Evidence For Prevention Of Progression By Bcg
As the ability of BCG to prevent tumor recurrence became increasingly well documented, it became less clear how this translated into preventing disease progression or attaching mortality. Several studies have attempted to define whether or not BCG immunotherapy can prevent progression. A meta-analysis by Sylvester et al in 2002 identified a total of 24 trials encompassing 4,863 patients comparing TUR and BCG with either TUR alone or TUR with another non-BCG treatment. This study found a reduction of 27% in the odds of progression in patients treated with BCG if given any period of maintenance therapy. This finding was supported in a meta-analysis by Böhle and Bock in 2004. Their study looked at the outcomes from nine clinical trials including a total of 1,277 patients comparing BCG and mitomycin C. Overall, there was no statistically significant difference in the odds ratio for progression between the two groups however, as determined by Sylvester et al, there was a statistically significant reduction in tumor progression in the subgroup of patients treated with BCG where maintenance therapy was also given.
What Do I Need To Know To Prepare For Bcg Treatment
- Restrict your fluid intake, caffeinated beverages and use of diuretics 4 hours prior to procedure if possible.
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Do not void for 1 to 2 hours after the procedure, if possible.
After your first urination following the procedure and for six hours afterward, you will be asked to follow these instructions:
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Sit to void to avoid urine splashing. Do not use public toilets or void outside.
- After each void add 2 cups undiluted bleach to toilet, close the lid and wait 15-20 minutes and then flush the toilet. Repeat with each void for 6 hours.
- Increase fluid intake to dilute the urine. Begin after the first void post procedure.
- If you are sexually active, wear a condom with intercourse throughout the entire treatment course.
- If you have urinary incontinence, immediately wash clothes in clothes washer. Do not wash with other clothes.
- If wearing incontinence pad, pour bleach on pad, allow to soak in, then place in plastic bag and discard in trash.
- Acetaminophen or ibuprofen may be used for fever and body aches.
- You may need antispasmodic medication to help with frequency and urgency.
What Are The Side Effects
Some patients have difficulty completing long-term BCG therapy because of irritation in the bladder.2 To help with this irritation, the treatment frequency may be adjusted to give you a longer break between treatments. You may not notice any reaction after the first few BCG treatments. After the third treatment, patients usually start to experience bladder irritation pain or burning during urination, joint pain, fatigue, and flu-like symptoms that can last a few days. Most symptoms and side effects can be treated with over-the-counter pain medicines.
While BCG is a fairly common treatment for bladder cancer, every person has different experiences. It’s important to talk to your doctor about any questions or concerns you may have at any point during your treatment. Being mentally prepared for what to expect can help to reduce stress or uncertainty about treatment or help you think of additional questions for your healthcare team.
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Whats Old Is New Again
Bacterial therapies for cancer are not new. They go back more than a hundred years to William Coley, whose eponymously named toxins were some of the first cancer immunotherapies ever developed. Dr. Coley was a surgeon at Memorial Hospital who noticed that people with cancer who got severe infections sometimes saw their cancers regress. He began administering a vaccine of heat-killed bacteria to patients in the hopes of spurring their immune systems to attack cancer. Dr. Coley had some success with his approach, but the results proved unpredictable and hard to replicate, so his toxins eventually faded from use.
Inspired by Dr. Coleys work, scientists at MSK continued to research immune-based treatments for cancer. This sustained research effort eventually led to the development of modern forms of immunotherapy, including immune checkpoint inhibitors. These drugs take the brakes off T cells and allow them to find and fight cancer cells that display unique neoantigens .
We show that BCG is similar to checkpoint inhibitors in that it works by eliciting an immune response against cancer neoantigens, says Gil Redelman-Sidi, a physician-scientist who collaborates with Dr. Glickman and is the co-corresponding author on the PNAS paper. These results bring BCG into the modern world of immunology.
Researchers Eye Cancer Drug Bcg As Potential Covid
The frantic search for ways to stop, prevent and treat COVID-19 has put the spotlight on a decades-old drug originally developed for tuberculosis , but currently used to treat bladder cancer. The Bacillus Calmette-Guerin vaccine, one of the most widely administered vaccines in the world to prevent TB, is now being researched as a potential COVID-19 vaccine. While the research into BCG has generated headlines worldwide, it may take some time to determine whether the drug is safe and effective against the virus, an often-painstaking process for any potential treatment.
