Prostate cancer - symptoms and treatment

Radical prostatectomy (RP) - complete removal of the prostate

Surgical intervention in the volume of total prostatectomy is the most radical method of treatment. Most urologists recommend radical prostatectomy as the treatment of choice for localized prostate cancer. Under such surgical treatment is meant the removal of the prostate gland with seminal vesicles and part of the urethra. The goal of surgery for localized and some types of locally advanced PCa is the complete cure of the patient. In rare cases, complete removal of the prostate is aimed at palliative care in the treatment of a locally advanced process, i.e., to improve the patient's condition. In these cases, the task of the operation is to remove the bulk of the tumor in order to increase the effectiveness of conservative treatment.

Radical surgical treatment is usually performed in patients with localized PCa with a life expectancy of more than 10 years.

Surgical access options for radical prostatectomy:

• retroposterior;
• perineal;
• laparoscopic (robot-assisted).

Indications for radical prostatectomy:

• T1a G1-G2 tumors with life expectancy greater than 15 years; T1a G3 tumors; tumors T1b-T2c; T3a tumors; limited extracapsular invasion.

Advantages of radical prostatectomy over conservative treatments:

• complete removal of the intracapsular tumor;
• accurate staging of the tumor process;
• treatment of associated symptomatic benign prostatic hyperplasia.21

In the past few years, laparoscopic radical prostatectomy has become widely used, which can be performed via transperitoneal or extraperitoneal approaches. The use of this technique allows to reduce the number of complications and speed up the process of rehabilitation of patients.

One of the options for laparoscopic surgery is robot-assisted radical prostatectomy (according to the EAU 2015 Guidelines - the clinical guidelines of the European Association of Urology). Robot-assisted radical prostatectomy (RARP) is actively replacing RP as the gold standard for surgical treatment of localized Prostate cancer worldwide. erectile function.14

Radiation therapy (RT)

Like prostatectomy, radiation therapy is considered a definitive treatment for localized prostate cancer. In locally advanced PCa, RT is performed to improve patient survival, and more often in combination with hormonal therapy. The goal of radiation therapy is the most accurate achievement of the therapeutic dose of ionizing radiation in the prostate tissue, subject to minimal radiation exposure to surrounding organs and tissues.23

Brachytherapy (interstitial RT) is the implantation of radioactive sources into the prostate tissue. For the treatment of prostate cancer, constant (low-dose) and temporary (high-dose) brachytherapy is used. For temporary brachytherapy, the isotope 192 Ir is used. Removal of radioactive needles is carried out after bringing the required dose to the prostate gland. High-dose brachytherapy is used for locally advanced prostate cancer (T3 N0 M0), combined with external irradiation. With localized prostate cancer, permanent brachytherapy is more often used: radioactive granules 125I (half-life - 60 days) or 103Pd (half-life - 17 days) are injected into the prostate gland. The more localized distribution of ionizing radiation during brachytherapy allows a higher dose of radiation to be delivered to the prostate gland with less radiation exposure to surrounding tissues than with remote RT. The introduction of radioactive sources is performed through the perineum under the control of transrectal ultrasound. The radiation dose for 125I implantation is 140-160 g, for 103Pd implantation - 115-120 g.24

Minimally invasive methods for the treatment of prostate cancer

Minimally invasive treatments for prostate cancer include prostate cryoablation and prostate ablation using High Intensity Focused Ultrasound (HIFU). Cryoablation of the prostate is a well-studied alternative method for the treatment of prostate cancer, while HIFU is not fully understood. Focal therapy of prostate cancer using various techniques such as cryoablation, ultrasound or laser ablation, etc.) is being actively studied in many clinics.14

Hormonal therapy

Hormone therapy, as an independent method of treating prostate cancer, is recommended for palliative purposes.At the same time, the appointment of hormonal drugs can be indicated in combination with radical surgery or radiation treatment as a combined antitumor therapy. The basis of the mechanism of action of endocrine treatment is a decrease in the concentration of testosterone in the cells of the prostate gland, implemented in one of the following ways:

The methods of hormone therapy include:

• bilateral orchidectomy (removal of both testicles);
• luteinizing hormone-releasing hormone (LHRH) agonist therapy using goserelin, leuprorelin, triptorelin, buserelin;
• therapy LHRH antagonists (degarelix);
• estrogen therapy (diethylstilbestrol);
• maximum (combined) androgen blockade;
• antiandrogen monotherapy (steroidal - cyproterone, megestrol and chlormadinone; non-steroidal - bicalutamide, flutamide, nilutamide).1425

Hormonal drugs of other classes

It is recommended to take ketoconazole, an antifungal drug that inhibits the synthesis of adrenal androgens. It is used as a second line of hormonal therapy for metastatic prostate cancer against the background of the progression of the process after the maximum androgen blockade. Ketoconazole is prescribed orally at a dose of 400 mg 3 times a day.

Immunotherapy for prostate cancer

Prostate cancer immune therapy activates lymphocytes that can destroy cancer cells. Target - antigens characteristic of prostate cancer. These are, first of all, PSA, as well as prostatic phosphatase and prostate-specific membrane antigen (PSMA). Dendritic cell vaccines, whole tumor cell vaccines, vector-linked vaccines and monoclonal antibodies are used in the immunological treatment of malignant tumors of the prostate.

