Neoadjuvant therapy for prostate cancer

Neoadjuvant therapy for prostate cancer

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What is the prostate gland? Benign prostatic hyperplasia Prostate Cancer Other oncourological diseases Other diseases of the genitourinary syste

TREATMENT OF PROSTATE DISEASES IN THE CLINIC OF UROLOGY OF THE MILITARY MEDICAL ACADEMY >>>

Influence of neoadjuvant hormone therapy on PSA, prostate volume, stage T, tumor percentage at the resection margin and survival. Currently, there is a new surge of interest in the possibilities of neoadjuvant hormone therapy before radical prostatectomy in patients with local (T1-T2) and locally advanced (T3) Prostate cancer. Unfortunately, in patients with T3, preoperative hormonal therapy only reduces the size of the prostate and does not provide a survival advantage (Oesterling et al., 1993).

The results of neoadjuvant treatment in stage T2 are much more optimistic. The main advantage is a significant reduction in the incidence of tumor at the resection margin. In five randomized clinical trials, the use of neoadjuvant hormonal therapy reduced the incidence of a tumor at the incision margin from an average of 47 to 22%, reduced preoperative PSA levels by 96%, prostate volume by 34% (Labrie et al., 1993, Soloway et al. , 1995). However, such a dramatic decrease in the volume of the prostate does not mean a corresponding decrease in the stage (T) of the disease. Due to insufficient follow-up, it remains unclear whether neoadjuvant hormone therapy provides a survival advantage. Preliminary results suggest that it has no effect in increasing the disease-free course.

Influence of neoadjuvant hormone therapy on the degree of tumor differentiation (G). This aspect is the most controversial. Changes in the epithelium of the prostate under the influence of hormone therapy include marked atrophy of the glandular epithelium with an increase in the fibromuscular component, nuclear pyknosis, vacuolization of the cytoplasm of tumor cells, and squamous metaplasia of the epithelium of the ducts. Decreasing G, i.e. an increase in the degree of differentiation, described by various authors (Feguson J. et al., 1994). Oddly enough, other publications say otherwise, and even increase G! (Smith D.M. Murphy, 1994). This phenomenon can be explained by selective apoptosis of the most hormonally dependent (well differentiated) cells. At the same time, low-differentiated cells begin to predominate in the tissue, which leads to an increase in the Gleason sum. That is why the Gleason sum is not indicative and reliable after neoadjuvant therapy. The question of the advisability of longer neoadjuvant therapy in patients with high G compared with patients with low G remains open.

The effect of neoadjuvant hormone therapy on operability. Hormone therapy does not make the surgeon's work easier and does not reduce blood loss as it was supposed to. The resulting fibrosis in periprostatic tissues makes it much more difficult to find the correct layer and landmarks for anatomical mobilization of the prostate (Schulman C.C. et al., 1996). It also increases the risk of damage to the rectum. To date, neoadjuvant hormonal therapy should not precede most radical prostatectomy and seems to be the most acceptable for patients with suspected distant metastases, as a method that allows in some cases to clarify the extent of the disease, and, at the same time, not to leave the patient without treatment.< /p>

05.10.2012 HIGH-TECH SURGICAL CARE FOR CANCER PATIENTS

Surgical treatment of oncological diseases according to QUOTAS read

March 12, 2011 prostate biopsy.

An elevated PSA level (>2.5ng/ml) may indicate PROSTATE CANCER. read

27.04.2015 Good afternoon! Please answer the following question: does prostate cancer always go through the stage of PIN vs and PIN ns.

04/17/2015To question 996. Hello. Thanks for the answer. Please specify: 4 months. took bicalutamide 150.psa dropped to.

April 17, 2015To question 996. Hello. Thanks for the answer. Please clarify: I took bicalutamide 150 for 4 months. Psa dropped to.

19.05.2015 Free hormonal treatment for PROSTATE CANCER

Science program at the National Medical Radiological Research Center read

03.01.2015 High-tech care for ONCOLOGICAL PATIENTS

26.11.2014 OPEN DAY,

Dedicated to the diagnosis and prevention of malignant skin tumors.read

Hormonal therapy in combined treatment of prostate cancer

Prostate cancer (PC) is currently one of the most common types of malignant neoplasms in the world. In terms of incidence, prostate cancer ranks 1st in the United States and 2nd (after lung cancer) in Western Europe. At the same time, in terms of the growth rate of the incidence rate, prostate cancer is significantly ahead of tumors of other localizations. This is due to the widespread use in clinical practice of the test to determine the level of prostate specific antigen (PSA) in blood serum and multifocal transrectal prostate biopsy. Diagnosis of prostate cancer based on the determination of PSA led not only to an increase in the detection of patients, but also changed the structure of the distribution of patients according to the stages of the tumor process towards the predominance of earlier stages of the disease. In 23.3% of patients, metastatic prostate cancer is initially diagnosed.