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When Is Bcg Treatment Used
You may have BCG directly into your bladder after surgery to remove non-muscle-invasive bladder cancer. This type of surgery is called a transurethral resection of a bladder tumour .
This treatment helps prevent the cancer from coming back in the bladder lining. It also reduces the risk of the cancer becoming muscle-invasive. Doctors usually suggest this treatment if you have a high-risk bladder cancer, or sometimes if you have an intermediate-risk bladder cancer.
There is usually at least 2 weeks between the surgery to remove the cancer and the start of BCG treatment. This is to give your bladder enough time to heal from the surgery.
You usually have BCG treatment once a week for 6 weeks. This is sometimes called the induction course. You may be offered more BCG treatments. This is usually called maintenance treatment.
Treatment times vary. Your doctor will explain what is best for you.
What Other Drugs Will Affect Bcg
If you have an infection that must be treated with an antibiotic, you may need to stop receiving BCG for a short time. Antibiotics can make BCG less effective and should be avoided during your treatment with BCG. Follow your doctor’s instructions and be sure to tell any other doctor who treats you that you are receiving BCG.
Tell your doctor about all your other medicines, especially
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Modified Tb Vaccine As Therapy For Bladder Cancer
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Treating Stage I Bladder Cancer
Stage I bladder cancers have grown into the connective tissue layer of the bladder wall , but have not reached the muscle layer.
Transurethral resection with fulguration is usually the first treatment for these cancers. But it’s done to help determine the extent of the cancer rather than to try to cure it. If no other treatment is given, many people will later get a new bladder cancer, which often will be more advanced. This is more likely to happen if the first cancer is high-grade .
Even if the cancer is found to be low grade , a second TURBT is often recommended several weeks later. If the doctor then feels that all of the cancer has been removed, intravesical BCG or intravesical chemo is usually given. If all of the cancer wasn’t removed, options are intravesical BCG or cystectomy .
If the cancer is high grade, if many tumors are present, or if the tumor is very large when it’s first found, radical cystectomy may be recommended.
For people who arent healthy enough for a cystectomy, radiation therapy might be an option, but the chances for cure are not as good.
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Treatment Of Bladder Cancer By Stage
Most of the time, treatment of bladder cancer is based on the tumors clinical stage when it’s first diagnosed. This includes how deep it’s thought to have grown into the bladder wall and whether it has spread beyond the bladder. Other factors, such as the size of the tumor, how fast the cancer cells are growing , and a persons overall health and preferences, also affect treatment options.
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.
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Can Response To Therapy Be Predicted
The potential for concentrations of urinary neutrophils to predict antitumor activity has already been discussed however, other parts of the immune response have also been put forward to perform the same purpose. Measurement of tumor-infiltrating dendritic cells and tumor-associated macrophages has been proposed as a means by which to predict the response to BCG therapy. Ayari et al assessed levels of CD83+ dendritic cells and CD68+ macrophages in patients with high-risk NMIBC treated with transurethral resection of bladder tumor and maintenance BCG. Their results suggested that patients with low levels of CD83+ tumor-infiltrating dendritic cells responded better to maintenance BCG than patients with higher levels at the time of resection. In the same cohort, a similar effect was seen in those patients who recruited more CD68+ tumor-associated macrophages, ie, there was an increased risk of recurrence. Further studies are required to confirm these preliminary findings, but if validated, the pretreatment levels of these immune cells may have relevance in determining the treatment regime for individual patients.
Tb Vaccine Being Used To Treat Bladder Lining Cancer
A vaccine for tuberculosis is now being used to treat early, potentially aggressive cancers of the lining of the bladder. These superficial, or shallow, cancers can progress to invasive forms that burrow into the bladder muscle and then spread to other parts of the body, becoming incurable.
The standard approach to one of the more aggressive types of superficial bladder cancer, carcinoma in situ , has been to surgically remove the bladder if the cancer cannot be eradicated quickly by more conservative means, said Dr. John A. Provet, a urologist at New York University Medical Center.
Previous medications instilled directly into the bladder for this type of cancer, also referred to as transitional cell carcinoma, have had limited success rates. The new treatment using bacille Calmette-Guerin may eradicate CIS in 60% of the cases.
