Advances in photodynamic therapy for ovarian cancer. New minimally invasive technologies for the treatment of prostate cancer

YAGUDAEV DANIEL MEEROVICH

INTRACAVITY PHOTODYNAMIC THERAPY

BLADDER CANCER AND PROSTATE ADENOMAS
14.00.40. – Urology

dissertations for a degree

doctors of medical sciences

Moscow - 2008
The dissertation work was carried out at the State Scientific Center for Laser Medicine of the Federal Agency for Health and Social Development.
Scientific consultants:

Martov Alexey Georgievich

doctor of medical sciences, professor Geinits Alexander Vladimirovich
Official opponents:

Doctor of Medical Sciences Dutov Valery Viktorovich

GU MONIKI them. M.F. Vladimirsky
doctor of medical sciences, professor Borisov Vladimir Viktorovich

GOU VPO MMA them. THEM. Sechenov Roszdrav

GUS GKUB No. 47 DZ of the city of Moscow

SEI VPO Peoples' Friendship University of Russia

The defense of the dissertation will take place "" _________ 2008 at 14 o'clock at a meeting of the dissertation council D 208.049.01 at the Moscow Regional Research Clinical Institute. M.F. Vladimirsky at the address: 129110, Moscow, st. Shchepkina, 61/2 building 15, conference hall.

The analysis of the results obtained made it possible to determine the indications, contraindications for PDT in RPM and AP, to analyze possible errors, dangers and complications, and to develop measures for their prevention.

Approbation of work. The main provisions of the dissertation are presented and discussed: at the scientific-practical conference "Laser and Health", Moscow, 2004; at the scientific-practical conference "Domestic anticancer drugs", Moscow, 2006; at the scientific-practical conference "Modern achievements of laser medicine and their application in practical healthcare", Moscow, 2006; at the All-Russian scientific and practical conference "Domestic anticancer drugs", Moscow, 2007; at the 1047th extended meeting of the Moscow Society of Urology "Prospects for photodynamic diagnosis and therapy in urology", Moscow, 2007, at the All-Russian scientific and practical conference "Domestic anticancer drugs", Moscow, 2008

The materials of the dissertation research were discussed at the meeting of the Academic Council of the Federal State Institution "State Scientific Center for Laser Medicine of the Federal Agency for Health and Social Development" on 19.03.08. and at a joint scientific conference of employees of the urological department and the department of urology of the Federal University of Education and Science of the MONIKI named after. M.F. Vladimirsky dated April 11, 2008

Implementation into practice

Photodynamic therapy for bladder cancer and APZh has been introduced into clinical practice at City Clinical Hospital No. 51, Federal State Institution SRC LM of Roszdrav. The method of local fluorescence spectroscopy has been introduced into the clinical practice of the city clinical hospital No. 51, the city clinical urological hospital No. 47.

The provisions and conclusions of the dissertation are used during practical classes, seminars and lectures for cadets, clinical residents and graduate students of the State Scientific Center for Laser Medicine of the Federal Agency for Health and Social Development.

Scope and structure of the dissertation

The dissertation work consists of an introduction, 6 chapters, a conclusion, conclusions, practical recommendations, an index of used literature. The volume of work is 200 pages of standard typewritten text. The work is illustrated with 39 tables, 44 figures. The list of used literature contains 215 sources, of which 49 are domestic and 166 are foreign.

The main provisions for the defense:

1. 
   Photodynamic therapy in urology is a modern, effective method of treatment in elderly and senile patients with a burdened somatic status and a high risk of anesthesia, with a mild postoperative period, and a small number of complications.
2. 
   Local fluorescence spectroscopy (LFS) is a method necessary to search for foci of increased accumulation of photoditazin in the bladder mucosa in order to detect cancer microfoci that are not detected by traditional diagnostic methods, and to clarify the boundaries of the tumor lesion; a method that made it possible to study the accumulation, distribution and excretion of the photosensitizer photoditazine from hyperplastic prostate tissue.
3. 
   The 2-stage photodynamic therapy of bladder cancer can be used as a stand-alone treatment for superficial bladder cancer and as neoadjuvant therapy for invasive bladder cancer followed by TURBT.
4. 
   The use of PDT of prostate adenoma according to the developed method allows to reduce not only irritative, but also obstructive symptoms, improve the quality of life of patients. The effectiveness of PDT in prostate adenoma is comparable to the results of standard TUR.

The studies were performed at the Federal State Institution "State Scientific Center for Laser Medicine of the Federal Agency for Health and Social Development", Federal State Institution "Research Institute of Urology of Rosmedtekhnologii", City Clinical Hospital No. 51, City Clinical Urological Hospital No. 47 in the time period from 1998 to 2007.

