Bladder cancer is the most common malignancy of the urinary tract and the tenth most common cancer globally. In Singapore, it is among the more prevalent urological cancers, with men affected approximately three to four times more frequently than women. The good news is that the majority of bladder cancers are diagnosed at an early, non-muscle-invasive stage -- where the prognosis is excellent and treatment is highly effective.
The key to early detection is simple and requires only one action: take blood in the urine seriously. Haematuria -- visible or microscopic -- is present in approximately 85% of bladder cancer cases and is, in most instances, the first and only early symptom. It is also the symptom most commonly dismissed, attributed to infection, or left uninvestigated until the disease has progressed.
What is Bladder Cancer?
The urinary bladder is a hollow, muscular organ in the lower pelvis that stores urine before it is passed out of the body through the urethra. It is lined by a specialised type of cell called the urothelium (transitional epithelium), which is uniquely able to stretch and contract as the bladder fills and empties.
Bladder cancer most commonly arises from these urothelial cells -- hence the most common type is called urothelial carcinoma (previously known as transitional cell carcinoma, or TCC). Less common types include squamous cell carcinoma (more common in areas with endemic schistosomiasis, or in patients with chronic bladder irritation) and adenocarcinoma.
Urothelial carcinoma is not confined to the bladder -- the same cell type lines the renal pelvis, ureters, and urethra. Upper urinary tract urothelial cancers (UTUC) are less common but clinically important, as patients with bladder cancer have an elevated lifetime risk of developing upper tract disease, and vice versa.
Symptoms of Bladder Cancer
Bladder cancer is known as a silent cancer in its earliest stages, but haematuria -- blood in the urine -- provides an early signal in the majority of cases. Recognising and acting on this signal promptly is the most important determinant of outcome.
The important symptom: haematuria
- Gross (visible) haematuria -- urine that is pink, red, rust-coloured, or cola-coloured. This is the presenting symptom in approximately 80-85% of bladder cancer diagnoses.
- Microscopic haematuria -- blood in the urine detectable only on urine dipstick or microscopy, not visible to the naked eye. Found in a further proportion of cases during routine health screening.
- Painless haematuria is the characteristic presentation -- the absence of pain does not reduce the significance of the finding and does not indicate a benign cause.
- Intermittent haematuria -- the bleeding may come and go. Resolution of visible haematuria without investigation is not reassurance; the tumour continues to be present between bleeding episodes.
Irritative urinary symptoms
Particularly associated with carcinoma in situ (CIS) and more advanced disease:
- Urgency: A sudden, compelling need to urinate that is difficult to defer
- Frequency: Urinating more often than usual without increased fluid intake
- Dysuria: Burning or painful urination (more commonly associated with infection; when persistent without infection, investigation is warranted)
Symptoms of advanced or metastatic disease
- Pelvic or lower abdominal pain -- from local tumour invasion
- Flank or back pain -- from ureteric obstruction causing hydronephrosis
- Leg swelling -- from lymph node involvement obstructing lymphatic drainage
- Bone pain, unexplained weight loss, and fatigue -- from distant metastasis
Most patients with early-stage bladder cancer have no symptoms other than haematuria. This is why the symptom must never be dismissed.
Causes and Risk Factors
Bladder cancer arises from accumulated genetic mutations in urothelial cells. Several factors significantly accelerate this process:
Tobacco smoking -- the dominant modifiable risk factor
Smoking is responsible for approximately 50% of all bladder cancer cases. Carcinogens in tobacco smoke are absorbed into the bloodstream, filtered by the kidneys, and concentrated in the urine -- where they are in prolonged contact with the bladder urothelium. The risk is dose-dependent: the more a person has smoked and the longer they have smoked, the higher the risk. Importantly, risk remains elevated for many years after cessation, though it does gradually decline.