BCG was first created in 1906 as a vaccine against human tuberculosis. It is a laboratory-weakened strain of a bacterium that causes TB in cows.
BCG solution is instilled directly into the bladder through a catheter, or soft tube. The treatment is generally performed in a urologists office. The normal course of therapy is one infusion a week for a period of six to 12 weeks. The bodys immune system reacts by attacking the foreign micro-organisms that have entered the bladder.
In the past, it was often necessary to sacrifice the bladder to save a life, concluded Provet. Now with BCG, it should be increasingly possible to save the bladder.
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Sex After Bcg Treatment
Men should use a condom during sex for the first week after each BCG treatment. If you are a woman having the treatment, your partner should use a condom during this time. This protects your partner from any BCG that may be present in semen or vaginal fluid. Your doctor or specialist nurse can give you more information about this.
Doctors do not yet know how BCG may affect an unborn baby. They will recommend you do not become pregnant or make someone pregnant while having it. You should use effective contraception during treatment. Your doctor or specialist nurse can give you more information about this.
Treating Stage 0 Bladder Cancer
Stage 0 bladder cancer includes non-invasive papillary carcinoma and flat non-invasive carcinoma . In either case, the cancer is only in the inner lining layer of the bladder. It has not invaded the bladder wall.
This early stage of bladder cancer is most often treated with transurethral resection with fulguration followed by intravesical therapy within 24 hours.
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Immunotherapy For Bladder Cancer
Some people with bladder cancer have immunotherapy. Immunotherapy helps to strengthen or restore the immune systems ability to fight cancer.
You may have immunotherapy to:
- kill bladder cancer cells
- stop bladder cancer cells from growing and spreading
- lower the risk that the cancer will come back
- help keep the cancer from coming back after it has already been treated
- control symptoms of bladder cancer
Your healthcare team will consider your personal needs to plan the drugs, doses and schedules of immunotherapy. You may also receive other treatments.
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 it’s 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 cases surgery 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, it’s important to understand the goal of the operation whether it’s 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.
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Treating Stage Iii Bladder Cancer
These cancers have reached the outside of the bladder and might have grown into nearby tissues or organs and/or lymph nodes . They have not spread to distant parts of the body.
Transurethral resection is often done first to find out how far the cancer has grown into the bladder wall. Chemotherapy followed by radical cystectomy is then the standard treatment.Partial cystectomy is rarely an option for stage III cancers.
Chemotherapy before surgery can shrink the tumor, which may make surgery easier. Chemo can also kill any cancer cells that could already have spread to other areas of the body and help people live longer. It can be especially useful for T4 tumors, which have spread outside the bladder. When chemo is given first, surgery to remove the bladder is delayed. The delay is not a problem if the chemo shrinks the cancer, but it can be harmful if it continues to grow during chemo. Sometimes the chemo shrinks the tumor enough that intravesical therapy or chemo with radiation is possible instead of surgery.
Some patients get chemo after surgery to kill any cancer cells left after surgery that are too small to see. Chemo given after cystectomy may help patients stay cancer-free longer, but so far its not clear if it helps them live longer. If cancer is found in nearby lymph nodes, radiation may be needed after surgery. Another option is chemo, but only if it wasn’t given before surgery.
History Of The Development Of Bcg
BCG was developed as a vaccine against tuberculosis . It is a live attenuated vaccine originally produced from the same bacterium that gives rise to bovine TB, ie, Mycobacterium bovis. Attenuation was achieved through manipulation of the bacillus by serial growths on a culture medium. This resulted in a gradual loss of the genes producing virulence such that it could be safely inoculated into humans. Importantly, it retains enough similarity to Mycobacterium tuberculosis that when a human is vaccinated with BCG a degree of immunity to TB ensues. It was originally developed by Calmette and Guerin at the beginning of the 20th century using a glycerinated bile potato medium in a process that began in 1908, leading to its first clinical use as a vaccine for TB in 1921. On average, a 50% reduced risk of TB with BCG can be expected according to a meta-analysis published in 1994. However, reductions in TB due to BCG do range considerably, with figures from 0% to 80% reported. It is thought that this, in part, reflects the genetic variability between the different strain preparations created around the world.,
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