One of the main types of treatment for PROSTATE CANCER is hormone therapy. At the stage of a generalized (metastatic) tumor process, hormone therapy is the leading and most effective treatment option, which allows achieving remission and stabilization of the disease in most patients. In localized (stage II) and locally advanced (stage III) prostate cancer, hormonal therapy can also be used as an independent method of treatment, but a more common treatment option is the use of endocrine effects in combination with surgery or radiation therapy.

Hormone therapy can be performed before surgery or radiation treatment, in which case it is commonly called neoadjuvant. When hormonal treatment is given after surgery or radiation, the therapy is referred to as adjuvant therapy. Currently, several different modes and schemes of combined treatment of prostate cancer with the use of hormonal therapy are used in clinical practice. The main goal of neoadjuvant and adjuvant hormonal therapy is to increase the overall and relapse-free survival of patients with prostate cancer, but hormone therapy solves different problems in different clinical situations.

Neoadjuvant hormone therapy before surgical treatment of prostate cancer

The most radical treatment for patients with intracapsular prostate cancer (T1-T2N0M0) and some patients with extracapsular tumor invasion (T3aN0M0) is radical prostatectomy (RP). surgical treatment does not lead to a large number of complications and provides high rates of overall and tumor-specific survival of patients. However, the difficulties of preoperative assessment of the degree of prevalence of prostate tumors and, accordingly, the clinical stage of prostate cancer lead to underdiagnosis of the prevalence of the process at the preoperative stage and, as a result, to a decrease in surgical radicalism.

According to the Mayo Clinic, which has the experience of several thousand RPs, in almost half of patients with clinically localized PCa, postoperative morphological examination revealed invasive growth in the paraprostatic tissue, germination in the seminal vesicles, or metastases in the pelvic lymph nodes. The increase in the number of non-radical operations is also facilitated by the surgeon's desire to achieve good functional results and, in this regard, the use of nerve-sparing (to maintain potency) and urethra-sparing (to improve the function of voluntary urination) techniques while underestimating the possibility of extracapsular spread of the tumor. Thus, according to various surgeons, the number of operations accompanied by the presence of a tumor along the resection line is 0-71% (average 28%).

In the analysis of surgical pathomorphological material after 1,088 RPs performed at the Mayo Clinic in patients with clinical stage T3 (tumor prolapse beyond the prostate capsule), the presence of tumor growth along the resection line was detected in 537 (49%) patients, and in 326 (30%) of patients found metastases in the regional lymph nodes. The method of neoadjuvant (preoperative) hormonal therapy was proposed in order to increase the radicalism of surgical intervention, reduce the number of relapses and, accordingly, to improve relapse-free survival. As early as 1944, Vallet proposed bilateral orchidectomy before perineal RP. Subsequently, data were published on the increase in 10- and 15-year survival rates in patients with locally advanced PCa who underwent surgical castration before RP. A pronounced decrease in tumor size and inhibition of tumor growth due to apoptosis (programmed death) of malignant cells as a result of neoadjuvant hormone therapy has been demonstrated in a number of experimental studies on transplanted tumors in mice.

But bilateral orchidectomy and estrogen therapy have not found wide use in the clinic as options for neoadjuvant hormone therapy due to a significant number of side effects.The method of preoperative hormone therapy began to develop most intensively after the use of LHRH agonists (Zoladex, leuprolide) and non-steroidal antiandrogens (Casodex, Flutamide) in clinical practice, which were used mainly in the combined (maximum) androgen blockade mode.

In a study by the Canadian group Labrie (1993), the use of a combined androgen blockade for 3 months led to a decrease in the incidence of tumor growth along the resection line to 13% compared with 38% in the group of patients who underwent only surgical treatment. Maximum androgen blockade has been used as neoadjuvant hormonal therapy and in other studies, which also showed a significant decrease in the frequency of non-radical operations in patients receiving neoadjuvant hormonal therapy (Table 1).

