“Superficial bladder cancer” is an older term for cancer confined to the bladder lining or the tissue immediately beneath it. The preferred modern term is non–muscle-invasive bladder cancer, usually abbreviated to NMIBC.

Although these cancers have not invaded the bladder muscle, they do not all behave in the same way. Some are small, low-grade tumours with a relatively low risk of causing serious harm. Others, particularly high-grade T1 cancer and carcinoma in situ, can recur frequently and may progress into the bladder muscle.

Accurate staging and risk classification are therefore essential when deciding between surveillance, intravesical treatment and removal of the bladder.

What is non-muscle-invasive bladder cancer?

The bladder wall consists of several layers. Most bladder cancers begin in the urothelium, the specialised lining on the inside of the bladder.

NMIBC includes three main stages:

• Ta: a papillary tumour growing from the bladder lining without invading the supporting tissue
• T1: cancer that has invaded the connective tissue beneath the lining but has not reached the bladder muscle
• Carcinoma in situ/CIS or Tis: a flat, usually high-grade cancer confined to the bladder lining

CIS can be difficult to see because it may look like a red or inflamed area rather than a typical bladder tumour. Despite being confined to the surface, CIS is biologically aggressive and requires active treatment.

Once cancer enters the bladder muscle, it becomes muscle-invasive bladder cancer—stage T2 or higher. This usually requires a different and more intensive treatment approach.

How common is superficial bladder cancer?

Approximately 70–75% of bladder cancers are non–muscle-invasive when first diagnosed. The remaining patients generally have muscle-invasive or metastatic disease at presentation.

Bladder cancer is considerably more common in men than women and occurs most frequently in people over 60. Women sometimes experience delays in diagnosis when blood in the urine is initially attributed to urinary infection.

Most bladder cancers are urothelial carcinomas. Less common types include squamous cell carcinoma, adenocarcinoma and small-cell or neuroendocrine carcinoma.

What symptoms can bladder cancer cause?

The most common presentation is visible blood in the urine, haematuria.

The urine may appear:

• Pink
• Red
• Rust-coloured
• Tea-coloured
• Normal between episodes

The bleeding is often painless and may disappear for days or weeks. Its disappearance does not mean the underlying problem has resolved.

Other possible symptoms include:

• Microscopic blood detected on a urine test
• Urinary frequency
• A sudden need to urinate
• Burning or discomfort when passing urine
• Recurrent symptoms resembling a urinary tract infection
• Difficulty emptying the bladder
• Pelvic discomfort

CIS may cause urinary urgency, frequency and burning without producing a large visible tumour.

Blood in the urine should always be investigated, particularly in an older adult or someone with a history of smoking. Infection, stones and benign prostate enlargement are common alternative explanations, but bladder and upper urinary tract cancers must be excluded.

What causes bladder cancer?

Bladder cancer develops when genetic damage causes cells in the bladder lining to grow abnormally. In many patients there is no single identifiable cause.

Cigarette smoking

Smoking is the most important preventable risk factor. Carcinogens from tobacco enter the bloodstream, are filtered by the kidneys and remain in contact with the bladder lining in the urine.

The risk increases with the amount and duration of smoking. Stopping smoking remains valuable even after diagnosis because continued smoking may increase the risk of recurrence and progression.

Occupational chemical exposure

Long-term exposure to certain aromatic amines and industrial chemicals can increase risk. Historically, higher-risk industries have included:

• Dye and pigment manufacturing
• Rubber and leather production
• Painting
• Printing
• Metal processing
• Petroleum and chemical industries

Modern workplace protections have reduced—but not eliminated—these exposures.

Other risk factors

Additional risk factors include:

• Increasing age
• Male sex
• Previous pelvic radiotherapy
• Previous cyclophosphamide chemotherapy
• Chronic bladder irritation or inflammation
• Long-term urinary catheterisation
• Certain inherited cancer syndromes, particularly Lynch syndrome
• A personal history of cancer elsewhere in the urinary tract

Bladder cancer is not generally considered hereditary, although familial and genetic risks exist in a minority of patients.

How is bladder cancer investigated?

Medical history and urine testing

Assessment begins with a history of the bleeding, urinary symptoms, smoking and occupational exposure. Urine testing may identify blood, infection or abnormal cells.

A negative urine test after an episode of visible haematuria does not remove the need for investigation.

Urine cytology

Urine cytology examines shed urinary cells under a microscope.

It is most useful for detecting:

• High-grade urothelial cancer
• Carcinoma in situ
• Cancer elsewhere in the urinary tract

Cytology is less sensitive for low-grade tumours, so a negative result does not exclude bladder cancer.

Urinary molecular-marker tests may occasionally provide additional information, but they do not usually replace cystoscopy.

Imaging of the urinary tract

A CT urogram is commonly used to assess:

• Kidneys
• Renal pelvises
• Ureters
• Bladder
• Enlarged lymph nodes or other abnormalities

An ultrasound may be appropriate for selected patients, particularly when CT contrast or radiation should be avoided. However, ultrasound cannot reliably exclude small bladder tumours or CIS.

Flexible cystoscopy

A flexible cystoscope is passed through the urethra under local anaesthetic to inspect the bladder directly.

If a suspicious lesion is found, the next step is generally a formal resection under anaesthesia.

Transurethral resection of bladder tumour: TURBT

TURBT is the central procedure for diagnosing and treating NMIBC.

A rigid telescope is passed through the urethra, and the visible tumour is removed using an electrical loop, bipolar instrument or other resection technique. Tissue is sent to a pathologist to determine:

• Cancer type
• Tumour grade
• Depth of invasion
• Whether bladder muscle is present in the specimen
• Whether muscle invasion has occurred
• Whether variant histology or lymphovascular invasion is present

A complete TURBT should remove all visible tumour where safely possible and include adequate sampling of the underlying bladder muscle.

