Bladder cancer is a heterogenous neoplasm that ranges from non-life-threatening, low-grade, superficial papillary lesions to high-grade invasive tumors that often metastasizes at the presentation.

It is the most common cancer involving the urinary system and it is the 11th most commonly diagnosed in the world.

Microscopic or gross painless hematuria is the most common presenting complaint.


  • Non-invasive-muscle disease may be diagnosed by initial cytoscopy & cytology
    • Once suspected, imaging of upper tract collecting system is required
  • Carcinoma in situ (CIS) is diagnosed by a combination of cystoscopy, urine cytology & histological evaluation of multiple bladder biopsies
  • Patients should be assessed for the presence of regional or distant metastases
    • Tests include cystoscopy, chest radiograph/CT scan, bone scan in patients w/ symptoms or high alkaline phosphatase, imaging of the upper tracts w/ a CT/MRI scan of abdomen & pelvis


Pathologic Staging

  • TNM staging system by AJCC is the most commonly used staging system
  • Grading the tumor is an important prognostic indicator w/ regard to the potential for disease recurrence & progression
  • After stage & grade have been identified, treatment decisions are based on the depth of invasion & extent of disease


Tumor specimen should be evaluated as follows:
  • Depth of invasion (categories pT2 vs pT3a, pT3b, or pT4)
  • Margins w/ special attention paid to the radial margin, prostate, ureter, urethra & peritoneal fat & uterus & vaginal top
  • Histological subtype, if it has clinical implications
  • Extensive lymph node representation (>9)
  • Bladder wall blood vessel invasion (optional evaluation)
  • Pattern of muscle invasion (optional evaluation)
Categories of clinical spectrum
  • Non-muscle-invasive tumors management is directed at reducing recurrences & preventing progression to a more advanced stage
  • Muscle-invasive lesions w/ the goal of therapy is to determine if the bladder should be removed or preserved w/out compromising survival, & to determine if the primary lesion can be managed independently or if patients are at high risk for distant spread requiring systemic approaches to improve the likelihood of cure
    • Metastatic lesions w/ therapy concern on how to prolong quantity & quality of life

Tumor Stage (T)

Primary tumor

Tx Tumor size cannot be assessed
T0 No primary tumor present
Ta Papillary tumors confined to the mucosa or non-invasive papillary carcinoma
Tis Flat, high-grade tumor confined to the mucosa/carcinoma in situ
T1 Papillary tumor invading the lamina propria
T2 Tumor is in the muscularis propria/muscles
pT2a Tumor is in the inner half/superficial muscularis propria
pT2b Tumor is in the outer half/deep muscularis propria
T3 Tumor is in the perivesical tissue
pT3a Microscopically
pT3b Macroscopically (extravesical mass)
T4 Tumor is in any of the following: prostatic stroma, seminal vesicles, uterus, vagina, pelvic wall, abdominal wall
T4a Tumor is in the prostatic stroma, uterus, vagina
T4b Tumor is in the pelvic wall, abdominal wall

Regional Lymph Node (LN) Evaluation

  • Consists of both primary & secondary drainage regions
  • Distant lymph nodes are all other nodes that are above the bifurcation
  • More than 9 lymph nodes should be investigated to reflect N0 appropriately
Nx Regional lymph nodes cannot be assessed
N0 Absence of regional lymph nodes
N1 Presence of a single regional LN metastasis in the true pelvis (hypogastric, obturator, external iliac, or presacral lymph node)
N2 Several regional LN metastasis in the true pelvis (hypogastric, obturator, external iliac, or presacral LN metastasis)
N3 LN metastasis to the common iliac LN

Metastatic Disease (M)

M0 Distant metastasis is not present
M1 Presence of distant metastasis
M1a Distant metastasis present is limited to lymph nodes beyond the common iliacs
M1b Distant metastasis in non-lymph node

Patient’s Stratification into Risk Groups

  • Essential in facilitating treatment recommendations
  • Low-risk tumors are characterized by primary, solitary, Ta, G1, <3cm, no CIS
  • Intermediate-risk tumors are all tumors not defined in the two adjacent categories (between category of low-& high-risk)
  • High-risk tumors can be any of the following:
    • T1 tumor
    • G3 or high-grade tumor
    • Carcinoma in situ
    • Multiple, recurrent & large (>3cm) Ta G1G2 tumors (all conditions must be presented in this point)