Table 1. Tumor detection rate at the resection line (%) in studies of neoadjuvant hormone therapy

In order to increase the effectiveness of preoperative hormone therapy, several methods are proposed, the main of which is to increase the duration of the course of hormonal treatment. Instead of the traditional 3-month course, it is proposed to carry out androgen blockade for 8 and 12 months. A number of authors consider it expedient to carry out hormonal therapy until the PSA level decreases as much as possible. However, it should be remembered that the lengthening of the preoperative period always carries the risk of progression of the tumor process, despite hormonal effects.

Another possible option to improve the results of combined treatment is the use of new hormonal therapy regimens, in particular antiandrogen monotherapy. Currently, in the Department of Oncourology, Moscow Research Institute of P.A. Preliminary results show that treatment with Casodex 150 mg results in an 86.1% reduction in PSA and a 44% reduction in prostate volume. The frequency of biochemical progression within 6-18 months after RP is 33.3% in the group of patients treated with Casodex and 54.6% in the surgical treatment group.

Adjuvant hormone therapy after surgical treatment of prostate cancer

Despite the fact that most patients with clinically localized (intracapsular) PCa achieve a complete cure of the disease as a result of surgery, 30% of patients after RP develop a recurrence of the disease. Initially, as a rule, these patients develop a biochemical relapse - (an increase in serum PSA levels) without signs of local relapse or generalization. At this stage, there are microscopic groups of PCa cells in the patient's body that cannot be detected by existing diagnostic methods.

The development of PSA progression can reflect both local recurrence of the disease and dissemination of tumor cells along the lymphatic tracts and internal organs. Conducting adjuvant hormonal treatment is most appropriate at this stage of the disease, since the effectiveness of therapy is higher with a small tumor mass. In addition, with minimal manifestations of the disease, the general condition of the patient remains good, which makes it possible to prescribe adequate doses and treatment regimens.

Adjuvant hormonal therapy after RP is prescribed mainly when tumor invasion beyond the prostate capsule, tumor growth along the resection line, or metastases in the pelvic lymph nodes is detected. To date, several large studies have been conducted that show the advantage of immediate adjuvant hormonal therapy over follow-up after RP. Patients who received immediate hormonal therapy were much less likely to develop such complications of prostate cancer as pain in metastatic foci, infravesical obstruction requiring transurethral resection of the prostate, pathological fractures, and spinal cord compression. In a special study on the use of postoperative hormone therapy in patients without lymph node metastases, recurrence-free survival for 5 years was recorded 25.2% more often. Most often, adjuvant hormone therapy is prescribed to patients who have metastatic lesions of the pelvic lymph nodes. The ECOG study demonstrated a statistically significant increase in overall survival during adjuvant treatment after RP in case of detection of metastases in the lymph nodes. PCa recurrence within 7 years after surgery was diagnosed only in 14.9% of patients who received immediate postoperative hormone therapy and in 89.4% of patients who have not received adjuvant treatment.

In the framework of the EPC (Early Prostate Cancer) program, a large study was conducted to evaluate the effectiveness of adjuvant hormone therapy (included 8,013 patients). Patients after local treatment (RP, radiation therapy or observation) were prescribed hormonal therapy with casodex at a dose of 150 mg, the control group received placebo.

After 3 years of follow-up, a significant reduction in the risk of prostate cancer progression (by 42%) and the risk of bone metastases (by 33%) was found in the group of patients treated with Casodex. It was also noted that the reduction in the risk of disease progression with the appointment of Casodex 150 mg is especially pronounced in the subgroup of patients with lymphogenous metastases.

Neoadjuvant hormone therapy before radiation therapy for prostate cancer

External radiation therapy according to a radical program and interstitial radiation therapy (brachytherapy), along with surgical treatment, are the main methods of treatment for localized and locally advanced PCa. The effectiveness of radiation therapy depends to a large extent on the dose of radiation delivered to the prostate gland. Numerous studies have shown that the best treatment results are achieved with a radiation dose of 70 Gy or more.

However, an increase in the dose of radiation therapy leads to an increase in the frequency and severity of toxic side effects from the surrounding organs, primarily the bladder and rectum. Conducting neoadjuvant hormone therapy before remote irradiation allows you to reduce the volume of the prostate gland and, accordingly, reduce the volume of surrounding tissues that fall into the irradiation zone. So, after 3 months of neoadjuvant therapy with Zoladex, the volume of the prostate gland decreases by 37%, and the radiation exposure to the bladder and rectum decreases by 46 and 18%, respectively. a higher dose of radiation, which leads to an increase in the effectiveness of radiation treatment. In a large randomized study, it was shown that local recurrence within 8 years after radiation therapy for localized and locally advanced forms of PCa developed in 37% of patients receiving neoadjuvant hormone therapy according to the maximum androgen blockade regimen (zoladex and flutamide), and in 49% of patients who have not received neoadjuvant hormone therapy. Survival of patients in the combined treatment group was also higher, but the differences were not statistically significant.

