MetroVan Urology

The drainage system of the urinary tract extends from the kidneys through to the end of the urethra. This includes the renal pelvis, the ureters, the bladder and parts of the urethra. This system is often divided into an upper urinary tract (the renal pelvis and ureters) and lower urinary tract (the bladder and urethra).

The urinary tract is lined by a mucosal (wet) surface called urothelium made up of several layers of cells. In a similar manner to our skin, the urothelium is constantly being renewed with the old cells being shed in the urine and new cells being produced. A number of conditions can arise in the urothelium, including cancer. Cancers of the urothelium most commonly present with blood in the urine. Even a single episode of blood in the urine (especially if the presence of infection cannot be confirmed) can be from such cancers. Bladder cancer is the most common serious cause of hematuria accounting for about 10% of all hematuria. See information on the evaluation of Hematuria.

The bladder constitutes a single greatest surface area of urothelium and as such is the most common location for urothelial tumors. Tumors of the renal pelvis urothelium and ureters are far less common; for every 50 new diagnoses of bladder cancers there might be one diagnosis of cancer of the renal pelvis or ureter.

There are many types of rare tumors which can originate in the bladder including those arising from the muscle itself, the nerves and blood vessels wall. These comprise less than 5% of bladder cancers.

Basic structure of the bladder and its relationship to urotheliali tumors of the bladder (starting from the inner surface in contact with the urine). The wall of the bladder is like the floor.

Similar to just about any other type of cancer, these tumors may occur with bad luck alone. However, in many cases there may be one or more risk factors.

The most common presenting symptom is blood in the urine (hematuria). Note that the hematuria may be intermittent and may not be visible to the naked eye (microscopic hematuria). Urinary urgency and frequency may rarely be presenting signs. All hematuria which is not confirmed to be from infection should be evaluated by a urologist - the most importnant test being a cystoscopy.

If bladder cancer is suspected at the time of cystoscopy (the appearance is usually distinct), further testing is performed and may include:

1. RESECTION/BIOPSY. The tumor can be sampled through the urethra with a special instrument called a resectoscope (TURBT - transurethral resection of bladder tumor). This does not require any cutting of the skin and may be curative if the tumor is superficial.
   1. REPEAT RESECTION/BIOPSY: IMPORTANT: for tumors that are high grade or if muscle invasion cannot be definitively excluded on the initial pathology, a repeat resection is almost always required. The reason for this is two fold: it is critical to ensure the tumor is not muscle invasive since the treatment for superficial and muscle invasive tumors are so different; the repeat resection can increase the chance of cure and help avoid much more invasive treatments if the tumor is superficial or has very limited muscle invasion.
   2. About 1 in 4 patients will have residual tumor and about 1 in 50 will have muscle invasive tumor
2. Imaging. Choice depends on the circumstances. CT scan, Ultrasound and Retrograde pyelogramare the options depending on the situation.

The goals of this process are diagnosis and staging. In many instances, the tumor will be completely removed and cured. Once a diagnosis is established, further management will depend on the specific risk of the tumor.

Superficial bladder cancers are those confied to the mucosa or lamina propria (the 'carpet or underlay'). They are designated by the stages Ta or T1, respectively. These tumors are frequently curable without major surgery but can, none the less, progress to very dangerous muscle-invasive disease. In many cases, the tumors are more 'nuisance' than 'life threatening', but knowing exactly what sort of risk the tumor brings with it will help individualize treatment.

Risk associated with the tumor. For superficial localized bladder cancers, the risks are of 2 sorts.

1. Progression: progression of bladder cancer takes 2 forms. Tumor can progress in terms of stage - that being from a superficial to a muscle-invasive tumor (i.e. it invades more deeply into the bladder wall). Tumor can also progress from low to high grade (grade is something established by looking at the cancer cells under a microscope.
2. Recurrence: bladder cancer has a predeliction for recurrence even if removed. Detecting recurrent tumor before it has the opportunity to progress can reduce the chances of requiring more extensive surgery and death from bladder cancer.

