Bladder Cancer

Bladder cancer is the fourth most common cancer in men and the ninth most common cancer in women. Urinalysis is used initially to identify hematuria. Diagnosis is dependent on cystoscopy with biopsy and imaging. Urine cytology is useful in high-grade tumors, but is neither sufficient nor necessary for diagnosis.

Diagnosis

Indications for Testing

  • Information from CDC, 2017
    • Hematuria
    • Urinary frequency
    • Urinary urgency
    • Dysuria
    • Pelvic/back pain in advanced disease

Laboratory Testing

  • Initial testing – urinalysis to confirm hematuria
  • Cystoscopy – fluorescence cystoscopy
  • Urine cytology – can be used to assist with diagnosis; however, neither sensitive nor specific
  • Noninvasive urinary tests
    • Cell-based (UroVysion fluorescence in situ hybridization [FISH], immunocytology) and noncell-based (bladder tumor antigen [BTA], urinary nuclear matrix protein [NMP22]) testing available
    • Sensitive for high-grade tumors (Witjes, European Association of Urology, 2016) 
    • Negative results do not rule out neoplasm
    • Positive results support neoplasm in urothelial cells in the genitourinary tract, not limited to bladder
    • Urinary markers – can be used to monitor response to Bacillus Calmette-Guérin treatment (UroVysion FISH) or clarify indeterminate cytology results (UroVysion FISH and immunocytology) (Chang, 2016)
  • Tumor markers – no tumor marker has been found to be specific for bladder cancer 

Histology

Imaging Studies/Procedures

  • Information from National Comprehensive Cancer Network (NCCN, 2018)
    • Nonmuscle-invasive bladder cancer (NMIBC)
      • Cystoscopy, upper tract computed tomography (CT) urography, retrograde pyelogram, CT of abdomen and pelvis, magnetic resonance imaging (MRI) urography, renal ultrasound
    • Muscle-invasive bladder cancer (MIBC)
      • CT of chest, brain MRI (for high-risk patients), MRI, positron emission tomography/CT, or bone scan if metastases indicated by laboratory testing
      • May require further imaging for staging

Differential Diagnosis

Screening

Not recommended in asymptomatic adults (U.S. Preventive Services Task Force [USPSTF], 2010

Monitoring

NCCN (2018) and AUA/ASCO/ASTRO/SUO (2017) Guidelines
  NCCN AUA/ASCO/ASTRO/SUO
Laboratory Tests Postcystectomy Postbladder-Sparing Surgery Postcystectomy

Renal function

Every 3-6 mos for the first yr

Annually, yrs 2-5

As clinically indicated after 5 yrs

Every 3-6 mos for first yr

As clinically indicated after 1 yr

Every 3-6 mos for 2-3 yrs

Annually after first 2-3 yrs

Liver function

Every 3-6 mos for the first yr

Annually, yrs 2-5

As clinically indicated after 5 yrs

Every 3-6 mos for first yr

As clinically indicated after 1 yr

n/a

B12

Annually for the first 5 years

As clinically indicated after 5 yrs

n/a

Every 3-6 mos for 2-3 yrs

Annually after first 2-3 yrs

CBC and CMPa

Every 3-6 mos for the first yr

Every 3-6 mos for the first yr

n/a

Urine cytology

Every 6-12 mos for first 2 yrs

As clinically indicated after 2 yrs

Every 6-12 mos for first 2 yrs

As clinically indicated after 2 yrs

n/a

Urethral wash cytologyb

Every 6-12 mos for first 2 yrs

As clinically indicated after 2 yrs

n/a

n/a

aOnly in cases of chemotherapy

bHigh-risk patients only

ASCO, American Society for Radiation Oncology; ASTRO, American Society for Radiation Oncology; AUA, American Urological Association; CMP, complete metabolic panel; n/a, not available; NCCN, National Comprehensive Cancer Network; SUO, Society of Urologic Oncology

Sources: NCCN, 2018; AUA/ASCO/ASTRO/SUO, 2017

Background

Epidemiology

  • Incidence – >79,000 new cases per year (Surveillance, Epidemiology, and End Results [SEER], 2017)
  • Age
    • ≥65 years
    • Rare in individuals <40 years
  • Sex – M>F, 3:1 (SEER, 2017)
  • Ethnicity (SEER, 2017)
    • Nearly twofold greater incidence in Caucasians than in African Americans
    • More than twofold greater incidence in Caucasians than in Asians or Native Americans

Risk Factors

  • Tobacco use (doubles risk of bladder cancer) (CDC, 2016)
  • Family history of bladder cancer or certain gene mutations)
  • Occupational exposure (rubber, leather dyes, and organic solvents)
  • Chronic urinary tract infections (including schistosomiasis)
  • Well water with arsenic exposure
  • Use of Chinese herb Aristolochia fangchi
  • History of external beam irradiation (European Association of Urology [EAU], 2016)
  • Previous bladder cancer
  • Previous cyclophosphamide chemotherapy

