Differences In Adverse Events Among Different Bcg Strains
Side effects seem similar for all BCG strains used , but frequency differs from one study to another. No differences between strains in side effects have been noted in a meta-analysis25 and in a recent study comparing Tice versus Connaught strain.26 The dose and treatment schedules used differ among studies, and therefore, comparison among them is difficult. Ideally, the dose should be expressed on colony-forming units as there are strong variations of factors 14 among the commercial preparations. Many studies do not mention this information and express the dose in milligrams.
Another problem is that the side effects of BCG have not been evaluated in a standard way in many studies, resulting in large differences in the frequency of local side effects of BCG. A classification of these side effects, taking into account severity and duration, has been proposed and validated,7 but this was not commonly applied by the urologic community.
What Is Bcg Treatment
Bacillus Calmette-Guerin treatment is a type of intravesical immunotherapy. This liquid drug is made from a strain of Mycobacterium bovis the same bacterium used to create the tuberculosis vaccine. When used in medicine, Mycobacterium bovis is weakened to reduce harm to your body.
BCG treatment is usually given after TURBT , which is a bladder surgery to remove any visible cancer.
Bcg Treatment For Bladder Cancer
BCG is the standard treatment used for early-stage bladder cancer, and is used specifically on a cancer type known as high-risk non-muscle invasive bladder cancer .
For high-risk stage 0a bladder cancers, BCG is often given shortly after surgery. BCG is also used for stage 0is and stage 1 cancers, which have only spread into the lining of the bladder and not into deeper layers of tissue, muscle or to other parts of the body. BCG isnt typically appropriate for cancer cells that have spread outside the bladders lining.
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Treating Stage Iv Bladder Cancer
These cancers have reached the pelvic or abdominal wall , may have spread to nearby lymph nodes , and/or have spread to distant parts of the body . Stage IV cancers are very hard to get rid of completely.
Chemotherapy is usually the first treatment if the cancer has not spread to distant parts of the body . The tumor is then rechecked. If it appears to be gone, chemo with or without radiation or cystectomy are options. If there are still signs of cancer in the bladder, chemo with or without radiation, changing to another kind of chemo, trying an immunotherapy drug, or cystectomy may be recommended.
Chemo is typically the first treatment when bladder cancer has spread to distant parts of the body . After this treatment the cancer is rechecked. If it looks like its gone, a boost of radiation to the bladder may be given or cystectomy might be done. If there are still signs of cancer, options might include chemo, radiation, both at the same time, or immunotherapy.
In most casessurgery cant remove all of the cancer, so treatment is usually aimed at slowing the cancers growth and spread to help people live longer and feel better. If surgery is a treatment option, its important to understand the goal of the operation whether its to try to cure the cancer, to help a person live longer, or to help prevent or relieve symptoms from the cancer.
Because treatment is unlikely to cure these cancers, many experts recommend taking part in a clinical trial.
What To Know About Bcg For Bladder Cancer
Did you know May is Bladder Cancer Awareness Month? It’s a time to raise extra awareness and promote facts about this disease. Education and raising awareness about bladder cancer is an important part of moving closer to a cure.
If you or a loved one is diagnosed with bladder cancer it can be frightening. However, your doctor and medical team are there to help you.
Talk with your healthcare team about all the available forms of treatment. They will tell you about possible risks and the side effects of treatment on your quality of life.
Your options for treatment will depend on how much your cancer has grown. Your urologist will stage and grade your cancer and assess the best way to manage your care considering your risk. Treatment also depends on your general health and age. Visit our condition article to learn more about treatment options for bladder cancer.
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Chemotherapy Following Bcg Failure
Although intravesical chemotherapy is a valid option for low-grade NMIBC BCG failure, the efficacy of chemotherapeutic agents is far from established in high-risk NMIBC. In a Scandinavian study, only 4 of 21 patients with BCG failure that were switched to MMC therapy remained recurrence-free.34
Recently, gemcitabine, which is considered standard treatment in systemic therapy for advanced bladder cancer, has been evaluated in the management of superficial disease. Dalbagni and colleagues reported on a Phase III trial of gemcitabine in patients refractory to BCG. Patients were considered at high risk for progression and were not candidates for cystectomy. Of 18 patients, 7 had a complete response , whereas 4 patients exhibited partial responses .35 We have had limited positive experience with intravesical gemcitabine in patients with very aggressive NMIBC following Chinese-herb nephropathy. Patients underwent kidney transplantation and could not receive BCG because of immunosuppression and therefore received gemcitabine.36 In another recent Phase II study using 2000 mg gemcitabine in BCG-refractory patients, 18 of 24 intermediate-risk patients and 7 of 16 high-risk patients remained recurrence-free, confirming the potential benefits of gemcitabine in these patients.37
In summary, intravesical chemotherapy using new compounds following BCG failure shows some promise but remains highly investigational at this stage.
