This oncopathology is usually registered in representatives of the stronger sex: men get sick 4 times more often than women. Seven out of ten cancer cases occur in people aged 65+.
Author:
- Sorokin Nikolai Ivanovich, head of the urological service of the university clinic of Moscow State University. M. V. Lomonosova
5.00 (Votes: 1)
Causes of the disease
There is no single and reliably proven cause of the tumor. Many risk factors contribute to the development of bladder cancer. Among them:
- Smoking. It is considered the main factor provoking bladder cancer. Approximately half of the detected cancer cases are associated with smoking; it is diagnosed in smokers 3 times more often than in non-smokers.
- Poor water quality and unfavorable environmental conditions. The chance of getting sick is increased by excess chlorine and fluorine in drinking water, and pollution of water and air by industrial waste.
- Abuse of alcohol, fried and fatty foods.
- Harmful working conditions – working with substances containing aromatic amines, phenols, phthalates. At risk are workers in the chemical, paint and varnish, rubber, oil, aluminum, leather and textile industries, artists, designers, and hairdressers. RMP often occurs in long-distance drivers due to prolonged sitting while driving, frequent hypothermia, and inability to urinate in a timely manner Source: Kulesh P.A. Study of clinical and morphological features of bladder cancer / P.A. Kulesh, A.A. Bagaeva // Eurasian Union of Scientists. — 2021..
- Non-infectious urogenital pathologies - chronic cystitis, urolithiasis, diverticulitis; genitourinary infections – chlamydia, mycoplasmosis, ureaplasmosis, trichomoniasis; parasitic diseases – schistosomiasis.
- Stagnation of urine or rare urination for various reasons - prostate adenoma, narrowing of the urethra, insufficient fluid intake.
- Radiation therapy for tumors of the cervix and ovaries, prostate gland, chemotherapy using Cyclophosphamide (increases the risk by 4.5 times), long-term use of phenacytin-containing analgesics (increases the risk by 2-6.5 times) Source: Kulesh P.A . Study of clinical and morphological features of bladder cancer / P.A. Kulesh, A.A. Bagaeva // Eurasian Union of Scientists. — 2021..
- In addition, the risk is significantly increased in people exposed to ionizing radiation Source: Kulesh P.A. Study of clinical and morphological features of bladder cancer / P.A. Kulesh, A.A. Bagaeva // Eurasian Union of Scientists. — 2021..
Prevalence.
RMP is the most common malignant tumor of the urinary tract and in terms of prevalence it ranks 7th in the structure of oncopathology in men and 17th in women. In the structure of cancer incidence in the Russian population, breast cancer ranks 9th among men and 16th among women. The incidence rate per 100 thousand population was 13.2 for men and 2.3 for women. There is a trend of increasing incidence for both sexes over the past 10 years, amounting to 28.3%. The standardized mortality rate for men and women was 4.7 and 0.5, respectively. The age composition is dominated by patients over 60 years of age, in Russia they account for 78.4%. BC occurs more often in men than in women (ratio 3:1), which is associated with a greater prevalence among men of smoking and occupations associated with carcinogenic substances, which increase the risk of developing the disease.
Symptoms of bladder cancer
The main symptom of bladder cancer is hematuria (blood in the urine), which is often transient in nature, its severity does not depend on the stage of the disease Source: Kulesh P.A. Study of clinical and morphological features of bladder cancer / P.A. Kulesh, A.A. Bagaeva // Eurasian Union of Scientists. - 2021.. Microhematuria is possible, when blood is not noticeable visually and is detected only during analysis, and macrohematuria - urine turns dark orange, pink, red, brown.
Early symptoms also include dysuric disorders: frequent or infrequent urination, accompanied by pain, stinging or burning, a weak, intermittent stream of urine.
All the first signs of bladder cancer are nonspecific, characteristic of other genitourinary diseases. It is important to seek medical help as early as possible in order to carry out a differential diagnosis, identify a tumor in time and begin treatment.
Pain syndrome in bladder cancer can have different characteristics depending on the nature of the spread of the tumor. With a locally advanced tumor process, pain initially most often occurs above the womb, provoked by the act of urination; subsequently, the pain becomes constant, pain appears in the perineum and in the sacral area. When the tumor obstructs the ureteral orifices, hydronephrosis develops, pain appears in the lumbar region, a positive symptom of effleurage in the lumbar region, and an enlarged kidney is palpated. Pain in the bones, as a rule, indicates metastatic damage to the skeleton Source: Kulesh P.A. Study of clinical and morphological features of bladder cancer / P.A. Kulesh, A.A. Bagaeva // Eurasian Union of Scientists. — 2021..
