Intermittent androgen deprivation (IAD)

Intermittent androgen deprivation is a strategy of stopping androgen deprivation after an induction period in men who have responded, allowing testosterone to recover, and restarting on a defined trigger. NICE NG131 recommendation 1.4.1 says to consider intermittent therapy for people having long-term androgen deprivation, other than in the adjuvant setting, and to discuss the rationale, the limited evidence for a reduction in side effects, and the effect on progression. Recommendation 1.4.2 sets the practical rule: measure prostate-specific antigen every 3 months, and restart androgen deprivation if the level reaches 10 nanograms per millilitre or above, or if there is symptomatic progression.

The evidence is SWOG 9346, and it is honestly inconclusive. Hussain and the Southwest Oncology Group enrolled 3,040 men with newly diagnosed metastatic hormone-sensitive prostate cancer, gave seven months of androgen deprivation, and randomised the 1,535 whose prostate-specific antigen fell to 4 nanograms per millilitre or below to continuous or intermittent therapy, with co-primary objectives of non-inferior survival, bounded by a hazard ratio of 1.20, and quality of life at three months. Median survival was 5.8 years continuous against 5.1 years intermittent, hazard ratio 1.10 with a 90 percent confidence interval of 0.99 to 1.23. That interval crosses the non-inferiority boundary, so a 20 percent greater risk of death could not be excluded, and too few events occurred to demonstrate inferiority either. Erectile function (p less than 0.001) and mental health (p equals 0.003) were better on intermittent therapy at month 3 and not afterwards. Median follow-up was 9.8 years.

That is why it is offered as a choice rather than recommended, and why the honest statement to a man weighing it is that the quality-of-life gain is real, measurable and brief, and the survival question is open rather than settled. Two further limits belong with the figures: only men whose prostate-specific antigen fell below 4 nanograms per millilitre after seven months were randomised, so the result does not apply to men who do not achieve that response; and standard of care has changed completely since enrolment, because androgen deprivation alone is no longer first-line treatment for metastatic disease, so the question would have to be re-asked on top of a modern backbone of an androgen receptor pathway inhibitor with or without docetaxel.