Note: Separate PDQ summaries on Bladder Cancer Treatment and Levels of Evidence for Cancer Screening and Prevention Studies are also available.
There is inadequate evidence to determine whether screening for bladder and other urothelial cancers has an impact on mortality.
Description of the Evidence
|Study Design: There are no studies that directly address this question.|
|Internal Validity: Not applicable (N/A).|
|Magnitude of Effects on Health Outcomes: N/A.|
|External Validity: N/A.|
Based on fair evidence, screening for bladder and other urothelial cancers would result in unnecessary diagnostic procedures with attendant morbidity.
Description of the Evidence
|Study Design: Opinions of respected authorities based on clinical experience, descriptive studies, or reports of expert committees.|
|Internal Validity: N/A.|
|Magnitude of Effects on Health Outcomes: Good evidence for rare harms.|
|External Validity: N/A.|
Bladder cancer is the fourth most commonly diagnosed malignancy in men in the United States. The incidence is about four times higher in men than in women. It is estimated that 81,180 new cases of bladder cancer are expected to occur in the United States in 2022.[
Bladder cancer is diagnosed almost twice as often in White individuals as in Black individuals of either sex. The incidence of bladder cancer among other ethnic and racial groups in the United States falls between that of Black and White individuals. The incidence of bladder cancer increases with age.[
Annual incidence rates of bladder cancer had been relatively stable from 1975 to 2017, ranging from 18.9 to 22.0 (per 100,000); however, more recently (2008–2017), rates have been declining by about 1% per year.[
Age-adjusted mortality from bladder cancer decreased in all races and sexes between 1975 and 2017.[
More than 90% of cancers in the bladder are transitional cell carcinomas, also called urothelial cancer. Urothelial cancer can also rarely develop in the lining of the renal pelvis, ureter, prostate, and urethra. Other important histologic types include squamous cell carcinoma and adenocarcinoma. Adenocarcinomas account for less than 2% of primary bladder cancers, including metastases from the rectum, stomach, endometrium, breast, prostate, and ovary.[
There are no definitive studies on the prevention of bladder or other urothelial cancers. Reduction in environmental and occupational exposures would presumably reduce urothelial cancer risk. Differences in age, sex, race, and geographic distribution may reflect differences in environmental and occupational exposure to possible toxicants. Relevant exposures include chemical exposures; cigarette smoking; infection with bacteria, parasitic fungi, or viruses; and treatment with certain chemotherapeutic agents. A positive family history of bladder cancer has also been associated with an increased risk of bladder cancer.[
Several populations with a variety of exposures appear to be at higher risk of developing bladder cancer. By far, the greatest known environmental risk factor in the general population is tobacco, especially cigarette smoking;[
Among the chemicals implicated in smoking-induced bladder cancer are aminobiphenyl and its metabolites.[
Environmental and Occupational Exposure to Certain Chemicals
A variety of industrial exposures have also been implicated as risk factors for developing bladder cancer, primarily aromatic amines, such as 2-naphthylamine, beta-naphthylamine, or 4-chloro-o-toluidine, present in the production of dyes and benzidine and its derivatives;[
Occupations reported to be associated with an increased risk of bladder cancer include those that involve processing paint, dye, metal, and petroleum products.[
It is estimated that 5% to 15% of patients in the United States who eventually die of bladder cancer will have strong exposure histories to the above-named environmental factors (other than smoking).[
The use of contaminated Chinese herbs is also reported to be a risk factor. The prime carcinogen in these herbs appears to be aristolochic acid (AA) extracted from species of Aristolochia.[
Exposure to Arsenic
Ingestion of large quantities of arsenic in well water has also been associated with numerous malignancies, including transitional cell carcinoma (TCC) of the bladder.[
Exposure to inorganic arsenic compounds, such as gallium arsenide, is also associated with an increased risk of bladder cancer.