The work consists of two parts. The first part is devoted to photodynamic diagnostics, in particular, the study of the accumulation and distribution of the photosensitizer photoditazine in hyperplastic prostate tissue, as well as the study of the accumulation of the photosensitizer photoditazine in bladder tumors with the aim of using it for photodynamic diagnosis and photodynamic therapy of bladder cancer, including the detection of latent tumor foci that are not detected known diagnostic methods. The method of local fluorescence spectroscopy was used as a research method.

The second part of the work is devoted to photodynamic therapy. The main clinical group included 100 patients, 1st group– 50 (50%) patients who underwent photodynamic therapy for a bladder tumor and 2nd group–50 (50%) patients after PDT of prostate adenoma.

The control group included 208 patients. Of these, 148 patients underwent TUR of the bladder, and 60 patients underwent TUR of the prostate. The average age of patients in the main group was 72.5±0.74 years, in the control group - 67.5±0.81 years. Obligatory methods of examination of patients with bladder cancer were: ultrasonography, fluorescent diagnostics, urethrocystoscopy and biopsy of the bladder tumor. If necessary, additional methods of examination were performed (cytological examination of urine, CT, MRI, X-ray examination).

In patients with APJ, the examination was also comprehensive and included: a survey of complaints using the I-PSS system, digital rectal examination, transabdominal and transrectal ultrasound, determination of the amount of residual urine, uroflowmetry, assessment of sexual function, blood test for PSA, if necessary, a wider urodynamic study.

The second generation photosensitizer based on chlorine derivatives photoditazine (registration certificate No. LS - 001246) was used in the work.

Photodynamic diagnostics.

As is known, many photosensitizers, including photoditazine, fluoresce in the red region of the spectrum, which, combined with their increased accumulation in the tissues of malignant neoplasms, forms the basis of fluorescent diagnostics (Chissov V.I. et al., 2003; Zaak D. et al. , 2001).

The fluorescence of photosensitizers also makes it possible to study the kinetics of their accumulation and excretion in tissues in vivo and ex vivo. In this work, the method of local fluorescence spectroscopy was used to detect photoditazine in hyperplastic prostate tissue. To excite the fluorescence of photoditazine, laser radiation with a wavelength of 638 nm was used near the last absorption maximum at 650 nm. This made it possible to selectively excite the exogenous fluorescence of the photosensitizer without excitation of the fluorescence of endogenous tissue fluorochromes.

To study the accumulation and distribution of the photosensitizer photoditazine in hyperplastic prostate tissue and bladder tumors, patients were divided into 2 groups.

The first group of the study included 10 patients diagnosed with AP. The above diagnosis was confirmed by histological examination. The volume of the prostate gland ranged from 70 to 120 cm 3 . The photosensitizer was administered intravenously at the rate of 0.5–1 mg/kg of body weight 2, 3, 6, 12, and 24 hours before the removal of hyperplastic tissue. After removal (transvesical adenomectomy), fluorescent detection of the photosensitizer photoditazine was performed on the removed material ex vivo.

Using local fluorescence spectroscopy, it was proved that within 24 hours after intravenous administration at a dose of 1 mg/kg of body weight, the photosensitizer photoditazine is detected in hyperplastic tissue of the human prostate gland, while the maximum intensity of exogenous fluorescence of photoditazine is recorded 3 hours after administration. After 12 and 24 hours, the intensity decreases significantly, which indicates the rapid removal of the photosensitizer (Fig. 1). The results obtained proved the possibility of using Photoditazine for the treatment of patients with prostate adenoma by PDT.

Rice. 1. Normalized fluorescence of hyperplastic pancreatic tissue, measuredex vivobefore administration (0), 2, 3, 6, 12 and 24 hours after intravenous administration of Photoditazine at a dose of 1 mg/kg of body weight.

The second group of the study also included 10 patients. In all patients, transitional cell carcinoma was morphologically confirmed in stages T a , T 1 and T is with varying degrees of cell differentiation. The size of tumor lesions reached 0.5–2.5 cm in diameter. A fluorescence study was performed before and 2–3.6 hours after the administration of the photosensitizer before and after the PDT session. To excite the fluorescence of photoditazine, laser radiation with a wavelength of 633 nm was used near the last absorption maximum. The power of laser radiation from the end of the fiber optic catheter was 3 mW, the exposure time was 100 ms, and the spatial resolution when scanning the tissue surface using a fiber optic catheter reached about 1 mm. It should be noted that at the specified power of laser radiation, there is no irreversible photodynamic damage to the mucous membrane of the bladder and discoloration of the photosensitizer.

The fluorescence spectra of the mucous membrane of the bladder were measured after a cystoscopic examination in white light before the start of the PDT session. A fiber optic catheter was inserted into the working channel of the cystoscope, the end of the catheter was brought to the surface of the tissue. Then, endoscopic illumination was turned off and, under illumination with laser radiation, fluorescence spectra were measured. The measurements were carried out in the following sequence: unchanged mucosa of the bladder outside the affected area, unchanged mucosa 1 cm from the visible border of the lesion, the visible border of the tumor lesion, the center of the tumor. The use of local fluorescence spectroscopy made it possible to study the accumulation and distribution of the photosensitizer photoditazine in the intact mucosa and tumor of the bladder (Fig. 2).

