Testosterone dynamics and oncologic safety in biochemically recurrent prostate cancer: An analysis of intermittent androgen deprivation therapy schedules

Continuous androgen deprivation therapy (cADT) remains the standard treatment for advanced prostate cancer; however, it is associated with morbidity and a reduced quality of life. Intermittent ADT (iADT) is a potential strategy to mitigate these effects; however, the optimal scheduling for iADT remains unclear. This study evaluates the testosterone (T) suppression efficacy and the oncologic safety of different iADT schedules in patients with biochemically recurrent (BCR) prostate cancer. We conducted a retrospective analysis of 119 men with castrate T levels (<20 ng/dL) and stable PSA nadirs following cADT for BCR after radical prostatectomy or radiotherapy. Patients underwent iADT using one of three schedules: 1-on/1-off, 1-on/2-off, or 3-on/3-off months. We tracked serum T and PSA kinetics, and incidence rates of T breakthrough during a median follow-up of 12.0 months. Predictors of T breakthrough were investigated. The three groups had no differences in baseline clinicopathological and laboratory features. The 1-on/1-off regimen effectively suppressed serum T for up to six months, while 1-on/2-off and 3-on/3-off schedules were associated with higher incidences of T breakthrough ( p = 0.002). Despite corresponding PSA rises, no radiographic progression was observed across groups. Predictors of successful T suppression included 1-on/1-off schedule and lower baseline T at iADT initiation. A 1-on/1-off iADT schedule may offer a clinically viable alternative to cADT in maintaining successful T suppression. iADT may be particularly useful in patients seeking to reduce ADT side effects. Further studies are needed to validate these findings and optimize iADT protocols.