Compared with continuous treatment intermittent androgen deprivation therapy (ADT) can improve patients’ quality of life and does not adversely affect survival, a study in the NEJM concludes.

A total of 1,386 patients were enrolled who had a PSA level > 3ng/ml more than a year after primary or salvage radiotherapy for localised prostate cancer, with no distant metastases. Patients were randomised to intermittent or continuous ADT. Intermittent therapy involved completion of eight-month treatment cycles, after which ADT was stopped provided the PSA was < 4ng/ml and there was no evidence of clinical disease progression. Treatment was restarted if the PSA rose subsequently to > 10ng/ml. Median follow up was 6.9 years.

Intermittent therapy showed a benefit in terms of quality of life and side effects, with improvements in hot flushes, libido, erectile function and urinary symptoms, and a trend towards improvement in levels of fatigue.

The primary end point of the study was overall survival, with the study powered to show ‘non-inferiority’ of intermittent ADT versus continuous treatment. Median overall survival was 8.8 years in the intermittent group versus 9.1 years in the continuous group, hazard ratio for death 1.02 (95% CI: 0.86-1.21). Seven year disease-related death rates were 18% and 15% for the two groups respectively (p=0.24 i.e. the difference was not significant).

The authors conclude that intermittent therapy is not inferior to continuous therapy in terms of survival, but with potential quality of life benefits to patients.

This conclusion in terms of quality of life is backed up by a literature review of intermittent ADT recently published in the International Journal of Urology.¹ Thirteen trials were examined, with benefits consistently seen in terms of improvement in the short-term side effects such as hot flushes and sexual function. Data for longer-term side effects was less conclusive. However, the overall conclusion was that the literature supported the view that intermittent therapy offers safety, tolerability and quality of life benefits to patients on ADT.

The study in the NEJM is described in an accompanying editorial2 as ‘the most definitive study to date comparing intermittent versus continuous androgen deprivation therapy in patients with non-metastatic cancer’.

Conceptually, intermittent use of ADT, based on PSA response, offers a number of advantages. As well as providing some relief from ADT-related side effects, intermittent exposure to ADT may prolong the time to development of androgen resistance. There is also the potential cost saving from reduced use of expensive ADT injections.

The message for primary care? Intermittent ADT is well worth consideration in patients with low PSA levels on long-term ADT, particularly those experiencing significant side effects. Many men can experience ‘hormone holidays’ which allow at least temporary improvement in highly bothersome side effects such as erectile dysfunction or loss of libido. It is worth the GP asking the oncologist about the possibility of intermittent therapy in these patients.

Dr Jonathan Rees