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).

Urothelium is the name for the surface lining of the urinary tract. Urothelium is composed of several cell layers. In a similar manner to our skin, the urothelium is constantly being renewed - the old cells are shed in the urine and replaced with new cells. Cancers of the urothelium most commonly present with blood in the urine but symptoms such as urgency and frequency of urination can occur. Even a single episode of blood in the urine (especially if the presence of infection cannot be confirmed) may be the result of cancer. Bladder cancer is the most serious cause of hematuria and is found in about 10% of patients with 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.

Any history of smoking is a major risk factor for bladder cancer (just as it is for kidney, lung, throat, esophageal, liver, stomach, pacreatic, colon, rectal cancers). Higher exposure is correlated with increased risk - more cigarettes over a longer duration are an issue. The risk of developing cancer from smoking never goes away completely.

THE BEST THING TO DO IS TO NEVER SMOKE OR IF YOU SMOKE TO QUIT OR SMOKE AS LITTLE AS POSSIBLE. IF YOU HAVE BLADDER CANCER AND SMOKE YOU MUST QUIT RIGHT NOW.

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: Generally recommended for tumors that are (1) high grade, (2) invasive into the lamina propria (stage T1), (3) no mucle in the specimen (with exception of TaG1 and primary cis) or (4) where a complete resection was not feasible. 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 pyelogram are the options depending on the situation.
3. Urine tests: urine cytology has a limited role in the diagnosis of bladder cancer and is NOT a substitute for cystoscopy. Additional urinary markers such as NMP22, Urovysion, Immunocyt, BTA stat, BTA TRAK are not accepted for diagnosis of follow-up because (1) they have limited specificity and (2) in those patients where they would be most useful, surveillance of high-grade tumors, they are counfounded by BCG treatment and bladder surgery.

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.

Worksheet for Surveillance and Treatment of Non-Muscle Invasive Bladder Cancer

NIMBC 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.

There are 2 types of risk associated with the NMIBC.

1. Progression: progression of bladder cancer takes 2 forms. 
   1. 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). 
   2. 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: Grade is determined by examing the specimen under a microscope. High grade tumors are at high risk of recurrence and progression. 
2. CIS: the presence of carcinoma in situ (CIS) is also a marker of progression and recurrence
3. Stage: tumors that invade into the lamina propria are staged T1 and have an increased risk of progression to muscle-invasive or systemic disease. All T1 tumors are high grade with rare exception. Technically speaking, T1 tumors are invasive (but not into the muscle).
4. Number: multiple tumors (multifocal) are at higher risk for recurrence
5. Size: larger tumors (over about 3 cm) are associated with a higher risk of recurrence
6. Prior recurrence rate: tumors that have a recur more frequently are more likely to do so in the future

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

Once the initial evaluation is complete. a patient can be assigned to a Risk Group for the purposes of determining (1) the need for adjuvant treatment and (2) intensity of surveillance. (From the EORTC Guidelines; AUA Guidelines are similar)

Additional (Adjuvant) treatment is sometimes administered at the time of initial resection. The most commonly used agent is a single dose of Mitomycin C (see below). The benefit is to reduce the chances of recurrence by 12% vs. resection alone. This beneficial effect is primarily with small or single tumors (especialest low grade). Post operative Mitomycin C instillation may be skipped if:

1. It is anticipated that BCG or other treatment will be utilized
2. Absorption of leakage of the Mitomycin may occur: extensive TURBT, perforation is suspected, significant bladder irrigation or tumor appears invasive.

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

The European Association of Urology has provided a set of tools for predicting recurrence and progression. It utilizes a scoring system based on the 6 most significant clinical and pathological factors.

IMPORTANT: This tool does NOT take into account the beneficial effects of adjuvant intravesical therapy. The Cueto risk tool does take this into account.