In the later stages of cancer, general weakness, pain in the lumbar and groin areas, in the lower abdomen, lack of appetite and weight loss, fever, swelling in the legs, and enlarged lymph nodes occur. Fistulas may develop between the bladder and rectum.
Immunotherapy
An important part of the immune system is its ability to avoid attacking normal cells in the body. To do this, the immune system uses “checkpoints”—proteins on immune cells that must be turned on (or off) to trigger an immune response. Cancer cells sometimes use these checkpoints to avoid being attacked by the immune system. But new drugs that target these checkpoints, called checkpoint inhibitors, may help restore the immune response against cancer cells. PD-1 and PD-L1 inhibitors Atezolizumab (Tecentriq) and avelumab (Bavencio) are drugs that target PD-L1, a protein on cells (including some cancer cells) that helps the immune system stop attacking them. By blocking PD-L1, these drugs enhance the immune system's response against cancer cells. This may shrink tumors or slow their growth. Nivolumab (Opdivo) and pembrolizumab (Keytruda) target PD-1, a protein on certain immune cells (called T cells) that normally helps these cells avoid attacking other cells in the body. Blocking PD-1 may allow the immune system to attack cancer cells, which can shrink some tumors or slow their growth. These drugs can be used in different situations to treat bladder cancer: Any of these checkpoint inhibitors can be used in people with advanced bladder cancer that has progressed after chemotherapy. Atezolizumab and pembrolizumab can be used in people who cannot receive chemotherapy (due to factors such as hearing loss, kidney failure, or heart failure). These drugs are given as intravenous infusions, usually every 2 to 6 weeks, depending on the drug.
Targeted therapy for bladder cancer
This is a new type of treatment for bladder cancer. Targeted drugs work differently than other treatments such as chemotherapy (chemotherapy). They may work in some cases where other treatments do not work. Targeted drugs also often have various side effects. FGFR Inhibitor Fibroblast growth factor receptors (FGFRs) are a group of proteins on bladder cancer cells that can help them grow. In some forms of bladder cancer, cells have changes in the FGFR genes (which control how much FGFR protein is made). Medicines that target cells with changes in the FGFR gene (called FGFR inhibitors) may help some people with bladder cancer. Erdafitinib (Balversa) This FGFR inhibitor can be used to treat locally advanced or metastatic bladder cancer that has certain changes in the FGFR2 or FGFR3 gene and continues to grow despite treatment with chemotherapy.
It is important to remember that treatment for bladder cancer depends on the stage, degree of differentiation of the cancer, and the size of the tumor.
Types of Bladder Cancer
By prevalence in the muscle layer:
- muscular non-invasive – located only on the mucous and submucous membranes;
- muscle-invasive - grows into the thickness of the bladder wall.
By location:
- on the dome - the upper wall of the bladder;
- on the side, front or back walls;
- in Lieto's triangle - a space in the form of a triangle with vertices at the mouths of the ureters and the exit of the urethra;
- on the neck of the bladder;
- in the area of the ureteric orifices;
- in the area of the urachus - a normally closed rudimentary primary duct located above the bladder;
- the tumor covers several areas.
By type of growth:
- exophytic (papillary) – the formation grows upward from the mucous membrane, initially looks like a polyp;
- endophytic (infiltrative) – grows inside the wall of the organ with a transition to the muscle layer, has no clear boundaries;
- mixed form - the tumor grows simultaneously inward and outward;
- flat;
- nodular;
- intraepithelial.
According to histological structure:
- Epithelial cancer. In 98% of cases, bladder tumors develop from epithelial cells Source: Kulesh P.A. Study of clinical and morphological features of bladder cancer / P.A. Kulesh, A.A. Bagaeva // Eurasian Union of Scientists. — 2021.. In 90-95% of cases, bladder tumors are morphologically transitional cell carcinoma Source: Dolgikh D.V. Diagnosis of bladder cancer / D.V. Dolgikh [and others] // Siberian Medical Journal. - 2015. - No. 6. - P. 141-147.. It can be low- and highly differentiated, which determines the degree of malignancy of the formation. Verrucous carcinoma, adenocarcinoma and clear cell adenocarcinoma, urachus cancer, and small cell carcinoma are diagnosed much less frequently.
- Non-epithelial cancer. Tumors from muscle, fibrous vascular and other tissues: rhabdomyosarcoma, fibrous histiocytoma, leiomyoma, hemangioma, melanoma, germ cell tumors.
Bladder cancer grades
At the first stage
RMP tumor cells are found only in the epithelial layer. The process does not affect the wall of the bladder, nearby and distant organs.
For the second stage
The tumor is characterized by invasion of the muscle layer. Adjacent organs are not affected, there are no distant metastases.
