Symptoms and diagnosis of bladder cancer

Symptoms of Bladder Cancer

The main symptom of bladder cancer is hematuria, which is detected in 85-90% of patients. Micro- and macrohematuria may occur, it is often transient, and its degree does not depend on the stage of the disease. In the early stages of the disease (Ta-T1), hematuria occurs much more often, other complaints are usually absent ("asymptomatic" or painless hematuria).

Symptoms of bladder cancer such as pain in the bladder area, complaints of dysuria (urgency, frequent urination, etc.) are more typical for carcinoma in situ (CIS) and invasive forms of bladder cancer.

In the later stages of the disease, signs of local spread and metastasis of the tumor can be detected: pain in the bones, pain in the side, which may also be associated with obstruction of the ureter).

Diagnosis of bladder cancer

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Clinical diagnosis of bladder cancer

In the late stages of the disease, signs of local spread and metastasis of the tumor can be detected: hepatomegaly, a palpable lymph node above the clavicle, edema of the lower extremities with metastasis to the pelvic lymph nodes. In patients with a large and/or invasive tumor, a palpable formation can be detected during bimanual (rectal or vaginal) palpation under anesthesia. In this case, immobility (fixation) of the tumor indicates a late stage of the disease (T4).

Laboratory diagnostics of bladder cancer

Routine investigations usually reveal hematuria, which may be accompanied by pyuria (in the presence of a urinary tract infection). Anemia is a sign of chronic blood loss, but it can also occur as a result of metastatic bone marrow disease. Occlusion of the ureters by a tumor or pelvic lymphatic metastases causes azotemia.

Cytological examination of urine

An important laboratory method for both the primary diagnosis of bladder cancer and monitoring of treatment results is considered to be a cytological examination of urine.

To do this, urine is examined under conditions of good hydration of the patient, or with a 0.9% sodium chloride solution, which is used to thoroughly irrigate the bladder using a cystoscope or urethral catheter.

The effectiveness of cytological diagnostics of bladder cancer depends on the research methodology, the degree of cell differentiation and the stage of the disease. The detection rate of low-differentiated invasive bladder tumors and CIS by the cytological method is very high (sensitivity is more than 50%, specificity is 93-100%), however, highly differentiated non-invasive tumors are not detected by this method. It should be taken into account that a positive result of the cytological study does not allow topical diagnostics of urothelial tumor (cups, pelvis, ureter, bladder, urethra).

Attempts to replace cytological diagnostics with the study of bladder cancer markers in urine (bladder cancer antigen, nuclear matrix protein 22, fibrin degradation products, etc.) have not yet provided grounds for recommending their widespread use.

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Instrumental diagnostics of bladder cancer

Excretory urography allows to detect tumors of the bladder, calyces, pelvis, ureter, and the presence of hydronephrosis by filling defects. The need for routine intravenous urography in bladder cancer is questionable, since combined lesions of the bladder and upper urinary tract occur rarely.

Ultrasonography is the most widely used, safe (no need to use contrast agents with the risk of allergic reactions) and highly effective method for detecting bladder tumors. In combination with a general X-ray of the kidneys and bladder, ultrasonography is not inferior to intravenous urography in diagnosing the causes of hematuria.

Computed tomography can be used to assess the degree of tumor invasion, but in inflammatory processes in the paravesical tissue, which often occur after TUR of the bladder. There is a high probability of overdiagnosis, so the results of staging based on surgical treatment and morphological examination correspond to the results of CT only in 65-80% of cases. The capabilities of CT in detecting metastases to the lymph nodes are limited (sensitivity is about 40%).

Based on the above, the main goal of CT in bladder cancer is to identify large affected lymph nodes and metastases in the liver.

Skeletal scintigraphy is indicated only in cases of bone pain. An increase in serum alkaline phosphatase is not considered a sign of metastatic bone disease.

Cystoscopy and TUR of the bladder with subsequent morphological examination of the resected (or biopsy) material are the most important methods of diagnosis and primary staging (non-invasive or invasive tumor) of bladder cancer.

