Editor's Commentary - The change of PSA doubling time and its association with disease progression in patients with biochemically relapsed prostate cancer treated with intermittent androgen deprivation

BERKELEY, CA (UroToday.com) - In The Prostate, Dr. Daniel Keizman and associates at Johns Hopkins University report on PSADT and its correlation with prostate cancer (CaP) progression in patients on intermittent androgen blockade (IAB).

PSADT in patients with a PSA recurrence after primary therapy stratifies them into high (PSADT <3 months), intermediate (PSADT 3-9 months), and low (PSADT >9 months) risk for future development of distant metastatic disease and death. Use of IAB permits cyclic administration of androgen deprivation therapy (ADT) with recovery of testosterone between treatment periods and possibly improved quality of life. However, the duration and frequency of IAB cycles is somewhat empirical; using either pre-defined durations, or PSA nadir. The objective of this study was to determine the change in PSADT and it correlation with disease progression in patients with non-metastatic biochemically relapsed prostate cancer (BRPC) treated with IAB. Ninety-six patients met these criteria, with relapse after local therapy and no evidence of distant metastases. PSA threshold for initiation of IAB was 10-20ng/ml. Treatment was reinitiated at the same level, and testosterone and PSA were monitored until the development of castration-resistant prostate cancer. PSADT from baseline to the off treatment intervals after IAB initiation were calculated.

The 96 patients treated between 1995 and 2010 had a mean followup of 71 months and received a mean of 2.85 cycles of IAB. Disease progression was independently associated with 3 variables; baseline pre-treatment PSADT ≥6 months vs. <6 months (HR2.17), first off treatment interval PSADT ≥3 months vs. <3 months (HR 2.4), and PSA nadir during the first treatment cycle <0.1 vs. ≥0.1ng/ml (HR 4.7). Not significantly associated with biochemical or clinical disease progression were age, pathologic Gleason score, primary treatment modality, post-primary treatment biochemical free survival time, baseline PSA level before the initiation of IAB, and off treatment interval duration during IAB. PSADT from PSA nadir to re-initiation of ADT during the first off treatment interval was 2.3 months, significantly shorter than the baseline pre-treatment PSADT, but stable when compared to PSADT on subsequent off treatment intervals. They also calculated PSADT based only on relapsed PSA values observed ≥3 months after testosterone recovery to≥150ng/dl. Interestingly, considering all PSA levels regardless of testosterone recovery, the PSADT was only 1.53 months. However, considering only PSA values obtained >3 months after testosterone recovery, the PSADT is 14.44 months. These data demonstrate that testosterone recovery affects the calculation of PSADT during off treatment intervals and may help identify patients who are more or less likely to benefit from IAB.

Keizman D, Huang P, Antonarakis ES, Sinibaldi V, Carducci MA, Denmeade S, Kim JJ, Walczak J, Eisenberger MA


Prostate. 2011 Mar 22. Epub ahead of print.

PubMed Abstract
PMID: 21432863

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