medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2020-20-100-108medsovet-5943Research ArticleОНКОУРОЛОГИЯONCOUROLOGYКастрационный уровень тестостерона и гормональная резистентность рака предстательной железы при андрогенной депривацииThe castration level of testosterone and hormonal resistance of prostate cancer in androgen deprivation therapyhttps://orcid.org/0000-0002-0945-2498РусаковИ. Г.RusakovI. G.

Русаков Игорь Георгиевич, доктор медицинских наук, профeccор, заместитель главного врача по онкологии

105077, Россия, Москва, ул. 11-я Парковая, д. 32

Igor G. Rusakov, Dr. of Sci. (Med.), Professor, Deputy Chief Physician on Oncology

32, 11ya Parkovaya St., Moscow, 105077, Russia

igorrusakov@mail.ruhttps://orcid.org/0000-0002-5160-925XГрицкевичА. А.GritskevichA. A.

Грицкевич Александр Анатольевич, доктор медицинских наук, старший научный сотрудник отделения урологии

117997, Россия, Москва, ул. Большая Серпуховская, д. 27

Alexander A. Gritskevich, Dr. of Sci. (Med.), the senior researcher of the Urology department

27, Bolshaya Serpukhovskaya St., Moscow, 117997, Russia

grekaa@mail.ruhttps://orcid.org/0000-0002-3646-1664БайтманТ. П.BaitmanT. P.

Байтман Татьяна Павловна, аспирант отделения урологии

117997, Россия, Москва, ул. Большая Серпуховская, д. 27

Tatiana P. Baitman, Graduate Student of the Urology department

27, Bolshaya Serpukhovskaya St., Moscow, 117997, Russia

bit.t@mail.ruhttps://orcid.org/0000-0002-6751-2399МишугинС. В.MishuginS. V.

Мишугин Сергей Владимирович, кандидат медицинских наук, заведующий отделением онкоурологии

105077, Россия, Москва, ул. 11-я Парковая, д. 32

Sergey V. Mishugin, Cand. of Sci. (Med.), Head of the Oncourological Department

32, 11ya Parkovaya St., Moscow, 105077, Russia

sergeymishugin@yandex.ruГородская клиническая больница им. Д.Д. ПлетневаРоссияCity Clinical Hospital D.D. PletnevaRussian FederationНациональный медицинский исследовательский центр хирургии им. А.В. ВишневскогоРоссияVishnevsky National Medical Research Center of SurgeryRussian Federation202019122020020100108Copyright © Русаков И.Г., Грицкевич А.А., Байтман Т.П., Мишугин С.В., 20202020Русаков И.Г., Грицкевич А.А., Байтман Т.П., Мишугин С.В.Rusakov I.G., Gritskevich A.A., Baitman T.P., Mishugin S.V.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/5943

В данной статье обсуждается влияние достижений в понимании механизмов развития рака предстательной железы (РПЖ) на определение и диагностику кастрационно-резистентного РПЖ (КРРПЖ), прогностические факторы прогрессирования РПЖ и стратегии лечения.

Более чувствительные анализы подтверждают, что при хирургической кастрации уровень сывороточного тестостерона (Т) снижается до < 20 нг/дл, а достижение Т < 20 нг/дл улучшает прогноз и увеличивает время до развития КРРПЖ. Регулярная оценка уровня Т позволяет понять, адекватно ли подавляется этот андроген в связи с потенциальным развитием КРРПЖ. Более совершенные методы визуализации и анализ биомаркеров позволяют раньше выявлять прогрессирование заболевания. Прогностически значимые факторы риска развития кастрационной резистентности включают балл по шкале Глисона, распространенность метастазов, наследственные факторы, такие как мутации генов, влияющих на амплификацию андрогеновых рецепторов (АР) или участвующих в репарации ДНК путем гомологичной рекомбинации, кинетику простат-специфического антигена (ПСА) и уровень биомаркеров. Сегодня варианты лечения КРРПЖ включают не только андроген-депривационную терапию (АДТ), но и терапию, которая блокирует синтез Т и/или подавляет активность АР. Перспективные направления включают терапию с использованием новых биологических мишеней, комбинаций лекарственных средств и персонифицированную терапию. Необходимо понимание различий фармакодинамики и фармакокинетики депо-форм препаратов для андрогендепривационной терапии, т к. эти показатели могут влиять на эффективность проводимой терапии.

Целью лечения распространенного РПЖ является увеличение времени до развития кастрационной резистентности и общей выживаемости больных. В связи с современным определением кастрационного уровня тестостерона и достижениями в понимании механизмов прогрессирования заболевания необходимо пересмотреть стратегии диагностики и лечения. АДТ, как основополагающий вектор лечения, необходимо продолжать даже при использовании новых методов лечения КРРПЖ.

This review is dedicated to the impact of modern achievements on the definition and diagnostics of castration-resistant prostate cancer (PCa) (CRPC), prognostic factors for its progression, and treatment strategies.

It was proven with new sensitive methods of diagnostics that surgical castration (CS) decreases serum testosterone (T) levels to < 20 ng/dL, while achieving T < 20 ng/dL improves outcomes and delays the development of CRPC. Regular assessment of the T level makes it possible to understand whether this androgen is adequately suppressed in the setting of potential progression of CRPC, given that late dosing may lead to an increase in T level. Improved imaging techniques and biomarker analysis enable early detection of disease progression. Prognostically significant risk factors for CRPC progression include Gleason score, the extent of metastatic spread, hereditary characteristics such as gene mutations affecting androgen receptor (AR) amplification or DNA repair deficiency mutations, prostate-specific antigen (PSA) kinetics, and biomarker levels. Today, treatment options for CRPC have gone beyond androgen deprivation therapy (ADT) to include therapy that blocks T-synthesis and/or suppresses its activity through various mechanisms. Future directions include therapies using new biological targets, drug combinations and personalized therapies. It is necessary to assess the possible reasons for the difference in the pharmacodynamics and pharmacokinetics of androgendeprivation drugs, to study the features of the processes of destruction of drugs under the action of endogenous enzymes and resorption in the subcutaneous or muscle depot, which may cause the resistance to therapy.

The aim of improved treatment and diagnostic options for PCa is to delay its progression to CRPC and to prolong patient survival. Rethinking of the castration concept and advances in understanding the biology of disease progression make it necessary to revise diagnostic and treatment strategies. ADT is a fundamental vector of treatment, and it should be continued even if some new ways of treatment for CRPC are introduced.

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The authors declare that there are no conflicts of interest present.