The tumors with the highest risks of progression are also the ones with the highest risk of recurrence. Risk factors for progression and recurrence include:

1. GRADE: This is the most important factor in determining the risk of recurrence and progression. High grade tumors (grade 3/3) or carcinoma in situ (CIS) have a high risk of progression to muscle-invasive or systemic disease
2. Stage: tumor into the lamina propria Ta ('the underlay') have an increased risk of progression to muscle-invasive or systemic disease
3. Multifocality: multiple tumors are at higher risk for recurrence
4. Size: larger tumors (over about 3 cm) are associated with a higher risk of recurrence

Risk associated with the treatment. Bladder cancers which are left untreated are often fatal. Except in the rarest of circumstances, bladder cancer should be treated. In some situations, there will be various options available, but in most circumstances the risk associated with the tumor is the over-riding feature. What can you expect?

1. TURBT: Everyone with a bladder tumor suspicious for cancer undergoes a Trans-Urethral Resection of Bladder Tumor.
2. Imaging: everyone will obtain either ultrasound or CT. The type will depend on the circumstances
3. Additional treatment will depend on the risk of the tumor
   1. Higher risk tumors: intravesical therapy (either Mitomycin C or BCG)
   2. Lower risk tumors: often managed with surveillance cystoscopy only

There are several strategies to minimizethe risk of bladder cancer recurrence and progression. The administration of medication directly to the bladder through a catheter has been used for superficial tumors. 2 commonly used treatments.

1. mitomycin-C
2. Bacillus Calmette Guerein (BCG)

BCG is an attenuated (weakened) strain of tuberculosis. It produces a very specific immune reaction which in addition to clearing the bladder of the bacteria also is capable of killing bladder cancer cells. This treatment was developed many years ago by a Canadian urologist and is the mainstay for treatment of high-grade non-invasive (superficial) bladder cancer throughout the world. it is indicated for any kind of high risk noninvasive tumor including carcinoma in situ, tumors with submucosal invasion (stage T1), high-grade tumors (Grade 3/3), and for multifocal tumors.

BCG treatment is typically withheld until the blood has visibly cleared following tumor resection - usually about 4 weeks. It is also with held if there are any concerns regarding immunodeficiency or active urinary tract infection. Administration occurs at the hospital with placement of a catheter into the bladder and then instillation of a small volume of the active bacteria. The treatment is always administered weekly.

1. Induction: This is a 6 week course (once per week) following which a bladder biopsy is usually performed to confirm complete response. The biopsy typically occurs 6 weeks after completion of the induction course. induction is the most important component of BCG treatment
2. Maintenance: this can reduce the frequency of recurrence is but is not always tolerated. These are 3 week treatments given at 3, 6, 12, 18, 24, 30 and 36 months

Side effects are generally well tolerated but can be similar to infection. There are a number of uncommon side effects which will be discussed with you by the medical oncologist. Ongoing evaluation with cystoscopy is necessary during this time.

Persistent or recurrent cancer despite treatment with BCG is serious and requires discussion of radical surgery or radiation.

BCG is administered to patients who are at higher risk of recurrence and progression. It is progression to muscle invasive disease which is the primary concern but persistence or recurrence despite BCG treatment are markers for disease progression and need to be handled carefully. Not all bladder cancer following treatment with BCG is treated the same and it is important to note that after the induction course it may take up to 6 months for a full response. Having said that, if there has not been eradicated of the disease at 3 months, there is only a small chance (roughly 25%) that further response will be seen by waiting an additional 3 months.

There are 3 ways to think about bladder cancer in the context of BCG treatment

1. BCG Refractory: No response to BCG - tumor is the same or worse than before treatment. The disease process despite induction. most patients should underggo cystectomy or  chemoradiation (NB: radiation not a good option for CIS). Salvage treatment withanother course of BCG is an option for those who decline upfront cystectomy - generally only if frail or 2 old to tolerate cystectomy.the respponse rate is abbout 30%-50%. A third course of BCG is successful less than 20% of the time.
2. BCG Resistant: recurrence or persistent disease but lower volume, lower stage or grade. A second course of BCG or BCG and interferon can be considered with a response rate of about 60%. Often a lower dose of BCG is combined wwith interferon and after 6 weeks of induction maintenance is 3 week courses at 3, 9 and 15 months
3. BCG Relapsing: recurrence after an initial complete response. A second course of BCG or BCG and interferon can be considered with a response rate of about 60%. often a lower dose of BCG is combined wwith interferon and after 6 weeks of induction maintenance is 3 week courses at 3, 9 and 15 months

Investigational treatments for recurrence after BCG include intravesical Gemcitabine (2 grams in 100 mL NS for post-operative instillation) and clinical trial (e.g. atezolizumab).

