History and exam

Key diagnostic factors

common

presence of risk factors

Risk factors include tobacco exposure, male sex, age >55 years, exposure to chemical carcinogens, pelvic radiation, systemic chemotherapy, and family history positive for bladder cancer.

haematuria (visible or non-visible)

Haematuria a common presentation of bladder cancer.[59][66]​​[86]

Episodes of haematuria may be intermittent and, therefore, resolution should not be attributed to treatment with, for example, antibiotics.

Absence of any symptom or finding on physical examination is common and illustrates the importance of screening urine for non-visible haematuria.

Other diagnostic factors

uncommon

urinary frequency

Rarely the sole symptom of bladder cancer, but does occur.

Benign prostatic hypertrophy and overactive bladder are more common, but if these do not respond to treatment, urinary cytology and cystoscopy are indicated.

dysuria

Burning with urination can occur with carcinoma in situ and high-grade bladder cancer.​[50]​​ However, risk of bladder or urinary tract cancer in a patient (≥60 years) presenting with dysuria (in the absence of visible haematuria) is low.[66][67]​​​

Common causes of dysuria (e.g., urinary tract infection, prostatitis) should be excluded. See Assessment of dysuria.

Risk factors

strong

tobacco exposure

Smoking is the most significant causative factor in bladder cancer.[11][20][21]​​​ Risk increases with an increase in intensity and/or duration of smoking.[44]

The population attributable risk (the proportion of disease incidence in a population [exposed and non-exposed] due to the exposure) for ever smoking in a large cohort was 50%.[45]

The relative risk of bladder cancer in people who have any history of smoking versus those who have never smoked is around 2-3.[20] The relative risk of bladder cancer from second-hand smoke is 1.4.[20]

Smoking cessation reduces the risk, but not to the level of non-smokers, and improves the prognosis of the disease.[46][47]

exposure to chemical carcinogens

Occupational exposure to chemical carcinogens such as aromatic amines used in rubber and dye industries; polycyclic aromatic hydrocarbons used in the aluminium, coal/oil/petroleum, and roofing industries; and exposure to arsenic in drinking water are recognised causative factors of bladder cancer.[11][22]

Other occupational groups at increased risk include firefighters, painters, dry cleaners, and hairdressers.[23]

age >65 years

Bladder cancer risk increases with age and primarily affects those ≥65 years.[48][15]​​​

In the US, more than 90% of patients present after the age of 55 years; median age at diagnosis is 73 years.[15] 

pelvic radiation

Radiation of the pelvic area, as commonly used for prostate cancer, significantly increases the risk of bladder cancer.[11][23][49]

Patients having pelvic radiation should be followed-up closely, especially those treated at a younger age.[50][51]​​

cyclophosphamide or ifosfamide use

Cyclophosphamide significantly increases the risk of bladder cancer.[11][23]

Ifosfamide can damage the lining of the bladder and may increase the risk of bladder cancer, although the link is not as well-established as with cyclophosphamide.[52]​​

Schistosoma infection

Infection with the parasite Schistosoma haematobium results in chronic bladder inflammation and an increased risk of squamous cell carcinoma (SCC) of the bladder.[11][32]​​

Public health interventions have changed the prevalence of S haematobium infection and this is likely to change the incidence and type of bladder cancer in countries where S haematobium infection is endemic.[53][54]

male sex

Incidence of bladder cancer in the US is estimated to be 31.2 per 100,000 population for males and 7.7 per 100,000 population for females (based on 2018-2022 data; all races).[15]

The gender difference in bladder cancer incidence appears to be independent of differences in exposure risk.​[55]​​ 

chronic bladder inflammation

Chronic urinary infections, kidney and bladder stones, long-term catheter drainage, and other causes of chronic bladder irritation have been associated with increased risk for bladder cancer (especially squamous cell carcinoma of the bladder).[11][31][32]​​​​

genetic predisposition

Familial cases of bladder cancer occur; 4.3% of bladder cancer patients have a first-degree relative with bladder cancer, and up to 50% of urothelial cancer patients have a family history of cancer.[11][33]

Studies have identified germline mutations associated with predisposition to bladder cancer (including MSH2 and MLH1 variants associated with Lynch syndrome).[33][34][35] Patients with germline variants were more often diagnosed at a younger age than those without variants.[34]

Lynch syndrome is associated with increased risk of bladder cancer (estimated cumulative risk to age 80 years: 2% to 7% with MLH1 variant; 4% to 13% with MSH2/EPCAM variants; 1% to 8.2% with MSH6 variant). Patients with MLH1 and MSH2 presented at an estimated average age of 59 years.[56]

weak

diabetes mellitus

Diabetes (primarily type 2) may increase risk of bladder cancer; evidence is conflicting​.[11][25]​​​[26]

There is some evidence to suggest that pioglitazone may be associated with an increased risk of bladder cancer in adults with type 2 diabetes.[27][28][29]

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