Side Effects Requiring Immediate Medical Attention
Along with its needed effects, bcg may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor as soon as possible if any of the following side effects occur while taking bcg:
More common
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Bcg Failure And Subclassification
About 40% of patients of NMIBC will fail intravesical BCG treatment. Although many factors might lead to BCG failure, the dose of BCG and type of T helper response may lead to dramatically diverging outcomes. Low-dose BCG might not trigger enough TH1-type immune response, which is the main response to BCG activity. Too high doses of BCG may paradoxically activate mixed TH1/TH2 responses which will counterbalance the TH1 response . Other factors of BCG failure include occult micrometastatic disease prior to BCG therapy .
Patients who fail intravesical BCG treatment are usually sub-classified into three categories based on the type of failure:
BCG refractory, which is the persistence of disease after induction or maintenance BCG treatment.
BCG relapse, the recurrence of disease after a disease-free period post BCG treatment.
BCG intolerance when the patient is not tolerating the completion of BCG induction .
The definitions, endpoints and clinical trial designs for NMIBC as recommended by the International Bladder Cancer Group might serve as an excellent current state-of-the-art resource . The type of failure should be clearly defined. Because stakes are very high for these patients, for whom BCG has failed, and options are limited, single-arm designs may be relevant for the BCG-unresponsive population. The consensus for a clinically meaningful initial complete response rate or recurrence-free rate is of at least 50% at 6 months, 30% at 12 months and 25% at 18 months.
Is Bcg Treatment Contagious
Because BCG contains live bacteria, precautions are necessary to prevent it from being passed to others.
Patients should go to the bathroom sitting down to reduce splashing and wash their hands thoroughly after urinating. Pouring bleach into the toilet after use may also prevent contamination.
Once home, a patient should drink plenty of liquids and avoid sexual contact with others for 24 hours.
Research has shown that BCG may also reduce the risk of contracting a respiratory tract infection, giving your immune system a boost. However, precautions are still necessary to stay healthy.
The care team will talk to the patient about what to expect and provide instructions to follow at home.
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Treating Bladder Cancer That Progresses Or Recurs
If cancer continues to grow during treatment or comes back after treatment , treatment options will depend on where and how much the cancer has spread, what treatments have already been used, and the patient’s overall health and desire for more treatment. Its important to understand the goal of any further treatment if its to try to cure the cancer, to slow its growth, or to help relieve symptoms as well as the likely benefits and risks.
For instance, non-invasive bladder cancer often comes back in the bladder. The new cancer may be found either in the same place as the original cancer or in other parts of the bladder. These tumors are often treated the same way as the first tumor. But if the cancer keeps coming back, a cystectomy may be needed. For some non-invasive tumors that keep growing even with BCG treatment, and where a cystectomy is not an option, immunotherapy with pembrolizumab might be recommended.
Cancers that recur in distant parts of the body can be harder to remove with surgery, so other treatments, such as chemotherapy, immunotherapy, targeted therapy, or radiation therapy, might be needed. For more on dealing with a recurrence, see Understanding Recurrence.
What Happens During Treatment
A urinary catheter is inserted through your urethra and into your bladder. Then the BCG solution is injected into the catheter. The catheter is clamped off so the solution stays in your bladder. Some doctors may remove the catheter at this time.
You have to hold the medicine in your bladder. Youll be instructed to lie on your back and to roll from side to side to make sure the solution reaches your entire bladder.
After about two hours, the catheter is unclamped so the fluid can be drained. If the catheter was already removed, youll be asked to empty your bladder at this time.
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Treating Complications Of Bcg Therapy
If you do experience a problem from BCG infection, you may need to receive targeted antibiotics, such as isoniazid and rifampin.
Complications of BCG therapy sometimes dont occur until years later. That can happen if the BCG bacteria that spread in the body become reactivated. These complications can sometimes be tricky to diagnose. Medical imaging might first make your clinician concerned about cancer or about another type of bacterial infection.
Make sure that all your medical care providers know that you have had BCG therapy. That will help guide their diagnostic process and ensure you get the best possible care. In some cases, your clinician will want a tissue sample from the involved area to make sure that the problem is from a BCG infection and not from some other source.
Box : Prognostic Factors For Recurrence
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Number of tumours more tumours mean more frequent recurrences.
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Previous recurrence rate* or a recurrence at three months.
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Size of the tumour those > 3 cm carry a worse prognosis.
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Grade of anaplasia.
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Presence of CIS.
*The recurrence rate being the number of positive cystoscopies per year over the number of cystoscopies performed per year.
For progression, tumour grade is the most important factor. It is also known that T1 tumours have a worse prognosis than Ta tumours. Using these factors patients with superficial bladder cancer can be divided into three groups: the lowest risk group with a single less than 3 cm Ta G1 tumour, and a recurrence rate of less than one tumour per year a high risk tumour of T1 G3, multifocal, large, highly recurrent, and CIS and other tumours of intermediate risk. Recent studies further confirm these criteria.