Fig.2. Local fluorescence spectroscopy of the bladder mucosa 3 hours after intravenous administration of Photoditazine at a dose of 1 mg/kg of body weight. Fluorescence spectra were measured in the center, along the visible border of the tumor and outside the zone of tumor lesion. The spectra are normalized by the magnitude of the signal of excitation laser radiation diffusely scattered in the tissue at a wavelength of 633 nm.

The LFS method in vivo showed that 2–3 hours after intravenous administration at a dose of 1 mg/kg of body weight, exogenous photoditazine fluorescence was detected in the tumor and was not detected in the unchanged mucosa of the urinary tract. The fluorescent coefficient of tumor lesions against the background of unchanged mucosa in all patients at these times after injection was significantly more than 1, its average value was 5 (maximum 10), which indicates the selective accumulation of photoditazine in bladder tumors.

The obtained results indicate the possibility of using the drug photoditazine for fluorescent diagnosis of bladder cancer. The LFS technique can be used to search for foci of increased accumulation of photoditazin in the mucosa of the bladder in order to identify microfoci of cancer, as well as to clarify the boundaries of the tumor lesion.

Researchers from Oregon State University (USA) announced a significant improvement in photodynamic therapy for ovarian cancer.

By combining the introduction of phthalocyanine and gene therapy, scientists have achieved amazing results in experiments on laboratory mice.

The results of the work of American scientists have just appeared on the pages of the journal Nanomedicine: Nanotechnology, Biology and Medicine.

According to experts, the proposed method of treatment can make a real breakthrough in the treatment of one of the most deadly types of cancer, which in the US alone claims more than 14,000 lives annually.

Ovarian cancer is considered one of the most deadly because it often has time to metastasize even before it is detected by doctors. Severe side effects and resistance of cancer cells greatly complicate the treatment of ovarian cancer with traditional methods.

A novel approach proposed by OSU Pharmaceuticals and their colleagues at the University of Nebraska is the already existing photodynamic therapy (PDT) with the photosensitizing agent phthalocyanine plus gene therapy, which reduces the protection of cancer cells and makes them especially vulnerable to free radicals produced by PDT.

“Surgical removal of the tumor and chemotherapy are traditional approaches, which, unfortunately, are not always effective. It can be very difficult to determine the place where the tumor has managed to get, and in some cases it can not be removed at all, ”explains Oleh Taratula, co-author of the latest study, a research fellow at the Oregon State University College of Pharmacy.

“Photodynamic therapy is a slightly different approach that can be used in addition to surgery and seems to be very effective and harmless. In the past, the effectiveness of PDT was limited, but our innovation has made it more effective than ever before,” the researcher continues.

First, scientists inject laboratory animals with ovarian cancer with the photosensitizing substance phthalocyanine, which, when irradiated with near-infrared light, releases reactive oxygen species that are deadly to cancer cells. At the same time, gene therapy minimizes the natural protection of cancer cells, and they die from PDT many times faster.

To simultaneously deliver phthalocyanine and RNA fragments for gene therapy to cancer cells, scientists used unique nanoparticles - dendrimer nanoplatforms. These particles, developed by OSU employees, find cancer cells and deliver a deadly cocktail directly to the address. Near-infrared light then penetrates deep into the abdominal cavity, reaching the cancer cells and activating the phthalocyanine accumulated in them.

When the researchers used PDT alone, tumors in some animals started growing again 2 weeks after treatment. But after PDT combined with gene therapy, they did not find a single case of cancer recurrence. At the same time, mice that were treated according to the new method continued to grow and gain weight, which indicates a good tolerability of therapy.

“Cancer cells are very smart, so to speak. They secrete a large number of protective proteins, including the DJ1 protein, which help them survive the onslaught of reactive oxygen species. An excess of the DJ1 protein is associated with metastasis and resistance of ovarian cancer, as well as with poor patient survival. But gene therapy deprives them of such protection and makes PDT more successful,” the scientists say.

There are certain limitations to active surveillance and effective treatments in Israel for localized prostate cancer. Because most cases of prostate cancer are low risk and the tumor is clinically localized, many men are faced with the question of how best to manage their disease.

A minimally invasive treatment for prostate cancer, vascular targeted photodynamic therapy can cure or control the disease, eliminating the risks of more active surveillance, radical prostatectomy, and radiation therapy. Vascular Targeted Photodynamic Therapy WST-09 VTP is a new strategy to achieve the goals of minimally invasive treatment of prostate cancer - a good prognosis and patient quality of life.