Enhanced cystoscopy using blue-light fluorescence or narrow-band imaging may help identify small tumours or CIS in selected patients.

When is a second TURBT required?

A repeat resection, usually within approximately two to six weeks, may be recommended when:

• The first resection was incomplete
• No bladder muscle was present in the specimen, apart from selected clearly low-risk Ta tumours
• The tumour is high-grade T1
• There is uncertainty about staging
• Residual tumour is suspected

Repeat TURBT may find residual cancer and occasionally identifies previously unrecognised muscle invasion. It can therefore materially change treatment.

Understanding low-, intermediate-, high- and very-high-risk disease

Treatment is based on more than the word “superficial.” Important risk factors include:

• Ta, T1 or CIS stage
• Low-grade or high-grade pathology
• Number of tumours
• Tumour size
• First occurrence or recurrence
• Frequency of previous recurrences
• Presence of CIS
• Depth and extent of T1 invasion
• Variant histology
• Lymphovascular invasion
• Involvement of the prostatic urethra
• Response to previous BCG treatment

Low-risk NMIBC

This usually involves a first, solitary, small, low-grade Ta tumour without CIS.

These cancers commonly recur but have a very low risk of progressing to muscle-invasive disease.

Intermediate-risk NMIBC

This is a broad group between low and high risk. It may include recurrent, multiple or larger low-grade tumours and selected other tumours without high-risk features.

The pattern and frequency of recurrence help determine treatment intensity.

High-risk NMIBC

High-risk disease includes most:

• High-grade T1 tumours
• Carcinoma in situ
• High-grade Ta tumours with adverse features
• Tumours with other aggressive pathological findings

These cancers have a meaningful risk of entering the bladder muscle and require more intensive treatment and surveillance.

Very-high-risk NMIBC

Very-high-risk disease may include combinations such as extensive high-grade T1 cancer with CIS, lymphovascular invasion, certain aggressive variant histologies or involvement of the prostatic urethra.

For these patients, early radical cystectomy may provide the best chance of cure.

Initial treatment after TURBT

Surveillance for selected low-risk disease

For a completely removed low-risk tumour, treatment may consist of:

• TURBT
• A single immediate dose of intravesical chemotherapy when safe
• Follow-up cystoscopy

Small, recurrent low-grade tumours may sometimes be treated with office fulguration or carefully selected surveillance, depending on the patient and tumour history.

Intravesical treatment

“Intravesical” means that a medication is placed directly into the bladder through a catheter. The medicine is retained for a prescribed time and then drained or passed in the urine.

Because the treatment remains mainly inside the bladder, it generally causes fewer whole-body effects than intravenous chemotherapy.

The role of intravesical mitomycin C

Mitomycin C is a chemotherapy medicine that damages the DNA of rapidly dividing cancer cells.

A single immediate postoperative dose

A single dose may be placed into the bladder shortly after TURBT—preferably within 24 hours—when the procedure has been uncomplicated.

Its purpose is to destroy floating tumour cells and reduce the chance that they implant elsewhere in the bladder. It also treats microscopic tumour cells remaining at the resection site.

This treatment is particularly useful for low-risk tumours and selected intermediate-risk tumours.

Mitomycin should not be administered immediately when there is:

• Suspected bladder perforation
• A very deep or extensive resection
• Significant ongoing bleeding
• A need for continuous bladder irrigation
• Concern that the drug could leak outside the bladder

A course of mitomycin

Patients with intermediate-risk disease may receive weekly mitomycin treatments followed by a variable maintenance schedule. The exact schedule depends on tumour characteristics, previous recurrence pattern and local protocol.

Side effects of mitomycin

Possible side effects include:

• Burning when urinating
• Urinary frequency and urgency
• Bladder discomfort
• Blood in the urine
• Chemical cystitis
• Skin irritation or a rash involving the hands or genital region
• Reduced bladder capacity after repeated severe inflammation
• Infection
• Rare injury if the medication leaks outside the bladder

Patients should follow the treatment unit’s instructions regarding fluid intake, urine handling and washing after treatment.

The role of intravesical BCG

BCG, Bacillus Calmette–Guérin, is a live, weakened form of Mycobacterium bovis. It was originally developed as a tuberculosis vaccine but also stimulates a powerful immune response against bladder cancer cells.

BCG is generally the preferred bladder-preserving treatment for:

• Carcinoma in situ
• High-risk high-grade Ta cancer
• High-grade T1 cancer after adequate resection
• Selected recurrent or aggressive intermediate-risk tumours

How is BCG given?

The usual initial course consists of one bladder instillation each week for six weeks. This is called induction BCG.

Patients who respond may then receive maintenance BCG. For high-risk disease, treatment may continue intermittently for one to three years, depending on tolerance, availability and individual risk.

Maintenance therapy is important because induction BCG alone provides less durable protection against recurrence and progression.

Side effects of BCG

Common short-term effects include:

• Burning when urinating
• Frequency and urgency
• Mild blood in the urine
• Bladder discomfort
• Fatigue
• Low-grade fever
• Flu-like symptoms

These effects usually settle within one or two days.

Less common but potentially serious complications include:

• Severe bacterial urinary infection
• Prostatitis
• Epididymo-orchitis
• Granulomatous inflammation
• Joint inflammation
• Hepatitis or pneumonitis
• Systemic BCG infection or sepsis

A high or persistent fever, shaking chills, breathing difficulty, confusion or severe illness after BCG requires urgent medical assessment.

When should BCG be postponed or avoided?

BCG should not be given:

• Within the early healing period after TURBT, generally the first two weeks
• After traumatic catheterisation
• When visible haematuria is present
• During a symptomatic urinary tract infection
• When bladder perforation is suspected
• In some patients with significant immune suppression
• When previous BCG caused a severe systemic reaction

BCG is handled differently from routine chemotherapy because it contains live bacteria. Patients must follow the treatment centre’s hygiene and urine-disposal instructions.

Mitomycin or BCG: which is better?

