Duration of First Off-Treatment Interval Is Prognostic for Time to Castration Resistance and Death in Men With Biochemical Relapse of Prostate Cancer Treated on a Prospective Trial of Intermittent Androgen Deprivation

Purpose This was an exploratory analysis of a trial of intermittent androgen deprivation (IAD) in men with biochemical relapse ( BR) to establish first cycle characteristics prognostic for progression to castration-resistant prostate cancer (CRPC) and death. Patients and Methods Men with BR of prostate cancer after radical prostatectomy ( RP) or radiation (RT) were treated with androgen deprivation therapy (ADT) comprised of leuprolide and flutamide. After 9 months on treatment, ADT was stopped, and monthly prostate-specific antigen (PSA) levels were observed during the off-treatment interval. When the PSA reached a threshold value ( 1 ng/mL for RP, 4 ng/mL for RT), ADT was resumed in a new cycle. Patients were treated intermittently in this manner until CRPC, which was defined as >= two consecutive increasing PSA values while on ADT with castrate testosterone levels. Results Seventy-two of 100 patients enrolled onto the study met criteria for this analysis. The duration of the first off-treatment interval (<= v > 40 weeks) was associated with shorter time to CRPC ( hazard ratio = 2.9; 95% CI, 1.1 to 7.7; P = .03) and death (hazard ratio = 3.8; 95% CI, 1.1 to 13.6; P = .04) after adjusting for age, stage, grade, and PSA at diagnosis. Conclusion In patients who completed the first cycle of IAD, a duration of the first off-treatment interval of < 40 weeks defines a subset of patients at higher risk of CRPC and death. Conversely, patients with an off-treatment interval of more than 40 weeks have a significantly better long-term prognosis. J Clin Oncol 28:2668-2673. (C) 2010 by American Society of Clinical Oncology