Tag Archive for: blood in urine

Tranexamic Acid for Radiation Cystitis: Benefits, Duration and Important Risks

/0 Comments/in , /by

Blood in the urine after pelvic radiotherapy can be frightening. It may appear months or even many years after treatment for prostate, bladder, rectal or gynaecological cancer. One possible cause is radiation cystitis: delayed injury to the bladder lining and its small blood vessels.

Tranexamic acid is sometimes considered when bleeding is troublesome. It can help stabilise blood clots, but it does not repair the radiation injury itself and it is not suitable for every patient. In urinary tract bleeding, preventing a clot from dissolving may reduce bleeding but may also allow a larger clot to obstruct the bladder or ureter. Careful patient selection and medical supervision are therefore essential.

Seek urgent medical attention if you cannot pass urine, are passing large clots, feel faint or breathless, develop fever or flank pain, or the bleeding is heavy or worsening.

What is radiation cystitis?

Radiotherapy can cause progressive damage to the bladder’s small blood vessels. These vessels may become fragile and bleed easily. Patients may experience visible haematuria, urinary frequency, urgency, pain or recurrent clot retention.

Radiation cystitis should not be assumed simply because a patient has previously received radiotherapy. Infection, urinary stones, recurrent or new cancer, kidney disease and medication-related bleeding must also be considered. Assessment may include urine testing and culture, a full blood count, renal function, imaging of the upper urinary tract and cystoscopy. Biopsy is used selectively because irradiated tissue heals poorly.

How does tranexamic acid work?

The body normally breaks down blood clots through a process called fibrinolysis. Tranexamic acid blocks the binding of plasminogen and plasmin to fibrin, slowing this breakdown. It is therefore an antifibrinolytic medicine: it helps a clot remain in place rather than acting as a blood-clotting factor itself.

For radiation cystitis, tranexamic acid is intended to control active bleeding. It does not remove abnormal radiation-induced blood vessels, reverse fibrosis or prevent future bleeding once the medicine is stopped.

How effective is it for radiation cystitis?

The evidence is limited. Tranexamic acid has been used for haematuria from several causes, and a small randomised emergency-department study found that intravenous treatment reduced the amount of bladder irrigation required to clear the urine. However, it did not significantly reduce haemoglobin loss or transfusion requirements. Importantly, this study included mixed causes of haematuria and was not designed specifically for radiation cystitis.

The Canadian Urological Association best-practice report concluded that evidence was insufficient to make a formal recommendation for tranexamic acid in radiation-induced haemorrhagic cystitis. Later narrative reviews have reached a similar conclusion. Intravesical tranexamic acid, placed directly into the bladder, has shown encouraging results in small emergency-department studies of gross haematuria, but evidence specific to radiation cystitis is still inadequate and this remains a specialist, non-standard use.

In practice, tranexamic acid may be considered as a temporary adjunct in selected patients while the cause and severity of bleeding are assessed, or while more definitive treatment is arranged. It should not delay bladder washout, clot evacuation, cystoscopic treatment, hyperbaric oxygen therapy, embolisation or other appropriate care when these are required.

How long can tranexamic acid be used?

There is no well-supported universal duration for radiation cystitis. The Australian product information for oral tranexamic acid describes treatment of haematuria while blood remains macroscopically visible, but radiation cystitis is a recurrent condition and that instruction should not be interpreted as approval for indefinite therapy.

For this indication, treatment is generally best regarded as a short, medically supervised course for an active bleeding episode. The exact dose and duration depend on:

  • whether bleeding is mild, ongoing or causing clot retention;
  • whether the source is the bladder or upper urinary tract;
  • kidney function, because tranexamic acid is largely eliminated in the urine;
  • previous blood clots, cardiovascular risk and pro-thrombotic medicines;
  • anticoagulant or antiplatelet therapy; and
  • the response to treatment and need for definitive therapy.

There is no good evidence supporting continuous long-term tranexamic acid as prophylaxis for recurrent radiation cystitis. If bleeding has not clearly improved within a short course, recurs promptly after treatment, or requires repeated courses, the diagnosis and management plan should be reassessed. Longer or repeated use should occur only under specialist supervision, with renal function and thrombotic risk reviewed.

Patients should not start, extend, repeat or stop prescribed tranexamic acid without discussing it with their treating clinician.

Important side effects

Common or less serious adverse effects may include:

  • nausea, vomiting, diarrhoea or abdominal discomfort;
  • headache, dizziness or fatigue; and
  • muscle or joint discomfort.

Potentially serious adverse effects include:

Blood clots

Deep-vein thrombosis, pulmonary embolism, stroke, heart attack and other arterial or venous thromboses are uncommon but potentially serious. Risk assessment is particularly important in patients with an active or previous clot, known thrombophilia, active malignancy, prolonged immobility or concurrent pro-thrombotic medication.

Urgent assessment is required for new unilateral leg pain or swelling, sudden chest pain, shortness of breath, coughing blood, weakness on one side, difficulty speaking or sudden severe headache.

Clot retention and urinary obstruction

Tranexamic acid may stabilise clots within the urinary tract. This can contribute to painful bladder clot retention. It is particularly concerning when bleeding arises from a kidney or ureter, because a clot may obstruct the ureter and cause flank pain, hydronephrosis or loss of kidney function. Upper-tract haematuria therefore warrants particular caution and specialist assessment.

Kidney impairment

Most tranexamic acid is excreted unchanged through the kidneys. The dose must be reduced when renal function is impaired; accumulation increases the risk of toxicity, including neurological adverse effects. Significant renal impairment may make treatment inappropriate or require a substantially altered regimen.

Seizures

Seizures are a recognised, dose-related risk, reported particularly with high intravenous doses and when the medicine accumulates in renal impairment. A history of seizures requires careful consideration.

Visual disturbance

Rare visual effects, including altered colour vision, have been reported. New visual symptoms require prompt review and usually discontinuation pending medical advice. Ophthalmic monitoring may be considered when prolonged treatment is unavoidable.

Severe allergy

Facial or throat swelling, wheeze, breathing difficulty or a widespread blistering rash requires emergency care.

Who may not be suitable for treatment?

Tranexamic acid may be contraindicated or require particular caution in people with:

  • active thromboembolic disease or a substantial history or risk of thrombosis;
  • significant kidney impairment;
  • upper urinary tract bleeding or suspected ureteric obstruction;
  • a history of seizures;
  • acquired disturbances of colour vision;
  • disseminated intravascular coagulation unless managed by an experienced clinician; or
  • hypersensitivity to tranexamic acid.

Medication review is essential. Anticoagulants and antiplatelet agents can worsen bleeding, but stopping them may cause stroke, pulmonary embolism, heart attack or coronary-stent thrombosis. They should not be stopped merely because haematuria develops without an individual risk assessment involving the prescribing clinician. Likewise, combining tranexamic acid with pro-thrombotic medicines requires caution.

Where does it fit in the management pathway?

Management is guided by severity. Initial care may include resuscitation, correction of significant anaemia or coagulopathy, a large-bore catheter, manual washout and continuous bladder irrigation. Cystoscopy permits clot evacuation, exclusion of tumour and cautery or laser treatment of bleeding areas.

For persistent or recurrent radiation cystitis, options may include intravesical agents, hyperbaric oxygen therapy, selective arterial embolisation and, rarely, urinary diversion or cystectomy. Hyperbaric oxygen is one of the better-studied treatments because it aims to improve tissue oxygenation and new blood-vessel formation rather than merely suppressing an episode of bleeding.

Tranexamic acid may have a role as a bridge or adjunct in a carefully selected patient. Its value must always be balanced against the danger of thrombosis and urinary tract obstruction.

The take-home message

Tranexamic acid can reduce haematuria in some patients, but evidence specifically for radiation cystitis is weak. It is not a cure and should usually be used only for a short, active bleeding episode under medical supervision. There is no established safe or effective duration for continuous long-term use in radiation cystitis. Kidney function, clotting history, the anatomical source of bleeding and concurrent medication must be reviewed before treatment.

Visible haematuria after radiotherapy always deserves proper investigation, particularly if it is recurrent, contains clots or is accompanied by difficulty passing urine.

This article provides general information and does not replace individual medical advice. Tranexamic acid is a prescription medicine in Australia; its use for radiation cystitis must be individualised by the treating clinician.

