respond appropriately, BCG can
instilled locally in the bladder cannot be a life-saving treatment that reduces death from bladder
reach other cells in the body. cancer. Over half of patients have a complete response to BCG
Intravesical Immunotherapy with BCG

without tumor recurrence for an extended period of time. In What can be done for symptoms associated with BCG?
order to achieve this, it is crucial that patients received at least
Make sure your bladder is emptied right before the BCG instillation.
one course of induction BCG (6 weeks) and at least one course
of maintenance BCG (at least 3 weeks) to allow the immune Limitation of fluids before the instillation can be helpful. Limiting
response to reach its peak. fluids will decrease urine production during the time you are
holding the treatment in your bladder. This will decrease your
BCG treatments do not require any additional adjunct
discomfort while you are being treated.
medications such as urinary alkalization. Although BCG has
some side effects, under the guidance of a diligent urologist You can ask your doctor for antispasmodic
the incidence of severe side effects are uncommon and most medication if you are having a lot of
patients are able to successfully complete their therapy course. bladder and urethral irritation symptoms
When mild BCG side effects do occur, they are often treated with known as lower urinary tract symptoms.
over the counter medications. These symptoms are common, but are an
uncommon cause of BCG discontinuation.
After BCG treatment, patients must be followed closely
with regular cystoscopy surveillance to detect any cancer If you have a mild fever or flu-like symptoms it is okay to take
recurrence or development of a new primary tumor in the medication to reduce fever, such as acetaminophen.
bladder or elsewhere within the urogenital tract (ureters, bladder,
urethra). What factors can influence BCG effectiveness?
Some antibiotics may weaken effects of BCG. If you are given
What are the risks?
antibiotics it is recommend you do not take them in the 24 hours
BCG often causes some burning with voiding before or within 6 hours after BCG unless specifically instructed by
after the treatments. It can also cause some your doctor.
urgency and frequency. These often resolve a
Too much lubricating jelly that is used to insert the catheter should
few days after the treatment, but the symptoms
be avoided. Excess jelly can trap the BCG and keep it from treating
can increase in intensity after each instillation.
the cancer. [4]
It is important to note that there may be no correlation of side
effects with the dose and duration of the BCG maintenance. [2] In addition lidocaine and lidocaine jellies should be avoided with
Most patients do well with BCG and a small minority discontinue the administration of BCG. The lidocaine can degrade the BCG
treatment because of side effects. [3] and this can decrease the effectiveness of the BCG. [4]
It is normal for patients who receive a BCG instillation to have What is the maintenance schedule for BCG?
some transient flu-like symptoms (fever <101.5F, chills, malaise,
joint aches, and fatigue). However, if BCG gets into the blood In addition to the induction course of
stream it can cause a bad infection or even sepsis. Symptoms of BCG, BCG maintenance is important in
sepsis are flu-like symptoms for greater than 72 hours or a fever reducing bladder tumor recurrence and
greater than 101.5F. With the appropriate precautions, such as progression. With BCG induction and
delaying instillation if you see visible blood in the urine, making maintenance 60% of patients with an
sure there is no trauma during instillation, etc, it is very rare for upfront tumor response will be tumor free
BCG to get in the blood stream. for more than 5 years. [1] Also, the addition of maintenance
decreases the risk of disease progression by 35%. [5] After the
BCG can cause infections in the other parts of the genitourinary first six weeks of BCG treatments if there is no tumor on the
system that are connected to the bladder such as the prostate follow up cystoscopy it is likely BCG maintenance treatments will
and testicles. This can cause prostatitis or orchitis, but these are be recommended. The most effective schedule would be BCG
usually managed conservatively. maintenance administered at months 3, 6, 12, 18, 24, 30, 36. At
The other risk is that the BCG may not work. After BCG other each of these time points of BCG is instilled once a week for three
treatments may be needed. If the BCG does work it will often be weeks (i.e. at 3 months there would be 3 weekly instillations). The
recommended to continue with maintenance BCG treatments. table on the next page shows the schedule of BCG induction,
 An Expert Explanation by Dr. Janet Kukreja and Dr. Ashish Kamat
maintenance and the cystoscopies that are needed to stay on are advised not to engage in sexual activity for 48 hours after
the treatment plan. The follow up schedule of treatments is the treatment. At other time points during the treatment it is
continued based on the risk category of the bladder cancer (for recommend you use a barrier, such as a condom, be used to
at least 1-year in intermediate-risk patients and the full 3-years prevent BCG transmission to your partner. Women are advised
in high-risk patients). If you are not offered BCG after the initial not to become pregnant while on BCG therapy.
6-week induction period, it is prudent to ask your provider if BCG
maintenance would be beneficial in your case. Why do I have to hold it in so long? How long does BCG
need to be held in the bladder?
Sex after BCG: Is there a risk to my partner?
BCG should stay in the bladder for 90 mins to 2 hours after it is
How long should I wait?
administered. This allows time for the BCG to
Both men and women undergoing BCG treatments make adequate contact with the tumor cells and
initiate the immune response.
[5]
Intravesical BCG Treatment/Cystoscopy Schedule
How does changing positions while
BCG Introduction the BCG is in my bladder help the
BCG work?
Month