In another study, prostate biopsy was performed in patients with prostate cancer 2 years after the end of external beam radiation therapy. Residual tumor in the biopsy material was detected in 29% of patients who underwent neoadjuvant therapy according to the maximum androgen blockade regimen for 3 months before irradiation, and in 69% of patients who did not receive hormonal treatment. Often, neoadjuvant hormone therapy to reduce the volume of the prostate gland is prescribed before brachytherapy, since effective implantation of radioactive seeds is possible with a prostate volume not exceeding 50-60 cubic meters. see

Adjuvant hormone therapy after radiation therapy for prostate cancer

Hormonal therapy during and after the end of radiation therapy also improves the results of treatment of patients with prostate cancer. A large study including 977 patients compared the efficacy of self-supporting external beam radiation therapy for PCa and radiation with subsequent adjuvant therapy with zoladex throughout the patient's life. Adjuvant hormonal therapy resulted in an increase in recurrence-free survival up to 60% compared to 44% in the radiation treatment group alone and a decrease in the incidence of biochemical recurrence of prostate cancer from 53% to 20% (with a mean follow-up of 4.5 years).

Adjuvant hormone therapy proved to be the most effective in a subgroup of patients with poor prognostic factors: pronounced tumor spread beyond the capsule and to surrounding organs and a low degree of histological differentiation of prostate cancer.

In another study by the European Cancer Research Group, zoladex therapy was administered for 3 years after external beam radiation therapy for locally advanced PCa. The overall 5-year survival rate of patients who received adjuvant hormonal therapy significantly exceeded the survival rate in the group of patients who received only radiation, and hormone therapy was prescribed for disease recurrence (79 and 62%, respectively). In addition, the disease-free survival rate was also significantly higher in the adjuvant group (85%) compared to the radiotherapy group (48%). The mean duration of relapse-free course was 6.6 years in the combined treatment group and 4.4 years in the group of patients who did not receive adjuvant hormonal treatment. less than 6 months does not improve the results of treatment. In recent years, regimens of intermittent (intermittent) hormone therapy have been used in clinical practice.Some studies have shown the same effectiveness of adjuvant intermittent and continuous hormone therapy after radiation or surgical treatment of prostate cancer, but the number of patients and the follow-up period are small, so the question of the possibility of intermittent hormone therapy with adjuvant purpose needs further study.

Thus, neoadjuvant and adjuvant hormonal therapy with the use of modern effective drugs can significantly improve the results of treatment of patients with prostate cancer.

Author: candidate of medical sciences B.Ya. Alekseev The material is taken from the journal Together Against Cancer, 3, 2004.

Neoadjuvant chemohormonal therapy and radical prostatectomy in a patient with lymphogenous disseminated prostate cance

Abstract of the scientific article on medicine and healthcare, author of scientific work - Nyushko K.M., Ustinova T.V., Paichadze A.A., Alekseev B.Ya., Krasheninnikov A.A., Gevorgyan G.S. , Bolotina L.V., Kalpinsky A.S., Vorobyov N.V., Kaprin A.D.

Prostate cancer (PC) is currently one of the most common malignant neoplasms in men. Radical prostatectomy is the most commonly used therapy in patients with localized PCa. The expediency of surgical treatment of locally advanced and lymphogenous disseminated forms of prostate cancer remains controversial, since the likelihood of non-radical intervention increases significantly and the risk of disease progression increases. At the same time, interest in surgical treatment in patients with PCa at a high risk of progression, including those with lymphogenous metastases, has recently increased significantly. There are a growing number of studies demonstrating improved survival rates in patients with high-risk PCa, including those with distant metastases, who underwent radical prostatectomy and lymphadenectomy, compared with a cohort of patients who received drug therapy alone. In addition to studies evaluating the effectiveness of neoadjuvant therapy before surgery in patients with high-risk localized or locally advanced PCa, there are also studies considering this option in patients with PCa with lymphogenous metastases. The article presents the results of a clinical observation demonstrating the high efficiency of a multimodal approach using neoadjuvant chemohormonal therapy followed by surgical treatment in a patient with metastatic lymphogenous disseminated prostate cancer.