WHO Grading

  • The 1973 WHO classification is the widely used classification for grading of non-muscle-invasive urothelial neoplasms
    • In 2004 members of WHO & Internationational Society of Urological Pathology (ISUP) published & recommended a revised consensus classification for papillary neoplasms
    • The 2004 WHO classification is yet to be validated by clinical trials therefore, tumors are graded using both the 1973 & 2004 WHO classifications, though the vast majority of clinicians now use the 2004 classification
    • 2004 WHO Classification (papillary lesions)
      • Urothelial papilloma (completely benign lesion)
      • Papillary urothelial neoplasm of low malignant potential (PUNLMP)
      • Low-grade papillary urothelial carcinoma
      • High-grade papillary urothelial carcinoma
  • 1973 WHO Classification
Grade 1 (G1) Well-differentiated urothelial papilloma
Grade 2 (G2) Moderately-differentiated urothelial papilloma
Grade 3 (G3) Poorly-differentiated urothelial papilloma
  • 2004/2016 WHO Classification (papillary lesions)
    • Urothelial papilloma (completely benign lesion)
    • Papillary urothelial neoplasm of low malignant potential (PUNLMP)
    • Low-grade papillary urothelial carcinoma
    • High-grade papillary urothelial carcinoma

Physical Examination

  • Rectal & vaginal bimanual palpation should be done
    • In patients w/ locally advanced tumors, a palpable pelvic mass can be found
    • To assess whether there is a palpable mass or if the tumor is fixed to the pelvic wall, a bimanual examination under anesthesia should be done before & after TURBT

Laboratory Tests

Lab tests

  • Lab studies (eg CBC, chemistry profile that includes alkaline phosphatase) must be performed before treatment to accurately determine clinical staging
    • Bone scan is performed if elevated alkaline phosphatase is present
Urinary Cytology
  • Examination of voided urine or bladder washings for exfoliated cancer cells have a high sensitivity in high-grade tumors & is a useful indicator in cases of high-grade malignancy or CIS, but low sensitivity in G1 tumors
  • Useful as an adjunct to cystoscopy when a G3 malignancy or CIS is present
  • Positive voided urinary cytology may indicate an urothelial tumor anywhere in the urinary tract; negative cytology, however, does not exclude the presence of a tumor


  • Chest imaging is indicated if invasive disease is suspected
  • CT or MRI is recommended if:
    • Tumor after cystoscopy appeared to be solid, high-grade or suggests muscle invasion
    • Radical treatment is being considered for locally advanced or metastatic disease
  • CT is the first choice for the workup of non-muscle-invasive bladder cancer in many Asian countries
  • 4-phase renal CT using multidetector CT (MDCT) machine has been used for detection & staging of bladder tumors
    • Includes pre-contrast phase, corticomedullary phase, nephrographic phase, & excretory phase
  • CT urography is used to detect papillary tumors in the urinary tract, which can be seen as filling defects or indicated by hydronephrosis
    • In patients who can safely receive intravenous agents this is the preferred procedure
  • Intravenous urography can be an alternative if CT is not available
  • Transabdominal ultrasound permits characterization of renal masses, detection of hydronephrosis, & visualization of intraluminal masses in the bladder
    • Useful tool for detection of obstruction in patients w/ hematuria



  • A cystoscopy should be done in patients presenting w/ symptoms of bladder cancer to determine if a lesion is present
    • If a lesion is present, the patient should undergo transurethral resection of the bladder (TURBT) to confirm the diagnosis & to determine the extent of disease within the bladder
    • Urine cytology may also be obtained around the time of cystoscopy
  •  Current standard in the evaluation & staging of bladder cancer is white light cystoscopy
  • In non-muscle-invasive bladder cancer detection particularly CIS, it was found that blue-light cystoscopy is more effective than white-light cystoscopy
  • Diagnosis of papillary bladder cancer ultimately depends on cystoscopic examination of the bladder & histological evaluation of the resected tissue
Photodynamic Diagnosis (Fluorescence Cystoscopy)
  • Performed using violet light after intravesical installation of 5-aminolaevulinic acid (ALA) or hexaminolaevulinic acid (HAL)
  • Fluorescence-guided biopsy & resection are more sensitive than conventional procedures for detection of malignant tumors, particularly for CIS
  • Photodynamic diagnosis had lower specificity than white-light endoscopy
Transurethral Resection of Bladder Tumor (TURBT)
  • TURBT w/ a bimanual examination under anesthesia is performed to resect visible tumor & to sample muscle within the area of the tumor to assess whether invasion has occurred
  • Main goal is to make the right histopathological diagnosis & staging as it is essential in the diagnosis & management decision-making process
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