Neither treatment is best for every patient.

• Low-risk disease: a single immediate chemotherapy instillation is usually sufficient after complete TURBT.
• Intermediate-risk disease: a course of chemotherapy or one year of BCG may be considered according to recurrence and progression risk.
• High-risk disease: induction and maintenance BCG is generally preferred when bladder preservation is appropriate.
• Very-high-risk disease: early radical cystectomy should be discussed, although BCG may remain an option in carefully selected patients who understand the risk.

BCG is more effective than chemotherapy for preventing recurrence and progression in appropriately selected high-risk disease, particularly when maintenance BCG is completed. It also tends to cause more local and systemic side effects.

What is the chance of developing muscle-invasive cancer?

There is no single percentage that applies to every NMIBC patient.

Across all NMIBC categories, approximately 10–20% of patients may eventually develop muscle-invasive disease, but this average hides enormous differences between low- and high-risk tumours.

Using contemporary EAU risk categories, estimated five-year progression risks can range approximately from:

• Around 1% or less for low-risk disease
• Several per cent for intermediate-risk disease
• Around 10% or higher for high-risk disease
• Approximately 40% or more for very-high-risk disease

At ten years, the estimated risk in very-high-risk patients may exceed 50% without effective additional treatment. These figures are estimates from risk models and do not precisely predict an individual patient’s outcome. BCG, repeat resection, early cystectomy and other treatments can substantially change the risk.

Progression risk is particularly concerning with:

• Persistent or recurrent high-grade T1 cancer
• T1 cancer associated with CIS
• Extensive or multifocal CIS
• Deep invasion into the lamina propria
• Lymphovascular invasion
• Aggressive variant histology
• Prostatic urethral involvement
• Failure to respond to adequate BCG
• Early high-grade recurrence following BCG

Recurrence and progression are different. A small low-grade Ta tumour may recur several times without becoming muscle invasive, while a high-grade T1 tumour may progress after relatively few visible recurrences.

What is BCG-unresponsive bladder cancer?

BCG-unresponsive disease is a specific high-risk situation in which high-grade cancer persists or returns despite an adequate course of BCG within a defined period.

Continuing the same BCG treatment in genuinely BCG-unresponsive disease is unlikely to provide meaningful benefit and could delay curative surgery.

For a patient fit enough for major surgery, radical cystectomy is generally the preferred oncological treatment for BCG-unresponsive high-risk NMIBC.

Alternative bladder-preserving treatments or clinical trials may be considered when a patient:

• Is medically unfit for cystectomy
• Declines cystectomy after informed discussion
• Has a strong preference for bladder preservation and accepts the additional risk

However, the possibility of losing the optimal window for curative surgery must be discussed clearly.

When should removal of the bladder be considered?

Radical cystectomy means removing the bladder, nearby lymph nodes and certain adjacent organs, followed by creating a new way for urine to leave the body.

It may be considered for NMIBC when there is:

• Very-high-risk NMIBC at initial diagnosis
• Persistent high-grade T1 cancer after repeat TURBT
• High-grade T1 cancer with CIS
• Lymphovascular invasion
• Aggressive variant histology, such as micropapillary, plasmacytoid or selected sarcomatoid differentiation
• Extensive CIS that does not respond adequately to BCG
• High-grade recurrence following adequate BCG
• BCG-unresponsive disease
• Tumour involvement of the prostatic urethra or ducts
• Disease that cannot be completely controlled endoscopically
• Frequent, extensive high-grade recurrences
• Progression to muscle-invasive bladder cancer

Cystectomy may sound excessive for a cancer described as “superficial,” but high-grade T1 disease can already possess the biological ability to spread. Delaying surgery until muscle invasion or metastasis develops can reduce the chance of cure.

What does radical cystectomy involve?

In men, surgery commonly removes the:

• Bladder
• Prostate
• Seminal vesicles
• Pelvic lymph nodes

In women, surgery is tailored individually and may involve removal of the bladder, pelvic lymph nodes and selected reproductive organs. Organ-preserving approaches may be possible in carefully selected patients.

Urinary reconstruction options include:

• Ileal conduit: urine drains through a short segment of bowel to a stoma and external bag
• Orthotopic neobladder: bowel is used to create an internal reservoir connected to the urethra
• Continent catheterisable reservoir: an internal pouch is emptied using a catheter through a small abdominal opening

The most appropriate option depends on cancer location, kidney function, bowel health, manual dexterity, general fitness and patient preference.

Radical cystectomy is major surgery. Potential effects on urinary, sexual and bowel function must be balanced against the danger of progression.

Why lifelong surveillance is important

NMIBC has a strong tendency to recur, even after apparently complete treatment. Follow-up commonly includes:

• Regular cystoscopy
• Urine cytology in higher-risk patients
• Periodic upper urinary tract imaging
• Biopsy or repeat TURBT when abnormalities are found
• Monitoring for late treatment complications

Low-risk patients generally require less intensive surveillance. High-risk patients need frequent cystoscopy and cytology, particularly during the first two years, followed by long-term or lifelong monitoring.

The exact schedule should be tailored to the patient’s EAU risk group, pathology, treatment response and general health.

Can recurrence be prevented?

Not every recurrence can be prevented, but patients can improve their general and bladder health by:

• Stopping smoking
• Avoiding occupational carcinogen exposure
• Completing recommended intravesical treatment
• Attending every surveillance cystoscopy
• Reporting recurrent blood in the urine promptly
• Treating urinary infections appropriately
• Maintaining good hydration unless medically restricted

Smoking cessation remains the most important modifiable step.

The bottom line

Most bladder cancers are diagnosed before they enter the bladder muscle, but the term “superficial” should not be mistaken for harmless.

Low-grade Ta tumours frequently recur but rarely progress. High-grade T1 cancer and CIS behave much more aggressively and require complete TURBT, appropriate intravesical therapy and close surveillance.