Related topics of scientific papers in medicine and healthcare , author of scientific paper - Nyushko K.M., Ustinova T.V., Paichadze A.A., Alekseev B.Ya., Krasheninnikov A.A., Gevorgyan G.S. ., Bolotina L.V., Kalpinsky A.S., Vorobyov N.V., Kaprin A.D.,

Neoadjuvant chemohormonal therapy and radical prostatectomy in a patient with lymphogenic metastatic prostate cancer

Prostate cancer (PC) is now one of the most common malignancies among men. Radical prostatectomy is the most commonly used therapy option for patients with localized PC. The appropriateness of surgical treatment for locally advanced and lymphogenic metastatic PC remains controversial, as the probability of non-radical intervention increases significantly and the risk for disease progression becomes higher. At the same time, interest in surgical treatment in patients with PC at high risk of progression, including those with lymphogenic metastases has recently increased greatly. There are more and more studies demonstrating improved survival rates in patients with high-risk PC, including those with distant metastases, who have undergone radical prostatectomy and lymphadenectomy compared with a cohort of patients who have received only drug therapy In addition to the studies evaluating the efficiency of neoadjuvant therapy before surgery in patients with localized or locally advanced high-risk PC, there are also investigations considering this option in PC patients with lymphogenic metastases. The paper gives the results of a clinical observation that shows the high efficiency of a multimodal approach with neoadjuvant chemohormonal therapy , followed by surgical treatment in a patient with lymphogenic metastatic PC.

Text of the research paper on topic "Neoadjuvant chemohormonal therapy and radical prostatectomy in a patient with lymphogenous disseminated prostate cancer"

Neoadjuvant chemotherapy and radical therapy

Prostatectomy in a patient with lymphogenous disseminated prostate cancer

K.M. Nyushko1, T.V. Ustinova2, A.A. Paichadze1, B.Ya. Alekseev3, A.A. Krasheninnikov1, G.S. Gevorgyan1, L.V. Bolotina1, A.S. Kalpinsky1, N.V. Vorobyov1, A.D. Kaprin3

Moscow Research Institute of Oncology named after V.I. P.And

Prostate cancer (RPG) is currently one of the most common malignant neoplasms in men. Radical prostatectomy - the most frequently used method of therapy in patients with localized-cooled RLPG. The feasibility of surgical treatment of local and lymphogenic-disseminated Forms of RPG K remains controversial, as the likelihood of non-radical intervention is significantly increasing and the risk of progress-2 diseases of the disease is increasing. At the same time, interest in conducting surgical treatment in patients with RPGs with a high risk of progress-2 of the scenaries, including the presence of lymphogenic metastases, has recently increased significantly. There is more and more consequences that demonstrate the improvement of the survival rate of patients of high-risk RIC patients, including the presence of remote metastases, which was carried out by radical prostatectomy and lymphadenectomy, compared with the cohort of the patients who received only medicinal therapy. In addition to evaluating the effectiveness of neoadjuvant therapy to chi-d rurgical treatment in patients with localized or local RPP, there are also studies that consider this option in patients with RPP with the presence of lymphogenic metastases.

The article presents the results of clinical observation demonstrating the high efficiency of a multimodal approach using neoadjuvante chemogoronotherapy with the subsequent conduct of surgical treatment in a patient with metastatic lymphogenic-disseminated RPP.

Keywords: neoadjuvant chemogoronotherapy, surgical treatment of metastatic prostate cancer, combined chemogoronotherapy, docetaxel, Novotax

Neoadjuvant Chemohormonal Therapy and Radical Prostatectomy In A Patient With Lymphogenic Metastatic Prostate Cancer

K.m. NYUSHKO1, T. V. USTINOVA2, A.A. Paychadze1, B. Ya. Alekseev1, A.A. Krasheninnikov1, G.S. Gevorgyan1, L. V. BOLOTINA1,

A.s. Kalpinskiy1, N. V. Vorob EV1, A.D. Kaprin3

1p. A. Hertzen Moscow Oncology Research Institute - Branch Of The National Medical Research Radiological Center, Ministry of Health Of Russia; 3 2nd Botkinskiy Proezd, Moscow 125284, Russia;

2peoples Friendship University of Russia; Build. 5, 8podol Skoe Shosse, Moscow 115093, Russia;

3National Medical Research Radiological Center, Ministry of Health of Russia; 3 2nd Botkinskiy Proezd, Moscow 125284, Russia