Vascular targeted photodynamic therapy for patients with localized prostate cancer is a new, minimally invasive procedure that uses an activated drug to destroy prostate cancer cells through a laser fiber. The technology has a high potential to destroy cancer without making incisions or causing any devastating sexual, urinary or reproductive side effects. This procedure only treats the cancerous parts of the prostate, similar to how removing a tumor can be done for breast cancer.

Photodynamic therapy is one of many individual options. For example, the medical center https://www.medicaltourisrael.com/?p=320 in Tel Aviv, in addition to the described method, has a wide range of the latest prostate cancer treatment options, including: radical prostatectomy with a Da Vinci robot, brachytherapy, external radiation therapy, cryotherapy and high intensity focused ultrasound (HIFU).

Recommendations for the use of photodynamic therapy are determined by the results of the biopsy and advanced imaging techniques. Some patients choose active surveillance, also known as watchful waiting. But targeted vascular photodynamic therapy for localized prostate cancer offers a better alternative. During the procedure, laser fibers are placed over the prostate where cancer cells have been identified.

The patient is injected intravenously with a photosensitizing drug called WST11, which circulates throughout the blood for ten minutes. Then, laser fibers in the area of ​​the prostate tumor activate the drug with light of a specific wavelength for twenty minutes. When light comes into contact with the drug, it destroys the blood vessels around the tumor, paralyzing the cancer's blood supply. After treatment for prostate cancer, patients undergo preventive diagnostics during the year: PSA levels are measured, MRI is performed, and a biopsy is performed every six months.

Photodynamic therapy is the activation of light-sensitive compounds in tissues to produce the desired therapeutic effect, including apoptosis and necrosis, and is also a method effectively used in various benign and malignant conditions to ablate tissue.

Tukada ® WST-09 and soluble Tukada WST-11, two derivatives of bacteriochlorophyll - photosynthetic pigment (Bchl), represent a new generation of photosensitizers. Studies of the mechanism of action, optimization of treatment parameters and a number of promising clinical procedures show great promise for this class of therapeutic agents in the treatment of human malignant tumors.

(APZH) is the most common disease of the genitourinary system of men of elderly and senile age. The social significance and urgency of this problem is emphasized by demographic studies, which testify to a significant increase in the world's population over the age of 60, the pace of which significantly outpaces the growth of the population as a whole. Clinically, APJ is manifested by symptoms from the lower urinary tract, which significantly reduces the quality of life of patients. Clinical manifestations of APZh, according to F. Schroder and I. Altwein, occur in 34% of men aged 40–50 years, in 67% of men aged 51 years - 60 years, in 77% of men aged 61 years - 70 years and 83% of men over the age of 70.

Treatment of patients with APZh is an important task of modern urology due to the prevalence of the disease and the unresolved many issues of its therapy. Drug therapy occupies an important place in the treatment of patients with AP and is based on the results of the latest studies of the pathogenesis of this disease. Despite this, the mechanisms of action of some drugs are not well understood. For drug treatment of patients with APZH, 5-α-reductase inhibitors, α1-adrenergic receptor blockers, polyene antibiotics, antiandrogens, preparations of plant and biological origin are used. However, many fundamental issues of drug therapy in patients with APZ still need further study. The mechanisms of action of some drugs have not been sufficiently studied, there are no specific indications for the use of these drugs, the criteria indicating the effectiveness of drug therapy have not been clarified, and there are disagreements regarding the timing of drug treatment.

One of the minimally invasive methods of treating prostate adenoma is photodynamic therapy. Photodynamic therapy (PDT) is a technology based on a chemical reaction catalyzed by oxygen activated by laser radiation energy and a photosensitizer. Over the past decades, photodynamic therapy has taken an increasingly strong position in the treatment of patients suffering from malignant neoplasms and some non-tumor diseases (Dougherty T.J. et al., 1980; Cortese D.A. et al., 1997; Lightdale C.J. et al., 1995). Over the past century, experts have repeatedly shown interest in the possibility of using photodynamic therapy in urological patients, in particular, with bladder cancer and prostate adenoma. The widespread use of PDT in urology was hampered by the high systemic and local toxicity of the applied photosensitizers (photofrin, photohem, photosan), as well as the imperfection of methods for conducting PDT (Uchibayashi T. et al., 1995; Nseyo U.O. et al., 1998;. Berger A.P., et al., 2003). The introduction of low-toxic photosensitizers such as photoditazine, photostim, radachlorin into practice has made it possible to use photodynamic therapy more widely in practical medicine.

The primary objectives of the study were:

• assessment of the dynamics of symptoms of benign prostatic hyperplasia according to the scale of the international system of total assessment of prostate diseases (IPSS-Q) against the background of a course of PDT;
• determining the severity of infravesical obstruction caused by prostate adenoma according to transrectal ultrasound, uroflowmetry, determining the volume of residual urine against the background of a course of PDT.

secondary target- assessment of the tolerability of the PDT course based on the analysis of registered adverse events and changes in laboratory parameters of clinical, biochemical blood tests and clinical urinalysis.