Mitomycin C is particularly useful for reducing recurrence after TURBT and treating selected low- or intermediate-risk disease. BCG is the main bladder-preserving treatment for high-risk NMIBC and CIS.

Radical cystectomy should be discussed early—not only after muscle invasion—in patients with very-high-risk features, persistent high-grade T1 cancer or BCG-unresponsive disease. For these patients, timely surgery may offer the best chance of cure.

This article provides general information and does not replace individual medical advice. Treatment should be based on formal pathology review, complete staging, medical fitness and multidisciplinary discussion.

References and further reading

• European Association of Urology—Non–Muscle-Invasive Bladder Cancer Guidelines
• American Urological Association—Non–Muscle-Invasive Bladder Cancer Guideline
• Healthdirect Australia—Bladder cancer
• Cancer Council Australia—Bladder cancer
• Cancer Australia—Bladder cancer

So, if you are experiencing blood in your urine and have been identified by your GP as having a possible bladder cancer, come see your Urologist in Brisbane, Dr Jo Schoeman to discuss options with you.

 

Treating the tumour and reducing the risk of it coming back

Bladder cancer has an inconvenient habit: even after a visible tumour has been completely removed, new tumours can sometimes return elsewhere in the bladder.

For selected patients with non-muscle-invasive bladder cancer (NMIBC), previously often called superficial bladder cancer, Mitomycin C can be placed directly into the bladder to destroy residual cancer cells and reduce the chance of recurrence.

This treatment is called intravesical Mitomycin C.

The advantage of intravesical treatment is rather elegant: instead of sending chemotherapy around the entire body, the medication is delivered directly to the bladder lining where it is needed.

What is Mitomycin C?

Mitomycin C is an anti-cancer chemotherapy medication originally derived from Streptomyces bacteria.

When used for bladder cancer, the medication is usually introduced directly into the bladder through a urinary catheter rather than being given intravenously.

This allows a relatively high concentration of chemotherapy to come into direct contact with the urothelium while limiting systemic exposure.

Intravesical Mitomycin is used particularly following transurethral resection of bladder tumour (TURBT) and in selected patients requiring an induction course of intravesical chemotherapy.

Why is Mitomycin C used?

The first and most important treatment for most visible non-muscle-invasive bladder tumours is a TURBT.

During TURBT, the visible tumour is removed and tissue is sent to pathology to determine:

• tumour type
• tumour grade
• depth of invasion
• presence or absence of carcinoma in situ (CIS)
• whether muscle is present in the specimen
• whether cancer has invaded the bladder muscle.

The pathology results allow the tumour to be classified into a recurrence and progression risk category.

Mitomycin C may then be recommended to reduce the risk of tumour recurrence.

When is Mitomycin C used?

There are several different situations in which intravesical Mitomycin C may be considered.

1. A single dose immediately after TURBT

In appropriately selected patients, a single dose of intravesical chemotherapy can be given following TURBT.

Australian eviQ guidance describes administration within 24 hours and preferably within six hours of TURBT. AUA guidance similarly recommends considering a single postoperative instillation within 24 hours for suspected or known low- or intermediate-risk disease.

The purpose is to destroy:

• microscopic tumour cells remaining after resection
• free-floating tumour cells released during surgery
• tumour cells that might otherwise implant elsewhere on the bladder lining.

Think of TURBT as removing the weeds you can see, while the immediate intravesical treatment targets some of the microscopic seeds left behind.

Importantly, a single postoperative instillation primarily reduces recurrence. It has not been shown to provide the same benefit for progression or survival.

2. Induction Mitomycin C

Some patients with intermediate-risk NMIBC may benefit from a course of intravesical chemotherapy rather than a single treatment.

A commonly used regimen is:

Mitomycin C once weekly for six weeks.

Australian eviQ protocols include a six-week induction course for appropriate patients with Ta, T1 or CIS-containing urothelial carcinoma classified as intermediate risk, as an alternative to BCG in selected circumstances.

The exact treatment schedule should be individualised according to:

• tumour grade
• pathological stage
• tumour size
• number of tumours
• previous recurrence rate
• previous intravesical therapy
• presence of CIS
• tolerance of treatment
• overall risk of progression.

What about aggressive superficial bladder cancer?

The term “superficial bladder cancer” can be misleading.

A cancer can remain confined to the bladder lining or lamina propria and still behave aggressively.

Higher-risk features include:

• high-grade urothelial carcinoma
• T1 disease
• carcinoma in situ
• multiple tumours
• large tumours
• frequently recurrent disease
• certain adverse pathological features.

For genuinely high-risk NMIBC, particularly high-grade T1 disease and CIS, intravesical BCG immunotherapy generally has a central role when bladder preservation is appropriate.

Mitomycin C should therefore not automatically be regarded as a substitute for BCG in every patient with aggressive NMIBC.

Treatment needs to be based on the patient’s pathological risk group and previous response to therapy.

In selected circumstances, Mitomycin may nevertheless be considered, including when BCG is unsuitable, poorly tolerated, unavailable or as part of specific sequential intravesical treatment protocols.

Patients with very-high-risk disease also require discussion about whether bladder-preserving intravesical treatment remains appropriate or whether radical cystectomy should be considered.

How does Mitomycin C work?

Mitomycin C is an alkylating anti-tumour agent.

After entering a cancer cell, the drug is activated and produces reactive metabolites that bind to DNA.

It causes cross-linking of DNA strands, preventing the DNA from separating normally.

As a result, the cancer cell has difficulty:

• replicating its DNA
• dividing
• repairing damaged DNA
• continuing normal cellular function.

Ultimately, susceptible tumour cells die.

Because Mitomycin is placed directly into the bladder, it can attack residual malignant cells while generally producing much less systemic exposure than intravenous chemotherapy.

What happens during treatment?

Intravesical treatment is usually performed as an outpatient procedure.

A small urinary catheter is passed through the urethra into the bladder.

