Relationship of time to testosterone (T) and PSA rises during the first “off treatment” interval (1OFF) of intermittent androgen deprivation (IAD) with time to castration resistance (CRPC) and prostate cancer mortality (PCM) in men with biochemical relapse (BR).

Abstract

99 Background: A recent phase III trial of intermittent vs. continuous AD supports IAD as standard of care for men treated with AD for BR. To identify potential factors during 1OFF prognostic for time to CRPC or PCM, relationships with times to T and PSA rises from our prospective trial of IAD in men with BR were analyzed. Methods: 72 patients were treated with IAD, each cycle consisting of 9 months of leuprolide and flutamide followed by a variable “off treatment” interval. T and PSA were followed monthly; AD was resumed when PSA reached a pre-specified value. Cycles repeated until CRPC, defined as ≥2 PSA rises with T<50 ng/dL. We evaluated patients who completed 1OFF and reached T>50 with a Cox proportional hazards model, controlling for age at study entry, to quantify association of time to first T>50 with time from this point to CRPC or PCM. Similarly we quantified association of PSA rise during 1OFF and after first T>50 with these endpoints. Results: A longer time to PSA rise during 1OFF or after T>50 was associated with longer time to CRPC, while longer time to first T>50 was marginally associated with shorter time to PCM. Specifically, a 30-day increase in time to PSA rise during 1OFF or after T>50 was associated with a 21% or 27% reduction in the risk of CRPC, while a 30-day increase in time to first T>50 was associated with a 39% increase in the risk of PCM. Conclusions: That longer time to PSA rise during 1OFF was associated with longer time to CRPC is not surprising, but the association between longer time to first T>50 and time to PCM has not been reported. To validate these findings, an extended analysis is underway and will be presented. [Table: see text]