Macroscopic haematuria is the most common first symptom of bladder cancer.
Macroscopic haematuria is an indication for urgent evaluation in a urological unit. The investigations to be carried out are cystoscopy, urinary cytology and upper urinary tract imaging either with ultrasonography or computed tomography (CT) scanning.
Although asymptomatic microscopic haematuria does not often need further evaluation, the decision must be taken with individual risk factors in mind.
Bladder cancer is associated with a very high risk of recurrence which warrants regular follow-up. Despite the recurrence the prognosis of superficial disease is good.
Epidemiology
Globally, there were over 570 000 cases of bladder cancer (77% in men, crude rate 7.4/100 000) in 2020, and about 220 000 cases in the WHO region Europe http://gco.iarc.fr/today/online-analysis-table.
The most important risk factor is smoking which causes about half of all cases. Smoking increases the risk of bladder cancer more than four fold. Other risk factors include chemicals used in the chemical, rubber, paint and oil industries.
About 75% of bladder cancers are superficial on diagnosis.
Macroscopic haematuria Haematuria is the most common first symptom of bladder cancer. About 90% of patients seek medical help due to haematuria. Haematuria is typically painless.
Irritative bladder symptoms, such as dysuria, frequency of urination and urgency occur in about 20% of patients.
Investigations
Cystoscopy is the most important investigation.
Urinary cytology will only detect about one in three bladder cancers. Normal cytology result does, therefore, not exclude bladder cancer nor the need for further investigations, but a positive result (Grades 4 and 5, in Paris classification high-grade urothelial carcinoma or suspicion of it) is almost a certain sign of cancer. A single cytology test is sufficient. Additionally, a urinalysis and, in men, a PSA test should be performed.
Upper urinary tract imaging, with ultrasound or, more commonly, with CT urography, should be carried out in all patients. A full body CT is performed to evaluate the extent of the disease when suspecting invasive cancer.
Treatment
The diagnosis is confirmed by performing transurethral electroresection (TUR). The purpose of the procedure is to send a sample to a pathologist for assessing the growth depth and degree of differentiation as well as to remove, if possible, the whole visible tumour. A single instillation of intravesical chemotherapy immediately after the resection procedure can reduce tumour recurrence.
The resection procedure can be aided with the use of fluorescence cystoscopy (photodynamic diagnosis). Despite this method being more sensitive than white-light cystoscopy for detection of small and flat ”in situ” tumours, its use is so far not warranted in each resection procedure.
The most common treatment of very high-risk, i.e. muscle-invasive, bladder cancer is cystectomy Surgery Versus Radiotherapy for Muscle Invasive Bladder Cancer. About half the patients have metastatic disease at the time of surgery. Surgical methods that preserve the ability to urinate normally have improved the quality of life of these patients.
Patients should be encouraged to stop smoking as this may reduce recurrence.
Referral criteria
The most common initial symptom of bladder cancer is macroscopic haematuria, which is almost always an indication for further urological investigations. However, the risk of malignancy is very small in a female patient aged under 40 years who presents with macroscopic haematuria associated with culture positive symptomatic urinary tract infection, and after antimicrobial therapy the urinalysis is back to normal and the patient is symptom free. In such a case further investigations are usually not indicated.
Haematuria is often periodic and, therefore, a normal urinalysis at the appointment time does not exclude the need for further evaluation. The bleeding should not be presumed to be associated with, for example, anticoagulant therapy, exercise or sporting activities.
Further investigations are indicated in microscopic haematuria with urinary symptoms, such as urinary frequency, urgency or dysuria.
As a rule, asymptomatic microscopic haematuria does not require further evaluation, but the decision must be taken with individual risk factors for bladder cancer in mind, including smoking, chemical exposure and age. No further evaluation is required for asymptomatic microscopic haematuria in a patient aged under 40 years.
Follow-up
Superficial bladder cancer is accompanied by about a 70% risk of recurrence and a 15% risk of progression, and the consequent need for follow-up means that superficial bladder cancer is one of the most costly cancers.
Follow-up is carried out by a urological unit.
Cystoscopy is the basis of follow-up. Urinary cytology is carried out in high risk patients. Rapid diagnostic tests, such as BTA stat® , have not established themselves in the bladder cancer follow-up. Imaging studies as indicated.
The follow-up schedule is planned individually according to the patient's prognostic factors (size of the tumour, number of tumours, the TNM classification, histological grade and previous recurrences). Annual follow-ups are sufficient if the risk of recurrence and progression is low. Follow-up initially every 3 months in high risk patients. As bladder cancer can recur even after several years the follow-up should be continued provided that the patient's health remains good. Should the disease recur, the follow-up schedule is started from the beginning.
References
Babjuk M, Burger M, Capoun O, et al. European Association of Urology Guidelines on Non-muscle-invasive Bladder Cancer (Ta, T1, and Carcinoma in Situ). Eur Urol 2022;81(1):75-94. [PubMed]
Maisch P, Koziarz A, Vajgrt J, et al. Blue versus white light for transurethral resection of non-muscle invasive bladder cancer. Cochrane Database Syst Rev 2021;(12):CD013776. [PubMed]
Advanced Bladder Cancer (ABC) Meta-analysis Collaborators Group. Adjuvant Chemotherapy for Muscle-invasive Bladder Cancer: A Systematic Review and Meta-analysis of Individual Participant Data from Randomised Controlled Trials. Eur Urol 2022;81(1):50-61. [PubMed]
Han MA, Maisch P, Jung JH, et al. Intravesical gemcitabine for non-muscle invasive bladder cancer. Cochrane Database Syst Rev 2021;(6):CD009294. [PubMed]