Treatment Bladder Cancer Using Tuberculosis

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

History Of Usage Of Bcg

Tuberculosis was noted to have an antitumour effect at the start of the 20th century. It was Pearl, who in an autopsy series at the Johns Hopkins Hospital in 1929 reported a lower frequency of cancer in patients with tuberculosis. In the 1930s the use of BCG as a cancer therapy was first raised, but enthusiasm for this did not mount until the 1950s and 1960s. In 1969, Mathe et al produced a paper on the treatment of lymphoblastoid leukaemia with BCG, which produced promising results, but unfortunately others could not reproduce their results. This coupled with the development of successful modern chemotherapy and radiotherapy meant enthusiasm for BCG as a treatment waned. Further research carried out by Coe and Feldman rekindled interest in BCG with the demonstration of a strong delayed hypersensitivity reaction to BCG in the guinea pig bladder. This knowledge aided Morales et al who in 1976 carried out the first clinical trial with intravesical BCG. They were able to demonstrate a remarkable decrease in the rates of recurrence of superficial bladder cancer in nine patients. A randomised prospective trial by Lamm et al in 1980 confirmed these earlier observations. Since this time it has been shown that BCG when used has inferred benefit to those with superficial bladder cancer in terms of decreased recurrence rate and increased time to recurrence.

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What Are The Side Effects Of Bladder Cancer Treatment

BCG remains the most important vaccine for tuberculosis 100 years after its first use, and over the past 4 decades it has become the most widely accepted, effective drug used in the treatment of aggressive localized bladder cancer. This review chronicles the narrow path that led to approval and world-wide acceptance of BCG immunotherapy for bladder cancer while

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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.

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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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From Bcg To Chemo Combos

Non-muscle-invasive bladder cancer is so called because the tumor resides strictly in the bladders interior lining, called the mucosa. Among other tasks, this mucosal lining operates as a barrier between the smooth muscle that encases the bladder and the urine within it.

About 70%75% of bladder cancer diagnoses are NMIBC and about 25% of these are at high risk of progressing to muscle-invasive bladder cancer.

A tumor is called high-risk when its size or other features suggest that its biologically aggressive. One form of high-risk NMIBC, for example, is called carcinoma in situ, in which the tumor spreads along the mucosa in a pancake-like shape. These tumors are not only aggressive, Dr. Packiam explained, but particularly resistant to treatment with BCG. And when they do come back, its often in a more invasive form.

The treatment course for high-risk NMIBC begins with removing the bladder tumors via a surgical procedure called TURBT. Surgery is followed by additional treatments, known as adjuvant therapy, to kill off any remaining cancer cells and reduce the risk of the cancer coming back.

For decades, adjuvant therapy with BCGa severely weakened form of a bacterium that was originally developed as a tuberculosis vaccinewas the gold standard for preventing progression and recurrence in high-risk NMIBC, he explained.

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 youâve 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.

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How Is Bcg Given

The combination of BCG and TURBT is the most effective treatment for high-risk non-muscle-invasive bladder cancer. BCG is given once a week for six weeks, starting 24 weeks after TURBT surgery. It is put directly into the bladder through a catheter. You may be asked to change position every 15 minutes so the vaccine washes over the entire bladder. This is usually done as a day procedure in hospital, and each treatment session takes up to two hours.

Your treatment team will outline some safety measures to follow afterwards at home. This is because BCG is a vaccine that contains live bacteria, which can harm healthy people.

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.

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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

What To Expect During Bcg Treatment

First, make sure you havent had any fluids for four hours before the treatment. Right before you go into the treatment room your doctor or nurse will have you empty your bladder.

Youll lie on your back, and the medical professional will insert a catheter into your urethra and into your bladder, likely using some local numbing, and use this tube to infuse the treatment.

Once the treatment is infused, your doctor or nurse will remove the catheter. Theyll have you lie on your back, each side, and your stomach for 15 minutes each. The BCG mycobacteria needs to touch the bladder cancer cells to activate the immune system. Youll then be free to go but will need to hold off on peeing for another hour.

Verywell / Alex Dos Diaz

For at least six hours after your infusion, youll need to disinfect your pee to ensure none of the mycobacteria spread to anyone else. Pour an equal amount of bleach into the toilet after you pee and let it sit for 15 minutes before flushing.

You will likely need multiple BCG treatments. They may be given weekly for a few weeks, then less often for months or years to prevent cancer from coming back.

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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

Who Treats Bladder Cancer

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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When Is Bcg Used

BCG is used to treat specific types of cancer, specifically high-grade non-muscle invasive bladder cancer and carcinoma in situ .

The first step in the treatment process is to remove all visible cancer cells from the bladder. Typically, this is done using a transurethral resection of the tumor . There are some situations where this might require more than one surgical procedure, but your doctor will do everything they can to remove as much of a tumor as possible.

Once done, the bladder will be given a chance to heal. Then, it might be time to go with BCG. This is an intravesical treatment option. That means BCG liquid is inserted directly into the bladder.

Once in the bladder, the BCG treatment will stimulate the immune system. Your immune cells will respond to fight cancer cells in the bladder. BCG is considered an immunotherapy because it uses your immune system to fight the cancer without harming healthy cells. Because BCG treatment uses live bacteria, it is important to speak with your healthcare provider about reducing the risk of contamination when you empty the solution from your bladder into the toilet at home.

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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Availability Of Data And Materials

The datasets supporting the conclusions of this article are available in the National Health Insurance Research Database, Taiwan .

Only citizens of the Republic of China who fulfill the requirements of conducting research projects are eligible to apply for the National Health Insurance Research Database . The use of NHIRD is limited to research purposes only. Applicants must follow the Computer-Processed Personal Data Protection Law and related regulations of National Health Insurance Administration and NHRI , and an agreement must be signed by the applicant and his/her supervisor upon application submission. All applications are reviewed for approval of data release.

Modified Tuberculosis Vaccine As A Therapy For Bladder Cancer

by Markus Berninger, Max Planck Society

The human immune system can recognize and eliminate not only germs but also cancer cells. This is why treatments with weakened germs can help the immune system in its fight against cancer. Researchers at the Max Planck Institute for Infection Biology in Berlin have genetically modified the tuberculosis vaccine BCG in a way that it stimulates the immune system more specifically. Consequently, the new vaccine offers much greater protection against tuberculosis. A clinical study with patients suffering from cancer of the bladder has now shown that a therapy with VPM1002 could successfully prevent the recurrence of tumors in almost half of the patients who had not responded previously to the BCG therapy. The results could lead to the early approval of the drug for the treatment of cancer of the bladder so that as many patients as possible can profit from this quickly.

At the end of the 19th century, doctors observed that the tumor in some cancer patients shrank if the patients suffered from a bacterial infection with a high fever. These findings sparked interest in immunotherapy for cancer. Immunomodulatory treatments can specifically stimulate the immune system. As a result, the body’s own immune system is supported in its fight against the tumor, leading to a reduction in the size of the tumor.

Bladder treatment with weakened germ

Vaccine development

Quick approval

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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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