At the third stage
, in addition to cancer growing into the muscle layer of the bladder, an increase in regional lymph nodes is observed.
Fourth stage
characterized by any tumor size, with regional lymph nodes affected and metastases observed in distant organs.
For international classification, the TNM system :
- T – indicates the extent of the tumor, indicated by numbers from 1 to 4.
- N – presence of metastases in lymph nodes. The number 0 indicates the absence of metastases in the lymph nodes, 1 - a single affected node, 2 - metastases in 2-5 lymph nodes.
- M – (x, 0 or 1) – impossibility of detection, absence or presence of distant metastases.
Risk group
As practice shows, the likelihood of tumors appearing in the genitourinary system increases in men:
- Those who abuse tobacco products. According to statistics, kidney cancer is diagnosed in smokers 2 times more often.
- Middle aged (after 45 years). This is due to a decrease in the level of male sex hormones along with an increase in female ones.
- People who work in hazardous industries (for example, when a person often comes into contact with hazardous chemicals).
- Those who have been on dialysis for a long time. This often leads to kidney cancer.
Diagnosis of bladder cancer
The first stage in diagnosing bladder cancer is examining the patient, collecting an anamnesis of life and illness, and conducting laboratory and instrumental studies. The doctor will ask the patient in detail about the symptoms, the time of their appearance, the frequency of occurrence, the presence of bad habits, and other factors that provoke the disease.
During a urological examination, the doctor will determine Pasternatsky's symptom
– the presence or absence of painful sensations when tapping on the lower back, and will also check the condition of the prostate gland using a digital examination through the rectum.
In addition to general and biochemical blood and urine tests, which are not informative in the diagnosis of cancer, the patient may be prescribed a microscopic examination of urine sediment
for the presence of pathological cells and determination
of window markers for bladder cancer
.
Ultrasound for bladder cancer allows you to visualize a tumor if its size exceeds 4 mm, determine the form of tumor growth (exophytic, endophytic or mixed) and the depth of its invasion into the wall Source: D.V. Dolgikh. Diagnosis of bladder cancer / D.V. Dolgikh [and others] // Siberian Medical Journal. - 2015. - No. 6. - P. 141-147..
Mandatory instrumental examination - cystoscopy
.
During cold cystoscopy, the bladder is examined and an area of affected tissue is excised for analysis. Another diagnostic and treatment method is TUR biopsy
, when the tumor is excised completely, capturing healthy tissue. During transurectal resection with photodynamic diagnostics, the doctor can see even the smallest areas of tumor damage in blue illumination.
To determine damage to the lymph nodes and metastasis to other organs, use:
- CT and MRI,
- scintigraphy,
- biopsy of sentinel lymph nodes,
- chest x-ray,
- ultrasound examination of the abdominal organs;
- tests for tumor markers.
Three markers have the greatest sensitivity and specificity in staging bladder cancer: UBC, TPS and VEGF. An increase in the level of UBC in urine characterizes the initial stages of bladder cancer and possible non-invasive tumor recurrence during organ-preserving treatment. In patients with non-muscle-invasive bladder cancer, an increased level of VEGF can serve as an additional criterion not only for relapse of the disease, but also for its progression. A simultaneous increase in the content of UBC in the urine and TPS, VEGF in the blood serum is associated with the progression of tumor growth and characterizes the initial stage of bladder cancer invasion into the muscle layer. A high level of VEGF is characteristic of a tumor extending beyond the organ, as well as with high tumor growth activity and a low degree of differentiation, which is a poor prognostic factor Source: D.V. Dolgikh. Diagnosis of bladder cancer / D.V. Dolgikh [and others] // Siberian Medical Journal. - 2015. - No. 6. - P. 141-147..
To determine the patency of the urinary tract, excretory urography . The study allows us to assess the patency of the ureters, identify neoplasms both in the upper urinary tract and in the bladder Source: Kulesh P.A. Study of clinical and morphological features of bladder cancer / P.A. Kulesh, A.A. Bagaeva // Eurasian Union of Scientists. — 2019..
The optimal method for diagnosing stage III and differentiating it from the stage of the disease, as well as for distinguishing between T2a and T2b degrees, is multiscan spiral computed tomography Source: D.V. Dolgikh. Diagnosis of bladder cancer / D.V. Dolgikh [and others] // Siberian Medical Journal. - 2015. - No. 6. - P. 141-147..
What kind of observation is required after treatment?
After treatment, recurrence of the tumor (relapse) may occur, the probability of which in superficial forms reaches 70%. A new tumor may appear in the same place as the primary one, and often relapses occur in another area of the bladder mucosa. Therefore, patients undergoing treatment for bladder cancer need to be examined every 3-6 months. One of the most important components of the examination is cystoscopy and urine cytology. The examination also includes an examination, blood and urine tests, and an ultrasound or computed tomography may be prescribed.
