Dr. med. Dirk Manski

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Bladder cancer (3/7): Symptoms and Diagnostic Work-Up

Review Literature: EAU guidelines: superficial bladder cancer (Babjuk et al, in 2008 and 2013). Advanced bladder cancer (Stenzl et al, 2009 and Witjes et al, 2013).

Signs and Symptoms of Bladder Cancer

Superficial bladder carcinoma:

Painless hematuria, rather intermittently, is the leading symptom (85–90%). Irritative symptoms like dysuria, frequency and urgency are not as common (30%). Most of the superficial bladder cancers are symptomatic.

Signs and symptoms of advanced bladder cancer:

Abdominal mass, bone pain, flank pain, hydronephrosis, weight loss, night sweats.

Diagnostic Work-Up of Bladder Cancer

Laboratory tests

Urinary sediment:

Microhematuria or macrohematuria.

Urine cytology:

Microscopic examination of exfoliated urothelial cells of the urine can reliably identify G2 and G3 cells of bladder carcinoma. Cells of well-differentiated tumors are less often exfoliated and are harder to distinguis from cells of inflammatory lesions.

Urine markers:

Urine markers improve the detection of bladder cancer and may reduce the frequency of cystoscopy in the follow-up of superficial tumors. The exact role of urine markers in the diagnostic work-up is unclear, see Tab. sensitivity and specificity of urine markers and section experimental diagnostics.

Sensitivity and specificity of urine markers, which are available as point-of-care tests (Babjuk et al, 2008).
Urine marker Sensitivity Specificity
NMP 22 47–100% 55–98%
BTA stat 29–83% 56–86%
ImmunoCyt 52–100% 63–75%

Laboratory tests:

Blood count may reveal a hypochromic anemia and iron deficiency due to chronic bleeding. Tumor anemia is possible in advanced disease. Elevated liver encymes are a symptom of liver metastasis. Hydronephrosis may cause elevated creatinine and urea serum concentrations. Elevated AP is caused by bone metastases.

Imaging of Bladder Cancer

Intravenous Pyelography (IVP):

IVP is indicated to rule out upper tract anomalies, which may be a sign of upper tract transitional cell carcinoma or hydronephrosis due to invasive bladder cancer. If invasive bladder cancer is suspected, IVP should be replaced by an CT abdomen. Bladder tumor may be seen in the bladder filled with contrast media. [fig. IVP of an advanced bladder cancer].

figure intravenous pyelographie of an advanced bladder cancer

IVP of an advanced bladder cancer: large right-sided bladder tumor, with a non-functioning right kidney and left-sided hydronephrosis. By courtesy Dr. R. Gumpinger, Kempten. See also OP specimen [fig. op specimen of advanced bladder cancer] and CT abdomen [fig. CT abdomen of advanced bladder cancer] of the same patient.

Ultrasound imaging:

Ultrasound imaging is done with a full bladder. Bladder cancer appears as echogenic mass that protrudes into the lumen [fig. ultrasound imaging of bladder cancer]. Invasive bladder cancer may be suspected, if the normally highly echogenic bladder wall is interrupted by less echogenic tissue from the bladder tumor (false-negativ 40%, false-positive in 10%).

Ultrasonography of the kidneys is done to detect hydronephrosis or a mass in the renal sinus as signs for upper tract transitional cell cancer.

Ultrasound imaging of bladder cancer: papillary TaG1 bladder cancer in the left image. An invasion of the bladder wall is not visible. The right image shows a T3 bladder carcinoma with significant interruption of the bladder wall and perivesical infiltration of the tumor.
figure Ultrasound imaging of bladder cancer

Staging of invasive bladder cancer:

CT or MRI of the abdomen is suited to stage advanced bladder cancer, in particular to detect visceral metastases or large lymph node metastates [fig. CT abdomen of an advanced bladder cancer]. An CT with excretory phase and opacification of the urinary collecting system is necessary for adequate imaging to detect a secondary carcinoma of the upper urinary tract. Local tumor stage or small lymph node metastases are not reliable detectable with both imaging techniques.

Further necessary imaging:

figure Computed tomography CT abdomen of advanced bladder cancer

CT abdomen of advanced bladder cancer: huge right-sided bladder tumor, with hydronephrosis on both sides. By courtesy Dr. G. Antes, Kempten. See also fig. IVP and fig. OP specimen of the same patient.

Cystoscopy and transurethral resection of the bladder (TURB)

Cystoscopy is the single most important procedure to diagnose bladder tumors. The location, size and appearance of the tumor is documented. Bladder tumors or suspicious tissue are treated by transurethral resection of the bladder (see section TURB) with deep resection into the tunica muscularis [fig. TURB]. Quadrant biopsy of the urinary bladder is a diagnostic procedure for patients with suspected high-grade bladder carcinoma (e.g. history of high grade tumor or urinary cytology with high-grade cells): small samples are taken from the anterior wall, the two side walls, the posterior bladder wall and prostatic urethra.

figure TURB transurethral resection of the bladder due to bladder cancer
Transurethral resection of the bladder (TURB) the resection loop is seen at the base of the papillary bladder cancer.

Fluorescence cystoscopy:

Standard cystoscopy is not able to visualize all forms of bladder carcinoma. Especially flat high-grade lesions may be overseen or may look like normal urothelium. The fluorescence cystoscopy improves the detection of CIS by 25–30%. The bladder is incubated for 1 h with hexaminolevulinate (HAL) and the cystoscopy is done with blue light (375–440 nm wave length). Hexaminolevulinate is a photosensitive porphyrin which accumulates preferentially in tissue with a high turn-over of cells like neoplastic tissues but also in inflammatory lesions. Tissues with a high concentration of HAL glow red under blue light. Clinically relevant improvement in sensitivity and specificity has been proved in several randomized trials (Jocham et al, 2005).

Experimental Diagnostic Techniques

Urine markers for the diagnosis of bladder cancer: urinary bladder cancer antigen (UBC), BTA stat, nuclear matrix protein (NMP22), telomerase, survivin, multi-target FISH (UroVysion), loss of chromosomes. No marker has sufficient sensitivity and specificity to replace cystoscopy or urine cytology.

Urine immunocytology improves the results of standard urine cytology. Detection of cytokeratin in serum or bone marrow with the help of PCR correlates with an advanced tumor stage.

Differential Diagnosis of Bladder Tumors

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