Adenocarcinoma of the prostate

Prostate adenocarcinoma is the most common malignant neoplasm of this organ (over 95% of all cases of prostate cancer), in which pathological proliferation of glandular epithelial cells occurs. Epithelial neoplasm can be limited to the capsule of the gland, or it can grow into nearby structures. Getting into the lymph, atypical tumor cells affect the iliac and retroperitoneal lymph nodes, and metastases to bone tissues spread hematogenously.

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

Causes of prostate adenocarcinoma

Numerous studies have proven that the causes of prostate adenocarcinoma, as well as its benign hyperplasia, are rooted in hormonal imbalance and disruption of their interaction in the male body.

In most cases, the imbalance of sex hormones is explained by natural aging - andropause. Until recently, it was believed that it was all about a decrease in testosterone levels. But with all the importance of this main androgen, it should be noted that the product of testosterone metabolism, dihydrotestosterone (DHT), which is supposed to accumulate in the cells of the gland tissue and activate their division, is involved in the occurrence of prostate adenocarcinoma. In addition, scientists have found that an 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 into DHT.

But, as is known, men also have female hormones (progesterone and estrogen), which must be balanced by their antagonist testosterone. With age-related hormonal imbalances, the increased level of estrogen begins to have a carcinogenic effect on the estrogen alpha receptors of prostate tissue. This is why the category of men after 60-65 years accounts for two thirds of clinical cases of prostate cancer.

However, prostate adenocarcinoma can also occur at a younger age. And doctors associate the reasons for its development with:

• with adrenal insufficiency (as a result of which the synthesis of the aromatase enzyme is disrupted, which secretes the transformation of testosterone into estrogen, which leads to a decrease in androgens);
• with obesity (adipose tissue contains aromatase, under the influence of which estrogen is synthesized from cholesterol, which is why 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 impact on hormone levels;
• with hereditary factors and genetic predisposition;
• with the influence of harmful environmental factors and production conditions.

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

Symptoms of prostate adenocarcinoma

Many problems with timely medical attention are related to the fact that at first, symptoms of prostate adenocarcinoma are simply absent.

In this case, the pathological process is latent, and its development at later stages of the disease, when the tumor begins to press on the urethra, is evidenced by complaints of increased urges to urinate (urinate) or their reduction, more frequent or, conversely, rare urination with a weakening of the stream. Many patients complain of the lack of a feeling of complete emptying of the bladder and painful urination. Incontinence is also possible - involuntary urination or urinary incontinence, which is associated with the fact that adenocarcinoma has penetrated into the neck of the bladder.

As the neoplasia grows, affecting the structures and organs located near the prostate, such signs of prostate adenocarcinoma as blood in the urine (hematuria) and in the sperm (hemospermia) are added; lack of erectile function; nagging pain of varying intensity in the anus, groin, lower abdomen, radiating back to the sacral area. If the legs swell, the pelvic bones, lower part of the spine, ribs hurt, then this is a sign of metastases. Patients' complaints of lack of appetite, weight loss, a feeling of constant weakness and rapid fatigue, as well as a decrease in the level of red blood cells in a general blood test indicate general intoxication of the body to doctors.

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

Types of prostate adenocarcinoma

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

• acinar adenocarcinoma (small acinar and large acinar);
• poorly differentiated adenocarcinoma;
• moderately differentiated adenocarcinoma;
• highly differentiated adenocarcinoma;
• clear cell adenocarcinoma;
• papillary adenocarcinoma;
• solid trabecular adenocarcinoma;
• glandular cystic adenocarcinoma, etc.

For example, acinar adenocarcinoma of the prostate gland occurs in numerous acini - lobules separated by connective-muscular partitions (stroma); the gland's secretion accumulates in the acini and there are tubular excretory ducts surrounded by glandular tissue. The most frequently diagnosed small-acinar adenocarcinoma of the prostate gland differs from large-acinar adenocarcinoma in the size of the formations: they are usually pinpoint, and biochemical analysis of the contents of the affected cells shows an increased level of mucoproteins in the cytoplasm.

Clear cell adenocarcinoma of the prostate gland is characterized by the fact that the affected cells (during their histological examination) are stained less intensely than normal ones. And in the glandular-cystic form, inclusions similar to cysts are found in the glandular epithelium of the prostate.

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

Well-differentiated adenocarcinoma of the prostate gland GI (1-4 points): small-sized neoplasms contain a sufficient number of unchanged cells; such adenocarcinoma is most often detected in the urethra during surgery for benign prostate enlargement. The development of the pathology corresponds to stage T1 according to TNM; with timely diagnosis, it is successfully treated.

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

Low-differentiated prostate adenocarcinoma GIII (8-10 points): all tumor cells are pathologically altered (polymorphic neoplasia); it is impossible to determine the initially affected cells; the tumor affects adjacent structures of the genitourinary system and metastasizes to other organs. Corresponds to stages T3 and T4 according to TNM; the prognosis is unfavorable.

In 2005, through the efforts of leading specialists of the International Society of Urological Pathology (ISUP), the Gleason system was slightly modified, and the grading criteria were clarified based on new clinical and pathological data: GI ≤ 6 points, GII ≤ 7-8 points, GIII 9-10 points. And specialists in oncological urology in Germany classify prostate adenocarcinoma depending on the stage of the disease, and the main criterion for assessing the development of pathology is the size of the tumor, its spread or non-spread beyond the prostate, as well as the presence and localization of metastases.