Prostate Cancer (PC) Is Now One of the Most Common Malignancies AMONG MEN. Radical Prostatectomy Is The Most Commonly Used Therapy Option for Patients with Localized PC. The Appropriateness Of Surgical Treatment for Locally Advanced and Lymphogenic Metastatic PC Remains Controversial, As The Probability of Non-Radical Intervention Increases Significantly and The Risk for Disease Progression Becomes Higher. AT The Same Time, Interest In Surgical Treatment in Patients with PC At High Risk Of Progression, Including Those with Lymphogenic Metastases Has Recently Increased Greatly. There are more and more studies demonstrating improved survival rates in patients with high-risk PC, including those with distant metastases, who have undergone radical prostatectomy and lymphadenectomy compared with a cohort of patients who have received only drug therapy In addition to the studies evaluating the Efficiency of NEOADJUVANT THERAPY BEFORE SURGERY IN PATIENTS WITH LOCALIZED OR LOCALLY ADVANCED HIGH-RISK PC, THERE ARE ALSO INVESTIGATIONS CONSIDERING THIS OPTION IN PC PATIENTS WITH LYMPHOGENIC METASTASES. The Paper Gives The Results of a Clinical Observation That Shows The High Efficiency Of A Multimodal Approach with Neoadjuvant Chemohormonal Therapy, Followed by Surgical Treatment in A Patient with Lymphogenic Metastatic PC.

Key Words: Neoadjuvant Chemohormonal Therapy, Surgical Treatment for Metastatic Prostate Cancer, Combined Chemohormonal Therapy, DoCetaxel, Novotax

Prostate cancer (RPG) is currently one of the most common malignant neoplasms in men. RPG in persons under 40 years old is rare, in average the age of the disease is 50-70 years. In 2015, this figure was somewhat higher - 70.6 years). The standardized rapid incidence rate in 2015 per 100 thousand. At an average annual growth rate of 6.68% increase in the incidence of RPG from 2005 to 2015 reached 105.65% 1.

Basic methods of radical treatment of patients with RPG - radical prostatectomy (RPE) and radiation therapy. RPE is the most frequently used method for the treatment of patients with localized RPG. The feasibility of surgical interference with the local and distributed and lymphogenic-disseminated Forms of the Russian Academy of Sciences remains controversial, as the likelihood of a non-radical operation is significantly increasing and the risk of progression of the disease 2 increases.At the same time, interest in surgical treatment in patients with PCa at a high risk of progression, including those with lymphogenous metastases, has recently increased significantly. There are a growing number of studies demonstrating improved survival rates in patients with prostate cancer with distant metastases who underwent RP and lymphadenectomy compared with a cohort of patients who received drug therapy alone. For example, in a study by I.M. Thompson et al. showed a significant reduction in the risk of death from PCa in patients with lymphogenous and distant metastases who received surgical treatment compared with a subgroup of patients who underwent only castration therapy (hazard ratio 0.77; 95% confidence interval 0.53, locally 0.89 ; p 0.014) 3. In another study by SH Culp et al. and including 8185 patients with metastatic PCa from the SEER database, showed a significant benefit of topical treatment compared with hormone therapy alone. Thus, 5-year overall and tumor-specific survival in the group of patients who underwent surgical treatment was 67.4 and 75.8%, respectively, in the radiation treatment group - 52.6 and 61.3%, respectively, in the hormone therapy group - only 22.5 and 48.7%, respectively (p 20 ng/ml and/or Gleason score (Gleason index) 8-10), demonstrated a significant decrease in serum PSA and a decrease in prostate volume during neoadjuvant therapy with docetaxel 5 In a multicentre phase II study conducted by KN Chi et al., neoadjuvant CHT was evaluated in 72 patients with PCa at high risk for T3N0 progression and/or PSA level >20 ng/mL and/or Gleason score >7). The median follow-up was 42.7 months, PSA-free survival was achieved in 70% of patients, and a complete pathomorphological response was observed in 3% of cases. docetaxel in patients with prostate cancer of intermediate and high risk of progression (cT2c-T3a and / or PSA level >10 ng / ml and / or Gleason index >7). In addition, an improvement in OS and disease-free survival was demonstrated in the combination therapy group compared to the surgical treatment group. However, there were no statistically significant differences in overall and disease-free survival rates. The authors concluded that early use of CHT in patients with a low risk of recurrence is inappropriate, since it increases the time to surgery and is associated with the possible occurrence of side effects. Neoadjuvant treatment is justified only in patients with lymph node (LN) metastases and locally advanced PCa 7. In another clinical study by K. Fizazi et al. and included 413 patients with prostate cancer with a high risk of progression of T3-4N0-, T3-4N+ and / or PSA level >20 ng / ml and / or Gleason index >8), demonstrated significant advantages of combined CHT compared with hormonal therapy in monomode in terms of rates reducing PSA levels and improving PSA-free survival. Thus, in the group of patients treated with CHT, PSA-free survival was 62%, in the group of hormonal treatment - only 50% (p 0.017) 8.