References

  1. Goucher G, Saad F, Lukka H, Kapoor A. Canadian Urological Association Best Practice Report: Diagnosis and management of radiation-induced hemorrhagic cystitis. Can Urol Assoc J. 2019;13(2):15–23. doi:10.5489/cuaj.5788
  2. Moharamzadeh P, Ojaghihaghighi S, Amjadi M, Rahmani F, Farjamnia A. Effect of tranexamic acid on gross hematuria: a pilot randomized clinical trial study. Am J Emerg Med. 2017;35(12):1922–1925. doi:10.1016/j.ajem.2017.09.012
  3. Abramowitz D, et al. Clinical management of radiation cystitis: a narrative review. AME Med J. 2021;6:30. Clinical management of radiation cystitis
  4. Choi H, et al. Impact of intravesical administration of tranexamic acid on gross hematuria in the emergency department: a before-and-after study. Am J Emerg Med. 2023;68:118–122. doi:10.1016/j.ajem.2023.03.010
  5. Pfizer Australia. Cyklokapron (tranexamic acid) Australian Product Information. Current product information should be checked through the Therapeutic Goods Administration or the sponsor before prescribing. Australian product information
  6. DailyMed. Tranexamic acid injection—prescribing information. US National Library of Medicine. DailyMed drug labelling
  7. Chauncey JM, Wieters JS. Tranexamic Acid. In: StatPearls. Updated 2025. NCBI Bookshelf

 

Cxbladder Urine Testing for Urothelial Cancer: Diagnosis, Surveillance, Accuracy and Pitfalls

/0 Comments/in , /by

Bladder cancer surveillance can feel repetitive: another cystoscopy, another urine sample and another anxious wait. This has driven interest in urine-based molecular tests that may help identify patients at very low risk of recurrent urothelial carcinoma.

One such platform is Cxbladder. It is sometimes informally called “Cx View,” but the established commercial name is Cxbladder. The version designed for patients who already have a history of urothelial cancer is Cxbladder Monitor.

Cxbladder can provide useful additional information, particularly when the clinical question is whether cancer is unlikely to be present. However, it is not a stand-alone diagnosis, does not show where a tumour is located and should not automatically replace cystoscopy, imaging or biopsy.

What is the Cxbladder test?

Cxbladder is a non-invasive laboratory test performed on voided urine. It measures the expression of five messenger RNA biomarkers associated with urothelial carcinoma:

  • IGFBP5
  • HOXA13
  • MDK
  • CDK1
  • CXCR2

The result is calculated using a proprietary algorithm. Depending on the particular Cxbladder assay, clinical variables may also be incorporated into risk assessment.

The test looks for a molecular signal shed into urine by urothelial cancer cells. It does not provide a picture of the bladder, determine tumour size or location, reliably assign stage or grade, or replace histopathological examination.

The different Cxbladder tests are not interchangeable

The name “Cxbladder” covers several tests developed for different clinical settings.

Cxbladder Triage

This is designed primarily to help identify patients with haematuria who have a low probability of urothelial cancer. It prioritises sensitivity and negative predictive value, accepting lower specificity.

Cxbladder Detect

This is intended to help identify urothelial cancer in patients undergoing diagnostic evaluation, such as those presenting with haematuria. It is not specifically designed for post-treatment surveillance.

Cxbladder Monitor

This is designed for patients with a previous diagnosis of urothelial carcinoma who are undergoing surveillance for recurrence. It is the most relevant assay for follow-up after treatment of non-muscle-invasive bladder cancer (NMIBC).

Newer or region-specific Cxbladder combinations may use different algorithms and thresholds. Performance figures from one assay should not be transferred uncritically to another.

How is the sample collected?

The patient provides a voided urine sample into the supplied collection system. No catheter is normally required. The sample is stabilised and sent to a specialised laboratory for analysis.

Collection instructions must be followed carefully. Insufficient urine, incorrect handling, contamination, excessive delay or failure to use the correct collection container may produce an invalid or unreliable result. A repeat sample may occasionally be required.

What role can Cxbladder have in initial diagnosis?

For a patient with visible or microscopic haematuria, Cxbladder may help refine the estimated probability of urothelial cancer. A low-risk result can be reassuring, especially in a carefully selected lower-risk patient.

However, haematuria can be caused by bladder cancer, upper-tract urothelial cancer, renal cancer, urinary stones, infection, benign prostate bleeding and other conditions. A urine biomarker cannot evaluate all these causes. Depending on age, symptoms and risk factors, the patient may still require cystoscopy and upper-tract imaging.

Current guideline-based haematuria assessment is risk stratified. Urine markers may support shared decision-making in selected patients, but should not delay investigation of visible haematuria or replace a complete assessment in a patient at significant risk.

How may Cxbladder Monitor be used in surveillance?

After treatment of NMIBC, conventional surveillance may include:

  • cystoscopy;
  • urine cytology in selected intermediate- and high-risk patients;
  • upper-tract imaging when indicated; and
  • biopsy or TURBT when a suspicious lesion is found.

Cxbladder Monitor may be added to this pathway to help identify patients with a low probability of recurrent disease. In selected lower-risk situations, a negative result may support extending the interval to cystoscopy or avoiding an additional cystoscopy, provided this forms part of a urologist-directed protocol.

A positive result does not prove that a recurrence is present. It usually means that further assessment, commonly cystoscopy, and sometimes cytology, enhanced cystoscopy, imaging or biopsy is warranted.

The test should be used particularly cautiously in patients with previous high-grade disease, carcinoma in situ (CIS), recent positive cytology, new haematuria, concerning symptoms or a history suggesting a high risk of progression. Missing high-grade recurrence carries much greater consequences than postponing a procedure in a genuinely low-risk patient.

How accurate is Cxbladder Monitor?

Published validation data have generally shown that Cxbladder Monitor is better at ruling out recurrence than confirming it.

Across key validation studies, reported performance has been approximately:

  • sensitivity: 91–93%;
  • negative predictive value (NPV): 96–97%;
  • specificity: approximately 34–39%; and
  • positive predictive value (PPV): approximately 21% in some validation cohorts.

One comparative study reported sensitivity of 91% and NPV of 96% for Cxbladder Monitor, outperforming cytology, NMP22 and UroVysion FISH for sensitivity in that study population. Another validation reported sensitivity of 93% and NPV of 97%.

These results need careful interpretation.

What does a negative predictive value of 97% mean?

In a study population similar to the one in which that figure was measured, about 97 of every 100 patients with a negative result did not have a detected recurrence, while approximately three could still have disease.

It does not mean the test is “97% accurate” in every patient. NPV changes with the underlying prevalence of recurrence. It will usually look higher in a low-risk population and lower when recurrence is common.

Why is the positive predictive value relatively low?

When specificity is low, many patients with a positive result will not have cancer confirmed on the subsequent assessment. A positive test is therefore a prompt to investigate, not a cancer diagnosis.

Does it detect high-grade disease better?

Urine-based biomarkers often perform better for biologically active high-grade tumours than for very small low-grade recurrences. Nevertheless, no negative urine test can guarantee that high-grade tumour or CIS is absent. Study populations also differ in the proportions of low-grade, high-grade and recently treated patients, making direct comparisons difficult.

Important pitfalls

1. A negative result can be falsely reassuring

False negatives occur. Small, low-volume or intermittently shedding tumours may release too little RNA into the urine. A diluted or poorly collected sample may also reduce the signal. A negative result must not override visible haematuria, positive cytology, a suspicious cystoscopy or a high-risk clinical history.

2. A positive result is not proof of cancer

Because Monitor is deliberately designed to be sensitive, specificity is modest. A positive result may lead to cystoscopy or biopsy that finds no tumour. The test cannot identify the lesion’s location, stage or grade.

3. Infection, inflammation and recent instrumentation complicate interpretation

Urinary infection, stones, bleeding, recent cystoscopy, catheterisation, TURBT, intravesical BCG or chemotherapy can alter urinary cellular material and the clinical context. Cxbladder includes an inflammatory-associated marker intended to reduce this “background noise,” but real-world confounding is not eliminated. Testing should be timed and interpreted by the treating urologist.

4. The test does not examine the upper urinary tract

Urothelial cancer may arise in the ureter or renal pelvis. A urine result cannot localise a tumour or replace CT urography, ureteroscopy or other upper-tract evaluation when clinically indicated.

5. It does not replace pathology

Only tissue examination can determine tumour grade, assess invasion and guide definitive treatment. Cxbladder is a risk-stratification tool rather than a histological diagnosis.

6. Performance may not generalise perfectly

Some studies were supported by or involved investigators connected with the test manufacturer. Many validation cohorts were enriched for particular risk groups and may not reflect every Australian practice. Independent prospective studies, longer follow-up and trials showing that biomarker-guided surveillance preserves oncological outcomes are especially important.

7. “Fewer cystoscopies” is not the same as “no cystoscopies”

Real-world studies suggest that Cxbladder Monitor can reduce cystoscopy frequency in selected low-risk patients. This should not be extrapolated to high-risk NMIBC or used to abandon risk-based surveillance. Cystoscopy remains the direct method of inspecting the bladder and permits immediate biopsy or resection planning.

