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Bladder cancer: Symptoms, Diagnosis and Imaging

Review Literature: EAU guidelines superficial bladder cancer. EAU guidelines of muscle-invasive and metastatic bladder cancer. German S3 guidelines bladder carcinoma Harnblasenkarzinom.

• Bladder carcinoma: Definition, Epidemiology and Etiology
• Bladder carcinoma: Pathology and TNM tumor stages
• Bladder carcinoma: Symptoms and Diagnosis
• Bladder carcinoma: Surgical Treatment
• Bladder carcinoma: Chemotherapy and Immunotherapy of Metastases

Signs and Symptoms of Bladder Cancer

Symptoms of 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, and night sweats.

Diagnostic Workup of Bladder Cancer

Laboratory tests

Urinary sediment:

Unspecific sign in urine analysis: 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 distinguish 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 workup is unclear; see Tab. sensitivity and specificity of urine markers and section experimental diagnostics below.

Laboratory tests:

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

Imaging of Bladder Cancer

Ultrasound imaging:

Ultrasound imaging is best done with a full bladder. Bladder cancer appears as an 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-negative in 40%, false-positive in 10%). Ultrasonography of the kidneys is done to detect hydronephrosis or a mass in the renal sinus as signs of upper tract urothelial 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.

Imaging of the upper urinary tract:

Imaging of the upper urinary tract is necessary after initial diagnosis of bladder carcinoma. The most suitable method is a contrast-enhancing CT (excretion phase). Alternative imaging option are an MRI abdomen with excretion phase or an intravenous urography [fig. IVP 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 fig. pathology specimen and fig. CT abdomen of advanced bladder cancer of the same patient.

Staging of invasive bladder cancer:

CT scan of the pelvis, abdomen and chest is standard to stage invasive bladder cancer [fig. CT scan of advanced bladder carcinoma]. Alternative option for staging are an abdominal MRI and chest X-ray.

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. Pathology specimen of the same patient.

Further facultative imaging: bone scintigraphy (for patients with bone pain or elevated AP), ultrasound of the liver (if CT or MRI is not available). PET has no additional value in staging of bladder carcinoma.

Cystoscopy and transurethral resection of the bladder (TURB)

Cystoscopy is the single most important procedure to diagnose bladder cancer. The location, size, and appearance of the tumor are 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. cystoscopy of bladder carcinoma]. 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.

Cystoscopy of bladder carcinoma: 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 one hour with hexaminolevulinate (HAL) and the cystoscopy is done with blue light (375–440 nm wavelength). Hexaminolevulinate is a photosensitive porphyrin that accumulates preferentially in tissue with a high turnover 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). However, in recent randomized controlled studies, this does not reduce the long-term recurrence rate (Heer et al., 2022).

Fluorescence cystoscopy of bladder carcinoma with hexaminolevulinate (Hexvix). Standard cystoscopy is shown on the left, the same location with fluorescence cystoscopy on the right side. All lesions were Ta low-grade.

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

• Inflammation or infection
• Tissue reaction due to foreign bodies, catheter, or bladder stones.
• Schistosomiasis
• Bladder fistula (birth trauma, diverticulitis, Crohn disease, rectal cancer)
• Benign and malignant bladder tumors: see section pathology

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  Deutsche Version: Symptome und Diagnose des Harnblasenkarzinoms