The castration level of testosterone and hormonal resistance of prostate cancer in androgen deprivation therapy

Abstract

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.