The change of PSA doubling time and its association with disease progression in patients with biochemically relapsed prostate cancer treated with intermittent androgen Deprivation

Daniel Keizman, Peng Huang, Emmanuel S. Antonarakis, Victoria Sinibaldi, Michael A. Carducci, Samuel Denmeade, Jenny J. Kim, Janet Walczak, Mario A. Eisenberger

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

BACKGROUND We sought to determine the change of PSA doubling time (PSADT) and its association with disease progression during intermittent androgen deprivation (IAD) therapy for prostate cancer. METHODS Data were retrospectively analyzed in 96 patients with biochemically relapsed prostate cancer (BRPC) treated with IAD since 1995. IAD consisted of LHRH-agonists ± antiandrogen given usually at PSA threshold (ng/ml) of 10-20, for 6-9 months. Cycles were repeated until the development of castration resistance. Mixed effects model was used to study PSADT change over cycles. Multivariate cox regression model was used to identify outcome-associated variables. RESULTS Patients received a mean of 2.8 treatment cycles over a mean follow-up time of 71 months. Fifty-seven (59%) remain on treatment and 39 (41%) developed PSA refractoriness (n = 8) or positive scans (n = 31). First off treatment interval PSADT (median 2.3 months) was significantly shorter than the baseline (median 7.34) but remained stable in subsequent cycles. Off treatment interval PSADT adjusted for testosterone recovery (median 3.7) was significantly longer than that based on all PSA determinations (median 2). Factors associated with disease progression were pre-treatment PSADT (≥6 vs. <6), first off treatment interval PSADT (≥3 vs. <3), and PSA nadir during the first treatment interval (<0.1 vs. ≥0.1). CONCLUSIONS During IAD for BRPC, PSADT becomes shorter, and is associated with testosterone recovery. PSADT before treatment and during the first off treatment interval is associated with disease progression. If prospectively validated these data may guide treatment with IAD and clinical trial design.

Original languageEnglish (US)
Pages (from-to)1608-1615
Number of pages8
JournalProstate
Volume71
Issue number15
DOIs
StatePublished - Nov 2011
Externally publishedYes

Keywords

  • PSA doubling time
  • disease progression
  • intermittent androgen deprivation therapy
  • non-metastatic biochemically relapsed prostate cancer
  • serum testosterone

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