ANDROGEN deprivation therapy (ADT) has been the cornerstone of treatment for advanced castration-sensitive prostate cancer (CSPC) for over fifty years. In recent years, the approach to treatment has evolved to include combinations of ADT with androgen receptor signalling inhibitors and docetaxel, leading to improved survival outcomes and establishing this intensification as the new standard for metastatic CSPC patients. Despite these advancements, ADT remains a primary treatment option for many patients in clinical practice.
ADT effectively suppresses testosterone production through the use of gonadotropin-releasing hormone (GnRH) antagonists or agonists. GnRH antagonists, such as degarelix or relugolix, bind directly to GnRH receptors, leading to their immediate inhibition. Conversely, GnRH agonists like leuprolide or goserelin bind to the receptors, resulting in their down-regulation. In cases where symptomatic bone metastases are present, combining GnRH agonists with antiandrogens such as bicalutamide is recommended to mitigate potential flare-up effects.
Traditional metrics for assessing treatment response, primarily reliant on prostate-specific antigen (PSA) levels, may not fully encapsulate the complexities of tumour behaviour under various treatment regimens. Therefore, there is a pressing need for innovative and precise evaluation methods. Some studies have utilised models based on PSA dynamics to measure cancer regression (d) and growth (g) rates, establishing a correlation between the g rate and overall survival in metastatic castration-resistant prostate cancer. However, comparative studies assessing these rates specifically in patients with CSPC treated with ADT are lacking.
Preliminary findings from recent research indicate that patients receiving combination therapy with GnRH agonists and bicalutamide exhibited higher regression and lower growth rates than those receiving GnRH antagonists alone. This suggests that the g rate could serve as a valuable prognostic indicator for treatment outcomes, including PSA progression-free survival (PSA-PFS) and overall survival (OS). Although further studies are warranted to validate these findings across larger and more diverse populations, incorporating g rate measurements into routine clinical practice may enhance treatment personalisation and prognostic accuracy for patients with advanced CSPC.
Reference
Blas L et al. Regression and growth rates in androgen deprivation therapy for advanced castration-sensitive prostate cancer. World J Urol. 2024;42(1):604.