The bladder is emptied completely and the Mitomycin solution is then introduced through the catheter.

The catheter may then be removed or temporarily clamped, depending upon the treatment protocol.

The medication is usually retained within the bladder for approximately one to two hours.

Patients are generally advised to restrict fluids beforehand so that the medication is not excessively diluted. Australian eviQ protocols advise restricting fluids for approximately four to six hours before and during treatment, with appropriate adjustment of diuretic medication where relevant.

After the prescribed treatment period, the medication is passed out with the urine or drained through the catheter.

Side effects of intravesical Mitomycin C

Most patients tolerate treatment reasonably well because relatively little of the medication is normally absorbed into the bloodstream.

The commonest problems involve irritation of the bladder.

Chemical cystitis

Mitomycin can irritate the bladder lining and cause:

• burning when passing urine
• urinary frequency
• urgency
• bladder discomfort
• pelvic discomfort
• mild haematuria.

These symptoms frequently develop within hours of treatment and usually settle over the following few days.

Urinary tract infection

A urinary infection can occasionally occur following catheterisation.

Symptoms may include:

• increasing dysuria
• cloudy or offensive urine
• fever
• chills
• worsening urinary frequency
• feeling generally unwell.

A urine culture may be required if infection is suspected.

Skin irritation

Mitomycin is a cytotoxic medication and contact with the skin should be avoided.

Urine containing residual medication may irritate the skin around the urethra or genital area.

Patients should therefore follow the specific hygiene and toilet precautions provided by their treating unit.

Allergic reaction

Hypersensitivity reactions are uncommon but possible.

Symptoms can include:

• skin rash
• itching
• facial redness
• wheezing
• breathlessness
• dizziness
• fever or chills.

Severe allergic reactions are rare but require urgent medical attention.

Less common but important complications

Although uncommon, Mitomycin can occasionally produce significant complications.

Severe chemical cystitis

Repeated bladder irritation can occasionally become severe.

Persistent inflammation may lead to:

• chronic bladder pain
• reduced bladder capacity
• bladder fibrosis
• rarely, bladder contraction.

Patients who already have a small-capacity bladder require particular caution because of the potential risk of further bladder contraction.

Extravasation

One of the most important complications is Mitomycin extravasation.

This means that Mitomycin escapes through an injured or perforated bladder wall into the surrounding tissues.

Although rare, this can produce significant tissue injury.

Reported complications include:

• severe pelvic inflammation
• tissue necrosis
• abscess formation
• bladder injury
• fistula formation
• damage to surrounding genital tissues.

Symptoms can occur immediately, but importantly they may also appear weeks or even months after treatment. Persistent or unexplained pelvic or abdominal pain following intravesical Mitomycin therefore deserves investigation.

An important precaution after TURBT

Intravesical Mitomycin should not simply be administered automatically following every TURBT.

If there is any suspicion that the bladder has been perforated, the medication should not be given.

AUA guidance advises against postoperative intravesical chemotherapy following a suspected perforation or extensive resection. Australian eviQ guidance similarly excludes postoperative Mitomycin when bladder perforation has occurred.

This is important because chemotherapy escaping through a bladder perforation can cause substantial tissue injury.

When should Mitomycin treatment be postponed?

Intravesical Mitomycin is generally avoided or postponed in the presence of:

• visible haematuria
• confirmed urinary tract infection
• traumatic catheterisation
• fever or unexplained febrile illness
• known allergy to Mitomycin
• suspected or confirmed bladder perforation
• significant bladder injury following surgery.

Australian protocols specifically advise against treatment following traumatic catheterisation, with visible haematuria, active UTI or recent bladder injury.

If catheterisation is traumatic or produces bleeding on the day of treatment, the treatment is usually deferred.

Does Mitomycin cause the usual chemotherapy side effects?

Usually not.

Because the medication is placed into the bladder rather than routinely given intravenously, systemic absorption is generally very low.

Therefore classic chemotherapy problems such as:

• hair loss
• severe nausea
• widespread immunosuppression
• profound fatigue
• bone marrow suppression

are unusual with standard intravesical therapy.

Systemic absorption can occur rarely, however, particularly when the bladder lining has been significantly disrupted. Myelosuppression is considered a potential but uncommon complication, and a full blood count may be appropriate if a patient becomes unexpectedly systemically unwell.

Precautions after treatment

Mitomycin remains a cytotoxic chemotherapy drug, even when delivered directly into the bladder.

Patients should therefore follow their treating unit’s instructions carefully regarding:

• toilet hygiene
• handling urine
• washing contaminated skin
• hand washing
• fluid intake following treatment
• management of contaminated clothing.

Patients should also tell their treating team about all medications they are taking and whether they are receiving antibiotics, diuretics or other cancer treatments.

When should you seek urgent medical advice?

Contact your treating team promptly if you develop persistent or worsening urinary symptoms after treatment.

More urgent assessment is required for symptoms such as:

• temperature of 38°C or higher
• inability to pass urine
• significant or persistent haematuria
• severe pelvic or abdominal pain
• chills or shaking
• shortness of breath
• severe rash or suspected allergic reaction
• persistent symptoms that are worsening rather than settling.

Severe pelvic or abdominal pain following intravesical Mitomycin is particularly important because, although uncommon, it may indicate bladder injury or extravasation.

Mitomycin does not replace surveillance

One of the most important points about NMIBC is that successful treatment does not mean surveillance can stop.

Even after apparently complete removal and intravesical chemotherapy, urothelial tumours can recur.

Depending upon the original tumour’s risk category, ongoing surveillance may include:

• flexible cystoscopy
• urine cytology
• repeat TURBT
• upper urinary tract imaging
• further intravesical treatment.

Patients with higher-risk disease require considerably closer surveillance than those with a solitary low-grade tumour.

Mitomycin C versus BCG

These treatments are sometimes discussed together, but they work differently.

Mitomycin C is chemotherapy. It directly damages the DNA of susceptible tumour cells.