The  bottom line  is that patients with BCG refractory disease nneed too be managed with great care as this can progress rapidly. Cystectomy should always be discussed.

Tumors which have invaded into the muscle of the bladder pose a significant and life-threatening risk to patients. These tumors inevitably spread through the body and if not treated before this occurs day become incurable (see Treatment – Systemic below). In fact, up to half of patients who are believed to have muscle invasive bladder tumor without spread to the rest of the body based on imaging tests will in fact have microscopic spread of the disease elsewhere.

For this reason, the treatment of these tumors is very aggressive since the alternative is likely death from the eventual spread of the cancer through the body. The mainstay of treatment is removal of the bladder. This treatment is called a radical cystectomy - you can find extensive information on this treatment option here.

Treatment Options for Muscle Invasive Bladder Cancer

1. Radical Cystectomy and Urinary Reconstruction
2. Radiation and Chemotherapy
3. Partial cystectomy (very limited application)

Alternatives to radical cystectomy are the 'bladder preservation' approaches: radiation plus chemotherapy or aggressive transurethral resection of the tumor or partial removal of the bladder (partial cystectomy). Bladder preservation approaches are used in select circumstances.

Additional treatment in the form of chemotherapy is often times administered prior to removal of the bladder or in conjunction with radiation. When chemotherapy is given prior to the main treatment is it called NEOADJUVANT. When chemotherapy is given after the main treatment it is called ADJUVANT. The duration of chemotherapy is 3-4 months. In select circumstances this can increase the chances that surgery or radiation will cure the bladder cancer. Is well tolerated in most patients though sometimes it can be associated with serious and significant side effects.

Once the bladder is removed, some sort of reconstruction of urinary tract is required to allow the urine to exit the body. You can find extensive information on reconstruction here. There are 2 major decisions which need to be made:

1. Orthotopic (in the same location as the bladder used to be) or ectopic (in another area of the abdomen)
2. Continent (requiring volitional voiding or catheterization) or non-continent (freely flowing requiring constant use of a collection bag)

A discussion with your urologist will clarify which would work best for you. In simple terms, the ileal conduit is similar to a Toyota in that is not fancy but tends to be quite reliable and simple with a lower chance of needing revision surgery (about 10% over 10 years). The Studer neobladder it is more like a Jaguar in that when it works dear fantastic but require more maintenance and are more likely to require revision surgery (about 10% over 10 years).

It is important to note that sexual function is always affected in both men and women following cystectomy.Your urologist is there to talk about these issues if they are important to you.

In males, the effects on erectile function are similar to those men undergoing radical prostatectomy (since the prostate is also removed with a radical cystectomy). Nerve-sparing surgery can be performed in select circumstances and some men will retain their ability to obtain erections on their own. Men who are younger and have good pre-operative erectile function are most likely to retain sexual function with nerve sparing. Almost all men, however, will see a decline in their ability to achieve an erection and it is common for the men who do retain erections to require a medication such as Viagra. There are other ways to obtain erections including injections, vacuum constriction devices and penile prostheses. All men lose the ability to ejaculation - and consequently the ability to have children with intercourse.

In females, the vagina is oftern decreased in length and size. Sometimes the nerves responsible for sexual stimulation are affected by surgery.

Unfortunately, once bladder cancer has spread through the body it is not curable. Bladder cancer can spread to many areas but most commonly the lung, liver, bone, kidneys and lymph nodes.

Palliative treatment can take many forms. These include:

1. Palliative chemotherapy
2. Surgery: Usually in the form of resection of bladder tumor for bleeding and pain
3. Radiation: to areas of cancer which of spread to the bone and are causing pain or sometimes to the bladder itself for bleeding not amenable to other treatments