Interesujący artykuł z 2015 roku analizujący zasadność kontynuowania deprywacji androgenowej po osiągnięciu hormonooporności.
Do we need to continue androgen deprivation therapy?
21 March 2015 Prof. Dr. Axel Merseburger
The European Association of Urology (EAU) guideline clearly states that patients with metastatic castrateresistant prostate cancer (mCRPC) should indefinitely continue androgen deprivation therapy (ADT); this recommendation applies to metastatic CRPC (mCRPC) and non-metastatic CRPC (nmCRPC)1. Other guidelines, such as that from the American Urological Association (AUA)2 and the National Comprehensive Cancer Network (NCCN)3, likewise mention the need to maintain ADT when mCRPC develops.
As support, all randomised controlled trials of the many newer agents for mCRPC, including abiraterone, enzalutamide, sipuleucel-T, radium 223 and cabazitaxel4-10 all had continuation of ADT and mainstay of castration levels of testosterone (<50 ng/ dl) as an inclusion criterion. However, this does not prove the value of ADT in this setting. In metastatic disease, while hormonal treatment improves symptoms11, there is no conclusive prospective evidence that lowering testosterone levels improves life expectancy12. With the event of evaluating novel substances in the setting of non-metastatic CRPC, the value of combining ADT with tertiary hormonal manipulation (e.g. Enzalutamide, Abiraterone, ARN-509, etc.) has not been investigated.
Sparse evidence
The evidence for continuing ADT in metastatic prostate cancer is based on sparse literature. A single study demonstrated that androgen priming in a small group of patients (n=85) using chemotherapy regimens that are now outdated altered the prognosis13.
However, it is becoming clear that within the prostate and prostate tumour microenvironment androgen activity continues even when serum testosterone levels are suppressed by ADT14, and intracrine androgen synthesis is sufficient to activate androgen receptor target genes15. Adaptive alterations include alternative androgen synthesis pathways, and androgen receptor overexpression, mutation and splice variations16. Furthermore, many mechanisms that may confer castration-resistance still require, or are enhanced by, the presence of androgens or androgen receptor ligands. Together these observations suggest that treatment combinations that include ADT and suppress intracrine and systemic androgen contributions are required in CRPC.
The presentation will cover the evidence and rationale for continuing ADT in CRPC when other treatments are initiated, and aim to provide clear statements on this issue.[Artykuł w dalszej części omawia uzasadnienia podawane dla kontynuacji ADT przy aleczeniu abirateronem, enzalutamidem i chemioterapią. Ważne są odniesienia do badań klinicznych.]
http://uroweb.org/do-we-need-to-continu ... n-therapy/