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 often has a transient nature, 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).

Such symptoms of bladder cancer as pain in the bladder, complaints about dysuria (imperative urge, rapid urination, etc.) are more typical for carcinoma in situ (CIS) and invasive forms of bladder cancer.

In the late stages of the disease, signs of local spread and metastasis of the tumor can be identified: bone pain, side pain, which may be associated with ureteral obstruction).

Diagnosis of bladder cancer

[1], [2], [3], [4], [5]

Clinical diagnosis of bladder cancer

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

Laboratory diagnosis of bladder cancer

Routine studies usually identify hematuria, which can be accompanied by pyuria (in the presence of a urinary tract infection). Anemia is a sign of chronic blood loss, but it can occur as a result of metastatic bone marrow damage. With occlusion of the ureters by a tumor or pelvic lymphatic metastases, azotemia occurs.

Cytological examination of urine

An important laboratory method as a primary diagnosis of bladder cancer, as well as monitoring the results of treatment is considered a cytological examination of urine.

To do this, examine the urine under conditions of good hydration of the patient, or 0.9% solution of sodium chloride, which is previously carefully minced the bladder with a cystoscope or a urethral catheter.

The effectiveness of cytological diagnosis of bladder cancer depends on the methodology of the study, the degree of differentiation of cells and the stage of the disease. Detection of low-grade 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 with this method do not reveal. It should be borne in mind that a positive result of cytological examination does not allow for a topical diagnosis of the urothelial tumor (calyx, pelvis, ureter, bladder, urethra).

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

[6], [7], [8], [9],

Instrumental diagnosis of bladder cancer

Excretory urography can be detected by the defect of filling the tumor of the bladder, calyx, pelvis, ureter, and the presence of hydronephrosis. The need for routine intravenous urography in case of bladder cancer is questionable, since the combined damage of the bladder and upper urinary tract is rare.

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

Computer tomography can be used to assess the extent of tumor invasion, however, with inflammatory processes in the paravezic tissue, often occurring after TUR of the bladder. The probability of overdiagnosis is high, therefore, the results of staging according to the data of surgical treatment and morphological examination correspond to the results of CT in only 65-80% of cases. The possibility of CT in the detection of metastases in the lymph nodes is limited (sensitivity about 40%).

Proceeding from the foregoing, the main goal of CT in bladder cancer is the detection of lesions of large lymph nodes and metastases in the liver.

Scintigraphy of the skeleton is indicated only for pain in the bones. An increase in the concentration of alkaline phosphatase in the blood serum is not considered a sign of metastatic bone damage.

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 with local anesthesia (anesthetic solutions or gels with an exposure of 5 min) are injected into the urethra by a flexible or rigid cystoscope.
  • Surface, 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.
  • Low-differentiated invasive tumors are usually larger and have a smoother surface.
  • CIS has the form of erythema with a rough surface, with cystoscopy it can not be detected.
  • If the bladder tumor was detected or suspected by other methods of investigation (ultrasonography or urine cytology), then cystoscopy is indicated under conditions of epidural or general anesthesia concomitant with TUR of the bladder.
• The purpose of transurethral resection of the bladder (and subsequent morphological study of the material) verification of the type and degree of tumor differentiation, the definition of invasion of the muscular layer of the bladder wall, the detection of CIS, and in the case of superficial tumors (stages Ta, T1) - their radical removal.
  • In transurethral resection of the bladder, the patient is placed in the lithotomy position. Carry out a thorough bimanual examination and determine the presence, size. Position and mobility of the palpable formation. Perform urethrocystoscopy with the use of optics, which allows a full examination of the urethra and bladder (30 °, 70 °). Then a resectoscope with optics of 30 ° is introduced into the bladder and visible tumors are removed by electrosurgical means. In suspicious areas in the CIS, cold biopsies are performed using biopsy forceps and subsequent coagulation of these areas. In superficial tumors, multiple biopsies are performed only with positive results of urinal cytology.
  • Small tumors can be removed with 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 tumor base). The depth of resection must necessarily reach the muscle tissue, otherwise it is impossible to perform the morphological staging of the disease (Ta, Tl, T2). In large tumors, the mucosa of the bladder is also resected around the base of the tumor, where CIS is often detected.
  • Operational material for morphological investigation is sent in separate containers (tumor, tumor base, bladder mucosa around the tumor, selective biopsy, multiple biopsy).
  • If the tumor is located in the neck of the bladder or in the region of the Lieto triangle, as well as in case of suspected CIS, with a positive cytological examination of urine, it is necessary to perform a biopsy of the prostate department of the urethra. The coagulation regimen should be used only for the purpose of hemostasis to prevent the destruction of tissues, which hampers the precise morphological study.
  • Upon completion of the transurethral resection of the bladder, repeated bimanual palpation is performed. The presence of palpable formation indicates the late stages of the disease (T3a and more).
  • In a number of cases (inferior tumor removal, multiple tumors and / or tumors of large size, absence of muscle tissue in the operating material from the results of the morphological study), a repeated TUR is shown. It is also shown in the early stages (Ta, T1) in the case of a low-grade tumor structure.
  • Repeated TUR is important for accurate morphological staging of the disease, and for 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 a second TUR, but most urologists perform it within 2-6 weeks after the first surgery.

