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.

Tabs Content

Clinical Overview

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

Classification and treatment decisions based on histology and staging
For detailed descriptions of useful immunohistochemical stains, including recommended use, refer to ARUP Laboratories’ Immunohistochemistry Stain Offerings
For more information, see the Paris System for Reporting Urinary Cytology

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

Cystitis/pyelonephritis
Nephrolithiasis
Prostatitis
Other malignancy
- Renal cancer
- Prostate cancer
Glomerular diseases
Stricture of ureter/urethra

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 CMP^a	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 cytology^b	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

Urinalysis, Complete 0020350

Method: Reflectance Spectrophotometry/Microscopy

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

Cytology, Non-Gynecologic 2000623

Method: Microscopy

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

UroVysion FISH 2001181

Method: Fluorescence in situ Hybridization/Computer Assisted Analysis/Microscopy

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

Bladder Tumor Associated Antigen 2000183

Method: Qualitative Immunoassay

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

NMP22, Urine 0080281

Method: Quantitative Enzyme Immunoassay