Posts Tagged ‘BCG’

Bladder Cancer Treatment With TB Vaccine

April 22, 2017

Andrew Siegel MD  4/22/17

The use of tuberculosis vaccine (a.k.a. bacillus Calmette-Guerin or BCG) to treat bladder cancer is one of the great success stories in the history of using the immune system to combat cancer. For 40 years, BCG has been recognized as the standard of care for high-grade, superficial bladder cancer and carcinoma-in-situ (CIS), a flat but high-grade bladder cancer. The use of BCG is responsible for significantly reducing bladder cancer progression and recurrence.


Image above: BCG in powdered form that needs to be reconstituted


Image above: Typical appearance of a superficial bladder cancer


Bladder cancer has a strong tendency to recur, despite cystoscopy-guided complete removal of visible tumors (using a “telescope” placed within the bladder via the urethra). This approach can only treat obvious and visible tumors, with the real possibility that there are additional tumors present that are not yet visible (microscopic), since bladder cancer is a “field” disease—capable of occurring anywhere within the bladder lining. One of the rationales for using a medication like BCG is that it is a liquid formulation that is instilled in the bladder and will bathe all inner surfaces of the bladder. I often use the analogy of plucking out dandelions in your lawn individually as opposed to using a weed spray with respect to the difference between bladder tumor resection (cystoscopic surgical removal) and using a BCG-like medication.

A Brief History of BCG

BCG is a unique strain of “weakened” mycobacterium bovis (cow tuberculosis bacterium) developed by Albert Calmette and Camille Guerin at the Pasteur Institute in Lille, France in 1921 as a tuberculosis vaccine. At the time of its development, there was a growing recognition of the relationship between the immune system and cancer. In 1929, it was discovered that BCG might also have a role in the treatment of cancer when autopsy findings in TB patients were correlated with a reduced prevalence of cancers. Early investigators found that mice given BCG were protected against cancers that were implanted. In 1975, Dr. Jean deKernion at UCLA reported a melanoma that had spread to the bladder that was eliminated by direct injection of BCG into the melanoma. In 1976, Alvaro Morales successfully instilled BCG inside the bladder to treat bladder cancer and after clinical trials it was FDA approved for use within the bladder in 1990…The rest is history.

How It Works

BCG activates the immune system and triggers an inflammatory response that destroys bladder cancer cells. A good response to BCG immunotherapy requires a patient with an immune system capable of mounting a cellular immune response. It is accomplished by infusing a sufficient quantity of BCG so that it has direct contact with cancer cells.

How It Is Used

BCG is instilled directly within the urinary bladder.  One cycle is a once per week treatment for 6 weeks.  A full course is two cycles, followed by maintenance therapy. Typically the BCG treatment is initiated two weeks or so following the bladder tumor resection to allow the bladder time to heal. BCG is placed inside the urinary bladder using a narrow catheter. Retaining it for two hours is ideal and rotating body position is important so that all areas of the bladder are adequately bathed with the BCG.

Side Effects of BCG

Low-grade fever, urinary urgency, frequency, burning and blood in the urine are typical symptoms, often indicative of the immune response being mounted.   Occasionally, flu-like symptoms may occur, including fever, chills, cough, muscle and joint aches. When severe symptoms occur, BCG concentration can be reduced to 1/3, 1/10, 1/30, or even 1/100th of a dose to prevent escalating side effects.

 Tips For Patients Receiving BCG

  • Avoid drinking any fluids for at least 2 hours and avoid caffeine-containing products for at least 4 hours prior to bladder instillation in order to be able to retain the BCG for a full 2 hours after the instillation and to avoid diluting the concentration of the BCG.
  • Rotate your body in order to bathe all surface areas of the bladder with the BCG (supine, left, right, prone).
  • Care should be used when urinating after the BCG is instilled to avoid contaminating one’s hands or genitals with the BCG. Men should sit to urinate to reduce the likelihood of self-contamination. Hands and genitals should be thoroughly washed afterwards, and household bleach should be added to the toilet immediately after urination. The bleach should stand for 15 minutes before flushing to deactivate the BCG.