8. Cost and access vary

Availability, laboratory turnaround time, out-of-pocket cost and reimbursement vary by location and insurer. Australian patients should confirm current access and costs with their urologist and testing provider before collection.

How does it compare with urine cytology?

Urine cytology is highly specific for high-grade urothelial carcinoma but has limited sensitivity, particularly for low-grade tumours. Cxbladder Monitor generally has higher reported sensitivity and NPV, but substantially lower specificity.

The tests therefore answer slightly different questions:

  • cytology: a clearly positive result strongly raises concern for high-grade disease;
  • Cxbladder Monitor: a negative result may help identify a low probability of recurrence; and
  • cystoscopy: directly visualises the bladder and remains central to surveillance.

Combining information may be more useful than treating any one result in isolation.

What do international guidelines say?

Major guidelines acknowledge that urinary molecular markers are improving, but remain cautious about their routine use as complete substitutes for cystoscopy.

  • The AUA/SUO NMIBC guideline states that urinary biomarkers should not replace cystoscopic evaluation during surveillance. Markers may be used in selected settings, including assessment of an equivocal cytology result or response to intravesical BCG.
  • The EAU NMIBC guideline recognises that molecular urine tests may have a future role in reducing cystoscopy frequency, particularly in lower-risk surveillance, but notes that evidence and prospective implementation data remain insufficient for a universal marker-driven schedule.
  • Guideline recommendations evolve as new trials emerge; decisions should be based on the patient’s individual recurrence and progression risk rather than the availability of a test alone.

A practical, balanced approach

Cxbladder Monitor is most helpful when the question is: “Is recurrence sufficiently unlikely that we can safely reduce or postpone an invasive investigation in this particular patient?”

It is less useful as a stand-alone answer to: “Does this patient definitely have cancer, where is it, and how aggressive is it?”

For a carefully selected patient with previous low-risk NMIBC, no new symptoms and a negative Monitor result, a biomarker-informed surveillance plan may reduce unnecessary cystoscopies. For a patient with previous CIS or high-grade tumour, positive cytology, visible haematuria or a suspicious finding, conventional investigation should not be deferred because of a negative urine test.

The result is best interpreted alongside tumour history, grade and stage, time since treatment, cystoscopy findings, cytology, imaging and the patient’s preferences.

References

  1. Kavalieris L, O’Sullivan P, Frampton C, et al. Performance characteristics of a multigene urine biomarker test for monitoring for recurrent urothelial carcinoma in a multicenter study. J Urol. 2017;197(6):1419–1426. PubMed search
  2. Lotan Y, O’Sullivan P, Raman JD, et al. Clinical comparison of noninvasive urine tests for ruling out recurrent urothelial carcinoma. Urol Oncol. 2017;35(8):531.e15–531.e22. PubMed search
  3. O’Sullivan P, Sharples K, Dalphin M, et al. A multigene urine test for the detection and stratification of bladder cancer in patients presenting with hematuria. J Urol. 2012;188(3):741–747. PubMed search
  4. Li KD, McLennan MT, Barocas DA, et al. Cxbladder Monitor testing to reduce cystoscopy frequency in patients with bladder cancer. J Urol. 2023. PubMed
  5. Konety B, Shore N, Kader AK, et al. Evaluation of Cxbladder and adjudication of atypical cytology and equivocal cystoscopy. Eur Urol. 2019;76(2):238–243. PubMed search
  6. Darling D, Luxmanan C, O’Sullivan P, et al. Clinical utility of Cxbladder for the diagnosis of urothelial carcinoma. Adv Ther. 2017;34:1087–1096. PubMed search
  7. Breen V, Kasabov N, Kamat AM, et al. A holistic comparative analysis of diagnostic tests for urothelial carcinoma: a study of Cxbladder Detect, UroVysion FISH, NMP22 and cytology. BMC Med Res Methodol. 2015;15:27. Full text
  8. Harvey JC, et al. Analytical validation of Cxbladder Detect, Triage, and Monitor assays for detection and management of urothelial carcinoma. Diagnostics. 2024;14(18):2061. Full text
  9. Holzbeierlein JM, Bixler BR, Buckley DI, et al. Diagnosis and treatment of non-muscle invasive bladder cancer: AUA/SUO guideline. American Urological Association; amended 2024. AUA guideline
  10. European Association of Urology. EAU Guidelines on Non-Muscle-Invasive Bladder Cancer. Current online edition. EAU guideline
  11. Barocas DA, Lotan Y, Matulewicz RS, et al. Updates to microhematuria: AUA/SUFU guideline. J Urol. 2025. PubMed

This article provides general information and does not replace personalised medical advice. Surveillance should be tailored to the original tumour’s stage and grade, prior treatment, current symptoms and the individual’s risk of recurrence and progression.

Vesico-ureteric reflux: when urine travels in the wrong direction

/0 Comments/in , /by

Vesico-ureteric reflux, also called vesicoureteral reflux or VUR, occurs when urine flows backwards from the bladder into one or both ureters and sometimes as far as the kidneys.

Normally, each ureter enters the bladder through a short tunnel in the bladder wall. As the bladder fills and contracts, this tunnel is compressed, acting like a one-way valve. In VUR, the valve does not close effectively.

VUR itself does not always cause symptoms. Its importance is that infected urine may travel towards the kidneys, increasing the risk of pyelonephritis, renal scarring and, in a small number of higher-risk patients, long-term kidney damage.

Primary and secondary reflux

Primary VUR

Primary VUR is usually a developmental condition. The ureter’s tunnel through the bladder wall is too short or positioned in a way that prevents reliable closure. It is most commonly diagnosed in infancy or childhood.

As a child grows, the bladder and ureteric junction mature. For this reason, many cases particularly lower-grade reflux, improve or resolve without surgery.

Secondary VUR

Secondary reflux develops because pressure within the bladder is abnormally high or because the bladder does not empty properly. Causes may include:

  • posterior urethral valves or another bladder-outlet obstruction
  • dysfunctional voiding
  • constipation and bladder–bowel dysfunction
  • neurogenic bladder, including spina bifida or spinal cord disease
  • urethral stricture or an enlarged prostate in adults
  • previous bladder or ureteric surgery
  • a poorly compliant, high-pressure bladder.

Treating the underlying bladder or outlet problem is essential. Correcting the reflux alone may fail if the bladder remains unsafe or under excessive pressure.

How does VUR present in children?

Most children do not feel the reflux itself. It is commonly discovered while investigating a urinary tract infection.

Possible presentations include:

  • a fever without an obvious cause, particularly in an infant
  • recurrent urinary tract infections
  • febrile UTIs or kidney infections
  • vomiting, lethargy, irritability or poor feeding in babies
  • abdominal, loin or back pain
  • painful or frequent urination
  • urinary urgency or wetting
  • poor urinary stream or straining
  • antenatal ultrasound showing hydronephrosis or an abnormal urinary tract
  • poor growth
  • high blood pressure or impaired kidney function in more advanced reflux nephropathy.

A child with fever, vomiting, flank pain or marked lethargy may have pyelonephritis and should receive prompt medical assessment.

How does VUR present in adults?

VUR is much less commonly diagnosed for the first time in adulthood. Some adults have persistent congenital reflux that was never detected in childhood, while others develop secondary reflux due to bladder dysfunction or obstruction.

Adults may present with:

  • recurrent febrile UTIs
  • repeated kidney infections
  • loin or flank pain
  • renal scarring found on imaging
  • high blood pressure
  • protein or blood detected in the urine
  • reduced kidney function
  • pregnancy-associated urinary infections
  • lower urinary tract symptoms or incomplete bladder emptying.

Adult VUR should prompt assessment for an underlying cause such as bladder-outlet obstruction, neurogenic bladder, poor bladder compliance or dysfunctional voiding. The evidence guiding adult treatment is less extensive than the paediatric literature, so management is individualised.

How is VUR investigated?

Not every child who has one uncomplicated UTI requires an invasive reflux study. Imaging is selected according to age, clinical presentation, ultrasound findings and whether the infection is atypical or recurrent.

Urine testing

Urinalysis and urine culture confirm infection and help guide antibiotic treatment. A properly collected urine specimen is particularly important in babies and young children.

Kidney and bladder ultrasound

Ultrasound is painless and does not use radiation. It can assess:

  • kidney size and development
  • hydronephrosis or ureteric dilatation
  • bladder-wall appearance
  • congenital urinary abnormalities
  • residual urine after voiding.

A normal ultrasound does not completely exclude VUR.

Micturating cystourethrogram

A micturating cystourethrogram, also called an MCUG or VCUG, is the standard test for confirming and grading reflux.

