Tests
1st tests to order
urinalysis
Test
Used to screen for or confirm presence of hematuria.
Nonvisible hematuria, defined as ≥3 red blood cells (RBCs) per high-power field, is a common presentation of bladder cancer.[49]
RBC casts and crenated red cells are seen with glomerular bleeding.
Result
hematuria is typical but may be absent; pyuria may also be seen, resulting in confusion with urinary infection
Tests to consider
cystoscopy
Test
Cystoscopy is key to making the diagnosis.[40][47][53] Low-grade tumors are papillary and readily visible, while high-grade tumors can be papillary, flat or in situ, and difficult to visualize with white light.
Visualization at cystoscopy may be improved by narrow-band imaging or blue light (fluorescence) cystoscopy in addition to white light; both appear to improve diagnostic accuracy compared with white light alone.[40][43][57][58]
Enhanced cystoscopy (narrow-band imaging or fluorescence) may improve detection of difficult-to-visualize lesions when used to guide transurethral resection of a bladder tumor (TURBT).[40][43][60][61][62] Blue light (fluorescence) cystoscopy is preferred to guide TURBT because it reduces the risk of recurrence.[40][60][61] The evidence for reduced recurrence is less certain for narrow-band imaging cystoscopy.[40][61][62][63][64]
Result
visualizes bladder tumors and enables pathologic diagnosis
urine cytology
Test
Cytology is not routinely indicated for initial evaluation of hematuria.[51][68] However, urine cytology has a high sensitivity for high-grade tumors and may be a useful adjunct for patients with irritative voiding symptoms or other risk factors for carcinoma in situ (e.g., smoking, exposure to chemicals, family history).[47][51] Urine cytology can also be used for posttreatment surveillance.[43][47]
The sensitivity of urine cytology for low-grade tumors is limited.[47][69] Using the Paris System for Reporting Urinary Cytology (TPS) improves the screening and surveillance potential of urine cytology.[70]
Freshly preserved urine from the second or subsequent void is best to prevent cellular decay.
Result
positive in up to 90% of patients with carcinoma in situ or high-grade tumors; positive in <33% of patients with low-grade urothelial carcinoma
CT urogram
Test
Recommended for investigation of high-risk microhematuria and gross hematuria.[51][52] All patients with suspicious lesions detected at cystoscopy should undergo imaging of the upper tract collecting system if they have not already done so. This serves to identify nodal metastasis and obstruction (hydronephrosis).[40] CT urography, which images the urinary tract with contrast during the excretory phase, is the preferred modality; it shows the urinary tract well and has the advantage of better imaging of the renal parenchyma, and soft tissue of the abdomen and pelvis, including lymph nodes.[40][43] May be obtained before or after TURBT; the National Comprehensive Cancer Network (NCCN) guideline recommends CT or MRI before resection if possible.[43]
Result
bladder tumors, upper tract tumors, and/or obstruction may be seen
MR urogram
Test
All patients with suspicious lesions detected at cystoscopy should undergo imaging of the upper tract collecting system if they have not already done so. This serves to identify nodal metastasis and obstruction (hydronephrosis). MR urography is an alternative if CT with contrast is contraindicated.[40][43] May be obtained before or after TURBT; the NCCN guideline recommends CT or MRI before resection if possible.[43]
Result
normal or may indicate presence of upper tract lesions
renal and bladder ultrasound
Test
Recommended for investigation of microhematuria in low- and intermediate-risk patients.[51] For high-risk patients with microhematuria or patients with suspicious lesions detected at cystoscopy, renal ultrasound with retrograde pyelogram is an alternative option if CT and MRI are contraindicated or unavailable.[40][43][51] Ultrasound has the advantage of avoiding radiation exposure, but provides less detail than CT urogram.
Result
bladder tumors and/or upper tract obstruction may be seen
CBC
Test
Recommended as part of subsequent workup for patients with presumptive (based on TURBT and imaging) or pathologically confirmed muscle-invasive bladder cancer.[43]
Hemoglobin levels are usually normal or slightly decreased if hematuria has been heavy and/or prolonged.
Result
normal or mild anemia
chemistry profile (including alkaline phosphatase)
Test
Recommended as part of subsequent workup for patients with presumptive (based on TURBT and imaging) or pathologically confirmed muscle-invasive bladder cancer.[43] If alkaline phosphatase is elevated or the patient has symptoms suggestive of bone pain, the patient should also have a bone scan.
Patients with symptoms or clinical suspicion of bone metastasis (e.g., bone pain or elevated alkaline phosphatase) should be evaluated with MRI, fluorodeoxyglucose-PET/CT, or a bone scan.[43][65]
Result
normal or may show elevated alkaline phosphatase
chest x-ray
Test
Recommended as part of subsequent workup for patients with presumptive (based on TURBT and imaging) or pathologically confirmed muscle-invasive bladder cancer.[43]
Result
usually normal
CT abdomen and pelvis
Test
Abdominal/pelvic CT or MRI is recommended as part of the subsequent workup for patients with presumptive (based on TURBT and imaging) or pathologically confirmed muscle-invasive bladder cancer.[43][65]
Used in the evaluation of gross hematuria in patients with symptoms of renal colic. May reveal upper and/or lower urinary tract stone disease.
Result
negative for stone disease; may reveal evidence of primary bladder cancer and/or metastatic disease
MRI abdomen and pelvis
Test
Abdominal/pelvic CT or MRI are recommended as part of the subsequent workup for patients with presumptive (based on TURBT and imaging) or pathologically confirmed muscle-invasive bladder cancer.[43][65]
MRI is considered the best modality for local staging of bladder cancer due to superior soft tissue contrast resolution compared with CT.[53][65]
Result
negative for stone disease; may reveal evidence of primary bladder cancer and/or metastatic disease
fluorodeoxyglucose (FDG)-PET/CT
Test
Patients with symptoms or clinical suspicion of bone metastasis (e.g., bone pain or elevated alkaline phosphatase) should be evaluated with MRI, fluorodeoxyglucose (FDG)-PET/CT, or a bone scan.[43][65]
PET/CT scan is useful in patients at high risk of metastatic disease (e.g., those with muscle invasion and lymphovascular invasion).[66]
CT, MRI, and PET/CT have similar specificities for detection of nodal metastasis, but MRI and PET/CT have superior sensitivity.[67]
Result
may show nodal involvement and metastases
bone scan
urine biomarkers
Test
Include bladder tumor antigen (BTA), nuclear matrix protein 22 (NMP22), ImmunoCyt/uCyt+ (a fluorescence immunocytologic diagnostic test using three tumor-related monoclonal antibodies), and UroVysion (a fluorescent in situ hybridization [FISH] of centromeres of chromosomes 3, 7, and 17 and to the 9p21 locus of chromosome 9 associated with bladder cancer).
Urine biomarkers for bladder cancer may help to determine the most appropriate frequency for follow-up cystoscopy and aid in the diagnosis of high-risk patients, but do not replace cystoscopy.[71]
Urine biomarkers for bladder cancer have increased sensitivity compared with urine cytology, but specificity is lower.[43][71]
UroVysion® FISH or ImmunoCyt™ may be useful if cytology results are atypical or equivocal cancer.[40] Persistence of positive UroVysion® FISH following intravesical BCG (in nonmuscle-invasive bladder cancer) suggests poor response and higher risk of progression.[40][72][73]
Result
positive
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