• Cystoscopy is performed on an outpatient basis under local anesthesia (anesthetic solutions or gels are injected into the urethra for 5 minutes) using a flexible or rigid cystoscope.
  • Superficial highly differentiated tumors can be either single or multiple. They have a typical villous structure. Their size, as a rule, does not exceed 3 cm.
  • Poorly differentiated invasive tumors are usually larger and have a smoother surface.
  • CIS has the appearance of erythema with a rough surface and may not be detected during cystoscopy.
  • If a bladder tumor is detected or suspected by other research methods (ultrasonography or cytological examination of urine), then cystoscopy is indicated under epidural or general anesthesia simultaneously with TUR of the bladder.
• The purpose of transurethral resection of the bladder (and subsequent morphological examination of the material) is to verify the type and degree of differentiation of the tumor, determine invasion into the muscular layer of the bladder wall, identify CIS, and in the case of superficial tumors (stages Ta, T1) - their radical removal.
  • During transurethral resection of the bladder, the patient is placed in the lithotomy position. A thorough bimanual examination is performed to determine the presence, size, position and mobility of the palpable formation. Urethrocystoscopy is performed using optics that allow a full examination of the urethra and bladder (30°, 70°). Then a resectoscope with 30° optics is inserted into the bladder and visible tumors are removed electrosurgically. In areas suspicious for CIS, a cold biopsy is performed using biopsy forceps, followed by coagulation of these areas. In superficial tumors, multiple biopsies are performed only if the results of a cytological examination of urine are positive.
  • Small tumors can be removed in one cut (bit), and in this case the removed piece contains both the tumor itself and the underlying bladder wall. Large tumors are removed fractionally (first the tumor itself, then the base of the tumor). In this case, the resection depth must necessarily reach muscle tissue, otherwise it is impossible to perform morphological staging of the disease (Ta, Tl, T2). In case of large tumors, the mucous membrane of the bladder around the base of the tumor is additionally resected, where CIS is often detected.
  • Surgical material for morphological examination is sent in separate containers (tumor, tumor base, bladder mucosa around the tumor, selective biopsy, multiple biopsy).
  • If the tumor is located in the bladder neck or in the area of Lieto's triangle, or if CIS is suspected, a prostatic urethra biopsy should be performed with a positive urine cytology. The coagulation regime should be used only for hemostasis to prevent tissue destruction, which would make accurate morphological examination difficult.
  • Upon completion of transurethral resection of the bladder, repeat bimanual palpation is performed. The presence of a palpable formation indicates late stages of the disease (T3a and higher).
  • In some cases (incomplete tumor removal, multiple tumors and/or large tumors, absence of muscle tissue in the surgical material based on the results of morphological examination), repeated TUR is indicated. It is also indicated at early stages (Ta, T1) in the case of a poorly differentiated tumor structure.
  • Repeated TUR is important for accurate morphological staging of the disease, and in superficial tumors it leads to a decrease in the frequency of relapses and improves the prognosis of the disease. There is no consensus on the timing of repeated TUR, but most urologists perform it 2-6 weeks after the first operation.

Algorithm for diagnosing bladder tumors

• Physical examination (bimanual rectal/vaginal-suprapubic palpation).
• Ultrasonography of the kidneys and bladder and/or intravenous urography.
• Cystoscopy with description of location, size, type of tumor (graphic diagram of the bladder).
• Urine analysis.
• Cytological examination of urine.
• TUR of the bladder, which is supplemented by:
  • biopsy of the tumor base, including the muscle tissue of the bladder wall;
  • multiple biopsies for large or non-papillary tumors and positive urine cytology results;
  • biopsy of the prostatic urethra in case of suspicion or presence of CIN, as well as in case of tumors located in the neck of the bladder and Lieto's triangle.

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Additional examinations of patients with invasive bladder tumors

• Chest X-ray.
• CT scan of the abdomen and pelvis.
• Ultrasonography of the liver.
• Skeletal scintigraphy for suspected bone metastases.

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Differential diagnosis of bladder cancer

Differential diagnosis of bladder cancer involves excluding possible tumor growth from neighboring organs (cervical cancer, prostate cancer, rectal cancer), which is usually not difficult due to the advanced stage of the underlying disease and the possibility of morphological verification of the disease.

Differential diagnostics of transitional cell carcinoma of the bladder with other histological types of neoplasms of metastatic, epithelial or non-epithelial origin is carried out according to the generally accepted diagnostic algorithm, including morphological examination of the material removed during TUR or biopsy, which helps to determine further treatment tactics. An exception is the relatively rare pheochromocytoma of the bladder (1% of all bladder neoplasms, 1% of all pheochromocytomas), which always has a typical clinical picture (episodes of increased blood pressure associated with the act of urination), and TUR is contraindicated due to the risk of cardiac arrest due to a massive release of catecholamines.

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Indications for consultation with other specialists

Diagnosis of bladder cancer involves close collaboration with radiologists, ultrasound specialists and, most importantly, morphologists. The participation of other specialists (oncologists, chemotherapists, radiation therapists) is necessary when planning further treatment of patients.

Examples of diagnosis formulation

• Urothelial (transitional cell) well-differentiated bladder cancer. Disease stage TaNxMx.
• Urothelial (transitional cell) poorly differentiated bladder cancer. Disease stage T3bNlMl.
• Squamous cell carcinoma of the bladder. Disease stage T2bN2M0.

The term "urothelial" is recommended by WHO (2004), but it has not found wide application, since some other forms of bladder cancer also originate from the urothelium (e.g. squamous cell carcinoma), and the term "transitional cell carcinoma" is still more commonly used. At the same time, the replacement of three degrees of atypia gradation (G1, G2, G3) with a two-stage (highly differentiated, poorly differentiated) has received general recognition.

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