Quick Links
About MyBladderCancerTeam
Powered By
When non-muscle-invasive bladder cancer (NMIBC) doesn’t respond to bacillus Calmette-Guérin (BCG) treatment, it can be disheartening — but there’s still reason to stay hopeful. While BCG is a common first-line treatment, it’s not the only option available.
Many people living with NMIBC respond well to BCG. But in some cases, the cancer persists or recurs (returns) soon after treatment. When this happens, it’s called BCG-refractory NMIBC, meaning the disease hasn’t gone away or has come back despite receiving adequate BCG therapy.
In this article, we’ll explain what BCG-refractory NMIBC means and explore the next steps your doctor may recommend.
Bacillus Calmette-Guérin is a liquid medicine made from weakened bacteria. Doctors usually place it directly into the bladder using a catheter (a soft, flexible tube) in a process called intravesical therapy. This treatment helps the immune system recognize and attack bladder cancer cells. BCG is named after the French scientists who first developed it as a tuberculosis vaccine.
Intravesical BCG is the standard first treatment for people diagnosed with intermediate- or high-risk non-muscle-invasive bladder cancer. For some people, it’s given after a procedure known as transurethral resection of bladder tumor (TURBT), which is used to remove visible cancer cells from the bladder lining.
BCG therapy works by triggering the immune system to kill remaining cancer cells and reduce the risk of recurrence. However, in some cases, the cancer doesn’t go away completely or returns soon after treatment. When this happens, doctors may describe it as “BCG-refractory” or “BCG-unresponsive” NMIBC.
Get more detail about what to expect with BCG therapy.
It’s not uncommon for NMIBC to resist BCG therapy. Studies show that between 30 percent and 50 percent of people have NMIBC that doesn’t respond well to BCG treatment. When this happens, it may suggest that the cancer is more aggressive, meaning it has a higher chance of growing deeper into the bladder wall or spreading beyond the bladder. That’s why doctors often recommend adjusting the treatment plan as soon as possible.
Even so, BCG-refractory NMIBC doesn’t mean you’re out of options. Many people go on to achieve a complete response — meaning no signs of cancer — with other therapies. Thanks to newer treatments and regular monitoring, survival rates can remain high for many people with BCG-refractory NMIBC.
When BCG doesn’t work, the next steps depend on several factors. These include:
One standard option is radical cystectomy (removing the entire bladder). But if surgery isn’t the right fit for you — or you want to try other options first — there are newer, effective therapies available.
Today, choices may include immunotherapy, gene therapy, or intravesical chemotherapy. Some people may also qualify to participate in clinical trials that test promising drugs. Each treatment approach has potential benefits and risks. Your urology and oncology team can discuss all your options with you in detail. Together, you can decide what’s best for your health and lifestyle.
Radical cystectomy means surgically removing the bladder. It’s considered the standard treatment for BCG-unresponsive NMIBC. During this procedure, doctors also remove nearby tissues and create a new way for urine to leave the body. This is called urinary diversion. Options include a urostomy bag (external bag to hold urine) or a neobladder (a surgically created bladder using part of the intestine).
If surgery is recommended after cancer comes back, it’s often scheduled as soon as possible. Waiting is avoided because it can increase the risk of cancer spreading. It can also lower the chances of removing cancer completely.
Studies show that people who have a cystectomy after BCG failure have better survival rates than those who try another course of BCG or other treatments. In one study, the cancer-related death rate was 31 percent for people who had surgery, compared to 48 percent for those who didn’t.
However, radical cystectomy is a major operation. From 30 percent to 70 percent of people experience complications afterward. Common issues include:
The risk of dying from the surgery itself is about 3 percent.
If you’re not in good health for major surgery or if you prefer to try other options, bladder-sparing therapies are available, too.
In recent years, several new therapies have been approved by the U.S. Food and Drug Administration (FDA) for BCG-unresponsive NMIBC. These treatments aim to control bladder cancer while preserving bladder function.
Nadofaragene firadenovec (Adstiladrin) is the first FDA-approved gene therapy for bladder cancer. It was approved in December 2022. This drug is used for adults with high-risk, BCG-unresponsive NMIBC. Specifically, it’s approved for those with CIS with or without papillary tumors (tumors that can grow on the bladder lining).
This treatment works by delivering a gene into bladder cells. There, it prompts them to produce interferon alfa-2b, a natural protein that activates the immune system to attack cancer cells. It’s given directly into the bladder through a catheter once every three months.
In clinical trials, about 51 percent of people achieved a complete response. After one year of follow-up, 46 percent remained cancer-free.
The most common side effects include:
Nadofaragene firadenovec is a bladder-sparing option for people seeking alternatives to surgery. Like any treatment, regular follow-up is essential to monitor treatment response and manage any side effects.
Pembrolizumab (Keytruda) is an immunotherapy drug given intravenously (by IV). Pembrolizumab is a type of monoclonal antibody, or immune protein. It helps the immune system better recognize and fight cancer cells by blocking a protein called PD-1. This releases a “brake” on the immune system, allowing it to attack the cancer more effectively. This kind of treatment is also known as an immune checkpoint inhibitor. It’s a form of systemic therapy — meaning it works throughout the whole body, not just in the bladder.
Pembrolizumab is FDA-approved for people with BCG-unresponsive carcinoma in situ (CIS) — with or without papillary tumors — who either can’t have or don’t want bladder surgery.
In a major clinical trial, about 41 percent of people showed a complete response three months after treatment. Among these complete responders, 46 percent stayed cancer-free for a year or more.
Common side effects include:
In rare cases, pembrolizumab can cause serious inflammation in the lungs, liver, or other organs, so people receiving this treatment are monitored closely.
Intravesical chemotherapy (chemo) isn’t usually a first-line option for NMIBC. However, it may be used when BCG therapy has failed or isn’t a good fit.
A 2023 study found that people treated with intravesical gemcitabine and docetaxel had better high-grade recurrence-free survival than those who received BCG. In other words, they were more likely to stay cancer-free longer.
Treatment usually involves weekly infusions for six weeks. Then, maintenance doses are given every month.
Common side effects may include:
You may be eligible to take part in a clinical trial. These studies test new treatments to see if they’re safe and effective for BCG-refractory NMIBC, either used alone or combined with other therapies.
Several types of treatments are currently being studied in clinical trials. These include:
If you’re interested in learning more, talk to your healthcare team. They can help you explore clinical trials that you may qualify for and that are currently recruiting in your area. Your doctor can also explain the possible benefits and risks, so you can make the most informed choice for your care.
On MyBladderCancerTeam, the social network for people with bladder cancer and their loved ones, members come together to ask questions, give advice, and share their stories with others who understand life with bladder cancer.
Do you have BCG-refractory non-muscle-invasive bladder cancer? What other treatments have you tried? Share your tips and experiences in the comments below, or start a conversation by posting on your Activities page.
Get updates directly to your inbox.
Sign up for free!
Become a member to get even more
Join
Your privacy is our priority.
We'd love to hear from you! Please share your name and email to post and read comments.
You'll also get the latest articles directly to your inbox.