Diagnosis of prostate adenocarcinoma

In practical oncological urology, diagnosis of prostate adenocarcinoma is carried out using:

• collecting the patient's anamnesis (including family history);
• rectal examination of the prostate by palpation;
• clinical analysis of blood and urine;
• blood serum tests for PSA (prostate-specific antigen - a specific protein synthesized by tumor cells of the gland's excretory ducts);
• survey and excretory urography;
• uroflowmetry (measuring the rate of urination);
• 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 neoplasms in the gland;
• lymphography;
• laparoscopic lymphadenectomy;
• histological examination of a biopsy of the prostate gland and lymph nodes.

Experts emphasize that due to the rather long 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 prostate adenocarcinoma

Today, treatment of prostate adenocarcinoma is carried out using 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 the 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 androgen blockade of prostate cells. Chemotherapy is used as a last resort to combat adenocarcinoma and its metastases when other methods are ineffective.

Surgical treatment of adenocarcinoma is open or laparoscopic prostatectomy (complete removal of the prostate), which is performed only if the neoplasia has not spread beyond the gland. Abdominal surgery to remove the prostate gland is performed under general anesthesia, endoscopic removal - under epidural (spinal) anesthesia.

Surgery to remove the testicles or part of them (bilateral orchiectomy or subcapsular orchiectomy) is used when oncologists decide on the advisability of a complete blockade of testosterone production. But for these purposes, hormonal drugs with the same therapeutic effect can be used (see below Treatment of prostate adenocarcinoma with hormonal agents), so this operation is done in rare cases.

Radiotherapy also gives the maximum effect only in the early stages of the disease (T1-T2 or GI). With remote radiotherapy, the prostate itself and neighboring lymph nodes are exposed to X-rays. Intra-tissue contact radiotherapy (brachytherapy) is carried out by introducing a microcapsule with a radioactive component (isotopes I125 or Ir192) into the gland tissue using an applicator needle. According to experts, brachytherapy gives much fewer side effects compared to remote irradiation. In addition, with remote radiotherapy it is not always possible to neutralize all atypical cells.

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

Since most patients survive after such treatment, and the tumor almost never relapses, oncourologists from the European Association of Urology recommended cryotherapy for all prostate cancer tumors, albeit as an alternative method.

Treatment with hormonal agents

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

In case of adenocarcinomas that have gone beyond the capsule of the prostate gland and metastasized to the lymph nodes, drugs with antiestrogenic and antiandrogenic effects are used as antitumor drugs aimed at blocking the pituitary gonadotropin-releasing hormone (which activates the synthesis of sex hormones): Triptorelin (Trelstar, Decapeptyl, Diphereline Depot), Goselerin (Zoladex), Degarelix (Firmagon), Leuprorelin (Lupron Depot). These drugs are administered intramuscularly or subcutaneously once a month or every three months (depending on the specific drug) for 1-1.5 years. Patients should be prepared for side effects, including itchy skin, headaches, joint pain, dyspepsia, impotence, increased blood sugar, changes in blood pressure, increased sweating, mood swings, hair loss, etc.

Antiandrogens are prescribed in parallel or separately from other drugs, which block the action of dihydrotestosterone (DHT) on prostate cell receptors. Most often, these are Flutamide (Flucinom, Flutacan, Cebatrol, etc.), Bicalutamide (Androblok, Balutar, Bikaprost, etc.) or Cyproterone (Androcur). These drugs also have many side effects, in particular, the cessation of sperm production and enlargement of the mammary glands, depression and deterioration of liver function. The dosage and duration of administration are determined only by the attending physician depending on the specific diagnosis.

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

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

According to numerous studies, hormonal treatment of prostate adenocarcinoma at stages T3-T4 (i.e. in the presence of metastases) inhibits the proliferation of cancer cells for a fairly long time with minimal possible complications.

Prevention of prostate adenocarcinoma

Prevention of prostate adenocarcinoma, which is available to everyone, is largely related to nutrition. If you have extra pounds, eat a lot of red meat, like fatty and sweet foods, regularly and in large quantities drink beer (which contains hop phytoestrogen), then know: the risk of this pathology increases several times!

Experts from the American Cancer Society, based on a study of various case histories and clinical cases of malignant neoplasms of the prostate gland, 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 meat of poultry and eggs. To ensure that body weight does not exceed the norm, nutrition 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, carbohydrates 50%, and fats only 20%.

Of the vegetables, tomatoes, sweet red peppers, carrots, and red cabbage are especially useful; of the fruits and berries, pink grapefruit, watermelon, sea buckthorn, and rose hips. All of them contain a lot of the carotenoid pigment lycopene (or lycopene), which is a powerful antioxidant. According to the results of some preliminary studies, eating tomatoes (including juice and tomato sauces) can reduce the risk of developing prostate cancer. However, the FDA has not yet seen convincing arguments confirming the effect of lycopene on the mechanisms of prostate cancer development, in particular, prostate adenocarcinoma. But in any case, a glass of tomato juice is healthier than a glass of beer…

But the role of leptin, synthesized by adipose tissue cells, in the production of sex hormones 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 differentiation of the tumor, the prognosis for prostate adenocarcinoma is as follows. After treatment of poorly differentiated adenocarcinoma at stage T1, 50% of patients live for at least five years, at stage T2 25-45%, at stage T3 20-25%. Adenocarcinoma of the prostate gland at the last stage (T4) leads to a rapid death, and only 4-5 patients out of 100 can survive for some time.