​Clinical Presentation

  • Painless hematuria – microscopic or gross
  • Dysuria, urinary frequency, urinary urgency
  • Pelvic and back pain in later disease
  • Bone pain (rare) – suggestive of metastatic disease

ARUP Lab Tests

Primary Tests

Confirm hematuria

Screen for various metabolic and kidney disorders

Time-sensitive test

Diagnose and/or monitor residual or recurring bladder cancer

Use for all nongynecologic sources EXCEPT specimens obtained by fine needle aspiration (FNA); for FNA specimens, refer to cytology, FNA

May aid in diagnosis of urothelial carcinoma in individuals with hematuria

Monitor tumor recurrence in patients previously diagnosed with urothelial carcinoma

Detect amplifications of chromosomes 3, 7, 17, and deletions of the 9p21 locus

Some urothelial cancers will not be detected

Negative results in the presence of other symptoms/signs of urothelial carcinoma may suggest possibility of false-negative test results

Gene variants other than amplification of chromosomes 3, 7, or 17 and deletion (loss) of 9p21 locus will not be detected

Aid in the management of bladder cancer patients in conjunction with cystoscopy

Qualitative assay detects bladder tumor associated antigen in urine of persons diagnosed with bladder cancer

Aid in the diagnosis of urothelial carcinoma in conjunction with standard diagnostic procedures and monitoring for tumor recurrence

Values obtained with different assay methods should not be used interchangeably

Aid in histologic diagnosis of bladder cancer

Stained and returned to client pathologist for interpretation; consultation available if needed

Aid in histologic diagnosis of bladder cancer

Stained and resulted by ARUP

Aid in histologic diagnosis of bladder cancer

Stained and returned to client pathologist for interpretation; consultation available if needed

Aid in histologic diagnosis of bladder cancer

Stained and resulted by ARUP

Aid in histologic diagnosis of bladder cancer

Stained and returned to client pathologist for interpretation; consultation available if needed

Aid in histologic diagnosis of bladder cancer

Stained and returned to client pathologist for interpretation; consultation available if needed

Aid in histologic diagnosis of bladder cancer

Stained and returned to client pathologist for interpretation; consultation available if needed

Aid in histologic diagnosis of bladder cancer

Stained and returned to client pathologist for interpretation; consultation available if needed

Aid in histologic diagnosis of bladder cancer

Stained and returned to client pathologist for interpretation; consultation available if needed

Aid in distinguishing bladder cancer from prostate cancer

Stained and returned to client pathologist; consultation available if needed

Aid in distinguishing bladder cancer from prostate cancer

Stained and returned to client pathologist; consultation available if needed

Can be used in a panel of antibodies for diagnosis of unknown primary carcinoma when carcinomas of the breast or bladder are a possibility; the pattern of reactivity should be nuclear

Stained and returned to client pathologist; consultation available if needed

Related Tests

Aid in detection of vitamin B12 deficiency

Assess for targeted variants that are useful for prognosis and/or treatment of individuals with solid tumor cancers, including melanoma, gastrointestinal stromal tumor (GIST), colorectal, bladder, and hepatocellular carcinomas, at initial diagnosis or in the presence of refractory disease

If the clinical indication is lung cancer, additional molecular genetic testing may be considered for detection of gene rearrangements and/or c-MET exon 14-skipping alterations

For evaluation of microsatellite instability, additional molecular testing should be considered

Genes included – AKT1, ALK, APC, ATM, BRAF, CDH1, CDKN2A, CTNNB1, DDR2, EGFR, ERBB2, ERBB4, EZH2, FBXW7, FGFR1, FGFR2, FGFR3, GNA11, GNAQ, GNAS, HRAS, IDH1, IDH2, KDR, KIT, KRAS, MAP2K1, MET, MTOR, NOTCH1, NRAS, NTRK1, PDGFRA, PIK3CA, PTEN, RB1, RET, ROS1, SMAD4, SMO, STK11, TERT promoter, TP53, VHL

Refer to Additional Technical Information document for further content and test limitations

Medical Experts

Contributor

Chadwick

Barbara E. Chadwick, MD

Assistant Professor of Anatomic Pathology, University of Utah

Medical Director, Cytology, and Staff Pathologist, Surgical Pathology at ARUP Laboratories

Contributor

Genzen

Jonathan R. Genzen, MD, PhD

Associate Professor of Clinical Pathology, University of Utah

Chief Operations Officer, Medical Director of Automated Core Laboratory and Farmington Health Center Clinical Laboratory, at ARUP Laboratories

References

Additional Resources