Analogues de la GnRH dans le traitement du cancer de la prostate

Abstract

Prostate cancer is currently the main indication of LH-RH analogs. This class, which in recent years has replaced diethylstilbestrol and surgical castration, now plays a major role at all stages of the disease. Numerous studies with contradictory results have compared total hormonal blockage, an LHRH analog combined with an anti-androgen, with analog alone in locally advanced prostate cancer. A recent metaanalysis showed a slight though globally non-significant advantage in favour of total blockage, but with a significant advantage in the case of a nonsteroidal anti-androgen. In stage T3 cancers, adjuvant hormone therapy over three years in combination with radiotherapy versus external radiotherapy alone was more effective in terms of local or metastatic progression and survival. Institution during radiotherapy and a prolonged duration of treatment gives a greater benefit though this was only significant for the subgroup of patients with a Gleason score ≥ 8. For localized stages but at high risk (PSA > 15 ng / ml and/or Gleason score > 7), adjuvant hormone therapy after prostatectomy improved recurrence-free survival in comparison with prostatectomy followed-up by simple monitoring. On the other hand, the administration of analogs two or three months before radical prostatectomy did not seem to provide any additional benefit. Medical castration prolonged by LH-RH analogs engenders multiple side effects which become all the more worrying as patient survival is prolonged by this hormone therapy. In phase I–II studies, intermittent treatment is equivalent to continuous treatment for “hormone sensitive” patients (PSA nadir at six months < 0.5 ng). Phase III studies are in progress to confirm this equivalence. This intermittent hormone therapy may be a useful solution for elderly patients (> 78 years old) with a biologically highly active cancer and remains to be evaluated in relatively young subjects after radical prostatectomy or radiotherapy. Combination of analogs with chemotherapy has been used very recently for patients who have reached hormonal escape and may be a useful immediate option for patients with cancers with a high risk of progression.