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Tuberculosis To Treat Bladder Cancer

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Is There Any Preparation Involved

When BCG for Bladder Cancer Goes Rogue and How It Impacts TB Clinicians

Its important that you follow your doctors instructions for what to do before and after the procedure. Tell your doctor about all the medications you take. Certain immunosuppressants, antimicrobial therapies, and radiation therapies can interfere with BCG treatment.

Youll be advised to limit your fluid intake for four hours prior to the procedure. You might be told to avoid caffeine for a few hours longer than that, because its a diuretic and could make things more difficult.

Youll be asked to urinate just before the procedure so youll be able to hold the medication in your bladder for several hours.

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 patients 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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Who Can Use Bcg

BCG is a treatment for early-stage bladder cancer that has not yet invaded the muscle of the bladder wall. Called non-muscle invasive bladder cancers or in situ bladder cancers, these account for about half of all bladder cancers.

For 2021, it was estimated that about 83,730 new cases of bladder cancer would be diagnosed in the United States, and about 17,200 American bladder cancer patients would die from the disease.

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How You Have It

BCG is a liquid. Your doctor or nurse puts the liquid into your bladder through a tube in the urethra . Usually, they then remove the catheter.

You must not pass urine for 2 hours. This gives the BCG time to be in contact with the lining of the bladder. Some hospitals may ask you to change position every now and again to make sure the drug reaches all parts of your bladder lining.

When you do pass urine, you need to be careful for 6 hours after the treatment because the vaccine contains bacteria. Men should sit down to pass urine to reduce the chance of splashing.

After you’ve been to the toilet, pour about half a pint of neat bleach into the toilet bowl and leave it for 15 minutes before flushing.

Wash your hands and genitals immediately with warm soapy water after you pass urine.

Whats Old Is New Again

BCG treatment for bladder cancer: What to know

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.

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Mechanism Of Action Of Bcg

The mechanism of action of bacillus Calmette-Guérin therapy is incompletely understood. Some early studies purported that an immune response against BCG surface antigens cross-reacted with putative bladder tumor antigens, and this was proposed as the mechanism for the therapeutic effect of BCG however, multiple subsequent studies refute this claim.

The most likely mechanism of action of BCG immunotherapy involves a combination of its direct effect on tumor cells along with the patients immune response to the therapy. These effects are summarized by Kawai et al into three categories: infection of cancer cells, induction of immune response, and antitumor effects.

The infection of cancer cells is mediated by the glycoprotein fibronectin, which allows the internalization of BCG, breakdown of proteins, and cellular changes that trigger the immune system. This is similar to the immunologic reaction that occurs in patients with tuberculosis. This immune response comprises specific cellular changes including surface receptor changes and release of various cytokines. Interferon is considered to be an important part of this process and has been used in the past to determine appropriate response to treatment. The immune response crescendos to antitumor activity in which cells recognize the cancer cells, target them for destruction, and subsequently decrease cancer burden.

The overall response to BCG is limited if the patient is immunosuppressed.

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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Impact Of Bcg Revaccination On Safety

The rates of adverse reactions to the first and second doses of BCG vaccination were evaluated from the findings of a large population trial carried out in Brazilian children aged 7 to 14 years. Although reaction to the second dose was more frequent than first BCG vaccinations , it was not statistically significant. The author concluded that there is insufficient safety data, but based on results, the adverse reactions to the second dose of BCG are uncommon .

Recently in the phase 3 of a double-blind, active randomized trial, it has been done to determine the potential of BCG vaccine for protecting the adult patients from infections, particularly respiratory infections. Outcomes demonstrate that vaccination of BCG is safe and it can reduce the number of infections in elderly at-risk population. Moreover, people in the treatment group took longer to occur the first infection in comparison with the placebo arm . The researchers did not found any significant difference between two groups in terms of adverse effects. Consequently, they concluded that BCG vaccination was safe among adult patients. The vaccine may also protect the adults from COVID-19, but this has not been thoroughly tested so far .

Analysis Of Countries With Discontinued Vaccination

Bladder Cancer – Overview (types, pathophysiology, diagnosis, treatment)

The mandatory BCG vaccination policy has been stopped in some countries where the incidence of TB declined. In Table , the incidence rates of COVID-10 in vaccinated and unvaccinated subpopulation of these countries were compared. Germany is a prominent example to examine the possible impact of the age of BCG vaccinations on COVID-19 susceptibility, as vaccination schemes were different before the unification of East and West Germany . In East Germany, BCG vaccination became mandatory in 1953. By contrast, this vaccination was much less common in West Germany and it was stopped completely between 1975 and 1977. As is shown in Table the relation between BCG and morbidity and/or mortality of coronavirus has been analyzed using Students t test approach and suggests it as an effective vaccination . An RD approach is used to study the correlation between BCG vaccine and COVID-19 severity in Sweden that stated this vaccination does not have any protective effect against infection . The benefit of a shift in BCG vaccinations policy was also taken to study the correlation between BCG vaccine and COVID-19 severity in Israel and Japan and two contradictions results have been reported .

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What To Expect Before Bcg Treatment

Before you are scheduled for BCG therapy, you will have to go through a screening test. This screening will determine whether you are eligible for BCG treatment or not. Factors considered during this screening test include the patients age, cancer type and stage, and overall health.

The doctor along with a radiation therapist will determine the best course of treatment for your condition and also ask you to avoid drinking too much fluid like water, juice, or caffeine.

If you are eligible, you will be given a date to schedule your treatment and will receive specific instructions on how to prepare. Once BCG is injected into the bladder, you will have to wait for 1-2 hours before urinating. This will allow the medicine to reach all the areas of the bladder.