BCG is immunotherapy. It stimulates a local immune response within the bladder that attacks urothelial cancer cells.

The appropriate treatment depends upon the biological behaviour and risk category of the tumour.

For some patients, Mitomycin provides an effective and relatively well-tolerated strategy for reducing recurrence. For patients with higher-risk disease, BCG or more aggressive treatment may be preferable.

The important question is therefore not simply:

“Mitomycin or BCG?”

It is:

“What is the risk of this particular bladder cancer recurring or progressing, and which treatment provides the safest and most effective way of reducing that risk?”

The Bottom Line

Intravesical Mitomycin C is an established treatment for selected patients with non-muscle-invasive urothelial carcinoma of the bladder.

It may be used as a single treatment immediately following TURBT or as a course of intravesical chemotherapy in appropriately selected patients.

By placing chemotherapy directly into the bladder, Mitomycin can destroy residual cancer cells and reduce tumour recurrence while limiting exposure of the rest of the body.

Most side effects are related to temporary bladder irritation. Serious complications such as bladder injury, extravasation, fibrosis and tissue necrosis are uncommon but important, which is why careful patient selection and attention to precautions are essential.

And perhaps the most important message: Mitomycin reduces risk. It does not make follow-up optional.

Bladder cancer has a reputation for making return appearances, so regular cystoscopic surveillance remains an essential part of treatment.

This information is intended for general education and should not replace individual medical advice. Treatment of non-muscle-invasive bladder cancer should be tailored to the tumour’s stage, grade and recurrence/progression risk, previous treatments and the individual patient’s circumstances.

So, there are options in reducing your risk for recurrences. Speak to your Brisbane urologist, Dr Jo Schoeman about reducing your risks.

Understanding non-muscle-invasive bladder cancer, TURBT, intravesical therapy and long-term surveillance

Being told that you have a bladder tumour is understandably alarming. The reassuring part is that many bladder cancers are discovered while they are still confined to the inner layers of the bladder and have not invaded the bladder muscle.

This is called non-muscle-invasive bladder cancer (NMIBC), historically referred to as superficial bladder cancer. NMIBC includes Ta tumours, T1 tumours and carcinoma in situ (CIS). These tumours behave very differently depending on their stage, grade and other pathological features, so treatment is tailored according to the risk of the cancer coming back (recurrence) or becoming more aggressive (progression).

The good news is that most NMIBC can initially be treated through the urethra without making an incision in the abdomen. The less convenient news is that bladder cancer has a habit of returning, which is why careful surveillance becomes an important part of treatment.

What is urothelial carcinoma?

The inside of the bladder is lined by specialised cells called urothelial cells. Cancer arising from these cells is known as urothelial carcinoma.

Urothelial carcinoma can develop anywhere along the urinary tract, including the:

• renal collecting system
• ureters
• bladder
• urethra

The bladder is by far the most common site.

When a bladder tumour has not invaded the muscular wall of the bladder, it is classified as non-muscle-invasive bladder cancer.

What causes bladder cancer?

There is rarely one identifiable cause. Instead, bladder cancer develops following genetic changes within urothelial cells, often influenced by environmental exposures over many years.

Smoking

Cigarette smoking is the most important preventable risk factor for bladder cancer.

Chemicals absorbed through cigarette smoke enter the bloodstream, are filtered by the kidneys and eventually become concentrated in the urine. The bladder lining is therefore repeatedly exposed to these carcinogens.

Stopping smoking after a bladder cancer diagnosis is strongly encouraged.

Other risk factors

These include:

• increasing age
• occupational exposure to certain industrial chemicals
• previous pelvic radiotherapy
• previous treatment with cyclophosphamide
• chronic urinary tract irritation in selected circumstances
• a personal history of urothelial carcinoma

Sometimes there is no obvious risk factor at all.

How does bladder cancer present?

Blood in the urine

The classic presentation is haematuria, or blood in the urine.

This may be:

Visible haematuria

The urine may suddenly become:

• pink
• red
• burgundy
• tea-coloured
• or contain blood clots

Importantly, bleeding from a bladder tumour is frequently painless and intermittent.

The bleeding may disappear completely for days, weeks or even months. Its disappearance does not necessarily mean that the underlying problem has resolved.

Unexplained visible haematuria should always be investigated.

Microscopic haematuria

Sometimes blood is detected only on urine testing and cannot be seen with the naked eye.

Other possible symptoms

Some patients, particularly those with carcinoma in situ (CIS), may experience bladder irritation rather than obvious bleeding.

Symptoms can include:

• urinary frequency
• urgency
• burning when passing urine
• nocturia
• pelvic or bladder discomfort
• recurrent symptoms resembling a urinary tract infection

Persistent urinary symptoms with repeatedly negative urine cultures may therefore warrant further investigation.

Investigating suspected bladder cancer

The investigation usually involves a combination of urine testing, imaging and direct examination of the bladder.

Urine testing

A urine sample may be checked for:

• blood
• infection
• inflammatory cells
• abnormal malignant cells

Urine cytology

Urine cytology examines cells shed from the urinary tract under a microscope.

It is particularly useful for detecting high-grade urothelial carcinoma and CIS, but is considerably less sensitive for low-grade tumours.

A negative cytology therefore does not exclude bladder cancer.

Imaging the urinary tract

Patients with haematuria may require imaging of the kidneys, ureters and bladder.

Depending on the clinical circumstances, this may include:

• renal tract ultrasound
• CT urinary tract imaging
• CT urography

CT urography is particularly useful when investigating haematuria because urothelial carcinoma can occasionally arise within the renal collecting system or ureters as well as the bladder.

Cystoscopy

A cystoscopy allows the urologist to look directly inside the bladder.

A thin flexible telescope is passed through the urethra, usually under local anaesthetic.

Most bladder tumours have a characteristic appearance. They may resemble delicate fronds, seaweed or a tiny underwater cauliflower attached to the bladder wall.

