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The Prostate Cancer Research Institute, Los Angeles, California, USA
Correspondence: Stephen B. Strum, MD, 4676 Admiralty Way, Suite #101, Marina del Rey, CA 90292, USA. Telephone: 310-827-7707; Fax: 310-574-4002; e-mail: sbstrum{at}mediaone.net
Objectives. We hypothesize that prostate cancer (PC) patients who achieve and maintain an undetectable prostate-specific antigen (UD-PSA) on androgen deprivation therapy (ADT) have a predominantly androgen-dependent cancer cell population sensitive to apoptosis that allows for a prolonged time off ADT. This study summarizes patient- and treatment-related factors associated with a prolonged time off ADT in patients electing intermittent androgen deprivation (IAD).
Methods. Hormone-naïve patients with PC were treated with ADT using an antiandrogen and a luteinizing-hormone-releasing hormone-agonist. Of 255 consecutive patients, 216 (85%) achieved a UD-PSA (<0.05 ng/ml). Ninety-three (43%) of 216 elected to stop ADT after maintaining a UD-PSA for a median of one year. Patients were followed off therapy and advised to restart ADT if the PSA level reached
Results. In the first IAD cycle, the median duration of the on-phase of IAD was 16 months (mean 19.0 months, range 3.6-71 months), and the median off-phase duration was 15.5 months (mean 24.1 months, range 3.2-87+ months). In 28 patients who maintained a UD-PSA for
Conclusions. Hormone-naïve patients who achieve and maintain a UD-PSA for at least one year during ADT may initiate IAD and anticipate a prolonged off-phase duration. Attainment of a UD-PSA on ADT may serve as an in vivo sensitivity test of a patient's tumor cell population, and allow for better selection of those best suited for IAD.
5.0 ng/ml. Forty-one patients received finasteride as part of IAD induction and as maintenance off therapy; these patients are excluded from the current study and are the focus of another publication. The remaining 52 patients are assessable for response being either in the off-phase of IAD 1 year or having restarted IAD. 1 year, their median off-phase duration was 29 months (mean 35.8 months, range 7.8-87+ months), with nine (32%) still off IAD after a median follow-up of 62 months. Significant (p < 0.05) independent factors associated with prolonged off-phase duration by multivariate analysis included UD-PSA on ADT 1 year (p = 0.010), PSA-only recurrence after local therapy (p = 0.039), and reaching a testosterone level 150 ng/dl in 4 months off ADT (p = 0.041). After a median of 66 months of follow-up, only one (2%) patient developed androgen-independent PC.
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