Treatment With Cyclophosphamide or Ifosfamide
Exposure to the cancer chemotherapy agent cyclophosphamide [
Pelvic Radiation Therapy
Pelvic radiation therapy for other malignancies, such as prostate cancer,[
Specific genetic mutations associated with bladder cancer include the following:[
Other Risk Factors
Additional risk factors associated with more aggressive forms of bladder cancer include neuropathic bladder and associated indwelling catheters [
Urothelial tumors other than TCC include adenocarcinoma, squamous cell carcinoma, and metastatic adenocarcinoma. Risks of squamous cell tumors in the bladder include indwelling catheters [
Although occasional familial clusters have been anecdotally reported [
Seventy percent of patients with bladder cancer have superficial disease at presentation.[
More than 90% of bladder cancers diagnosed in the United States are pure transitional cell carcinomas (TCCs) or TCCs mixed with other histologies, primarily squamous cell carcinoma (SCC), adenocarcinoma, or both. An additional 3% to 4% are pure SCCs, which are approximately twice as likely to occur in women as in men. SCCs also represent a greater proportion of bladder cancers occurring in individuals who have S. haematobium infections of the bladder or who have histories of long-term indwelling urinary catheters, bladder stones, or recurrent bladder infections.[
Both the grade and stage at diagnosis of TCC have extremely important prognostic and therapeutic implications. Nontransitional cell histologies, however, all behave very aggressively and are less responsive to treatments other than extirpative surgery.[
The critical nature of the histologic grade and stage of index lesions for individual prognosis and management decisions has been well recognized for many years. In a study that attempted to evaluate grade and stage in newly diagnosed bladder tumors in a population-based setting, 89% of all newly diagnosed bladder cancers in men aged 50 years and older reported to the state of Wisconsin tumor registry in calendar year 1988 had blocks and slides reviewed by a single pathologist who did not know the original diagnosis.[
Almost all bladder malignancies originate on the uroepithelial surface. Most patients who die of bladder cancer do so from metastatic disease; treatment for metastatic bladder cancer is rarely, if ever, curative.[
Because bladder cancer is almost never incidentally found at autopsy, the preclinical duration in which it has not yet caused symptoms, but in which it can be detected by cystoscopy, is probably brief. This rapid growth rate is supported by clinical experience [
Cystoscopy and Cytology
The use of cystoscopies and bladder wash/urinary cytologic examinations has proven quite successful in the surveillance and management of patients with previously treated bladder cancers.[
Although hematuria is the most common presenting sign of bladder cancer, most individuals with hematuria do not have bladder cancer. In the general population, the prevalence of asymptomatic gross hematuria is about 2.5%, while the prevalence of asymptomatic microhematuria is about 13%.[
One-Time Hematuria Testing
Two groups have reported on the use of testing a single urine specimen for blood to detect urologic malignancies, serious urinary tract diseases, and bladder cancers. Both studies were performed retrospectively to ascertain information from patients who were seen at a large multispecialty clinic [
Repetitive Hematuria Testing
Two studies using Ames Hemastix, a chemical reagent strip for hemoglobin that correlates with microscopic urinalysis in detecting hematuria,[
Other Possible Screening Modalities
The accuracy of voided urine cytology in detecting bladder cancer has been evaluated primarily in patients with histories of bladder cancer who are undergoing cystoscopic surveillance or as a routine test performed in all patients attending a large urology office in a multispecialty clinic. In the studies of patients with histories of bladder cancer, voided urinary cytology was effective in diagnosing 20% to 40% of grade 1 TCCs, 20% to 50% of grade 2 malignancies, and 60% to 80% of grade 3/Tis cancers.[
The outcomes of men diagnosed with bladder cancer through a hematuria home screening program using a chemical reagent strip were compared with a statewide population-based sample of 87% of all men aged 50 years and older from the Wisconsin tumor registry.[
The measurement of a variety of molecules and cellular elements screened in urine has been proposed, and in some cases marketed, to monitor previously diagnosed bladder cancer patients; however, the specificity and sensitivity of these markers have not been assessed in a screening setting in a general population, but several such studies are under way.
In populations at particularly high risk of developing bladder cancer (other than those with histories of bladder cancer), few screening studies that have assessed bladder cancer mortality have been published.[
No randomized controlled bladder cancer screening trials have been conducted in environmentally or industrially exposed cohorts. Completed studies have usually not had comparable control groups, have not been of sufficient sample size to show an effect on outcome, and have been of insufficient length to show a mortality benefit (or lack thereof) for the modality or modalities being assessed.[
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Incidence and Mortality
Updated statistics with estimated new cases for 2022 (cited American Cancer Society as reference 1).
Updated statistics with estimated deaths for 2022.
Revised text to state that from 2015 to 2019, urinary bladder cancer mortality decreased by 1.7% per year.
This summary is written and maintained by the PDQ Screening and Prevention Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the screening of bladder and other urothelial cancers. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Screening and Prevention Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.
Levels of Evidence
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Screening and Prevention Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
Permission to Use This Summary
PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as "NCI's PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary]."
The preferred citation for this PDQ summary is:
PDQ® Screening and Prevention Editorial Board. PDQ Bladder and Other Urothelial Cancers Screening. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/bladder/hp/bladder-screening-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389217]
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Last Revised: 2022-04-29
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