Flat lesions such as CIS can be much more difficult to see.

If a suspicious lesion is identified, the next step is usually a transurethral resection of bladder tumour (TURBT).

TURBT: biopsy and removal of the bladder tumour

TURBT stands for:

Transurethral Resection of Bladder Tumour

This procedure serves two important purposes:

1. Treatment: removing all visible tumour where possible.
2. Diagnosis and staging: providing tissue for the pathologist to determine exactly what type of tumour is present and how deeply it has invaded.

The procedure is usually performed under general or spinal anaesthesia.

A telescope called a resectoscope is passed through the urethra into the bladder. The tumour is carefully removed, usually using an electrical or bipolar resection system.

There is therefore generally no external incision or abdominal scar.

Why obtaining bladder muscle matters

An adequate TURBT should establish how deeply the tumour extends.

For many tumours, particularly T1 and high-grade lesions, the specimen should contain muscularis propria (detrusor muscle) so that the pathologist can determine whether the cancer has reached the muscle layer. The pathological report should document the presence and involvement of muscularis propria where applicable.

This distinction dramatically changes treatment.

Understanding bladder cancer staging

A simplified view of the bladder wall is:

Urine

↓

Urothelium

↓

Lamina propria

↓

Detrusor muscle

↓

Fat surrounding the bladder

The important early stages are:

Ta

The tumour is confined to the urothelial surface and has not invaded the supporting tissue underneath.

Tis: carcinoma in situ

CIS is a flat, high-grade malignant lesion confined to the urothelium.

Unlike the typical papillary bladder tumour, CIS may be difficult to identify visually.

Despite being superficial anatomically, CIS is biologically aggressive and requires appropriate treatment.

T1

The tumour has invaded into the lamina propria, but has not invaded the muscularis propria.

T1 disease, particularly high-grade T1 disease, carries a greater risk of recurrence and progression.

T2

The cancer has invaded the bladder muscle.

Once muscle invasion is identified, the disease is no longer classified as NMIBC and requires a different treatment pathway.

Stage and grade are not the same thing

This distinction frequently causes confusion.

Stage describes how deeply the cancer has travelled into the bladder wall.

Grade describes how abnormal and biologically aggressive the cancer cells appear under the microscope.

A tumour may therefore be superficial but still be high grade.

Broadly, urothelial tumours are classified as:

Low grade

These generally grow more slowly and have a relatively low risk of progressing to muscle-invasive cancer, although they may recur.

High grade

These cells look significantly abnormal and have a greater potential for:

• recurrence
• invasion
• progression
• spread beyond the bladder

Risk stratification

Following TURBT, the tumour is classified into a risk category.

Risk assessment considers factors such as:

• stage
• grade
• tumour size
• number of tumours
• previous recurrence rate
• presence of CIS
• T1 disease
• pathological features including lymphovascular invasion
• certain variant histological subtypes

This classification helps determine whether the patient requires:

TURBT alone → intravesical chemotherapy → BCG → or, in selected very-high-risk situations, consideration of radical cystectomy.

Modern guidelines emphasise risk-adapted rather than one-size-fits-all management.

Do I need another TURBT?

Sometimes.

A second-look or re-staging TURBT may be recommended when:

• the initial tumour was incompletely removed
• adequate muscle was not present in an important specimen
• high-grade disease is present in selected circumstances
• T1 disease is identified
• there is concern that the original tumour may have been understaged
• certain variant histologies are identified

The aim is to ensure that residual tumour has not been left behind and, crucially, that muscle-invasive disease has not been missed.

Intravesical treatment

Intravesical simply means that medication is placed directly into the bladder through a catheter.

This allows the treatment to come into direct contact with the bladder lining while reducing systemic exposure compared with intravenous chemotherapy.

Two important treatments are:

Mitomycin C

and

BCG

They are not interchangeable and are used for different risk groups.

Intravesical Mitomycin C

Mitomycin C is a chemotherapy drug that can be placed directly into the bladder.

Immediate Mitomycin C following TURBT

For appropriate patients with suspected low- or intermediate-risk NMIBC, a single postoperative instillation of intravesical chemotherapy may be given soon after TURBT.

Current guidelines recommend that, when used, the immediate instillation should generally occur within 24 hours of TURBT.

Its purpose is to destroy microscopic tumour cells remaining in the bladder and tumour cells released during the resection.

This reduces the risk of recurrence.

When should immediate Mitomycin C be avoided?

It should generally not be administered if there is:

• suspected bladder perforation
• significant bleeding requiring bladder irrigation
• an extensive or very deep resection where perforation is a concern

This is important because chemotherapy leaking outside the bladder can cause significant local tissue injury.

Further courses of intravesical chemotherapy

Selected patients with recurrent or intermediate-risk low-grade NMIBC may receive a course of intravesical chemotherapy rather than simply a single postoperative dose.

The exact drug, schedule and duration depend upon the tumour risk profile and local treatment protocols.

Side effects of intravesical Mitomycin C

Most patients tolerate treatment reasonably well.

Possible side effects include:

• urinary frequency
• urgency
• burning
• bladder discomfort
• haematuria
• chemical cystitis
• skin irritation if the medication contacts the genital skin

Rarely, severe bladder inflammation or tissue injury can occur.

Intravesical BCG

BCG stands for Bacillus Calmette-Guérin.

Yes, it originated as a tuberculosis vaccine. In the bladder it performs a completely different job.

BCG stimulates a powerful local immune response against urothelial cancer cells and remains one of the most effective bladder-preserving treatments for high-risk NMIBC.

Who should receive BCG?

BCG is principally considered for patients with:

• high-grade Ta tumours
• high-grade T1 tumours
• carcinoma in situ
• other appropriately selected high-risk or intermediate-risk NMIBC

For high-risk NMIBC, full-dose BCG with maintenance treatment for one to three years remains a guideline-supported treatment, while immediate radical cystectomy should also be discussed in appropriate high-risk and particularly very-high-risk disease.