Today, new drugs have appeared that can become first-line drugs for the treatment of this disease. Abiraterone (Zytiga) is an Israeli approved drug for the treatment of castrate-resistant prostate cancer. Prostvak, like a vaccine, stimulates the immune system to mobilize the body to fight cancer cells. The survival rate of patients with severe forms of prostate cancer taking Prostava increases from 16 months to 24 months. Alfaradin is a radiopharmaceutical that releases radioactive alpha particles, they locally affect metastases. Denosumab protects bones in the event of metastasis, preventing the removal of calcium from the bones, slowing down the development of the metastatic process 5 times more effective than other drugs.14

Chemotherapy for prostate cancer

In the early stages of prostate cancer, chemotherapy is ineffective. This is due to the fact that malignant tumor cells of the prostate gland grow in the same way as healthy ones. Cytostatics act exclusively on fast-growing cellular structures. Most often, antitumor drugs are prescribed at III-IV stages of the disease - with a large size of the primary tumor, severe pain, metastases and the presence of several foci in the bone tissue.

The advantage of antitumor chemotherapy drugs is the ability to use them for aggressive prostate tumors that have already metastasized and cannot be removed surgically. In combination with surgery and hormonal drugs, chemotherapy can stabilize or improve the patient's condition.

Chemotherapy is the intravenous administration of special chemotherapeutic agents. On average, one cycle of chemotherapy for prostate cancer lasts 1-4 weeks. For prostate cancer, Docetaxel is used with Goserelin, Buserelin and Triptorelin.

When Docetaxel is ineffective or resistant, Cabazitaxel (Jevtana) is used. The results of the studies showed that this chemotherapy drug is much more effective than Mitoxantrone, which was previously chosen to replace Docetaxel.

Chemotherapy drugs stop the division of malignant cells, slowing down or completely stopping tumor growth. At the same time, these drugs cause severe side effects, such as:

• decrease in white blood cells and immunity;
• anemia, worsening of blood clotting and a predisposition to bleeding;
• nausea, vomiting and diarrhea;
• stomatitis and ulcers in the oral cavity;
• loss of appetite, taste disturbances;
• hair loss;
• general weakness and fatigue;
• delay fluids and edema;
• peripheral neuropathy.

Virotherapy

Viral therapy for prostate cancer is being investigated by scientists and is considered a promising direction 27. However, this method has not yet been used to treat patients.

Rescue Therapy

All patients with bone metastases treated with docetaxel have experienced progression. In this regard, numerous studies have been carried out related to the study of the role of salvage therapy.The results of these studies showed that cabazitaxel therapy, docetaxel intermittent chemotherapy, and molecular targeted therapy are the most appropriate treatment regimens. Currently, these methods are not recommended due to the small number of randomized trials.

Palliative care

• Therapy aimed at treating skeletal lesions in castration-resistant prostate cancer

In most patients with bone-advanced prostate cancer (CRPC), bone metastases are accompanied by severe pain. Two radioisotopes, Sr-89 and Sa-153, are able to reduce or stop bone pain in 72% of patients. In patients with bone metastases, which are accompanied by pain, the use of Ra-233 proved to be very effective.

Complications caused by bone metastases are expressed in pain in the bones, destruction of the vertebrae, deforming pathological fractures and compression of the spinal cord. Another cause of pathological fractures is osteoporosis, so its prevention is necessary.

The use of bone cement is a productive method of treating pathological fractures, which can significantly reduce pain and improve the quality of life. If spinal cord compression is suspected, high doses of corticosteroids and an MRI should be performed as soon as possible.

Bisphosphonates are used to inhibit bone resorption. With the use of zoledronic acid, an increase in the time to the appearance of the first skeletal complication was noted, which improved the quality of life of patients. Currently, bisphosphonates are indicated in patients with CR PCa with bone metastases for the prevention of skeletal complications, although there is no clear optimal interval between doses (currently 3 weeks or less).

It is always worth remembering that these drugs have side effects, especially with amino bisphosphonates (eg, maxillary necrosis). Bisphosphonates are prescribed early in the treatment of symptomatic CR PCa. With additional systemic therapy, methods are found to eliminate possible side effects - pain, constipation, lack of appetite, nausea, fatigue, depression, which develop during palliative treatment. Therapy includes palliative EBRT, cortisone, analgesics and antiemetics.

• Inhibitors of nuclear factor activator RANK receptor ligand

Denosumab, a human monoclonal antibody directed against the receptor-activator of nuclear factor B-ligand, is a key mediator of the formation of osteoclasts (large multinucleated cells). In patients with CR stage M0 PCa, denosumab resulted in an increase in bone metastasis-free survival compared to placebo. During the third phase of treatment, it was noted that the efficacy and safety of denosumab is comparable to zoledronic acid in patients with metastatic CR PCa. Denosumab is approved by the US Food and Drug Administration for the prevention of skeletal complications in patients with cancer-related bone metastases.

After therapy with docetaxel, with the progression of prostate cancer, the use of cabazitaxel is recommended.

Next, consider the complications of various methods of treating prostate cancer.

Complications of radical prostatectomy:

• mortality - 0-1.3%;
• rectal injury - 0.5-2.8%;
• ureter injury - 0.3%;
• lower extremity vein thrombosis - 1.2-1.5%;
• pulmonary embolism - 0.6-1.4%;
• acute infarction myocardium - 0.4-0.7%;
• urinary incontinence - 0.8-12%.

Erectile dysfunction can develop in all patients after radical prostatectomy without using a nerve-sparing technique. In order to preserve erectile function, a surgical technique has been developed that allows preserving cavernous neurovascular bundles.

Complications of external beam radiotherapy:

• urinary incontinence - 0.2-1.5%;
• erectile dysfunction - 54-66%;
• diarrhea - 1.4-7.7% ;
• urethral strictures - 2.6-11.0%;
• hematuria - 2.5-10.0%:
• rectal bleeding - 2, 5-14.2%.