Bladder cancer treatment methods
In the early stages of bladder cancer, when the spread of the tumor is limited to the epithelial layer, transurethral resection
followed by
intravesical chemotherapy
or
immunotherapy
- the introduction of drugs into the bladder cavity. The advantage of intravesical administration is the absence of side effects of systemic chemotherapy, such as nausea, vomiting, and hair loss.
The anti-tuberculosis vaccine BCG is used for intravesical immunotherapy. Weakened Koch bacilli activate immune system cells, which begin to attack the tumor.
A more modern method of immunotherapy is the use of checkpoint inhibitor drugs. Checkpoints are molecules that suppress the immune response, including to prevent the occurrence of autoimmune diseases. Inhibitors remove the blockage of these points and stimulate the immune system to fight cancer cells.
Another low-traumatic treatment method is en-bloc laser resection.
, which allows you to remove neoplasms in the mucous and submucosal membranes, the muscle layer as a single block. This method is not suitable for large formations without clear boundaries.
In late stages of bladder cancer, the process is very widespread, if the above methods do not help, they resort to complete removal of the organ - cystectomy
, followed by radiation or chemotherapy.
Isolated cystectomy (removal of only the bladder) for invasive cancer is rarely performed. More often it is combined with the removal of neighboring organs: the prostate gland and seminal vesicles in men, the appendages and uterus in women. At the same time, the entire urethra or part of it and the pelvic lymph nodes are excised.
After cystectomy, it is possible to perform a reconstructive operation - neocystoplasty, when the removed bladder is replaced with an isolated section of the intestine, to which the ureters and urethra are connected.
Disease prognosis
The survival prognosis depends on the stage at which the tumor is diagnosed and how timely and complete the treatment is. If a single epithelial lesion is detected and TUR is performed in conjunction with chemotherapy or immunotherapy, the chances of recovery are about 91%. In the second stage, without cancer spreading to other organs, timely transurethral resection and chemotherapy (less commonly, radiation) allow hope for recovery without relapse in 73-75% of patients. In the third stage and the process spreads to nearby organs, even after removal of the bladder and chemotherapy, there is a possibility of relapse; five-year survival is observed in 50% of patients. At the fourth stage, the process is considered inoperable, palliative methods are used, five-year survival rate is less than 7%.
Prevention of bladder cancer
Quitting smoking and alcohol and eating plenty of fresh fruits and vegetables, which contain antioxidants that prevent cell degeneration, will help reduce the likelihood of developing a tumor. Bladder cancer is less likely to occur in those who drink enough water per day. It is believed that the risk of neoplasm is reduced by 7% for every 240 ml of added fluid.
It is necessary to be attentive to your health and consult a doctor when the first, even minor, signs of illness appear. It is important to monitor the regularity of urination, protect against genitourinary infections, and promptly diagnose and treat inflammatory processes in the urinary tract. Workers in hazardous industries should not neglect medical examinations. People over 40 years of age are recommended to undergo annual medical examination.
Sources
- Dolgikh D.V. Diagnosis of bladder cancer / D.V. Dolgikh [and others] // Siberian Medical Journal. - 2015. - No. 6. - P. 141-147.
- Dolgikh D.V. Bladder cancer (issues of etiology and pathogenesis) / D.V. Dolgikh [and others] // Siberian Medical Journal (Irkutsk). - 2015. - No. 7. - P. 26-30.
- Dunaev M.G. MRI diagnosis of bladder cancer / M.G. Dunaev // Remedium Volga region. — 2021. — No. 6 (156). — P. 22.
- Karyakin O.B. Bladder cancer: what's new in 2019-2020. / ABOUT. Karyakin // Oncourology. - 2021. - No. 4. - P. 147-154.
- Kulesh P.A. Study of clinical and morphological features of bladder cancer / P.A. Kulesh, A.A. Bagaeva // Eurasian Union of Scientists. — 2021.
- Nemtsova M.V. Molecular pathogenesis of bladder cancer / M.V. Nemtsova, N.E. Kushlinsky // Almanac of Clinical Medicine. - 2015. - No. 41. - P. 79-88.
- Startsev V.Yu. Modern possibilities of organ-preserving treatment of patients with muscle-invasive bladder cancer / V.Yu. Startsev [et al.] // Urological Gazette. - 2021. - T.9. - No. 1. — P. 29-38.
The information in this article is provided for reference purposes and does not replace advice from a qualified professional. Don't self-medicate! At the first signs of illness, you should consult a doctor.
