Adenocarcinoma of the prostate

Adenocarcinoma of the prostate is the most common malignant neoplasm of this organ (over 95% of all cases of prostate cancer), at which pathological proliferation of cells of glandular epithelium occurs. Epithelial neoplasm can be limited to the glandular capsule, and can sprout into nearby structures. Getting into the lymph, atypical tumor cells affect the iliac and retroperitoneal lymph nodes, and the metastases to the bone tissues are spread by the hematogenous way.

[1], [2], [3], [4], [5], [6], [7], [8], [9], [10]

Causes of adenocarcinoma of the prostate

Numerous studies have shown that the causes of adenocarcinoma of the prostate, as well as its benign hyperplasia, lie in the imbalance of hormones and the violation of their interaction in men.

In most cases, the imbalance of sex hormones is due to natural aging - andropause. Until recently, it was believed that it was all about lowering testosterone levels. But with all the importance of this major androgen, it should be noted that the adduct of adenocarcinoma of the prostate gland has a product of the metabolism of testosterone dihydrotestosterone (DHT), which is supposed to accumulate in the cells of the gland tissues and activate their division. In addition, the researchers found that the increase in the level of certain hormones is largely associated with a decrease in the rate of their inactivation and catabolism, as well as with an increase in the activity of the enzyme 5-alpha-reductase, which converts testosterone to DHT.

But, as is known, men also have female hormones (progesterone and estrogen), which must be balanced by their testosterone antagonist. At age disproportions of hormones, an elevated level of estrogen begins to have a carcinogenic effect on the estrogenic alpha receptors of the prostate tissue. That is why the category of men after 60-65 years accounts for two-thirds of clinical cases of oncology of the prostate.

However, adenocarcinoma of the prostate gland can occur at a younger age. And the reasons for its development are linked by physicians:

• with insufficiency of the adrenal glands (as a result of which the synthesis of the aromatase enzyme, which secretes the transformation of testosterone into estrogen, is violated, which leads to a decrease in androgens);
• with obesity (fatty tissue contains aromatase, under the action of which cholesterol is synthesized again, estrogen, so excess fat leads to its excess in men);
• with excess or deficiency of thyroid hormones;
• with impaired liver function, which is involved in the metabolism of most sex hormones;
• with alcohol and smoking abuse;
• with excessive consumption of foods that have a negative effect on the level of hormones;
• with hereditary factors and genetic predisposition;
• with the influence of harmful environmental factors and production conditions.

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

Symptoms of adenocarcinoma of the prostate

Many problems with the timely access for medical care are due to the fact that at first the symptoms of adenocarcinoma of the prostate gland are simply absent.

At the same time, the pathological process proceeds latently, and its development in later stages of the disease when the tumor starts to press on the urethra is indicated by complaints of increased urge to urinate (urination) or their contraction, more frequent or, on the contrary, rare rituals with a decrease in the head of the jet. Many patients complain of a lack of full bladder emptying and soreness of the urination process. It is also possible to incontinence - involuntary urination or urinary incontinence, which is due to the fact that adenocarcinoma has entered the neck of the bladder.

With the growth of neoplasia, which affects the structures and organs located near the prostate, such signs of adenocarcinoma of the prostate gland as impurities of blood in the urine (hematuria) and in the sperm (hemospermia) join; absence of erectile function; pulling pains of varying intensity in the anus, in the groin, in the lower abdomen, giving back - in the sacral area. If the legs swell, the pelvic bones, the lower part of the spine, the ribs hurt, then this is a sign of the presence of metastases. About the general intoxication of an organism to doctors complaints of patients on absence of appetite, weight loss of the body, sensation of constant weakness and fast fatigue, and also reduction of a level of erythrocytes in the general analysis of a blood speak.

Initial problems with urination can be associated with prostate inflammation - prostatitis, and with adenoma (benign prostate formation), so only a comprehensive examination allows you to put the correct diagnosis.

Varieties of adenocarcinoma of the prostate

Depending on the location, degree of development and histological features of the tumor, the following are distinguished:

• acinar adenocarcinoma (small-acinar and large-acinar);
• low-grade adenocarcinoma;
• moderately differentiated adenocarcinoma;
• highly differentiated adenocarcinoma;
• clear cell adenocarcinoma;
• papillary adenocarcinoma;
• solid-trabecular adenocarcinoma;
• glandular-cystic adenocarcinoma, and others.

For example, acinar adenocarcinoma of the prostate appears in numerous acini - lobules, separated by connective-muscular septa (stroma); Acinuses accumulate the secret of the gland and are surrounded by a glandular tissue tubular excretory ducts. The most often diagnosed small-acinar adenocarcinoma of the prostate gland differs from the large-scale size of the formations: they are usually point-like, and the biochemical analysis of the contents of the affected cells shows an increased level of mucoproteins in the cytoplasm.

The light-celled adenocarcinoma of the prostate gland is characterized by the fact that the affected cells (with their histological examination) are colored less intensively than normal cells. And with a glandular-cystic form in the glandular epithelium of the prostate, inclusions similar to cysts are found.