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Urinary Microbiome In Bladder Cancer Patients
Urinary dysbiosis can be defined as the loss of beneficial bacteria from a healthy urinary bacterial community . As was previously described, determining commensal microbes as beneficial is challenging additionally, several studies have reported interpersonal variation even among healthy patients . Recently, dysbiosis of the urinary microbiome has been linked to pathological conditions such as urinary urge incontinence, interstitial cystitis, and overactive bladder . Although a similar speculation was made for BC patients, it is still unknown whether dysbiosis of the urinary microbiome at baseline precedes and is a risk factor for BC, or whether BC is responsible for the alteration of the microbiome. To date, few studies analyzing the urinary microbiome in bladder cancer have been performed, limiting our ability to draw definitive conclusions. A summary of the results from the available studies is given in Table 2.
What Can I Expect Following Treatment
You may be advised to drink plenty of fluid to flush the rest of the medication from your bladder.
For six hours after each treatment, youll have to be very careful when you urinate to avoid transmitting BCG to others. Men should urinate while seated to avoid splashing.
Disinfect the urine by adding 2 cups of bleach into the toilet. Let it stand for about 20 minutes before flushing. You should also wash your genital area very carefully after you urinate, so your skin doesnt become irritated from the BCG. Wash your hands thoroughly, too.
Men can pass BCG to their partner during sex. For that reason, you should avoid sex for 48 hours after each treatment. Use a condom between treatments and for six weeks following your final treatment.
Women should avoid getting pregnant or breastfeeding while on BCG therapy.
Treatment is usually given every week for six weeks. After that, you might need to do it once a month for six months to a year.
One benefit of BCG is that while it affects the cells in your bladder, it doesnt have a major effect on any other part of your body. But there can be a few side effects such as:
When comparing BCG to other bladder cancer treatments, its important to remember that treatment isnt the same for everybody. Some of the factors that determine your options are:
- type of bladder cancer
- your age and general health
- how well you tolerate certain treatments
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Aftereffects Of Bcg Bladder Treatment
Just trying to see if anyone else has had the same experience. Recently finished my second ‘maintenance’ treatment after being passed ‘clear’ following the main 6 treatments. So really good news but the aftereffects seem to be lasting much longer than previously. The bladder irritation after treatment usually went after two or three days but with this last treatment l still have a constant ache in the bladder/scrotum area three weeks after treatment? Pain is controlled by Paracetamol so not that severe but would like to hear from other sufferers to see if this eventually goes away?
Welcome to Cancer Chat Dave.
It’s great to read that you’ve finished the second maintenance treatment after being passed clear following the main 6 treatments although I’m sorry the after-effects you’re experiencing are lasting longer than usual.
I know you said the paracetemol is controlling the pain but do let your medical team or GP know about this as they may be able to help. I’ve had a quick look around the forum and thought you may like to connect with @Sharonna as she’s having some difficulty managing the pain from her BCG treatment at the moment and you may be able to help each other.
You can chat with our cancer nurses about your situation as well if you like. They’re available Monday – Friday between 9a.m – 5p.m on 0808 800 4040.
I hope this helps and that the after-effects disappear soon Dave.
All the best,
Failure Of Bcg Contact With The Target
Gradual waning of the immune response. Intravesical BCG instillations induce a transient peripheral immune activation against BCG antigens. Reactivation is observed in most cases after additional BCG courses. The absence of long-lasting immune activation after a single 6-week course of BCG could be related to the increased clinical efficacy observed with BCG maintenance instillations.12,13,14
Inadequate immune response. There is strong evidence that the success of BCG therapy might be due to a preferential induction of a TH-1 response .15,16 Although somewhat controversial, TH-2 responses detected either in the peripheral circulation or locally in the bladder are associated with poorer outcomes and might explain failure to respond to BCG therapy.17
Natural resistance-associated macrophage protein gene polymorphisms. The NRAMP1 gene has been implicated in susceptibility to infectious diseases and in response to BCG. Data suggest implication of the NRAMP1 gene in bladder cancer recurrence and response to BCG.18
Unresponsive tumour. Many recent investigations have determined whether biological markers might predict disease progression and/or response to treatment.19 An excellent review was provided a couple of years ago by Saint and colleagues.20
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Highlighting The Value Of Genetic Modeling Of Bladder Cancer
Is genetic modeling of bladder cancer still useful in the postHuman Genome Project era? The answer is a resounding yes, according to NYU Langones Xue-Ru Wu, MD, the Bruce and Cynthia Sherman Professor of Urological Research and Innovation and vice chair of urological research, in a special supplement on bladder cancer published in 2020 in Clinical Cancer Research by the American Association for Cancer Research.
We need genetically tractable experimental systems more than ever to validate the biologic potential of combinatorial bladder tumor drivers, says Dr. Wu, whose research has helped illuminate how non-muscle-invasive bladder tumors form along the receptor tyrosine kinase RAS-PI3K signaling pathway. By interrogating the effects in mice of systematically deleting individual genes residing on chromosome 9p21, Dr. Wu demonstrated that common mutations must be accompanied by certain collaborative events in order for tumors to arise.
Genetic modeling is also key to better understanding the effects of lifestyle-associated carcinogens, such as tobacco and e-cigarette smoke, and environmental factors, including industrial chemicals found in many manufactured products, he says. In addition, scientists have an ongoing need for tools to evaluate novel diagnostic, treatment, and preventive strategies.