Bladder Cancer in Adults: Screening -- Asymptomatic Adults


General

Grade: I

Specific Recommendations

The USPSTF concludes the current evidence is insufficient to assess the balance of benefits and harms of screening for bladder cancer in asymptomatic adults. Literature scans conducted in April 2019 in the MEDLINE and PubMed databases and the Cochrane Library showed a lack of new evidence to support an updated systematic review on the topic at this time. See the Literature Surveillance Report under the Supporting Evidence section of this webpage.

Frequency of Service

No information available.

Risk Factor Information

This evidence update focused on the benefits and harms of screening for bladder cancer among people without symptoms, the accuracy of screening tests done in primary care settings, and the benefits and harms of treatment. The updated evidence review did not find any new high quality evidence to adequately determine the balance of benefits and harms of screening for bladder cancer. However, bladder cancer is a common cancer and can cause considerable health problems including death. Therefore, the USPSTF determined that the evidence was insufficient to provide a recommendation for or against bladder cancer screening. The USPSTF emphasizes the need for additional research in this area.


Clinical

Clinical Considerations

Patient Population Under Consideration

This recommendation applies to asymptomatic adults. Although adults with mild lower urinary tract symptoms (such as urinary frequency, hesitancy, urgency, dysuria, or nocturia) are not strictly asymptomatic, these symptoms are quite common and are not believed to be associated with an increased risk for bladder cancer. The USPSTF considered it reasonable to include these persons in the population under consideration for screening. Adults with gross hematuria or acute changes in lower urinary tract symptoms are not included in this population.

Screening Tests

Primary care-feasible screening tests for bladder cancer include identifying hematuria with a urine dipstick or microscopic urinalysis, urine cytology, and tests for urine biomarkers.

Treatment

Once bladder cancer has been diagnosed, several factors determine treatment, including tumor grade, cancer stage (superficial vs. invasive), whether the tumor is recurrent, the patient's age and overall health status, and patient and physician preferences. The principal treatment for superficial (Ta or T1) bladder cancer is transurethral resection of the bladder tumor, which may be combined with adjuvant radiation therapy, intravesical chemotherapy, immunotherapy, or photodynamic therapies. Radical cystectomy, often with adjuvant or neoadjuvant systemic chemotherapy, is used in cases of surgically resectable invasive bladder cancer.

Suggestions for Practice Regarding I Statement

In deciding whether to screen for bladder cancer, clinicians should consider the following.

Potential Preventable Burden

Bladder cancer is similar to many other types of cancer in that it is a heterogeneous condition. Approximately 70% of all cases of newly diagnosed transitional cell carcinomas present as superficial tumors (including in situ); some of these tumors may never progress to advanced disease. However, some cases of bladder cancer invade the muscle tissue, progress, and metastasize; treatment has limited efficacy in these cases. Early detection of tumors with malignant potential may have an important effect on the mortality rate of bladder cancer. One challenge of screening for bladder cancer is accurately identifying cases of early-stage cancer (subepithelial and in situ) with a high risk for progression. Another area of uncertainty is determining whether providing earlier, less toxic treatment (such as immunotherapy) with the intention of preventing symptomatic progression results in fewer overall harms to the patient than providing more toxic treatment (such as radical cystectomy) only to those patients who develop symptomatic or advanced tumors. Persons at increased risk for bladder cancer include those who work in the rubber, chemical, or leather industries, as well as those who smoke, are male, are older, or have a family or personal history of bladder cancer.

Potential Harms

False-positive test results may result in anxiety and unneeded evaluations, diagnostic-related harms from cystoscopy and biopsy, harms from labeling or unnecessary treatments (such as transurethral resection of a bladder tumor, intravesical chemotherapy, or biologic therapies), and overdiagnosis.

Current Practice

Screening tests feasible for use in primary care include urine dipstick or microscopic urinalysis for hematuria, urine cytology, and tests for urine biomarkers. Tests for urine biomarkers are not commonly used in primary care in part because of their cost, although this varies substantially. Patients with positive screening results are typically referred to a urologist for further evaluation, which may include cystoscopy (and biopsy if a tumor is found), imaging, and other studies.

