Superficial Bladder Cancer: Diagnosis, Treatment and the Risk of Progression

“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

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.