- Current smokers have 2-4 times the bladder cancer risk of non-smokers
- Ex-smokers retain elevated risk for 10-20 years after quitting
- Both conventional and electronic cigarettes deliver bladder carcinogens
Occupational chemical exposure
Aromatic amines and polycyclic aromatic hydrocarbons used in certain industries are established bladder carcinogens. Occupational exposure accounts for approximately 20-25% of bladder cancer cases:
- Rubber and tyre manufacturing -- aromatic amines
- Dye industry -- benzidine and beta-naphthylamine
- Leather and textile processing
- Petroleum refining and petrochemical work
- Printing and hairdressing (hair dye chemicals)
- Aluminium production
Other risk factors
- Age -- bladder cancer incidence rises sharply above the age of 55; the median age at diagnosis is approximately 73
- Sex -- men are 3-4 times more likely to develop bladder cancer than women, though women tend to present with more advanced disease at diagnosis
- Prior pelvic radiation -- radiation therapy for cervical, prostate, or rectal cancer increases the risk of bladder cancer in the radiation field
- Cyclophosphamide chemotherapy -- this alkylating agent is a recognised bladder carcinogen
- Chronic bladder inflammation -- recurrent urinary tract infections, bladder stones, and indwelling catheters are associated with squamous cell carcinoma of the bladder
- Family history -- first-degree relatives of bladder cancer patients have a modestly elevated risk; hereditary predisposition is less prominent than in colorectal or breast cancer but does exist
How is Bladder Cancer Diagnosed?
Bladder cancer diagnosis requires both visualisation of the bladder interior and tissue confirmation. The diagnostic pathway is systematic and well-established.
- Urine Dipstick and Microscopy: The first investigation for haematuria. Confirms the presence of red blood cells. Dipstick testing is highly sensitive but non-specific -- positive results require further evaluation. Urine culture to exclude urinary tract infection as the cause is always performed alongside.
- Urine Cytology: Examination of cells shed from the urothelium into the urine under microscopy. High sensitivity for high-grade urothelial carcinoma and CIS; low sensitivity for low-grade papillary tumours. Used as an adjunct to cystoscopy, not a replacement. A positive cytology in the absence of a visible cystoscopic lesion should prompt investigation of the upper urinary tract.
- Cystoscopy: Direct visualisation of the urethra and bladder interior using a flexible or rigid cystoscope. The gold standard investigation for haematuria. Identifies tumour location, number, size, and morphology (papillary vs flat). Biopsies of suspicious areas can be taken. Flexible cystoscopy under local anaesthetic is well-tolerated as an outpatient procedure.
- CT Urogram (CTU): CT imaging with contrast of the kidneys, ureters, and bladder. Evaluates the entire urothelial tract for tumours. Assesses the upper urinary tract for UTUC, hydronephrosis, and other causes of haematuria. Standard imaging investigation alongside cystoscopy in haematuria workup.
- CT / MRI Staging: CT chest, abdomen, and pelvis (or MRI pelvis) for staging following confirmed muscle-invasive bladder cancer. Assesses extent of local invasion and lymph node or distant metastasis. MRI of the pelvis provides superior soft tissue resolution for assessing extravesical extension and is used in pre-operative surgical planning.
- PET-CT Scan: Positron emission tomography combined with CT for metabolic imaging of lymph node and distant metastatic disease. Used in staging of muscle-invasive or metastatic bladder cancer, and to assess treatment response. Not routine for NMIBC.
- Urine Biomarkers: Molecular urine tests (UroVysion FISH, BTA, NMP22) detect genetic changes or bladder tumour antigens in urine. Used as adjuncts to cystoscopy in surveillance of known bladder cancer. Not yet standard as primary screening tools but increasingly used in high-risk populations.
Surveillance After Treatment
Bladder cancer has one of the highest recurrence rates of any cancer -- particularly NMIBC. Surveillance after treatment is not optional: it is the mechanism through which early recurrence is detected and treated before progression occurs.
Surveillance for non-muscle invasive bladder cancer
- Low-risk NMIBC: cystoscopy at 3 months post-TURBT, then annually for 5 years
- Intermediate-risk NMIBC: cystoscopy at 3 months, then every 6 months for 2 years, then annually
- High-risk NMIBC: cystoscopy every 3 months for 2 years, then every 6 months for 3 years, then annually; urine cytology at each visit; CT urogram annually for 5 years
Surveillance after radical cystectomy
- CT chest, abdomen, and pelvis every 3-6 months for 2 years, then annually
- Urine cytology from the urinary diversion
- Renal function monitoring
- Vitamin B12 supplementation (ileal conduit or neobladder uses bowel, which absorbs B12)
- Urethral wash cytology if the urethra has been preserved