It should be noted that in addition to the international classification of stages of cancer tumors (TNM Classification of Malignant Tumors) in clinical oncology, the prognostic grading system of adenocarcinoma of the prostate gland based on its histological specificity is used for the last half century. The Gleason classification (developed by Donald F. Gleason, pathologist of the American hospital for veterans of the war in Minneapolis ).

Highly differentiated adenocarcinoma of the prostate GI (1-4 points): in quite small neoplasms, there are quite a few unchanged cells; this adenocarcinoma is most often found in the urethra during surgery for a benign enlargement of the prostate. The development of pathology corresponds to stage T1 in TNM; with timely diagnosis is successfully treated.

Moderately differentiated adenocarcinoma of the GII prostate gland (5-7 points) corresponds to stage T2 of TNM: it is usually localized in the posterior part of the gland, and it is found either in digital rectal examination of patients or according to the results of the analysis of the prostate specific antigen (PSA). In most cases, such a tumor is treatable.

Low-grade adenocarcinoma of the prostate GIII (8-10 points): all tumor cells are pathologically altered (polymorphic neoplasia); It is impossible to determine the initially affected cells; the tumor captures adjacent structures of the genitourinary system and gives metastases to other organs. Corresponds to stages T3 and T4 according to TNM; the forecast is unfavorable.

In 2005, by the efforts of the leading specialists of the International Society of Urological Pathologies (ISUP), the Gleason system was slightly modified, and grading criteria was refined based on new clinical and pathological data: GI ≤ 6 points, GII ≤ 7-8, GIII 9-10. And experts of oncological urology of Germany classify adenocarcinoma of the prostate gland depending on the stage of the disease, and the main criterion for assessing the development of pathology is the size of the tumor, the spread or non-distribution of it outside the prostate, and the presence and localization of metastases.

Diagnosis of prostatic adenocarcinoma

In practical oncological urology, the diagnosis of adenocarcinoma of the prostate gland is carried out with the help of:

• collection of anamnesis of the patient (including family one);
• rectal examination of the prostate by palpation;
• clinical analysis of blood and urine;
• serum studies on PSA (prostate-specific antigen - a specific protein, synthesized by tumor cells of excretory ducts of the gland);
• review and excretory urography;
• uroflowmetry (measuring the speed of mochespuskanya);
• TRUS (transrectal ultrasound examination of the prostate gland);
• Ultrasound of the abdominal cavity;
• MRI (magnetic resonance imaging, including dynamic MRI with contrast, MR spectroscopy and diffusion-weighted MRI);
• radioisotope study of the structure of the neoplasm in the gland;
• lymphography;
• laparoscopic lymphadenectomy;
• histological examination of the biopsy specimen of the prostate and lymph nodes.

Experts emphasize that because of the long-term development of the pathological process in the prostate and the practical absence of specific symptoms, early diagnosis of adenocarcinomas is associated with great difficulties and in some cases can lead to an incorrect diagnosis.

[15], [16], [17], [18], [19], [20]

Treatment of adenocarcinoma of the prostate

To date, the treatment of adenocarcinoma of the prostate gland is carried out by various methods, the choice of which depends on the type of tumor and the stage of the pathological process, as well as the age of patients and their condition.

Oncologists-urologists use surgical methods, radiotherapy, tumor destruction (ablation) by ultrasound (HIFU-therapy) or freezing (cryotherapy), as well as drug treatment aimed at androgenic blockade of prostate cells. Chemotherapy is used as a last resort to fight adenocarcinoma and its metastases with ineffectiveness of other methods.

Surgical treatment of adenocarcinoma is an open or laparoscopic prostatectomy (complete removal of the prostate), which is carried out only with the nonproliferation of neoplasia outside the gland. The abdominal surgery to remove the prostate gland under general anesthesia, endoscopic removal - under epidural (spinal) anesthesia.

An operation to remove the testicles or part of them (bilateral orchctomy or subcapsular orchiectomy) is resorted when oncologists decide on the feasibility of a complete blockade of testosterone production. But hormonal preparations with the same therapeutic effect can be used for these purposes (see further Treatment of adenocarcinoma of the prostate with hormonal means), therefore this operation is done in rare cases.

Radiotherapy gives the maximum effect, too, only in the first stages of the disease (T1-T2 or GI). In the case of remote radiation therapy, the prostate itself and adjacent lymph nodes are exposed to X-rays. Interstitial contact radiotherapy (brachytherapy) is carried out by inserting into the tissue of the gland microcapsules with a radioactive component (isotopes I125 or Ir192) using a needle-applicator. According to specialists, brachytherapy gives much fewer side effects than remote irradiation. In addition, with remote radiotherapy, it is not always possible to disable all atypical cells.

Treatment of localized adenocarcinoma of the prostate by ultrasound ablation (HIFU) is performed under epidural anesthesia transrectally, that is, through the rectum. When the tumor is exposed to a clearly focused ultrasound of high intensity, the affected tissues are destroyed. And in the course of cryoablation, when the tumor is exposed to liquefied argon, the intracellular fluid crystallizes, which leads to necrosis of the tumor tissue. At the same time, healthy tissues are not damaged by a special catheter.

