Bladder Cancer


Estimates for bladder cancer based on the American Cancer Society report for 2012:

  • 73,510 total estimated new cases (55,600 men, 17,910 women)
  • 14,880 total estimated deaths (10,510 men, 4,370 women)

Risk Factors

  • Age
  • Race (Caucasian>African-American)
  • Gender (male>female)
  • Prior pelvic radiation
  • Prior cyclophosphamide (a chemotherapy medication) treatment
  • Prior or current tobacco use
  • Occupational or other chronic exposure to aromatic amines and other chemical carcinogens
  • Chronic indwelling urinary catheter use
  • Chronic bladder inflammation
  • Poor fluid ingestion
  • Significant, chronic use of phenacatin containing anti-inflammatories
  • Consumption of aristolochia fanchi (weight reduction aid)


Layers of the bladder:

  • Urothelium

    : Innermost layer. Cellularl lining.

  • Lamina Propria

    : Layer of abundant connective tissue with lymphatic and vascular structures which lies between the urotheliuml and muscle layers

  • Muscularis Propria

    : Muscular layer surrounding the Lamina Propria (i.e. Detrussor Muscle).

  • Adventitia or Serosa

    : Outer layer of the bladder surrounding the muscularis propria.

  • **Tumors limited to the Urothelium and Lamina Propria are typically referred to as non-muscle invasive lesions. Lesions invading the Muscularis Propria are referred to as muscle invasive lesions.

Types of lesions:

  • Urothelial Carcinoma (the vast majority of bladder cancers in USA and Europe = 90-95%) (i.e. Papilloma, Papillary Urothelial Neoplasia of Low Malignant Potential (PUNLMP), Papillary Carcinoma (Low Grade), Papillary Carcinoma (High Grade), Carcinoma In-Situ (CIS))
  • Variants of Urothelial Carcinoma (i.e. micropapillary, nested variant, clear cell variant, mixed tumor with squamous cell or glandular differentiation)
  • Squamous Cell Carcinoma
  • Adenocarcinoma
  • Sarcomas
  • Undifferentiated carcinomas (i.e small cell carcinoma)
  • Metastatic carcinoma
  • Other

Route of Spread

Bladder Cancer spreads by:

  • Local invasion into surrounding pelvic organs or pelvic wall structures
  • Hematogenous spread (i.e. to metastatic sites through the blood by way of vascular channels)
  • Lymphatic spread (i.e. by way of lymphatic channels to lymph nodes)

Clinical Features

Hematuria (i.e. blood in the urine):

  • 80-90% of patients have either gross (visible) or microscopic (non-visible) hematuria
  • Bladder cancer is the most common cause of gross hematuria in patients >50yrs old

Irritative voiding symptoms (i.e. frequent urination, urgent need to urinate, discomfort with urination):

  • 20-30% have irritative voiding symptoms (approximately 50% without hematuria)
  • More common with high grade aggressive disease.

Usual Work-up

  • Urine Markers (cytology, FISH, NMP22, or other)
  • Cystoscopic exam (i.e. using a scope to look into the bladder)
  • Upper tract imaging to evaluate for any tumors of the upper urinary tract (i.e. ureters or kidneys)
  • Staging images to evaluate for any metastatic disease (i.e CT scan, PET/CT, MRI, Bone Scan)
  • Pathologic analysis of any lesions found on cystoscopy

Tumor Grade

  • Refers to the visual and microscopic appearance of a tumor with respect to cellular growth pattern, the cohesiveness of cells, nuclear features, and the invasiveness of cells to deeper layers.
  • Lower grade lesions have an appearance which is closer to that of normal tissue when compared to higher grade lesions.

Staging (TNM)

Primary Tumor (T):

  • TX-primary tumor cannot be assessed
  • T0-No evidence of primary tumor
  • Ta-Noninvasive papillary carcinoma
  • Tis-Carcinoma in situ
  • T1-Tumor invades subepithelial connective tissue
  • T2-Tumor invades muscularis propria (T2a=superficial, T2b=deep)
  • T3-Tumor invades perivesical tissue (T3a=microscopic, T3b=macroscopic)
  • T4-Tumor invades any of the following: prostate stroma, seminal vesicles, uterus, vagina, pelvic wall, abdominal wall (T4a=prostate stroma, uterus, vagina, T4b=pelvic wall, abdominal wall)