Materials and methods

The work is based on the results of the analysis of examination data and treatment of 42 patients with benign prostatic hyperplasia. The studies were carried out at the clinical base of the medical centers Alliance MedCo and Edis MedCo from 2006 to 2009. Examination of patients with BPH included: history taking, physical examinations, questionnaires using the International Prostatic Symptom Scale (IPSS), laboratory (clinical blood test, general urinalysis, biochemical blood test, PSA level determination in blood serum), instrumental (transrectal ultrasound examination of the prostate and seminal vesicles (TRUS), uroflowmetry (UFM), determination of the volume of residual urine). The follow-up period was 1,3,6 months.
The mean age of the patients was 56.13±3.2 years. The patients observed by us were prescribed a course of photodynamic therapy with the following indicators of the clinical course of the disease:

1. the sum of scores of symptoms of the disease according to the International IPSS scale averaged 16.42±3.25, with this indicator fluctuating from 7 to 24 points;
2. QOL life quality assessment index averaged 2.9±0.18;
3. the value of the maximum urine flow rate (Qmax) according to uroflowmetry was equal to 11.16±0.42 ml/s with this indicator fluctuating from 7 to 14 ml/s;
4. the amount of residual urine in the bladder averaged 48.16±2.86 ml, with this indicator fluctuating from 0 to 102 ml;
5. the volume of the prostate gland averaged 48.44±3.46 cm³ with this indicator fluctuating from 32.6 to 78.4 cm;
6. the level of prostate specific antigen (PSA) averaged 1.19±0.18 ng/ml, with this indicator fluctuating from 0.1 to 3.4 ng/ml.

Photodynamic therapy course

During the PDT sessions, an apparatus for photodynamic and quantum therapy was used. - "LAMI" (LLC "Polyronic", Russia) and photosensitizer radachlorin (registration number LS-001868) produced in the form of a sterile aqueous solution for intravenous administration. The PDT session was carried out 3 times a week every other day. Number of procedures 12.

results

As a result of the treatment, it turned out that all patients (n=42) with AP who completed the course of PDT noted a positive effect.
Table No. 1 shows the results of treatment of patients with APZh. By the end of treatment, all indicators of the clinical course of the disease had improved.
Thus, the average score of symptoms of the disease according to the International IPSS scale after 30 days of treatment decreased from 16.42±3.25 to 10.4±0.46 points, i.e. by 6.02 points, and after 90 days on the background of treatment - up to 10.02±0.64 points, i.e. by 6.4 points. 180 days after treatment, the level of symptomatology remained (10.02±0.64).
In patients with APZh, after the treatment, a statistically significant improvement in the quality of life was revealed. The average value of the quality of life by the 30th day of treatment decreased from 2.9±0.18; up to 2.6±0.6 points, and after 90 days of treatment - up to 2.4±0.42 points. The quality of life index remained at the same level (2.4±0.42 points) even after 180 days of treatment.

The maximum urine flow rate after 30 days of treatment increased from 11.16±0.42 ml/s to 13.66±0.62 ml/s, and after 90 days of therapy - up to 14.84±0.32 ml/s.
In patients with APZh, during treatment, a decrease in the amount of residual urine was noted. If before treatment the average value of residual urine volume was 48.16±2.86 ml, then after 30 days of treatment it was 24.42±4.6 ml, after 90 days of treatment it was 18.21±3.4 ml.
Against the background of treatment with organ preparations, the volume of the prostate gland significantly decreased. Before treatment - 48.44±3.46 cm3, by the 30th day of treatment 47.32±2.84 cm³, after 90 days of treatment (46.82±4.62).

Table number 1. Results of a course of PDT in patients with prostate adenoma.

None of the 42 patients with APJ observed by us had any adverse events during the treatment, which indicates good tolerability and safety of PDT.

conclusions

The conducted clinical study showed that a course of PDT with the use of a low-toxic photosensitizer radachlorin as a monotherapy for AP has a positive effect on both subjective and objective symptoms of AP. A course of PDT significantly reduces the clinical manifestations of the disease and improves the quality of life, reduces the severity of infravesical obstruction (according to uroflowmetry, determining the volume of residual urine). Against the background of treatment, a moderately pronounced decrease in the average volume of the prostate gland was also revealed.

Positive changes in the clinical course of the disease persist for 180 days after discontinuation of the course of PDT, which confirms the high assessment of efficiency in patients with AP.

Considering that no side effects were registered during the treatment, as well as statistically significant changes in clinical and laboratory parameters, we can state that this type of treatment was well tolerated.