In addition to studies evaluating the effectiveness of neoadjuvant therapy before surgical treatment in patients with high-risk localized or locally advanced PCa, there are

Also studies considering this option in patients with prostate cancer with the presence of lymphogenous metastases. So, A. J. Zurita et al. conducted a phase II study that included 26 patients with PCa with clinically detectable metastases in regional lymph nodes in the pelvic cavity >2 cm in diameter or at a very high risk of lymphogenous progression (Gleason index >8 and PSA level >25 ng / ml, cT3 and Gleason index >7 or ST4). All patients underwent CHT for 12 months (docetaxel and luteinizing hormone-releasing hormone (LHRH) analogue a bicalutamide). In case of a decrease in the level of PSA 10 years. Patients were randomized into 2 groups: monotherapy and neoadjuvant therapy followed by surgical treatment. By 2015, 780 patients were randomized. The study's primary endpoint of 3-year disease-free survival will be achieved by 2018. Patient follow-up is planned to be extended up to 15 years from randomization. The results of the study may help develop specific recommendations for neoadjuvant therapy in patients with lymphogenous disseminated prostate cancer.

Thus, today the view on the problem of treating prostate cancer with the presence of metastases in the lymph nodes has changed towards the use of an aggressive multi-modal approach using the most rational combinations among all available methods of exposure. The appointment of early HCG seems to be an extremely relevant direction and requires further research.

The article presents the results of a clinical observation demonstrating the high efficiency of a multimodal approach using neo-adjuvant CHT followed by surgical treatment in a patient with metastatic lymphogenous disseminated prostate cancer.

Patient Z., aged 57, was treated at the MNIOI them. P. A. Herzen from August 2016 to March 2017. From the anamnesis it is known that in July 2016, during examination at the place of residence, an increase in the PSA level to 262 ng/ml was noted. Performed transrectal biopsy of the prostate under the control of ultrasound (ultrasound). Histological examination revealed a picture of acinar adenocarcinoma, Gleason index 9 (5 + 4), occupying up to 70-90% of the biopsy area. At the place of residence, the patient was recommended to conduct independent androgen-deprivation hormone therapy, an injection of an LHRH analogue was performed. For additional examination and treatment in August 2016, the patient independently applied to the MNIOI. P.A. Herzen.

A comprehensive examination was performed aimed at staging the tumor process and including computed tomography (CT) of the chest, abdominal cavity and retroperitoneal space, ultrasound of the pelvic organs, transrectal ultrasound, magnetic resonance imaging of the pelvic organs and regional lymph nodes, osteoscintigraphy (OSG).

According to CT of the abdominal cavity and retroperitoneal space dated 02.08.2016, an increase in paracaval and paraaortic lymph nodes up to 15 x 20 x 28 mm was noted, single lymph nodes at the level of the right renal pedicle measuring 23 x 35 mm, at the level of the common right iliac arteries on the right, 20 x 33 mm in size, para-aortic at the level of the bifurcation, 31 x 17 mm in size ( 1). According to the results of MRI of the pelvic organs dated July 27, 2016, the prostate gland with a volume of 47 cm3, a tumor lesion of the seminal vesicles is determined (2). In the right iliac region and retroperitoneal space, numerous enlarged LNs with a maximum size of 2.5 x 3.3 x 3.0 cm are noted mainly at the level of the right iliac artery. not received. According to the results of CT scan of the chest

2. Magnetic resonance imaging of the pelvic organs before drug treatment: a tumor lesion of the seminal vesicles is determined (arrow)

Fig. 2. Pelvic magnetic resonance imaging prior to drug treatment: tumor lesion of the seminal vesicles (arrow)

As of August 2, 2016, no pathological changes were detected in the lungs.

Treatment tactics were developed at an interdisciplinary consultation with the participation of surgeons, radiation therapists and chemotherapists. Taking into account the prevalence of the oncological process, the data of the morphological study of the biopsy material, the level

PSA, as well as the young age of the patient and a healthy general condition, it is recommended at the 1st stage to conduct HCG with docetaxel (Novotax) at a dose of 75 mg / m2 intravenously every 3 weeks for 6 courses in combination with a daily dose of prednisolone at a dose of 10 mg/day against the background of castration therapy with LHRH analogues.