Wishing you the best of health,

2014-04-23 20:16:29

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Dr. Andrew Siegel is a practicing physician and urological surgeon board-certified in urology as well as in female pelvic medicine and reconstructive surgery.  Dr. Siegel serves as Assistant Clinical Professor of Surgery at the Rutgers-New Jersey Medical School and is a Castle Connolly Top Doctor New York Metro Area, Inside Jersey Top Doctor and Inside Jersey Top Doctor for Women’s Health. His mission is to “bridge the gap” between the public and the medical community that is in such dire need of bridging.

Author of MALE PELVIC FITNESS: Optimizing Sexual & Urinary Health

Author of THE KEGEL FIX: Recharging Female Pelvic, Sexual and Urinary Health

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Vidscrip site (for short educational videos):


Bladder Cancer

February 2, 2013

Bladder Cancer

Andrew Siegel, MD  Blog #92


Bladder cancer is such a common public health problem that I thought it would be worthy of an educational blog.  Few people realize that its occurrence is more highly linked to tobacco than is lung cancer.

In the USA, the incidence of bladder cancer has increased greatly over the last few decades, with more than 60,000 new cases diagnosed each year.  It is the fourth most common cancer in men and the eighth in women. With the exception of skin cancers, bladder cancers are the most frequently recurring cancer, with up to 70% of patients experiencing recurrence.  The occurrence of bladder cancer increases with age and is three times more common in men than women.  80% of newly diagnosed individuals are 60 years of age or older.  At present, about 20% of patients die each year, but when the disease is diagnosed and treated in the early stages, the chances of survival are excellent, highlighting the importance of a timely and accurate diagnosis.  More than 90% of newly diagnosed bladder cancers are urothelial cell carcinomas  (cancers originating from the unique lining of the urinary tract).

The majority of patients with newly diagnosed bladder cancer have superficial cancer that involves the very inner layers of the bladder wall.  About 20% have invasive disease that involves the deeper layers of the bladder wall.  The remaining 5% present with metastatic disease, defined as spread beyond the confines of the bladder.

The highest prevalence of bladder cancer is in industrialized nations.  Cancer-causing agents (carcinogens) are most often responsible for bladder cancer.   Bladder cancer is highly associated with tobacco smoking—even if one stopped smoking years ago, the risk is related to the quantity of tobacco smoked over the years.  The carcinogens that are present in tobacco are absorbed through the lungs into the bloodstream and are filtered through the kidneys directly into the bladder, where their prolonged contact time with the lining of the bladder leads to cancerous changes.   Certain occupations are at higher risk for bladder cancer because of exposure to chemicals—these include: hairdressers, painters, machinists, printers, and those who work with dyes, textiles, rubber, leather, and petrochemicals.

Bladder cancer most commonly manifests with blood in the urine, either visible or microscopic (seen only under microscopic magnification).  It may also cause irritative lower urinary tract symptoms including urgency, frequency, discomfort with urinating, and urinary leakage.

The evaluation for blood in the urine includes imaging, cytology, and cystoscopy.  Imaging tests are means of visualizing the anatomy of the urinary tract, typically through ultrasound, computerized tomography (CT), or magnetic resonance imaging (MRI).  Cytology is a microscopic inspection of a urine sample by a pathologist for the presence of abnormal or cancerous cells that slough off the lining of the bladder, similar to a Pap smear done to screen for cervical cancer.  Cystoscopy is a visual inspection of the entire lower urinary tract (bladder and urethra) using a tiny, flexible, lighted instrument attached to a camera and monitor.

When a bladder tumor is identified on cystoscopy, attention is directed to the number of tumors present, their size, location within the bladder, and physical appearance.  A papillary appearance consists of fronds (finger-like projections floating in the bladder) with a narrow attachment to the bladder lining versus a sessile appearance, in which the tumor appears solid and is widely attached to the bladder lining.

Once a bladder tumor is recognized, it needs to be removed and sent for pathological evaluation.  This is performed under general or spinal anesthesia via cystoscopy, using an electric loop which is used to remove the area of concern as well as cauterize (use electricity to coagulate tissue) the underlying and adjacent tissue, both to stop bleeding and further destroy tumor cells.