The results obtained in the course of this study make it possible to recommend a course of PDT for use as monotherapy for APZh with moderate infravesical obstruction in patients of all age groups, regardless of the presence of concomitant diseases.

Literature:

1. Photodynamic therapy in urology // Laser medicine. - 2006. - T.10. Issue 3.– P. 58–61. (Sorokaty A.E., Yagudaev D.M., Markova M.V.)
2. Modern view on the mechanism of photodynamic therapy. Photosensitizers and their bioavailability // Urology -2006. - No. 5 - P. 94-98. (Yagudaev D.M., Sorokaty A.E., Geinits A.V., Trukhmanov R.S.)
3. Photodynamic therapy. The history of the creation of the method and its mechanisms // Laser medicine. - 2007. - T.11. Issue 3–pp.42–46. (Geinits A.V., Sorokaty A.E., Yagudaev D.M., Trukhmanov R.S.)
4. Photodynamic therapy of prostate adenoma // Urology. -2007. - No. 4 - P. 34-37. (Yagudaev D.M., Sorokaty A.E., Martov A.G., Geinits A.V., Markova M.V.)
5. The method of photodynamic therapy of benign prostatic hyperplasia // Russian Authors' Society, certificate of deposit and registration of an intellectual property object - manuscript of scientific work No. 9754 dated March 09, 2006. (Yagudaev D.M., Sorokaty A.E.)
6. Lopatkin N.A. (ed.). Rational pharmacotherapy in urology - M., 2006; 258.
7. Emberton M., Andriole G., De la Rosette I. et al. BPH. A progressive disease of the aging male. Urology, 2003; 61:267–273.
8. Schroder F., Altwein I. Development of Benign Prostatic Hyperplasia. B book: Benign Prostatic Hyperplasia. A Diagnosis and Treatment Primer. Oxford, 1992. 31–50.
9. Tkachuk V.N., Al-Shukri S.Kh., Lukyanov A.E. Drug treatment of patients with benign prostatic hyperplasia. - SPb., 2000; 104 p.

In modern medical practice, there are certain standards for the treatment of prostate cancer.

As a rule, after the diagnosis of local prostate cancer is established, radical prostatectomy, brachytherapy, radiation and hormone therapy, and dynamic monitoring are offered as approved methods.

The goal of radical prostatectomy is to completely remove prostate tissue, often with regional pelvic lymph nodes, either by open or laparoscopic procedures.

Brachytherapy is the introduction of isotopes into cancer cells, which make the tumor tissue more sensitive to ionizing radiation, followed by irradiation.

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For prostate cancer that extends beyond the organ, in the presence of metastases, hormonal drugs are used for treatment aimed at suppressing the male hormone testosterone, as well as the use of cytostatic drugs.

Oncological diagnosis of prostate cancer is coded TNM, where:

• T - tumor - extent of the tumor
• N - nodulus - metastases to regional lymph nodes
• M - metastasis - separated metastases

T or the extent of the tumor has 5 options:

• T0 - no tumor detected
• T1 - local
• T2 - within the organ
• T3 - germinates the capsule
• T4 - grows into neighboring organs

N or metastasis to the lymph nodes has four options:

• N0 - lymph nodes are intact
• N1, 2, 3 - varying degrees of metastasis to regional lymph nodes

M has only 2 variants, M0 when there are no distant metastases, and M1 when they are.

There is also an Nx or Mx coding when there is not enough data to accurately determine the stage or diagnosis is difficult.

Treatment of prostate cancer with and without metastases has significant differences. It has been noted that after the removal of the main tumor, metastasis cells, if present, “raise their heads” and their development is more active than before the operation. Therefore, in the presence of metastases only in the regional lymph nodes during the operation, a total lymphadenectomy of all available regional lymph nodes is performed, followed by radiation or chemical exposure.

In the presence of distant metastases, and prostate cancer is characterized by bone metastasis, it is possible to use hormonal treatment, systemic chemotherapy in combination with or without surgical treatment.

• How to fight prostate cancer? With the involvement of all possible methods and achievements of modern medicine, under the supervision of a doctor and preferably in the early stages.
• How to relieve pain in prostate cancer? Relief of pain in prostate cancer is carried out with the help of narcotic and non-narcotic analgesics, according to the prescription of the attending physician.

Treatment of prostate cancer in an elderly man, especially in old age, presents serious difficulties:

• In the event that surgical treatment poses a serious threat to the patient's health or if he has other diseases with an unfavorable prognosis. These can be serious problems of the heart, blood vessels, decompensated heart failure, a disease of the central nervous system, such as a stroke, or other oncological diseases.
• If the patient's life expectancy is less than 5-10 years or the body is severely weakened. Given the slow development of this type of tumor, dynamic monitoring and palliative care are recommended for such a patient.