How is BCG given?

BCG is inserted into the bladder through a small catheter.

A typical induction course consists of:

One treatment per week for six weeks.

The solution is retained within the bladder for a prescribed period and then passed out in the urine.

Patients who respond may subsequently receive maintenance BCG.

A commonly used maintenance approach involves three weekly treatments at defined intervals after induction. In high-risk disease, guideline schedules may continue maintenance for up to three years depending upon tumour risk, treatment tolerance and BCG availability.

When should BCG not be given?

BCG is a live attenuated organism and must be administered carefully.

Treatment should generally be postponed in patients with:

• visible haematuria
• symptomatic urinary tract infection
• traumatic catheterisation
• very recent TURBT

The EAU lists the first two weeks following TURBT, visible haematuria, traumatic catheterisation and symptomatic urinary infection as absolute contraindications to an intravesical BCG instillation.

Side effects of BCG

A degree of bladder irritation is common.

Patients may experience:

• frequency
• urgency
• burning
• bladder discomfort
• mild haematuria
• fatigue
• low-grade fever
• flu-like symptoms

These symptoms usually settle.

Rarely, BCG can cause a more significant systemic infection or inflammatory reaction.

Persistent high fever, chills, marked deterioration or severe illness following BCG requires urgent medical assessment.

What if BCG does not work?

Persistent or recurrent high-grade cancer despite adequate BCG treatment requires careful reassessment.

This situation should not simply be managed by repeatedly giving more BCG indefinitely.

Patients meeting criteria for BCG-unresponsive NMIBC should be counselled regarding further treatment, and radical cystectomy remains the oncological standard for suitable patients with BCG-unresponsive high-risk disease. Bladder-preserving alternatives may be considered for patients who are medically unsuitable for cystectomy or decline surgery, ideally within appropriate specialist or clinical-trial pathways.

When should radical cystectomy be considered?

Most patients with superficial bladder cancer will never require removal of their bladder.

However, early radical cystectomy may be discussed for very-high-risk disease, including selected patients with:

• aggressive high-grade T1 disease
• associated CIS
• variant histology
• lymphovascular invasion
• persistent high-grade disease
• BCG-unresponsive disease
• other features associated with a high risk of progression

The decision involves balancing the risks of major surgery against the danger of allowing biologically aggressive disease to progress.

Surveillance after treatment

Removing the tumour is only the first chapter.

NMIBC has a significant tendency to recur, and some high-risk tumours can progress. Consequently, regular cystoscopic surveillance is essential.

The first surveillance cystoscopy is generally performed approximately three months after TURBT.

After this, surveillance is tailored to the patient’s risk category.

A practical risk-adapted surveillance framework

Risk group	Typical cystoscopy schedule	Cytology	Upper tract imaging
Low risk	3 months, 12 months, then annually	Usually not routinely required	Not routinely required
Intermediate risk	3 months, then approximately every 6 months for 2 years, then annually	Risk-dependent	Selected patients
High / very high risk	Approximately every 3 months initially, with intervals gradually extended	Usually included	Periodic upper urinary tract imaging

The 2026 EAU guidance continues to recommend that follow-up intensity and duration be determined by the patient’s risk category, with the first cystoscopy at three months.

Individual surveillance schedules may differ depending on pathology, previous recurrences, treatment response, age, comorbidities and the treating urologist’s protocol.

Why is surveillance so important?

A recurrence does not automatically mean that treatment has failed or that the cancer has become life-threatening.

Low-grade papillary tumours may recur while remaining superficial and biologically low risk.

The purpose of surveillance is to identify recurrence early, while it can still be treated appropriately.

High-grade disease requires closer attention because the consequences of missing progression are considerably greater.

Can bladder cancer come back after years?

Yes.

This is why follow-up for intermediate- and particularly high-risk NMIBC can continue for many years.

The frequency of cystoscopy usually decreases when repeated examinations remain clear, but high-risk patients generally require prolonged surveillance.

What can I do after a diagnosis?

One of the most important modifiable factors is:

Stop smoking

Smoking cessation reduces exposure to the carcinogens responsible for many urothelial cancers and provides substantial additional cardiovascular, respiratory and general health benefits.

Patients should also:

• attend every scheduled cystoscopy
• report recurrent visible haematuria
• complete prescribed intravesical treatment
• report significant side effects from BCG or chemotherapy
• maintain appropriate hydration unless medically restricted
• discuss occupational chemical exposure where relevant

The bottom line

Non-muscle-invasive urothelial carcinoma is bladder cancer that has not invaded the muscular wall of the bladder.

The pathway typically involves:

Haematuria or urinary symptoms
↓
Urine tests + imaging
↓
Cystoscopy
↓
TURBT and pathological examination
↓
Stage + grade + risk classification
↓
Risk-adapted treatment

For some patients, TURBT followed by surveillance may be sufficient.

Others benefit from intravesical Mitomycin C or another intravesical chemotherapy to reduce recurrence.

Patients with high-grade disease, T1 cancer or CIS frequently require intravesical BCG, usually incorporating induction and maintenance treatment.

Very-high-risk or BCG-unresponsive disease may require consideration of radical cystectomy.

Most importantly, bladder cancer treatment does not finish when the initial tumour has been removed. Long-term cystoscopic surveillance is an integral part of treatment.

A final word

Bladder cancer can be a persistent visitor, but surveillance means we do not leave the front door unattended.

Early detection, complete TURBT, accurate pathological staging, appropriate intravesical therapy and structured follow-up provide the best opportunity to keep non-muscle-invasive bladder cancer under control.

This information is intended as general patient education and does not replace individual assessment or treatment advice from your urologist. Management should be tailored to the pathology, tumour risk category, general health and individual circumstances of each patient.

So, come see your friendly Brisbane urologist, Dr Jo Schoeman to discuss this with you.