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The success rate of bladder cancer treatment will vary depending on the age of the patient and the stage of the disease. Bladder cancer is a common and treatable disease, but bladder cancer treatment can be complex and challenging.

There are different treatment options available, each with different pros and cons. The best treatment option for you will depend on your situation and health.

We hope the information was helpful for you to understand what BCG treatment is, its symptoms, and what you can expect after the treatment. This method of treatment is considered a form of immunotherapy, which is an emerging form of cancer treatment.

Other Treatments For Bladder Cancer

For many early-stage bladder cancers, BCG is the best option for treatment. Other treatments for bladder cancer include:

  • Surgery to remove the tumor: Early cancers can be removed with TURBT surgery. More advanced cancers may require more extensive surgery, like removal of part or all of the bladder .
  • Intravesical chemotherapy: This treats the inside of the bladder with chemotherapy drugs. Chemotherapy drugs commonly used for bladder cancer include Mutamycin , Gemzar , or Valstar .
  • Radiation therapy
  • Clinical trials

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In Vitro Evidence Of Human Immune Responsiveness Shows The Improved Potential Of A Recombinant Bcg Strain For Bladder Cancer Treatment

  • 1Laboratório de Desenvolvimento de Vacinas, Instituto Butantan, São Paulo, Brazil
  • 2Programa de Pós-Graduação Interunidades em Biotecnologia USP-I.Butantan-IPT, São Paulo, Brazil
  • 3Laboratório de Imunologia Aplicada, Departamento de Genética e Evolução, Universidade Federal de São Carlos, São Carlos, Brazil
  • 4Institute of Genetic and Biomedical Research, National Research Council, Cagliari, Italy
  • 5Institute of Protein Biochemistry, National Research Council, Naples, Italy

Who Treats Bladder Cancer

Tuberculosis Cancer Treatment

Based on your treatment options, you might have different types of doctors on your treatment team. These doctors could include:

  • Urologists: surgeons who specialize in treating diseases of the urinary system and male reproductive system
  • Radiation oncologists: doctors who treat cancer with radiation therapy
  • Medical oncologists: doctors who treat cancer with medicines such as chemotherapy and immunotherapy

You might have many other specialists on your treatment team as well, including physician assistants, nurse practitioners, nurses, nutrition specialists, social workers, and other health professionals.

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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 its 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 wasnt 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 its 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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Origin Of Bcg And Its Relationship With Bladder Cancer

Mycobacterium bovis Bacillus Calmette-Guérin is a species originated after 230 recultures of the pathogen M. bovis. Over a period of thirteen years, Albert Calmette and Camille Guérin recultured isolated colonies from the originally pathogenic M. bovis. In 1921, they demonstrated that the obtained bacillus was not only non-pathogenic in animal models but also protected against tuberculosis challenge in vaccinated animals. Afterwards, the massive production of BCG was initiated for use in tuberculosis prevention in humans, and it is still the only commercially available vaccine against tuberculosis. At that time, the use of a mixture of two bacteria, Serratia marcescens and Streptococcus pyogenes, was investigated for cancer treatment, and the possibility to use the newly developed and safe BCG offered a novel therapeutic option for some cancer patients. Although some studies demonstrated the potential efficacy of the new BCG as a treatment for diverse types of cancer, it was not until the 1970s that BCG was approved as an immunotherapeutic treatment for bladder cancer patients.

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Optimization Of The Use Of The Scarce Vials Of Bcg

As soon as BCG shortages began, different strategies were adopted at different levels, from improvements in BCG production to modifications of the recommended treatment.

Improving BCG Production

The production of BCG is not an easy matter. Due to the slow growth of the mycobacteria, any inaccuracy during the manufacturing process can lead to a large loss of time and money, as the BCG shortages have proven. For this reason, some researchers proposed optimizing BCG bulk production by modifying the growth in pellicles to the use of bioreactors or evaluating the possibility of extending the shelf life of the already manufactured BCG vials.

Regulatory Issues/Favorable Policies

Variations in Clinical Guidelines Recommendations

For intermediate-risk NMIBC patients

  • Intravesical chemotherapy must be used as a first-option treatment instead of BCG. Induction once a week for six to eight weeks plus a monthly maintenance schedule for one year.

  • For second-line treatment, a one-third dose of BCG instead of full-dose BCG can be used. In that case, different patients can be treated the same day clustered in groups of three to avoid BCG wastage.

  • Maintenance BCG can be omitted.

For high-risk NMIBC

Treating Stage 0 Bladder Cancer

Bladder Cancer Treatment

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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When You Go Home

Some hospitals allow you to go home with the medicine in your bladder if you live close by and are okay with the treatment. Your team will let you know if you can do this. You should follow the advice on what to do when you pass urine.

You need to drink lots of fluid after this treatment for 24 hours. It helps clear your system of the BCG.

You should not have sex for 24 hours after each treatment. During your course of treatment and for a week afterwards, you should wear a condom during sex.

Having bladder cancer and its treatment can be difficult to cope with. Tell your doctor or nurse about any problems or side effects that you have. The nurse will give you telephone numbers to call if you have any problems at home.

Treatment Of Bladder Cancer By Stage

Most of the time, treatment of bladder cancer is based on the tumors clinical stage when its first diagnosed. This includes how deep its 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.

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Is There A Risk Of Bladder Cancer After Bcg Treatment

Like most cancers, bladder cancer can potentially return after treatment. Statistically, cancer will recur in up to 40% of people who receive BCG treatment. Its important to note, however, that even if the cancer comes back, it may not progress.

Low-grade bladder cancer usually doesnt spread to other areas of your body. But people who have low-grade bladder cancer have a higher risk of developing other low-grade cancers throughout their lifetime.

Less often, aggressive bladder cancer can develop after BCG treatment. If this happens, cystectomy is usually recommended.

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