Radical prostatectomy, like other operations under general anesthesia, is not recommended for patients over the age of 70, but this recommendation requires an individual approach.

An inoperable tumor is considered to be characterized by symptoms of grade 4 prostate cancer, in the case when there is significant germination in neighboring organs and the presence of distant metastases. All palliative measures to slow down the growth of the neoplasm and maintain the functioning of the body come to the aid of such a patient.

How to Treat Prostate Cancer with Hormone Therapy

In the presence of widespread metastases, the question "how to treat prostate cancer" can be solved with hormone therapy. With the help of hormonal therapy, tumor cells are not eliminated, but their growth is significantly suppressed.

The fact is that one of the reasons for the development of prostate cancer may be a high content of testosterone in the blood, it also stimulates tumor growth. Its elimination of androgens from the body or blockade of receptors of cells sensitive to them has a positive effect and can slow down the growth and spread of the malignant process.

Treatment of prostate cancer in this direction is possible in various ways. In the last century, such a radical remedy as orchidopexy or removal of the testicles was often used.

Currently, hormonal therapy for prostate cancer is carried out mainly with the help of medications.

At the disposal of medicine there are the following groups of hormonal drugs for prostate cancer:

• Releasing hormone or releasing factor agonists that reduce testosterone production at the level of luteinizing hormone production in the pituitary gland. These are Zoladex, Lupon and Trelstar. The drugs are administered once a month. At the very beginning of taking releasing hormone agonists, there is a short-term testosterone surge, which requires the use of antiandrogens.
• Antiandrogens prevent the binding of testosterone and receptors of prostate and tumor cells, and therefore block its action. These are Nitulamide, Flutamide and others. Their use is associated with the risk of developing diabetes, there is an assumption about an increased risk of developing cardiovascular diseases and their complications.
• Estrogens or female sex hormones. They act as testosterone antagonists, are indicated in cases where antiandrogens do not work, and have a large number of side effects, one of which may be breast enlargement.

Hormone therapy for prostate cancer can be carried out continuously or in courses.

Currently, a scheme of intermittent hormone therapy has been developed, when drugs are taken for several months to a year. After that, under the control of PSA, they take a break and, when the PSA level rises, a new course of hormone therapy is started. According to observations, the number of complications with such therapy is less than with continuous use.

With a significant decrease in testosterone levels in the male body, symptoms of the so-called male menopause are observed - fatigue, anemia, memory impairment, hot flashes, weight gain with a decrease in muscle mass, impotence, cardiovascular diseases “bloom”.

In some cases, prostate tumor cells become insensitive to hormone therapy, or hormone-resistant, that is, during antiandrogen therapy and low testosterone levels, PSA levels continue to rise.

In such cases, the maximum antiandrogenic blockade, the abolition or replacement of antiandrogenic drugs, the addition of estrogens, the appointment of ketoconazole and other drugs that suppress adrenaline, as well as chemotherapy, immunotherapeutic methods are carried out.

Hormonal drugs for prostate cancer have a specific elimination time, and while the releasing hormone agonist can be administered once a month, androgenic and estrogenic drugs have a relatively short duration of action and can be administered daily. After stopping the use of hormonal drugs, their elimination from the body is carried out gradually.

How to treat prostate cancer with chemotherapy drugs

According to international recommendations on how to treat prostate cancer in complex therapy and in the presence of metastases, chemotherapy is supposed to be used.

Chemotherapy involves the use of cytotoxic drugs that block the growth and development of rapidly dividing cells, which include undifferentiated malignant cells.

Chemotherapy is especially indicated for inoperable cancer, bone metastases, and hormone therapy failure.

Chemotherapy drugs for prostate cancer have different mechanisms of action.

• Mitoxantone and Vinblastine are antitumor antibiotics, they inhibit the growth, reproduction and development of growing cells, primarily cancer cells, but along with them goes to hair and red bone marrow.
• Doxorubicin - connects to the DNA of cells and blocks protein synthesis in them.
• A group of Taxanes, Paclitaxel, Docetcasel, which prevent the division of tumor cells by affecting their microtubules.
• Estramustine and Etaposid are also used.

All chemotherapy drugs are prescribed in several courses, under the control of PSA and blood tests. Courses can be repeated after three weeks in the absence of pronounced side effects and in the presence of stable remission.

Chemotherapy for prostate cancer has significant side effects on the organs and systems in which fast-growing cells are present, these are the epithelium of the skin and hair, the hematopoietic system and the mucous membranes of the gastrointestinal tract.

Fighting prostate cancer with testicle removal (castration)

The fight against prostate cancer in the past, in the absence of modern medicines and technology, was much more difficult. In the middle of the last century, doctors used the most radical and reliable way to lower testosterone levels, namely castration or orchidectomy.