A small catheter is placed into the bladder, contrast is introduced, and X-ray images are taken while the bladder fills and during urination. The test shows whether contrast travels backwards into the ureters or kidneys and also provides information about the bladder and urethra.

Because catheterisation and a small radiation exposure are involved, MCUG is generally reserved for children in whom the result is likely to influence management.

Contrast-enhanced voiding urosonography

In centres where it is available, contrast-enhanced ultrasound can identify reflux without ionising radiation. Availability and local expertise vary, and conventional MCUG may still be required when detailed urethral anatomy needs assessment.

DMSA renal scan

A DMSA scan assesses the functioning renal cortex and can identify established renal scars. It is not required for every child but may be considered after recurrent febrile infections, in higher-grade reflux, when ultrasound is abnormal or when renal damage is suspected.

Additional assessment

Depending on the circumstances, investigation may also include:

  • blood pressure measurement
  • serum creatinine and estimated kidney function
  • urine protein assessment
  • a bladder and bowel history
  • uroflowmetry and measurement of residual urine
  • a bladder diary
  • urodynamic studies when a high-pressure, neurogenic or poorly emptying bladder is suspected
  • CT or other upper-tract imaging in selected adults.

The five grades of reflux

VUR is graded from I to V according to the international grading system.

Grade Imaging appearance General interpretation
Grade I Reflux reaches the ureter but not the kidney Mild
Grade II Reflux reaches the renal pelvis without dilatation Mild
Grade III Mild to moderate dilatation of the ureter and renal collecting system Moderate
Grade IV Moderate ureteric and collecting-system dilatation with some twisting of the ureter High-grade
Grade V Severe dilatation and tortuosity with loss of normal calyceal detail Severe

The grade is important, but it is not the only factor determining treatment. Age, recurrent infections, kidney scarring, bladder and bowel function, whether reflux affects one or both sides, and family preferences all matter.

What is the aim of treatment?

Treatment aims to:

  • prevent febrile UTIs and pyelonephritis
  • reduce the risk of further renal scarring
  • preserve kidney function
  • treat bladder, bowel or outlet dysfunction
  • avoid unnecessary medication, radiation and surgery.

It is important to understand that repairing reflux cannot reverse established renal scars. Treatment is intended to prevent further infection and injury.

Observation and conservative management

Observation is appropriate for many children, particularly those with lower-grade reflux, healthy kidneys and no recurrent febrile infections.

Conservative care may include:

  • prompt urine testing when fever or urinary symptoms occur
  • regular and complete bladder emptying
  • adequate fluid intake
  • avoiding prolonged holding of urine
  • treating constipation
  • timed voiding
  • management of daytime wetting or dysfunctional voiding
  • periodic clinical and ultrasound review.

Lower-grade reflux is more likely to resolve as the child grows. Higher grades, bilateral reflux and reflux associated with renal abnormalities are less likely to resolve spontaneously.

Continuous low-dose antibiotic prophylaxis

A low dose of antibiotic may be prescribed daily to reduce recurrent infections while waiting for reflux to improve or while deciding whether intervention is required.

Prophylaxis is more likely to be considered in:

  • infants with VUR following a febrile UTI
  • recurrent febrile UTIs
  • higher-grade reflux
  • bladder–bowel dysfunction
  • renal cortical abnormalities
  • children considered at increased risk of another kidney infection.

Antibiotics can reduce recurrent UTIs in appropriately selected children, but they do not mechanically correct the reflux. Disadvantages include medication side effects, adherence difficulties and antibiotic resistance. The need for ongoing prophylaxis should therefore be reviewed rather than continued automatically.

Treating bladder and bowel dysfunction

Constipation, urinary urgency, wetting, infrequent voiding and incomplete bladder emptying increase the risk of recurrent infection and may reduce the success of reflux treatment.

Management can include:

  • regular timed voiding
  • relaxed toilet posture
  • treatment of constipation
  • pelvic-floor or continence physiotherapy
  • medication for selected bladder conditions
  • intermittent self-catheterisation when emptying is inadequate.

In secondary reflux, treating the bladder or outlet disorder may reduce or occasionally eliminate the reflux.

When is a procedure considered?

Intervention may be discussed when there is:

  • a febrile breakthrough UTI despite appropriate prophylaxis
  • recurrent pyelonephritis
  • new or progressive renal scarring
  • persistent high-grade reflux
  • reflux unlikely to resolve spontaneously
  • difficulty tolerating or adhering to antibiotic prophylaxis
  • an anatomical abnormality requiring correction
  • significant family preference after discussion of the alternatives
  • persistent symptomatic reflux in a carefully selected adult.

The two main corrective options are endoscopic injection and ureteric reimplantation.

The STING procedure

STING stands for subureteric transurethral injection. A small telescope is passed through the urethra into the bladder under anaesthesia. A bulking material is injected beneath or within the lower end of the ureter to support and lengthen the valve mechanism.

Dextranomer/hyaluronic-acid copolymer, commonly known by the brand name Deflux, is the best-known injection material. Modified techniques such as HIT or double-HIT place the material within the intramural ureter rather than only beneath its opening.

Advantages

  • minimally invasive
  • no abdominal incision
  • usually performed as day surgery
  • relatively short anaesthetic and recovery
  • low risk of major complications
  • can be repeated if reflux persists.

Limitations and risks

  • success is lower and less predictable than formal reimplantation
  • results are generally better for lower grades of reflux
  • more than one injection may be required
  • reflux may persist or recur
  • temporary blood in the urine, discomfort or infection can occur
  • ureteric obstruction is uncommon but important
  • reflux may occasionally appear on the opposite side
  • long-term durability is not as certain as with successful reimplantation.

Published cure rates vary considerably because they depend on reflux grade, anatomy, injection technique, material used and how success is defined. A single injection commonly corrects approximately 70–80% of refluxing ureters overall, with lower success in grades IV–V. Additional injections can increase the cumulative success rate.

Ureteric reimplantation

Ureteric reimplantation is reconstructive surgery that creates a longer tunnel for the ureter through the bladder wall, restoring the one-way valve mechanism.

The operation may be performed using:

  • an open extravesical approach
  • an open intravesical approach
  • laparoscopic surgery
  • robot-assisted surgery in selected centres and patients.

Open reimplantation has a long-established success rate of approximately 95–98% for primary VUR when performed in suitable patients.

Advantages

  • highest and most durable anatomical correction rate
  • effective for high-grade reflux
  • allows correction of some associated ureteric abnormalities
  • usually requires only one definitive operation.

Limitations and risks

  • more invasive than injection
  • longer anaesthetic and recovery
  • temporary bladder spasms, pain or blood in the urine
  • urinary infection
  • transient urinary retention, particularly after some bilateral extravesical repairs
  • ureteric obstruction
  • persistent reflux or reflux on the opposite side
  • rare need for further surgery.

Robotic or laparoscopic reimplantation can reduce incision size, but it is still major reconstructive surgery and has not made open surgery obsolete. The best approach depends on the child’s anatomy, age, surgeon’s expertise and the reason for intervention.

STING versus reimplantation

Consideration Endoscopic injection Ureteric reimplantation
Invasiveness Minimally invasive Reconstructive surgery
Typical stay Usually day surgery Often one or more nights
Recovery Generally quicker Longer
Success after one procedure Lower and grade-dependent Approximately 95–98%
Repeat treatment Sometimes required Uncommon after successful repair
Best suited to Selected low- or moderate-grade reflux and families prioritising minimal invasiveness High-grade, persistent or complicated reflux; failed injection; selected anatomical abnormalities
Main trade-off Easier recovery but less predictable cure More invasive but more reliable correction

Neither operation is automatically “best.” STING may be attractive when a minimally invasive approach is preferred and its probability of success is acceptable. Reimplantation may be more appropriate when the highest likelihood of definitive correction is important.

VUR in adults

Adults with incidentally detected reflux and no infections, renal deterioration or high-pressure bladder may not require corrective surgery.

Treatment is more likely to be considered when there is:

  • recurrent febrile UTI or pyelonephritis
  • progressive kidney damage
  • troublesome reflux-associated flank pain
  • an untreated bladder-outlet or functional abnormality
  • pregnancy planning in a patient with recurrent infections or reflux nephropathy.

The underlying bladder problem must be identified before anti-reflux surgery. Endoscopic injection can be effective in selected adults, although the supporting evidence is mainly from smaller observational studies. Ureteric reimplantation remains an option when a durable anatomical repair is required.

Women with previous VUR or reflux nephropathy who are considering pregnancy may benefit from pre-pregnancy assessment of blood pressure, kidney function, urine protein and infection risk.

Follow-up

Follow-up should be tailored to reflux grade, renal findings, treatment and infection history.