Algorithm for diagnosis of neoplasms of the bladder

• Physical examination (bimanual rectal / vaginal-suprapubic palpation).
• Ultrasonography of the kidney and bladder and / or intravenous urography.
• Cystoscopy with a description of the location, size, type of tumor (graphic diagram of the bladder).
• Urinalysis.
• Cytological examination of urine.
• TOUR of the bladder, which is complemented by:
  • biopsy of the base of the tumor, including the muscular tissue of the wall of the bladder;
  • Multiple biopsy in large or non-papillary tumors and with positive results of urine cytology;
  • biopsy of the prostate department of the urethra with suspected or present CIN. As well as with tumors located in the neck of the bladder and the triangle of Lieto.

[10], [11], [12], [13], [14]

Additional examination of patients with invasive tumors of the bladder

• Radiography of the chest.
• CT of the abdominal cavity and pelvis.
• Ultrasonography of the liver.
• Scintigraphy of the skeleton with suspicion of metastases in the bones.

[15], [16], [17]

Differential diagnosis of bladder cancer

Differential diagnosis of bladder cancer involves the exclusion of a possible germination of the tumor from neighboring organs (cervical, prostate, rectal cancer), which usually does not present difficulties due to neglect of the underlying disease and the possibility of morphological verification of the disease.

Differential diagnosis of transitional cell cancer of the bladder with other histological types of metastatic, epithelial or non-epithelial neoplasms; are carried out according to the generally accepted diagnostic algorithm, which includes the morphological study of the material removed from TUR or biopsy, which helps to determine the further therapeutic tactics. The exception is the relatively rare pheochromocytoma of the bladder (1% of all neoplasms of the bladder, 1% of all pheochromocytomas), in which there is always a typical clinical picture (episodes of high blood pressure associated with the act of urination), and TUR is contraindicated due to the risk of cardiac arrest because of the massive release of catecholamines.

[18], [19], [20], [21], [22], [23]

Indications for consultation by other specialists

Diagnosis of bladder cancer is associated with close cooperation with radiologists, specialists in ultrasonography and, most importantly, with morphologists. Participation of other specialists (oncologists, chemotherapists, radiation therapists) is necessary in planning further treatment of patients.

Examples of the formulation of the diagnosis

• Urothelial (transitional cell) highly differentiated bladder cancer. The stage of the disease is TaNxMx.
• Urothelial (transitional-cellular) low-grade bladder cancer. Stage of disease T3bNlMl.
• Squamous cell carcinoma of the bladder. Stage of the disease T2bN2M0.

The term "urothelial" is recommended by WHO (2004), but it has not found wide application, since some other forms of bladder cancer also come from urothelium (eg, squamous cell carcinoma), and the term "transitional cell carcinoma" . At the same time, the replacement of the three degrees of gradation of atypia (G1, G2 "G3) by a two-degree (highly differentiated, low-differentiated) has been universally recognized.

[24], [25], [26], [27]