Other Considerations

Research Needs and Gaps

Several gaps in the evidence led the USPSTF to issue an I statement. Addressing these research needs could potentially provide sufficient evidence for the USPSTF to issue future screening recommendations. Cohort studies are needed to evaluate the natural history of early-stage, untreated bladder cancer (particularly that detected by screening) to allow a greater understanding of the potential overdiagnosis and overtreatment associated with screen-detected bladder cancer. Studies that compare the diagnostic accuracy of urine screening tests in representative populations are needed, as well as studies that assess the effect of screening on the incidence of bladder cancer, tumor characteristics, and subsequent treatments. Randomized, controlled trials or well-designed case-control studies that evaluate clinical outcomes in screened versus unscreened populations, which would provide direct evidence on benefits and harms of screening, have highest priority. Targeting populations at increased risk for bladder cancer because of patient characteristics or occupational exposure may be preferred to enhance feasibility and maximize clinical relevance. A better understanding of the harms related to screening and treatment are required. Methods for evaluating these harms could include conducting observational studies based on patient registries or large pharmacoepidemiologic databases. As noted, prospective cohort studies are needed to more accurately identify cases of early-stage cancer (subepithelial and in situ) with a high risk for progression. Future research should also clarify the trade-offs of using less-toxic treatments earlier and more frequently, to prevent symptomatic progression, versus using treatments with greater toxicity, which are typically reserved for those patients who develop symptomatic or advanced tumors.

Update of Previous USPSTF Recommendation

In 2004, the USPSTF recommended against routine screening for bladder cancer in adults because the USPSTF concluded that the harms outweighed the benefits of screening (D recommendation)2. In 2009, the USPSTF performed a targeted literature review and found insufficient evidence to assess the benefits and harms of screening for bladder cancer. In 2004, the USPSTF concluded that the harms outweighed the benefits; however, this time the USPSTF reviewed mortality statistics and other epidemiologic data that suggested heretofore undemonstrated benefits of screening. As a result, the USPSTF changed its recommendation from a D to an I statement (insufficient evidence).


Rationale

Rationale

Importance

Bladder cancer is the fourth most commonly diagnosed cancer in men and the ninth most commonly diagnosed cancer in women in the United States. It is the seventh-leading cause of solid cancer-related deaths. An estimated 70,980 new cases of bladder cancer were diagnosed in the United States during 2009 (52,810 cases in men and 18,170 cases in women), and approximately 14,330 people died of the disease (10,180 men and 4150 women). More than 90% of all cases of bladder cancer are classified as transitional cell carcinomas. Most newly diagnosed transitional cell carcinomas present as superficial tumors. The stages of bladder cancer include superficial (Ta or T1) and muscle-invasive tumors. Many superficial tumors (50% to 70%) will recur after treatment, with a 10% to 20% risk for the tumor to progress to the invasive stage. One fourth of all cases of bladder cancer and 20% to 40% of all invasive tumors have already metastasized to the lymph nodes at the time of diagnosis. Invasive bladder cancer is associated with a poor prognosis.

Detection

The evidence is inadequate regarding the diagnostic accuracy of potential tests (urinalysis for microscopic hematuria, urine cytology, or tests for urine biomarkers) for identifying bladder cancer in asymptomatic persons with no history of bladder cancer.

Benefits of Detection and Early Intervention

The USPSTF found inadequate evidence that screening for bladder cancer or treatment of screen-detected bladder cancer leads to improved disease-specific or overall morbidity or mortality.

Harms of Detection and Early Intervention

Screening may yield false-positive results. False-positive results may lead to anxiety, labeling, pain, and additional complications that result from diagnostic cystoscopy and biopsy (such as bladder perforation, bleeding, and infection) or imaging. The USPSTF found inadequate evidence on the harms of screening for bladder cancer. Evidence on the harms associated with early treatment, which may occur more frequently with greater detection of cases of early-stage cancer, is also inadequate.

USPSTF Assessment

The USPSTF concludes that the evidence is insufficient to determine the balance of benefits and harms of screening for bladder cancer in asymptomatic adults.


Others

Recommendations of OthersNo major organization recommends screening for bladder cancer in asymptomatic adults. In 2011, the American Academy of Family Physicians endorsed the USPSTF recommendation9. The European Association of Urology states that the best approach to primary prevention of muscle-invasive bladder cancer is to eliminate active and passive smoking10. The American Cancer Society states that prompt attention to bladder symptoms is the best approach for finding bladder cancer in its earliest, most treatable stages in persons with no known risk factors11.


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