During observation

Review may include:

  • interval history of UTIs or unexplained fevers
  • height, weight and growth in children
  • blood pressure
  • urine testing when symptoms occur
  • assessment of constipation and bladder symptoms
  • renal and bladder ultrasound
  • serum creatinine and urine protein testing when renal damage is present or suspected
  • selective repeat MCUG, contrast-enhanced urosonography or radionuclide cystography
  • DMSA scanning when new scarring is suspected.

Routine repeated invasive imaging is not necessary for every child. The timing and type of imaging should be chosen only when the result is likely to alter management.

After STING

Follow-up commonly includes an ultrasound to exclude obstruction and clinical monitoring for further UTIs. A repeat reflux study may be recommended after several months, particularly in high-grade reflux, recurrent febrile infection or when confirmation of cure will affect treatment.

Any fever or urinary symptoms after injection should prompt urine testing. Flank pain, vomiting, reduced urine output or significant hydronephrosis requires assessment for the uncommon complication of ureteric obstruction.

After reimplantation

Ultrasound is commonly performed after surgery to check drainage. Routine postoperative MCUG may not be necessary after an uncomplicated reimplantation with a reassuring recovery, but it may be appropriate after breakthrough infection, persistent hydronephrosis or an atypical clinical course.

Long-term surveillance

Patients with renal scarring, bilateral severe reflux, a solitary functioning kidney, proteinuria, hypertension or impaired renal function may require long-term follow-up into adulthood.

Monitoring can include:

  • blood pressure
  • kidney function
  • urine protein
  • recurrent infection
  • pregnancy counselling when relevant.

Even when reflux has resolved, established reflux nephropathy can remain clinically important.

When should urgent medical advice be sought?

Seek prompt medical assessment for:

  • fever with loin or back pain
  • vomiting or marked lethargy
  • reduced urine output
  • a very unwell infant
  • urinary symptoms during pregnancy
  • fever or flank pain after a reflux procedure.

Early diagnosis and treatment of pyelonephritis are particularly important in patients with known VUR.

The key message

Vesico-ureteric reflux ranges from a mild childhood condition that resolves with growth to high-grade reflux associated with recurrent kidney infections and renal scarring.

Treatment should not be based on grade alone. The safest plan considers infection history, kidney health, age, bladder and bowel function, likelihood of spontaneous resolution and the advantages and disadvantages of observation, antibiotic prophylaxis, endoscopic injection and ureteric reimplantation.

References and further reading

  1. European Association of Urology. EAU Guidelines on Paediatric Urology: Vesicoureteric reflux. EAU Paediatric Urology Guidelines
  2. American Urological Association. Management and Screening of Primary Vesicoureteral Reflux in Children. AUA Vesicoureteral Reflux Guideline
  3. National Institute for Health and Care Excellence. Urinary tract infection in under 16s: diagnosis and management (NG224). NICE guideline NG224
  4. RIVUR Trial Investigators. Antimicrobial prophylaxis for children with vesicoureteral reflux. New England Journal of Medicine. 2014;370:2367–2376. PubMed
  5. Mattoo TK, Chesney RW, Greenfield SP, et al. Renal scarring in the Randomized Intervention for Children with Vesicoureteral Reflux trial. Clinical Journal of the American Society of Nephrology. 2016;11:54–61. PubMed
  6. Läckgren G, Cooper CS, Neveus T, Kirsch AJ. Management of vesicoureteral reflux: what have we learned over the last 20 years? Frontiers in Pediatrics. 2021;9:650326. Full text
  7. Salib A, Pizzi M, Landman J, et al. Vesicoureteral reflux in adults with urinary tract infections: is there a role for treatment? Current Urology Reports. 2020. PubMed record

This article provides general education and does not replace individual medical advice. Decisions about imaging, antibiotic prophylaxis or surgery should be made with an appropriately experienced urologist or paediatric urologist.

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

/0 Comments/in , /by

“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.

 

Urethral Caruncle: A Small Lump That Can Cause Big Concern

/0 Comments/in , /by

Finding a red or fleshy lump around the opening of the urethra can understandably be alarming. Fortunately, one of the most common causes, particularly in women after menopause, is a urethral caruncle.

A urethral caruncle is usually benign (non-cancerous) and may cause no problems at all. However, because several other conditions can look similar, a new, enlarging, bleeding or unusual urethral lesion deserves proper assessment.

What is a urethral caruncle?

A urethral caruncle is a small, fleshy growth arising from the lining of the urethral opening, or urethral meatus.

It typically appears as a soft red, pink or sometimes darker-red polypoid lesion at the edge of the urethral opening. It most commonly arises from the posterior or lower margin of the urethral meatus.

Caruncles occur predominantly in postmenopausal women, although they can occasionally occur in younger women.

Importantly, a urethral caruncle is not considered a precancerous condition. Its significance lies mainly in the symptoms it can produce and the fact that other urethral conditions can occasionally imitate its appearance.

What causes a urethral caruncle?

The exact cause is not completely understood, but several factors are thought to contribute.

Reduced oestrogen after menopause

This is probably the most important association.

After menopause, falling oestrogen levels cause thinning and reduced elasticity of the tissues surrounding the vagina and urethra. This is part of what is now commonly called genitourinary syndrome of menopause (GSM).

The urethral lining may become more fragile and susceptible to irritation, inflammation and prolapse.

Chronic inflammation and irritation

Repeated local irritation may contribute to inflammation around the urethral opening and subsequent formation of a caruncle.

Urethral mucosal prolapse

A caruncle may represent a localised form of prolapse of the urethral lining. This helps explain why the lesion usually occurs at the edge of the urethral opening.

What does a urethral caruncle look like?

A typical caruncle is:

  • Small and fleshy
  • Red or pink
  • Soft
  • Usually located along the lower edge of the urethral opening
  • Occasionally friable, meaning that it bleeds easily when touched
  • Sometimes tender or inflamed

They vary considerably in size. Some are barely noticeable, while larger lesions may protrude sufficiently to be felt or seen by the patient.

Although the appearance may be quite characteristic, appearance alone should not always be relied upon when a lesion is atypical.

What symptoms can it cause?

Many urethral caruncles are discovered incidentally during a pelvic examination and cause absolutely no symptoms.

When symptoms do occur, they may include:

Bleeding

The surface of a caruncle can be delicate and vascular. Patients may notice:

  • Spotting on underwear
  • Blood after wiping
  • Bleeding after intercourse
  • Blood noticed after passing urine

One important distinction is determining whether the blood is actually coming from the urethral lesion or whether there is true blood within the urine (haematuria).

Persistent haematuria may require additional investigation.

Pain or tenderness

An inflamed caruncle can become uncomfortable, particularly with wiping, intercourse or local pressure.

Burning when passing urine

Some patients experience dysuria or a stinging sensation as urine passes across the inflamed tissue.

A visible or palpable lump

Some women first become aware of the condition because they see or feel a small lump at the urethral opening.

Urinary symptoms

Large caruncles only rarely interfere significantly with urinary flow. If there is difficulty passing urine, a weak stream or urinary retention, other causes should also be considered.

How is a urethral caruncle diagnosed?

Diagnosis usually begins with a careful examination of the urethral opening and surrounding genital tissues.

A typical small caruncle in a postmenopausal woman often has a characteristic appearance.

Your doctor may also assess for associated vaginal and urethral atrophy and ask about urinary symptoms, recurrent urinary infections, bleeding and haematuria.

Depending on the circumstances, investigations may include:

  • Urinalysis
  • Urine culture if infection is suspected
  • Assessment for haematuria
  • Cystoscopy if there are unexplained urinary symptoms or blood in the urine
  • Biopsy or removal of the lesion when its appearance is atypical

Does a urethral caruncle need treatment?

Not necessarily.

A small, typical caruncle that causes no symptoms may simply be observed.

Treatment is generally considered when the lesion causes bleeding, pain, irritation or bothersome urinary symptoms, or when there is uncertainty about the diagnosis.

1. Observation

If the lesion is small, has a typical appearance and causes no symptoms, reassurance and observation may be all that is required.

This avoids treating something that is essentially harmless.

2. Topical vaginal oestrogen

In postmenopausal women, topical oestrogen therapy is frequently used, particularly when there are accompanying features of genitourinary syndrome of menopause.

Oestrogen can improve the quality and thickness of the tissues around the urethra and vagina and may allow a small caruncle to shrink considerably or resolve.

Treatment usually requires several weeks rather than several days.

The suitability of vaginal oestrogen should be discussed with your doctor, particularly if you have a history of an oestrogen-sensitive malignancy or another reason to avoid hormonal therapy.