Regional Lymph Nodes (N):

  • Nx-Lymph nodes cannot be assessed
  • N0-no lymph node metastasis
  • N1-single regional lymph node metastasis in the true pelvis
  • N2-Multiple regional lymph node metastasis in the true pelvis
  • N3-Lymph node metastasis to the common iliac lymph nodes

Distant Metastasis (M):

  • M0-No distant metastasis
  • M1-Distant metastasis

Treatment Options

Non-muscle invasive urothelial carcinoma:

  • Surgery to trim out tumor/ tumors. Surgery is performed through the urinary tract using special scopes (known as a transurethral resection of bladder tumor, i.e. TURBT)
  • Possible bladder treatment with medications that are delivered directly to the bladder (i.e. BCG, Interferon, mitomycin, or other)
  • Regular follow up cystoscopic exam, urine markers and imaging of the upper urinary tract (i.e. ureters and kidneys)
  • For extremely aggressive tumors or in cases where tumors are not controllable by scopes and/or bladder medications, options exist for surgical complete or partial bladder removal vs extensive surgery to trim out bladder tumors using scopes in combination with chemotherapy and/or radiation.

Muscle invasive urothelial carcinoma:

  • Complete surgical removal of the bladder (i.e. radical cystectomy) with urinary tract reconstruction
  • Bladder preservation therapy:
    • Partial surgical removal of the bladder (i.e. partial cystectomy) limited to the area of the lesion only. (this approach is limited by location and type of tumor and is not typically preferred)
    • Extensive surgery to trim out bladder tumors using scopes and potentially in combination with chemotherapy and/or radiation.

Metastatic urothelial carcinoma (i.e. disease outside of the bladder which has gone either to lymph nodes that drain the bladder or to other organs in the body:

  • Systemic treatment with chemotherapy with or without local treatment to the bladder and surrounding lymph nodes with surgery or radiation depending on an individual’s clinical conditions

Prognostic Factors

  • Stage and grade of the tumor
  • Tumor size
  • Number of tumors present
  • Appearance of the tumor
  • Whether a tumor invades lymphatic/vascular channels
  • Type of tumor present (i.e. urothelial carcinoma vs other type)
  • Health of the patient (i.e. other medical conditions present)


Similar to other cancers, survival is related to whether bladder cancer is confined to the bladder or not. Patients with bladder cancer confined to the bladder will have better outcomes than those whose cancer has spread to other parts of the body or whose cancer has invaded tissues surrounding the bladder. Non-muscle invasive bladder cancer is treated with scopes to remove the bladder cancer and in many cases with medications which are placed in the bladder to prevent recurrence and potentially progression of the tumor. When tumors are either muscle invasive or there is significant concern for a non-invasive tumor progressing to a more invasive stage, surgical removal of the bladder (i.e. radical cystectomy) with urinary tract reconstruction is typically advised to improve the chances of survival by controlling the tumor while it is still confined to the bladder.

Recommended Follow-up

  • Non-muscle invasive tumors: periodic cystoscopic exam, urine cytology (+/- other urine markers), and imaging of the upper urinary tract (i.e. kidneys and ureters)
  • Muscle invasive tumors treated with radical cystectomy: periodic imaging of the upper urinary tract, blood tests, urine cytology from the upper urinary tract, potential scoping and cytology from the urethra in men who retain their urethra, and monitoring of a patient’s urinary tract reconstruction.
  • Muscle invasive tumors treated with bladder preservation therapy (i.e. treated using scopes +/- radiation and/or chemotherapy or treated with partial cystectomy): periodic cystoscopic exam, urine cytology (+/- other urine markers), and imaging of the upper urinary tract (i.e. kidneys and ureters)

About Bladder Cancer

Risk Factors
Route of Spread
Clinical Features
Usual Work-up
Tumor Grade
Staging (TNM)
Treatment Options
Prognostic Factors
Recommended Follow-up

Urothelial Images

Urothelial ca LG noninvasive 2Urothelial ca LG noninvasive

Urothelial ca HG invasive 1 of 2Urothelial ca HG invasive 1 of 2

Urothelial ca HG invasive 2 of 2 in deep muscleUrothelial ca HG invasive 2 of 2 in deep muscle

Urothelial ca HG invasive in a blood vesselUrothelial ca HG invasive in a blood vessel