Castration for prostate cancer was performed to remove the testicles as glands that produce testosterone. However, it turned out that its effectiveness is low, since it was not possible to achieve the complete disappearance of testosterone from the body. It is also necessary to take into account the fact that in 30% of men with prostate cancer, the tumor is resistant to testosterone. In addition, the man received psychological trauma and a male menopause clinic in addition to his illness.

Is the penis removed for prostate cancer? The penis does not contain testosterone-producing glands, so it will not need to be removed.

In the elderly, the removal of the testicles for prostate cancer may not have a special effect due to involutive changes and the extinction of the hormonal function of the testicles.

At present, this method of treatment is rather of historical significance.

Breakthrough in prostate cancer therapy: revolutionary cancer treatment in Israel, Russia, Germany

A patient can receive help for prostate cancer either at the expense of state medicine, or for a fee in any clinic both at home and abroad.

Treatment of prostate cancer in Israel is also carried out for foreign citizens, using both surgical and medical methods, as well as with the use of innovations.

As well as the treatment of prostate cancer in Germany, surgical treatment in leading centers in Israel and Korea can be performed using robot-assisted prostatectomy. This technique appeared as a result of improvements in laparoscopic surgery. Its essence is that the surgeon is assisted by the DaVinci robot, equipped with all the necessary tools.

Treatment of prostate cancer in Israel, Germany and other countries is currently available to citizens of the former CIS at quite reasonable prices. At the same time, the price of treatment does not include accommodation of relatives and transportation to the clinic and back.

Treatment of prostate cancer in Russia is carried out according to the standards of medical care, which include prostatectomy, chemotherapy, hormone therapy and rehabilitation after interventions. Large medical clinics in Russia, Ukraine and Kazakhstan also perform robot-assisted surgeries.

• In which city of Russia is prostate cancer treated? Qualified assistance in the treatment of prostate cancer can be obtained at any specialized center or urological clinic in Russia.
• Where in Moscow to treat prostate cancer? In Moscow, prostate cancer is treated by urological, surgical and oncological departments of hospitals, as well as specialized centers.

Research into new methods of cancer treatment is currently being carried out in leading scientific centers.

Some time ago, scientists announced a breakthrough in the treatment of prostate cancer. Speech in this news was about the directed action of high-frequency ultrasound on the tumor. A focused high-intensity beam of ultrasound is directed to the tumor tissue, which destroys cancer cells, while healthy cells remain unaffected.

There is also information about the detection of a specific protein in cancer cells and the synthesis of a drug that affects only it. This method was called a revolutionary treatment for prostate cancer, however, there are no reviews from specialists and reliable data on the results of clinical trials to date.

Alternative treatment of prostate cancer: a list of new methods

It is possible to answer whether prostate cancer is treated only taking into account the stage of the disease. Prospects are more favorable in the early stages, the absence of metastases and the good condition of the body as a whole.

In addition to the methods that are proven effective and are part of the standard of care, there are many more treatments for prostate cancer that are at the stage of experimental use, are additional methods, or may be a gesture of desperation.

Ozone therapy as a treatment for prostate cancer

In the treatment of cancer, ozone therapy is used as a method that accompanies the main treatment. Its goal is to reduce the severity of side effects from chemotherapy and hormone therapy, to improve the general condition of the body.

Ozone therapy is used in the form of insufflations - the introduction of a gas mixture into the intestines, in the form of autohemotherapy, microinjections, gassing of cavities and sinuses.

Ozone therapy for prostate cancer may be contraindicated in ozone intolerance, stroke, coagulation disorders, thrombocytopenia and bleeding.

A desperate and radical method, for example, may be an orchiectomy for prostate cancer.

The following methods can serve as innovative developments:

• Radiotherapy for prostate cancer is now represented not only by transcutaneous irradiation, but also by brachytherapy, as well as three-dimensional conformal radiotherapy - irradiation of an irregularly shaped object with a calculated radiation dose and saving surrounding tissues.
• Photodynamic therapy for prostate cancer involves the administration of a sensitizing agent that accumulates in cancer cells and increases their sensitivity to a laser, followed by targeted irradiation with this laser.
• Laser therapy for prostate cancer shows good results in the early stages. At the same stages, a green laser can be used to vaporize or vaporize the tumor.
• Cryotherapy for prostate cancer consists in local freezing of the tumor, refers to minimally invasive surgical measures. The results of cryotherapy for prostate cancer depend on the stage. This method is most effective at an early stage and without metastases, as well as with a benign variant - adenoma.
• There is also an alternative treatment for prostate cancer, which is offered in abundance by Tibetan medicine clinics, traditional healers and on forums and Internet sites. These are also folk methods such as herbal treatment, fasting, psychology and so on.

Despite the fact that prostate cancer is life threatening, the patient should not develop a panic and desire to try all the new treatments for prostate cancer. The cure is possible in the early stages, in the later stages it is possible to maintain a satisfactory quality of life for the patient.