3. Anti-inflammatory and supportive treatment

Where local inflammation is prominent, conservative measures may occasionally include:

  • Avoidance of irritating soaps and products
  • Treatment of associated infection if present
  • Appropriate topical therapy
  • Simple analgesia when required

These treatments may improve symptoms but do not necessarily remove the lesion itself.

When is surgery required?

Surgical removal may be recommended when the caruncle is:

  • Persistently painful
  • Repeatedly bleeding
  • Large or bothersome
  • Not responding to conservative treatment
  • Increasing in size
  • Firm, irregular, ulcerated or otherwise atypical
  • Associated with uncertainty about the diagnosis

Surgery usually involves excision of the lesion at its base, often as a relatively minor procedure.

The removed tissue can then be sent to a pathologist for examination under the microscope.

Possible complications are uncommon but can include bleeding, infection, discomfort, recurrence and, rarely, scarring or narrowing of the urethral opening.

Can a urethral caruncle be cancerous?

A true urethral caruncle is benign.

The more important question is whether a lesion that looks like a caruncle could occasionally be something else.

Several conditions may resemble a caruncle, including:

  • Urethral mucosal prolapse
  • Urethral polyps
  • Periurethral cysts
  • Urethral diverticulum
  • Genital warts
  • Inflammatory lesions
  • Melanoma
  • Urethral carcinoma
  • Other uncommon benign or malignant tumours

Cancer masquerading as an apparently innocent urethral lesion is uncommon, but this is precisely why an atypical lesion should not simply be labelled a caruncle and forgotten.

When should a biopsy be considered?

Biopsy or complete excision is particularly worth considering when a lesion is:

  • Irregular or unusually firm
  • Ulcerated
  • Pigmented
  • Rapidly enlarging
  • Persistently bleeding
  • Unusually large
  • Not responding as expected to conservative treatment
  • Associated with enlarged groin lymph nodes
  • Clinically inconsistent with a typical caruncle

In medicine, sometimes the smallest lump deserves a second look rather than a dramatic name.

Urethral caruncle versus urethral prolapse

These conditions can look similar but are not quite the same.

A urethral caruncle generally involves only a portion of the circumference of the urethral opening, most commonly its posterior margin.

A urethral prolapse usually involves the entire circumference of the urethral lining, creating a circular or doughnut-shaped ring of tissue surrounding the opening.

The distinction can influence management.

What about blood in the urine?

This is particularly important.

A caruncle may bleed externally and make it appear that blood has come from the urine. However, visible haematuria should not automatically be attributed to a urethral caruncle.

Depending on age, symptoms and individual risk factors, haematuria may require investigation of the bladder, kidneys and urinary tract.

The presence of a convenient little red lump should therefore not distract from investigating genuine haematuria appropriately.

Will a urethral caruncle come back?

Recurrence after treatment is possible, particularly if the underlying postmenopausal tissue changes persist.

Treatment of associated genitourinary syndrome of menopause may therefore remain useful even after the immediate caruncle has improved or been removed.

When should you see a urologist?

Consider seeking medical assessment if you notice:

  • A new lump around the urethral opening
  • Persistent urethral pain
  • Recurrent bleeding
  • Blood in the urine
  • A lesion that is enlarging
  • Difficulty passing urine
  • Recurrent urinary infections
  • A lesion that does not improve with treatment

Most urethral caruncles turn out to be harmless, but examination provides reassurance and ensures that less common conditions are not overlooked.

The Bottom Line

A urethral caruncle is a common benign lesion of the urethral opening, seen particularly in postmenopausal women.

Many require no treatment at all. When symptoms occur, topical vaginal oestrogen and conservative measures are often appropriate first-line options. Persistent, troublesome or atypical lesions may require surgical excision and pathological examination.

The most important message is simple: a typical urethral caruncle is usually nothing to fear, but an unusual urethral lesion deserves proper assessment rather than assumption.

Patient information disclaimer

This information is intended for general education and should not replace individual medical advice. A urethral or vulval lump, unexplained bleeding or blood in the urine should be assessed by an appropriately qualified healthcare professional.

Intravesical Therapy for High-Risk Bladder Cancer

/0 Comments/in , /by

BCG treatment, what is it?

BCG, short for Bacillus Calmette–Guérin, is one of the most effective treatments available for high-risk non-muscle-invasive bladder cancer (NMIBC).

BCG is best known as a vaccine originally developed against tuberculosis. In bladder cancer, however, it is used in a very different way. Rather than being injected as a vaccination, a solution containing BCG is placed directly into the bladder through a fine urinary catheter.

BCG is not conventional chemotherapy. It is a form of local immunotherapy. Its purpose is to stimulate the body’s immune system inside the bladder so that immune cells recognise and attack remaining bladder cancer cells.

For appropriately selected patients, BCG can significantly reduce the risk of bladder cancer returning and, importantly, reduce the risk of progression to more invasive disease.

Which bladder cancers are treated with BCG?

BCG is primarily used for high-risk or locally aggressive non-muscle-invasive urothelial carcinoma following adequate transurethral resection of the bladder tumour (TURBT).

Typical indications include:

  • Carcinoma in situ (CIS or Tis)
  • High-grade Ta urothelial carcinoma, particularly when large, multifocal or recurrent
  • High-grade T1 urothelial carcinoma
  • Recurrent high-grade non-muscle-invasive bladder cancer
  • Selected patients with multiple adverse pathological features
  • Selected patients with urothelial CIS involving the prostatic urethra as part of a bladder-preserving strategy

Current international guidelines recommend a six-week induction course of BCG for high-risk NMIBC, followed by maintenance treatment in patients who respond.

BCG is generally not required for a solitary low-risk, low-grade Ta bladder tumour. These cancers have a different biological behaviour and are usually managed with TURBT, sometimes combined with immediate intravesical chemotherapy and subsequent surveillance.

Why is BCG particularly important for carcinoma in situ?

Carcinoma in situ (CIS) deserves special attention.

Unlike the familiar papillary bladder tumour that projects into the bladder cavity, CIS can appear as a relatively flat, red or velvety abnormality of the bladder lining. Despite looking less dramatic, it is biologically aggressive.

CIS has a significant risk of recurrence and progression to muscle-invasive bladder cancer if inadequately treated. It cannot simply be “scraped away” by TURBT and forgotten.

For this reason, CIS generally requires either:

BCG immunotherapy
or, in selected very-high-risk circumstances,
radical cystectomy.

BCG produces substantially better response rates for CIS than intravesical chemotherapy in appropriate patients and has been shown to reduce the risk of progression.

How does BCG actually work?

The mechanism is fascinating because BCG does not simply poison cancer cells in the way traditional chemotherapy does.

Think of it less as dropping a bomb on the tumour and more as turning on the bladder’s local security system.

After BCG is introduced into the bladder, organisms interact with the urothelial surface and tumour cells. This produces a strong local inflammatory and immune response.

The process includes:

BCG attachment and internalisation

BCG interacts with urothelial cells, tumour cells and immune cells within the bladder.

Activation of innate immunity

Neutrophils, macrophages, dendritic cells and other immune cells are recruited into the bladder.

Cytokine release

A complex inflammatory signalling response develops, involving multiple cytokines and chemokines.

Activation of adaptive immunity

T lymphocytes and other components of the immune system become involved in recognising and destroying malignant urothelial cells.

The end result is an intentionally stimulated immune environment that makes the bladder a considerably less comfortable neighbourhood for residual cancer cells.

Before starting BCG

Successful BCG treatment starts with adequate staging and tumour clearance.

Patients will usually have undergone TURBT with pathological assessment confirming the tumour grade and stage.

In high-grade T1 disease, a repeat or second-look TURBT is frequently recommended to ensure complete resection and exclude previously unrecognised muscle-invasive disease.

Depending upon the tumour characteristics, assessment may also include:

  • Urine cytology
  • CT urography or other upper urinary tract imaging
  • Repeat cystoscopy
  • Re-resection of the original tumour site
  • Assessment of the prostatic urethra in selected patients
  • Review of pathology where variant histology or unusual findings are present

Very-high-risk cases are increasingly appropriate for multidisciplinary discussion because some patients may benefit more from early radical cystectomy than prolonged attempts at bladder preservation.

How is BCG given?

BCG is administered as an outpatient procedure.

A small catheter is gently passed through the urethra into the bladder. After the bladder has been drained, the BCG solution is instilled through the catheter.

The catheter is then removed unless there is a particular reason for it to remain temporarily.

The BCG solution is generally retained within the bladder for approximately two hours, where tolerated.

Patients receive specific instructions regarding fluid intake before treatment and safe handling of urine afterwards because BCG contains live attenuated Mycobacterium bovis.

The standard induction course

The traditional induction course consists of:

BCG once weekly for six weeks

This remains the standard initial regimen for high-risk disease.

