Antiandrogen withdrawal syndrome (AAWS) in the treatment of patients with prostate cancer
- Gianmarco Leone1,*,
- Marcello Tucci1,*⇑,
- Consuelo Buttigliero1,
- Clizia Zichi1,
- Daniele Pignataro1,
- Paolo Bironzo1,
- Francesca Vignani2,
- Giorgio V Scagliotti1 and
- Massimo Di Maio2
- 1Division of Medical Oncology, Department of Oncology, University of Turin, San Luigi Gonzaga Hospital, Turin, Italy
- 2Division of Medical Oncology, Ordine Mauriziano Hospital, Turin, Italy
- Correspondence should be addressed to M Tucci: marcello.tucci{at}gmail.com
Abstract
Antiandrogen withdrawal syndrome is an unpredictable event diagnosed in patients with hormone-sensitive prostate cancer treated with combined androgen blockade therapy. It is defined by prostate-specific antigen value reduction, occasionally associated with a radiological response, that occurs 4–6 weeks after first-generation antiandrogen therapy discontinuation. New-generation hormonal therapies, such as enzalutamide and abiraterone acetate, improved the overall survival in patients with metastatic castration-resistant prostate cancer, and recent trials have also shown the efficacy of abiraterone in hormone-sensitive disease. In the last few years, several case reports and retrospective studies suggested that the withdrawal syndrome may also occur with these new drugs. This review summarizes literature data and hypothesis about the biological rationale underlying the syndrome and its potential clinical relevance, focusing mainly on new-generation hormonal therapies. Several in vitro studies suggest that androgen receptor gain-of-function mutations are involved in this syndrome, shifting the antiandrogen activity from antagonist to agonist. Several different drug-specific point mutations have been reported. The association of the withdrawal syndrome for enzalutamide and abiraterone needs confirmation by additional investigations. However, new-generation hormonal therapies being increasingly used in all stages of disease, more patients may experience the syndrome when stopping the treatment at the time of disease progression, although the clinical relevance of this phenomenon in the management of metastatic castration-resistant prostate cancer remains to be defined.
- Received 17 September 2017
- Accepted 27 September 2017
- Made available online as an Accepted Preprint 28 September 2017
- © 2018 Society for Endocrinology