The biopsed tissue is carefully examined by a pathologist, who will provide valuable information regarding malignancy vs. benignity, the type of tumor, depth of tumor, and grade of tumor.   Again, the vast majority of bladder tumors are urothelial cancers, referring to the cells that line the bladder.  A minority of bladder tumors are squamous cell cancers or adenocarcinomas.   Depth refers to the degree that the cancer is growing into the bladder wall.  Bladder cancers are broadly categorized into superficial and deep.  Superficial tumors are largely confined to the bladder lining and superficial layers and do not penetrate the muscle layer of the bladder, whereas deep tumors have “roots” that penetrate the muscular wall of the bladder.  Tumor grade refers to how much the microscopic appearance of the cancer deviates from the microscopic appearance of healthy bladder cells.  Low-grade cancers are similar in cellular appearance to normal bladder cells and generally behave in an indolent (slow) fashion versus high-grade cancers that can often behave aggressively.  Other factors of prognostic importance are the number of tumors present, the size of the tumors, and their physical characteristics.

In general, the best prognosis is for a solitary, small, superficial, low-grade papillary tumor and the worst prognosis is for multi-focal (originating from many different areas of the bladder), large, invasive (deep), sessile, high-grade tumors.

The biopsy information will enable the staging of the bladder cancer, a means of classifying the cancer.  It is extraordinarily unlikely for a superficial cancer to cause lymph node or distant spread, these events occurring with much greater likelihood with more deeply invasive cancers.

Staging of bladder cancer is as follows:

  • Ta: Superficial cancer is found only in polyps (papillary) on the surface of the inner lining of the bladder.
  • Tis: Carcinoma-in-situ. Tumor is found only in flat lesions on the surface of the inner lining of the bladder.
  • T1: Tumor is found in the connective tissue below the lining of the bladder but has not spread to the bladder muscle.
  • T2: Tumor has spread to the muscle layer deep to the lining of the bladder.
  • T3a: Tumor has spread through the muscular wall of the bladder into the fatty tissue layer as identified under microscopic examination.
  • T3b: Tumor has spread through the muscular wall of the bladder into the fatty tissue layer and is capable of being identified without a microscope.
  • T4: Tumor has spread to the prostate in men and to the uterus or vagina in women, or to the pelvic or abdominal wall in either gender.

Superficial cancers are usually managed with cystoscopy, with regular “surveillance” due to the high predilection for recurrence.  It is imperative to have frequent check-ups (every 3 months for the first year after initial diagnosis), consisting of periodic urinalysis, urine cytology, imaging, and cystoscopy.  If surveillance does not demonstrate any recurrences, the interval between follow up can gradually be increased (to every 6 months in the 2nd year; if there are no recurrences, to an annual check-up).  If a recurrence is found, treatment must be repeated and the surveillance frequency then starts anew with the every 3-month cycle.

To help prevent recurrence, under certain circumstances it is beneficial to use a medication that is instilled in the bladder on a weekly basis—this is especially useful when many tumors are present, in the presence of a high-grade tumor, or cancers that have recurred.   It is particularly useful for carcinoma-in-situ (CIS), a variant of bladder cancer that is very superficial, flat, yet of a high-grade pathological nature.  The medication of choice is tuberculosis vaccine—BCG (bacillus Calmette Guerin), which is a live, attenuated (weakened) form of tuberculosis bacteria!

Muscle-invasive cancers most often need to be treated with a major surgical procedure involving either partial or complete removal of the urinary bladder.  In the circumstance that the entire bladder needs to be removed, the ureters (tubes that conduct the urine from the kidneys to the bladder) need to be diverted to a piece of intestine that is either attached to the skin to a collection bag (ileal conduit) or attached to the urethra (neo-bladder or “reconstructed” bladder).  At times, in lieu of surgery, chemo-radiation can be utilized (a combination of radiation therapy provided by the radiation oncologist and chemotherapy provided by the medical oncologist).

Bladder cancer often behaves as two separate types of diseases—one that typically presents as multiple, superficial papillary tumors that have a tendency to recur but are not lethal (similar to many skin cancers), versus another, more deadly form characterized by high-grade, non-papillary, muscle-invasive tumors that have a tendency to metastasize.  Fortunately, the vast majority of bladder cancers are the superficial type.

Andrew Siegel, M.D.

Author of Promiscuous Eating: Understanding and Ending Our Self-Destructive Relationship with Food:

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For an educational video on bladder cancer that I have done, please go to the following link:

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