Importantly, attempts to substantially reduce the number of induction and maintenance instillations have resulted in inferior cancer control. The six-week induction course therefore remains an important part of established treatment.

What happens after the first six treatments?

Following induction BCG, the bladder is reassessed.

This will generally involve:

  • Cystoscopy
  • Urinary cytology
  • Biopsy or repeat TURBT if an abnormality is detected
  • Additional investigation when cytology remains suspicious despite a normal-looking bladder

The key question is simple:

Has the cancer responded?

If it has, the next step is usually maintenance BCG.

Maintenance BCG

BCG works better in high-risk bladder cancer when appropriate maintenance treatment is added rather than simply giving six doses and stopping.

A widely used maintenance schedule consists of:

Induction

Once weekly × 6 weeks

followed by:

Maintenance

Once weekly × 3 weeks at:

  • 3 months
  • 6 months
  • 12 months
  • 18 months
  • 24 months
  • 30 months
  • 36 months

This is often referred to as a SWOG-style maintenance schedule.

Current European guidance recommends full-dose BCG for one to three years in high-risk disease, with the benefit of years two and three balanced against toxicity, patient tolerance and BCG availability. Three years of maintenance provides additional protection against recurrence in high-risk patients compared with one year.

Not every patient will receive every planned dose. Treatment may need to be delayed, reduced or discontinued because of side effects, infection, BCG availability or changes in the cancer.

When should BCG NOT be given?

Because BCG contains live attenuated bacteria, certain precautions are essential.

BCG should not be administered:

  • Within the first two weeks after TURBT
  • When there is visible haematuria
  • Following traumatic catheterisation
  • In the presence of a symptomatic urinary tract infection

Treatment should instead be delayed until it can be administered safely.

Additional caution is required in significantly immunocompromised patients, and individual circumstances should be discussed with the treating urologist.

Common side effects of BCG

BCG deliberately produces inflammation within the bladder, so some urinary symptoms are expected.

The most common side effects include:

Urinary frequency and urgency

Patients may feel the need to urinate frequently or suddenly.

Burning during urination

Mild-to-moderate dysuria is common for a day or two following treatment.

Blood in the urine

A small amount of haematuria can occur.

Bladder discomfort

Some patients describe suprapubic discomfort, cramping or a sensation resembling cystitis.

Flu-like symptoms

Fatigue, muscle aches, chills and a low-grade temperature can occur as the immune system responds to treatment.

These symptoms usually settle within approximately 24–48 hours.

The bladder may complain rather loudly about BCG, but mild short-lived irritation is usually part of the intended inflammatory response rather than evidence that something has gone wrong.

When should you contact your urologist?

Patients should contact their treating team if symptoms are unusually severe or fail to settle.

Particular attention should be paid to:

  • Persistent fever
  • High fever or rigors
  • Severe urinary symptoms
  • Inability to pass urine
  • Persistent or heavy haematuria
  • Significant deterioration in general wellbeing
  • Symptoms continuing substantially longer than expected

Persistent fever after BCG deserves particular attention.

Serious complications of BCG

Serious complications are uncommon, but they are important because BCG contains viable attenuated bacteria.

Potential complications include:

Severe BCG cystitis

Persistent bladder inflammation may occasionally become sufficiently troublesome that treatment needs to be delayed or discontinued.

Granulomatous prostatitis

BCG can produce an inflammatory reaction within the prostate. This can occasionally produce an abnormal prostate examination or elevated PSA and may mimic prostate cancer clinically.

Epididymo-orchitis

Rarely, BCG-related inflammation or infection can involve the epididymis or testis.

Upper urinary tract involvement

Granulomatous infection of the kidney is uncommon but recognised.

BCG infection

Localised or systemic infection with Mycobacterium bovis can occur.

BCG sepsis

This is a rare but potentially life-threatening complication.

A patient who becomes systemically unwell with persistent high fever, rigors, hypotension, respiratory symptoms or other features of sepsis following BCG requires urgent medical assessment.

Treatment may require hospital admission, infectious diseases involvement, anti-mycobacterial therapy and other supportive treatment.

BCG should therefore be respected. It is an extraordinarily useful treatment, but it is not simply another bladder wash.

What if BCG is poorly tolerated?

Treatment does not always have to proceed according to the calendar regardless of symptoms.

Depending upon severity, management can include:

  • Postponing the next instillation
  • Symptomatic treatment
  • Investigation for bacterial urinary infection
  • Assessment for BCG-related infection
  • Dose modification in selected circumstances
  • Discontinuation of BCG when toxicity becomes unacceptable

Persistent significant symptoms should be assessed rather than repeatedly giving further BCG and hoping the bladder eventually stops protesting.

What if the cancer returns after BCG?

This is one of the most important aspects of BCG treatment.

Not every recurrence after BCG means the same thing. The timing, pathology and amount of previous BCG exposure all matter.

Terms such as:

  • BCG-exposed
  • BCG-relapsing
  • BCG-refractory
  • BCG-unresponsive

describe different clinical situations.

Of these, BCG-unresponsive disease is particularly important because these tumours are unlikely to benefit from simply giving more BCG.

Current guidelines recommend radical cystectomy as the oncologically preferred treatment for appropriate patients with BCG-unresponsive high-grade disease.

When should radical cystectomy be considered?

BCG is intended to preserve the bladder, but preserving the bladder should never become more important than controlling the cancer.

Early radical cystectomy should be discussed in patients with very-high-risk features such as:

  • Persistent high-grade T1 disease
  • Recurrent high-grade disease despite adequate BCG
  • BCG-unresponsive disease
  • T1 disease associated with CIS
  • Certain variant histologies
  • Lymphovascular invasion
  • Extensive or multifocal high-grade disease
  • Other features suggesting a particularly high risk of progression

For very-high-risk NMIBC, current EAU guidance recommends discussing radical cystectomy upfront. BCG for one to three years remains an option for appropriately selected patients, particularly those who decline cystectomy or are medically unsuitable for major surgery.

Delaying cystectomy in a biologically aggressive tumour that is clearly failing BCG may compromise cancer outcomes.

Are there alternatives when BCG fails?

For patients with BCG-unresponsive disease who are unable or unwilling to undergo radical cystectomy, bladder-preserving alternatives are evolving rapidly.

Depending upon availability, tumour characteristics and local regulatory approval, options may include:

  • Sequential intravesical gemcitabine/docetaxel
  • Other intravesical chemotherapy combinations
  • Novel intravesical therapies
  • Systemic immunotherapy for selected CIS
  • Gene-based intravesical therapy in jurisdictions where available
  • Device-assisted intravesical therapy
  • Clinical trials

These treatments should not automatically be considered equivalent substitutes for radical cystectomy in a surgically fit patient with genuinely BCG-unresponsive aggressive disease. The risk of progression needs to remain at the centre of the decision.

Surveillance after BCG

BCG treatment does not eliminate the need for careful surveillance.

High-risk bladder cancer requires long-term follow-up because recurrence can occur even after an excellent initial response.

Follow-up generally involves:

Cystoscopy + urine cytology

initially at approximately 3 months, with subsequent surveillance determined by tumour risk and previous findings.

High-risk patients typically undergo frequent cystoscopy during the first two years, with gradually increasing intervals thereafter if they remain disease-free.

Periodic upper urinary tract imaging is also appropriate because high-risk urothelial carcinoma can occasionally develop within the ureters or kidneys.

Surveillance is usually long term and, for high-risk disease, often lifelong.

A practical BCG pathway

A typical pathway for high-risk non-muscle-invasive urothelial carcinoma is:

TURBT

↓

Histological confirmation of high-risk NMIBC

↓

Repeat TURBT when indicated, particularly high-grade T1 disease

↓

BCG induction: weekly × 6

↓

Cystoscopy + cytology and assessment of response

↓

If responding:

Maintenance BCG

3 weekly treatments at 3, 6 and 12 months, with continued maintenance to as long as 36 months in appropriate high-risk patients.

↓

Long-term cystoscopic surveillance

If persistent or recurrent high-grade disease:

Re-stage the bladder and determine whether the tumour represents BCG-unresponsive disease.

↓

Discuss radical cystectomy versus carefully selected bladder-preserving alternatives/clinical trials where appropriate.

The bottom line

Intravesical BCG remains a cornerstone of treatment for high-risk non-muscle-invasive urothelial carcinoma of the bladder.

Its strength lies in stimulating a powerful local immune response that reduces recurrence and helps prevent progression of aggressive superficial bladder cancer.

The usual treatment begins with six weekly instillations, followed by maintenance therapy for appropriately responding high-risk patients.

But BCG is not appropriate for every bladder tumour, and it should not be continued indefinitely when aggressive cancer is clearly failing treatment.