Since most patients survive after such treatment, and the tumor almost does not relapse, oncology specialists of the European Association of Urology (the European Association of Urologists) recommended cryotherapy for all cancers of the prostate, although, as an alternative method.

Treatment with hormonal means

Drug treatment of prostatic adenocarcinoma involves chemotherapy (referred to in the previous section) and the use of hormonal drugs that affect the synthesis of endogenous testosterone in order to suppress it. However, with hormone-resistant adenocarcinomas they are not used. And to make sure that hormone therapy is necessary, it is necessary to examine the blood for testosterone and dihydrotestosterone levels.

With adenocarcinomas that have passed beyond the capsule of the prostate and gave metastases to the lymph nodes, antitumor drugs used to block the gonadotropin-releasing hormone of the pituitary gland (which activates the synthesis of sex hormones) are used drugs with anti-estrogenic and anti-androgenic effects: Triptorelin (Trevelstar , Decapeptil, Diferelin depot), Gozererin (Zoladex), Degarelix (Firmagon), Leiprorelin (Lupron Depot). These drugs are administered intramuscularly or subcutaneously once a month or three months (depending on the specific agent) for 1-1.5 years. Patients should be prepared for side effects, including pruritus, headaches and joint pains, dyspepsia, impotence, increased blood sugar levels, changes in blood pressure, increased sweating, worsening of mood, loss of hair, etc.

In parallel or separately from other drugs, antiandrogens are prescribed, which block the action of dihydrotestosterone (DHT) on the receptors of prostate cells. Most often this is Flutamide (Flucine, Flutacan, Cebatrol, etc.), Bicalutamide (Androblock, Balutar, Bicaprost, etc.) or Cyproterone (Androkur). These drugs also have many side effects, in particular, the cessation of sperm production and breast enlargement, depressive condition and impaired liver function. Dosage and duration of admission are determined only by the attending physician depending on the specific diagnosis.

To reduce the activity of the aromatase enzyme (see Reasons of adenocarcinoma of the prostate gland), its inhibitors Aminoglutethimide, Anastrozole or Exemestane can be used. These drugs are used in stages of disease of stage T2 in TNM, as well as in cases of tumor recurrence after orchiectomy.

Proscar (Dutasteride, Finasteride) is an inhibitor of 5-alpha-reductase, an enzyme that converts testosterone into DHT. Its appointment to patients with adenocarcinoma of the prostate gland leads to a reduction in prostate size and a PSA (prostate-specific antigen) level. Among the side effects of this drug are a decrease in libido, a decrease in the volume of sperm, erectile dysfunction, and breast engorgement.

According to numerous studies, the hormonal treatment of adenocarcinoma of the prostate gland in stages T3-T4 (that is, in the presence of metastases) inhibits the proliferation of cancer cells for a sufficiently long time with the minimum possible complications.

Prophylaxis of prostatic adenocarcinoma

Accessible to all prophylaxis of adenocarcinoma of the prostate gland is largely related to nutrition. If you have extra pounds, eat lots of red meat, love fatty and sweet, regularly and in large quantities drink beer (which contains phytoestrogen of hops), then you know: the risk of this pathology increases several times!

Experts from the American Cancer Society, based on the study of various case histories and clinical cases of malignant neoplasms of the prostate, recommend a balanced diet with an emphasis on plant foods: vegetables, fruits, whole grains, nuts, seeds (pumpkin, sunflower, sesame), beans and peas. Red meat, as a source of animal protein, is best replaced with fish, white poultry meat and eggs. To the body weight did not exceed the norm, the food should be well balanced in calories and comparable to the level of physical activity. At the same time, protein in the daily diet should account for no more than 30% of calories, 50% for carbohydrates, and only 20% for fats.

Vegetables are especially useful for tomatoes, sweet red pepper, carrots, red cabbage; from fruits and berries pink grapefruit, watermelon, sea buckthorn and rosehip. They all contain a lot of carotenoid pigment lycopene (or lycopene), which is a powerful antioxidant. According to some preliminary studies, the use of tomatoes (including juice and tomato sauces) can reduce the risk of developing prostate cancer. However, the FDA does not yet see convincing arguments confirming the effect of lycopene on the mechanisms of prostate cancer, in particular, adenocarcinoma of the prostate gland. But in any case, a glass of tomato juice is more useful than a glass of beer ...

But the role in the development of sex hormones leptin, synthesized by cells of adipose tissue, is no longer in doubt, for more details, see What is leptin and how does it affect weight?

Depending on the stage of the disease and the differentiation of the tumor, the prognosis of adenocarcinoma of the prostate gland is as follows. After treatment of low-grade adenocarcinoma in stage T1, 50% of patients live at least five years, in stage T2 25-45%, in stage T3 20-25%. Adenocarcinoma of the prostate gland in the last stage (T4) leads to an early lethal outcome, and only 4-5 patients out of 100 can survive some more time.