From August to December 2016, 6 courses of drug treatment were performed: docetaxel (Novotax) at a dose of 75 mg/m2 intravenously on day 1 of a 21-day cycle in combination with oral prednisolone 10 mg/day. Before each cytostatic infusion, a standard sedation with dexamethasone was performed. Hormonal therapy was performed with a depot form of an LHRH analog in the form of injections every 28 days. Before each course of drug therapy, the parameters of the general and biochemical blood tests were evaluated, and the PSA level was determined. In dynamics, the indicators of the general blood test were evaluated on the 3rd and 7th days of drug treatment in order to monitor the safety of therapy. It was possible to implement 6 courses of chemotherapy in full. The patient tolerated drug treatment without severe toxic reactions. The initial PSA level in August 2016 was 117.87 ng/ml (in the process of castration hormone therapy since July 2016), upon completion of treatment in February 2017 - 0.89 ng/ml. According to the instrumental methods of examination conducted after drug treatment, a picture of positive dynamics was noted in the form of a decrease in the size and number of retroperitoneal and iliac lymph nodes (3).A few secondarily altered LNs in the retroperitoneal space and small pelvis were identified: paracaval and paraaortic lymph nodes up to 1.7 x 0.9 cm in size, at the level of the common right and iliac arteries on the right and abdominal aortic bifurcations up to 1.6 x 1.1 cm in size, single iliac on the right, up to 1.2 x 0.9 cm. According to MRI of the pelvic organs, a pronounced positive trend was also noted in the form of a decrease in the tumor in the prostate gland and in size

3. Computed tomography of the abdominal cavity and retroperitoneal space after drug treatment: metastatically altered retroperitoneal lymph nodes are noted (arrow)

Fig. 3. Magnetic resonance imaging of the abdominal cavity and retroperitoneal space after drug treatment: metastatic lymph nodes (arrow) in the retro-peritoneal space

4. Computed tomography of the abdominal cavity and retroperitoneal space after drug treatment: reduction of metastatically altered retroperitoneal lymph nodes after drug treatment (arrow) 4. Magnetic resonance imaging of the abdominal cavity and retroperitoneal space after drug treatment: drug-induced changes in the metastatic lymph nodes (arrow) in the retroperitoneal space

Iliac LN ( 4). According to the results of chest CT scan dated 01/24/2017 and OSG dated 02/03/2017, there are no data on the presence of distant metastases.

The patient's condition was re-discussed at the consultation in the oncourology department. Taking into account the presence of pronounced positive dynamics according to the data of a comprehensive examination, the next stage of combined therapy is recommended to perform surgical treatment. On February 28, 2017, the patient underwent RP (standard retropubic approach) with extended pelvic and retroperitoneal lymphadenectomy (5-8), as well as extended pelvic and para-aortic lymphadenectomy: obturator, external, internal, common iliac and presacral tissue with lymph nodes on the right and left were removed , para-aortic tissue to the level of the renal vessels.

According to the results of a planned morphological study in all areas, including the apex in the right and left lobes of the prostate gland, acinar adenocarcinoma was registered with therapeutic grade II pathomorphosis, perineural growth, ingrowth into the capsule of the gland, exit into the adjacent fatty tissue along the anterior surface on the right. The prostatic part of the urethra and seminal vesicles on the right and left are intact. There is no tumor growth in the surgical margin of resection. In 21 out of 58 LNs studied, metastases of acinar adenocarcinoma with therapeutic pathomorphosis of the II degree, ingrowth into the capsule of nodes, extracapsular spread in some of them are determined.

The postoperative period in the patient proceeded without complications. Retroperitoneal drains

5. Pelvic lymphadenectomy and lymphadenectomy in the area of aortic bifurcation: 1 - inferior vena cava; 2 - right ureter 5. Pelvic lymphadenectomy and lymphadenectomy at the bifurcation of the aorta: 1 - inferior vena cava; 2 - right ureter

6. Type of surgical field after performing paracaval, inter-aortocaval and para-aortic lymphadenectomy: 1 - inferior vena cava; 2 - aorta; 3 - right common iliac artery; 4 - left common iliac artery; 5 - left ureter 6. View of the surgical field after paracaval, interartocaval, and paraaortic lymphadenectomy: 1 - inferior vena cava; 2 - aorta; 3 - right common iliac artery; 4 - left common iliac artery; 5 - left ureter

Media registration certificate El FS77-52970