The most important principle is therefore not simply:

“Can we preserve the bladder?”

It is:

“Can we preserve the bladder safely without compromising cancer control?”

For patients with very-high-risk or BCG-unresponsive disease, timely discussion of radical cystectomy can be every bit as important as the BCG treatment itself.

This information is intended as general patient education and does not replace individual assessment by a urologist. BCG protocols, product availability and management of BCG-resistant disease may vary between patients and treatment centres.

Superficial Urothelial Carcinoma of the Bladder

/0 Comments/in , /by

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.

https://images.openai.com/static-rsc-4/y3Nkc3nnwnLWbduLwtOBo9wlGDPYvlRZ3hqmZmerWsmC4HUjhpIEvsXgWPs9IwZOQ9PLgJllQH1edLQmAni1U_538dO2IEbu48myP0AM4El4gyVQqzEuJjxyZdTq2Ak6qThyv190dh_MhP59fXKNJByHY8EL-AhSnzHK3LUJq2tbc5vhmHhLL8WBeJitn-Wb?purpose=fullsize

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.

Renal angiomyolipoma (AML): when to watch, when to treat and when to seek urgent help

/0 Comments/in , /by

An angiomyolipoma, usually shortened to AML, is a growth in the kidney made up of blood vessels, muscle-like tissue and fat. Most are found by chance on a scan and never cause trouble. The main concern is that some AMLs can bleed, occasionally quite severely. The right plan depends on the diagnosis, the growth’s features and your circumstances, not its diameter alone. [1,2]

In this article, “AML” means angiomyolipoma, not acute myeloid leukaemia.

Is an AML cancer?

A classic renal AML is generally a benign tumour. Most occur on their own (sporadic AML). Some occur with tuberous sclerosis complex (TSC) or, less commonly, lymphangioleiomyomatosis (LAM); these can be multiple, affect both kidneys and require a different surveillance and treatment approach. A rare epithelioid AML can behave aggressively and needs specialist assessment. Not every solid renal mass presumed to be an AML can be confidently identified on a scan, particularly when little visible fat is present. [1,3,4]

What symptoms can it cause?

Many AMLs have no symptoms. Possible symptoms include aching or pain in the side, visible blood in the urine, or, less commonly, a palpable swelling. A sudden bleed into or around the kidney may cause abrupt, severe flank or abdominal pain, sometimes with dizziness, fainting, weakness or a racing heart. Blood in the urine and flank pain can also have other causes, including stones or cancer, so they should be assessed rather than attributed automatically to a known AML. [1–3]

Emergency warning: If you develop sudden severe side or abdominal pain, especially with faintness, collapse, a racing heart or visible bleeding, call 000 in Australia or attend an emergency department immediately. A bleeding AML can cause major blood loss even when blood is not visible in the urine. Do not wait for a routine appointment. [1,3]

How is it diagnosed?

An AML may first appear on an ultrasound performed for another reason. CT or MRI helps confirm whether it contains fat and assess its size, location, blood vessels and any evidence of bleeding. Contrast-enhanced imaging may be needed for an indeterminate lesion or procedural planning, with the choice adapted to kidney function, pregnancy and other factors. A classic fat-rich AML is often diagnosed on imaging alone. A fat-poor AML may resemble kidney cancer; specialist review, further imaging or a biopsy may be appropriate if the result would change management. Biopsy has limitations and is chosen case by case. [1,3,4]

The assessment may also include blood pressure, kidney function and a blood count if bleeding is suspected. Multiple or bilateral AMLs, especially in a younger person, should prompt consideration of TSC or LAM and appropriate specialist input. [3,5]

Is there a critical size that must be treated?

There is no single diameter at which every AML must be removed. The traditional rule to treat an AML once it reaches 4 cm is no longer considered an automatic trigger. The European Association of Urology (EAU) states that the relationship between size and bleeding risk is uncertain and that no universal intervention threshold exists. Some larger AMLs can still be watched safely; a smaller one may need treatment if it bleeds or causes persistent symptoms. [1,2]

Size remains one part of the discussion. The team may also consider growth, vascular features or aneurysms seen on imaging, prior bleeding, pain, kidney function, pregnancy plans, blood-thinning medicines and access to urgent care. An aneurysm measurement such as 5 mm has been proposed as a risk marker, but recent evidence questions how reliably it predicts bleeding on its own. These findings guide an individual discussion; they do not supply a stand-alone rule. [1,3,6]

Management options

Active surveillance

For a confidently diagnosed, symptom-free AML, monitoring is often appropriate. It avoids exposing people with stable lesions to procedure risks. A surveillance plan records the starting size and imaging characteristics, checks for new symptoms and uses ultrasound, MRI or CT when appropriate to look for change. There is no single imaging interval suitable for all sporadic AMLs. A small, stable lesion may need little or no ongoing imaging after specialist review; a larger or changing lesion usually needs closer follow-up. Agree on the next scan, who will review it and what changes should prompt earlier contact. [1–3]

Selective arterial embolisation

An interventional radiologist passes a catheter into the blood vessels feeding the AML and blocks selected branches. Embolisation can control active bleeding and can be considered in advance for selected higher-risk or symptomatic tumours, while preserving kidney tissue. Pain, fever and nausea can occur afterwards; infection, non-target embolisation and repeat treatment are possible. In the EAU systematic review, around 30% of embolised cases required a further intervention, although individual outcomes vary. [1,2]

Kidney-sparing surgery

A partial nephrectomy removes the AML while aiming to preserve the rest of the kidney. Open, laparoscopic or robotic approaches may be considered depending on anatomy and surgical expertise. Surgery may be useful when imaging is uncertain, symptoms persist, embolisation is unsuitable or a definitive removal is preferred. It carries anaesthetic, bleeding, urine leak and kidney-function risks. Removal of the whole kidney is generally reserved for situations where kidney-sparing care is not feasible, especially in an emergency. [1–3]

Ablation and medicines

Thermal ablation is used less often for AML, and the evidence is more limited than for surveillance, embolisation and surgery. For TSC-associated AML, specialist teams may use an mTOR inhibitor such as everolimus for an asymptomatic but growing lesion over 3 cm when treatment is appropriate. This TSC recommendation should not be applied automatically to an isolated sporadic AML. Medicines require monitoring for adverse effects and interactions. [1,2,5]

What happens if an AML bleeds?

In hospital, the immediate priorities are resuscitation, blood tests and imaging to locate the bleed. Treatment may include intravenous fluids, blood transfusion and urgent selective arterial embolisation to stop the bleeding. Surgery is considered if embolisation is unavailable, unsuccessful or otherwise unsuitable. After recovery, follow-up checks the AML, remaining kidney function and whether further treatment is needed. [1,3]

How is surveillance different with tuberous sclerosis?

TSC-related AMLs require a coordinated long-term plan because lesions may occur in both kidneys and kidney function needs protection over a lifetime. The 2021 international TSC recommendations advise abdominal MRI every 1–3 years, with blood pressure, kidney function and urine protein checked at least yearly; the interval is tailored to individual risk. Growing AMLs greater than 3 cm may merit first-line mTOR treatment when intervention is indicated, while acute bleeding is generally managed with embolisation. A TSC specialist team can help balance treatment against the need to preserve kidney tissue. [5]

Questions to bring to your appointment

  • Is the imaging diagnosis of a classic AML secure, or is more investigation needed?
  • What are its size, growth pattern and vascular features?
  • What is my personal risk of bleeding, and how does kidney function affect my options?
  • If we monitor it, when is my next scan and what result would change the plan?
  • If treatment is recommended, why is embolisation, surgery or another option best for me?

This article provides general information and does not replace individual assessment or advice.

References

  1. European Association of Urology. EAU Guidelines on Renal Cell Carcinoma, section on other renal tumours and AML. Accessed September 2026.
  2. Fernández-Pello S, et al. Management of sporadic renal angiomyolipomas: a systematic review to guide EAU recommendations. European Urology Oncology. 2020;3:57–72. doi:10.1016/j.euo.2019.04.005.
  3. Guo Y, et al. Canadian Urological Association best practice report: Diagnosis and management of sporadic angiomyolipomas. Canadian Urological Association Journal. 2020;14–E536. doi:10.5489/cuaj.6942.
  4. Wilson MP, et al. Diagnostic performance of MRI in detection of renal lipid-poor angiomyolipomas: systematic review and meta-analysis. Radiology. 2020;296:511–520.
  5. Northrup H, et al. Updated international TSC diagnostic criteria and surveillance and management recommendations. Pediatric Neurology. 2021;123:50–66. See also Tuberous Sclerosis Australia: Kidneys.
  6. Swärd J, et al. Renal angiomyolipoma: investigating radiological signs indicative of bleeding risk. Insights into Imaging. 2025.