BCG #1
BCG #2 Rotating positions when BCG is instilled was
BCG #3 previously recommended. However, there is
BCG #4 no current evidence to support the practice of
BCG #5
changing positions with intravesical BCG. [5]
BCG #6

3 Approximately 6-8 weeks from 6th BCG Cystoscopy

BCG Maintenance #1 - start within 0 to 3 weeks
BCG #1
BCG #2
BCG #3
Copy and cut out
6 Approximately 9-12 weeks from last BCG Cystoscopy
BCG Maintenance #2 - start within 0 to 3 weeks this Intravesical BCG
BCG #1
Treatment/Cystoscopy
BCG #2
BCG #3 Schedule to keep track
of your treatments.
9 Approximately 9-12 weeks from last BCG Cystoscopy

12 ~3 months from last Cystoscopy Cystoscopy

BCG Maintenance #3 - start within 0 to 3 weeks
BCG #1
BCG #2
BCG #3

Note: Your doctor may modify schedule based on your individual needs.
 References:
AUT H OR BI OG RAPHIES
1. Sylvester RJ, van der MEIJDEN AP, Lamm DL. Intravesical bacillus Calmette-Guerin reduces
the risk of progression in patients with superficial bladder cancer: a meta-analysis of the
published results of randomized clinical trials. J Urol 2002;168:1964–70.
Ashish Kamat, MD
MD Anderson Cancer Center 2. Oddens J, Brausi M, Sylvester R, et al. Final results of an EORTC-GU Cancers Group
randomized study of maintenance bacillus Calmette-Guerin in intermediate- and high-risk Ta,
T1 papillary carcinoma of the urinary bladder: one-third dose versus full dose and 1 year versus
Ashish M. Kamat is Professor of 3 years of maintenance. Eur Urol 2013;63:462–72.
Urologic Oncology (Surgery) 3. Witjes JA, Palou J, Soloway M, et al. Current clinical practice gaps in the treatment of
and Cancer Research at M.D. intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC) with emphasis on
Anderson Cancer Center; Associate Head of the the use of bacillus Calmette-Guerin (BCG): results of an international individual patient data
Cancer Center, Reliance Foundation Hospital survey (IPDS). BJU Int 2013;112:742–50.
in Mumbai, and President of the International 4. Lamm DL, Blumenstein BA, Crissman JD, et al. Maintenance bacillus Calmette-Guerin
Bladder Cancer Group (IBCG). He is Associate immunotherapy for recurrent TA, T1 and carcinoma in situ transitional cell carcinoma of the
Editor for European Urology Oncology, served bladder: a randomized Southwest Oncology Group Study. J Urol 2000;163:1124–9.
as the Director of the MD Anderson Urologic 5. Shah JB & Kamat AM. Strategies for Optimizing Bacillus Calmette-Guerin. Urologic Clinics of
Oncology Fellowship from 2005-2016 and is a North America. May 2013; 40 (2):211-218.
graduate of the AUA Leadership Program.

Dr. Kamat’s focus in urologic oncology is on Intravesical BCG Treatment/Cystoscopy Schedule

bladder cancer, especially immunotherapy
and organ sparing therapies. He maintains 15 Approximately 9-12 weeks from last BCG Cystoscopy
an active research portfolio in this area. His
research laboratory focuses on identifying 18 ~3 months from last Cystoscopy Cystoscopy
and developing predictive markers of response BCG Maintenance #4 - start within 0 to 3 weeks
to therapy, and research into mechanisms of
BCG #1
inducible cancer stem cells. These findings
have been published in high impact journals BCG #2
and he has over 275 publications to his credit. BCG #3
Dr. Kamat has received commendations for his
educational efforts, is listed in ‘Who’s Who in 21 Approximately 9-12 weeks from last BCG Cystoscopy
Medicine’ and ‘Best Doctors in America’, and
has won the ‘Compassionate Doctor Award’ 24 ~3 months from last Cystoscopy Cystoscopy
from patient groups. He has been involved
BCG Maintenance #5 - start within 0 to 3 weeks
with BCAN since its inception and is a strong
advocate for patients. BCG #1
BCG #2
BCG #3
Janet Krukeja, MD
MD Anderson Cancer Center 30 Approximately 21-24 weeks from last BCG Cystoscopy
BCG Maintenance #6 - start within 0 to 3 weeks
Dr. Kukreja attended the
University of Missouri-Kansas BCG #1
City 6-year combined BCG #2
BLA/MD program. She then completed her BCG #3
residency in Urology at the University of
Rochester Medical Center in Rochester, 36 Approximately 21-24 weeks from last BCG Cystoscopy
NY. While in residency she was able to earn
BCG Maintenance #7 - start within 0 to 3 weeks
her MPH from the University of Rochester
School of Medicine and Dentistry. She is BCG #1
currently a Urologic Oncology fellow working BCG #2
on clinical trials, health services research BCG #3
and translational research at MD Anderson
Cancer Center. She has interest in research for Note: Your doctor may modify schedule based on your individual needs.
all genitourinary malignancies. ©Kamat & Abraham (2015)